Sex differences in self-regulation in early, middle and late adolescence: A large-scale cross-sectional study.

This large-scale cross-sectional study had the aim to investigate whether adolescent males and females differ in self-perceived self-regulation. The large sample size allowed us to investigate sex differences in three age-groups of young (n = 161), middle (n = 133) and late (n = 159) adolescents. Self-regulation was evaluated with a self-report questionnaire, the Amsterdam Executive Functioning Inventory (AEFI). This questionnaire gives a proxi for three executive functions that are important for proper self-regulation: (1) self-control & self-monitoring, (2) attention, and (3) planning & initiative taking. Results revealed clear sex differences in the self-regulation as perceived by mid-adolescents (i.e., 13-16 years). In this age period, females evaluated their attention higher than males, and they reported higher levels of self-control & self-monitoring. Our findings offer important new insights with respect to the decision making, academic achievements and behaviour of 13-16-year olds. Self-regulation is known to have a central role in academic achievement and in behavioural organisation. The sex differences in self-regulation in mid-adolescence may therefore explain part of the difference which males and females in this age-group exhibit in academic achievements and behavioural organisations. The results imply that self-regulation may be a relevant intervention target: rather than focussing on changing behaviour, interventions may focus more on self-insights and thereby changing the adolescent's perceptions about their behaviour. Increased self-insight may have the potency to actually change behaviour, which might be an interesting target for future investigation.

Quality of life, delinquency and psychosocial functioning of adolescents in secure residential care: testing two assumptions of the Good Lives Model.

BACKGROUND: In this study, two assumptions derived from the Good Lives Model were examined: whether subjective Quality of Life is related to delinquent behaviour and psychosocial problems, and whether adolescents with adequate coping skills are less likely to commit delinquent behaviour or show psychosocial problems. METHOD: To this end, data of 95 adolescents with severe psychiatric problems who participated in a four-wave longitudinal study were examined. Subjective Quality of Life was assessed with the ten domains of the Lancashire Quality of Life Profile and coping skills with the Utrecht Coping List for Adolescents. RESULTS: Results showed that adolescents who reported a lower Quality of Life on the health domain had more psychosocial problems at follow-up. No relationship was found between Quality of Life and delinquent behaviour. In addition, active and passive coping were associated with delinquent behaviour and psychosocial functioning at follow-up. CONCLUSIONS: Based on the results of this longitudinal study, the strongest support was found for the second assumption derived from the Good Lives Model. Adolescents with adequate coping skills are less likely to commit delinquent behaviour and have fewer psychosocial problems at follow-up. The current study provides support for the use of strength-based elements in the treatment programmes for adolescents in secure residential care.

The role of confinement and corona crystallinity on the bending modulus of copolymer micelles measured directly by AFM flexural tests.

We present an approach which makes it possible to directly determine the bending modulus of single elongated block copolymer micelles. This is done by forming arrays of suspended micelles onto microfabricated substrates and by performing three-point bending flexural tests, using an atomic force microscope, on their suspended portions. By coupling the direct atomic force microscopy measurements with differential scanning calorimetry data, we show that the presence of a crystalline corona strongly increases the modulus of the copolymer elongated micelles. This large increase suggests that crystallites in the corona are larger and more uniformly oriented due to confinement effects. Our findings together with this hypothesis open new interesting avenues for the preparation of core-templated polymer fibres with enhanced mechanical properties.

In vivo biodistribution of stable spherical and filamentous micelles probed by high-sensitivity SPECT.

Understanding how nanoparticle properties such as size, morphology and rigidity influence their circulation time and biodistribution is essential for the development of nanomedicine therapies. Herein we assess the influence of morphology on cellular internalization, in vivo biodistribution and circulation time of nanocarriers using polystyrene-b-poly(ethylene oxide) micelles of spherical or elongated morphology. The glassy nature of polystyrene guarantees the morphological stability of the carriers in vivo and by encapsulating Indium-111 in their core, an assessment of the longitudinal in vivo biodistribution of the particles in healthy mice is performed with single photon emission computed tomography imaging. Our results show prolonged blood circulation, longer than 24 hours, for all micelle morphologies studied. Dynamics of micelle accumulation in the liver and other organs of the reticuloendothelial system show a size-dependent nature and late stage liver clearance is observed for the elongated morphology. Apparent contradictions between recent similar studies can be resolved by considering the effects of flexibility and degradation of the elongated micelles on their circulation time and biodistribution.

Induction of a monocyte/macrophage phenotype switch by mesenchymal stem cells might contribute to improved infarct healing postacute myocardial infarction.

Inadequate healing following acute myocardial infarction (AMI) can lead to the development of heart failure. The ischemic myocardium triggers an inflammatory response that clears cell debris and initiates the onset of scar tissue formation. The duration and intensity of this inflammatory response have been linked to the cardiac functioning post-AMI. In order to diminish scar tissue formation and stimulate regeneration of cardiac tissue, mesenchymal stem cell (MSC) have been applied post-AMI and showed beneficial effects on cardiac function. However, other than the expected regeneration of cardiac tissue, modulation of the inflammatory response post-AMI, especially related to an effect on monocytes/macrophages, was recently found to be an important aspect of MSC therapy. In healing post-AMI, monocytes and macrophages are key players that can either stimulate or repress inflammation using different phenotypes. Increased levels of the proinflammatory phenotype have clinically been associated with poor cardiac functional outcome post-AMI. MSC have been suggested to switch the monocytes/macrophages phenotype into a more anti-inflammatory state and might therefore beneficially influence the duration and intensity of the inflammatory response and subsequent cardiac function post-AMI. To gain more insight into this effect of MSC, this review provides an overview of the most relevant studies regarding this modulatory effect of MSC on monocytes/macrophages including its mechanisms to improve cardiac functioning post-AMI.

Clinical parameters associated with collateral development in patients with chronic total coronary occlusion.

OBJECTIVE: Well-developed collaterals provide survival benefit in patients with obstructive coronary artery disease (CAD). Therefore, in this study we sought to determine which clinical variables are associated with arteriogenesis. DESIGN: Clinical and laboratory variables were collected before percutaneous coronary intervention. Multivariate analysis was performed to determine which variables are associated with the collateral flow index (CFI). PATIENTS: Data from 295 chronic total occlusion (CTO) patients (Bern, Switzerland, Amsterdam, the Netherlands and Jena, Germany) were pooled. In earlier studies, patients had varying degrees of stenosis. Therefore, different stages of development of the collaterals were used. In our study, a unique group of patients with CTO was analysed. INTERVENTIONS: Instead of angiography used earlier, we used a more accurate method to determine CFI using intracoronary pressure measurements. CFI was calculated from the occlusive pressure distal of the coronary lesion, the aortic pressure and central venous pressure. RESULTS: The mean CFI was 0.39 ± 0.14. After multivariate analysis, ß blockers, hypertension and angina pectoris duration were positively associated with CFI (B: correlation coefficient ß=0.07, SE=0.03, p=0.02, B=0.040, SE=0.02, p=0.042 and B=0.001, SE=0.000, p=0.02). Furthermore also after multivariate analysis, high serum leucocytes, prior myocardial infarction and high diastolic blood pressure were negatively associated with CFI (B=-0.01, SE=0.005, p=0.03, B=-0.04, SE=0.02, p=0.03 and B=-0.002, SE=0.001, p=0.011). CONCLUSIONS: In this unique cohort, high serum leucocytes and high diastolic blood pressure are associated with poorly developed collaterals. Interestingly, the use of ß blockers is associated with well-developed collaterals, shedding new light on the potential action mode of this drug in patients with CAD.

Brody syndrome: a clinically heterogeneous entity distinct from Brody disease: a review of literature and a cross-sectional clinical study in 17 patients.

Brody disease is a rare inherited myopathy due to reduced sarcoplasmic reticulum Ca(2+) ATPase (SERCA)1 activity caused by mutations in ATP2A1, which causes delayed muscle relaxation and silent cramps. So far the disease has mostly been diagnosed by measurement of SERCA1 activity. Since mutation analysis became more widely available, it has appeared that not all patients with reduced SERCA1 activity indeed have ATP2A1 mutations, and a distinction between Brody disease (with ATP2A1 mutations) and Brody syndrome (without ATP2A1 mutations) was proposed. We aim to compare the clinical features of patients with Brody disease and those with Brody syndrome and detect clinical features which help to distinguish between the two. In addition, we describe the Brody syndrome phenotype in more detail. We therefore performed a literature review on clinical features of both Brody disease and Brody syndrome and a cross-sectional clinical study consisting of questionnaires, physical examination, and a review of medical files in 17 Brody syndrome patients in our centre. The results showed that Brody disease presents with an onset in the 1st decade, a generalized pattern of muscle stiffness, delayed muscle relaxation after repetitive contraction on physical examination, and autosomal recessive inheritance. Patients with Brody syndrome more often report myalgia and experience a considerable impact on daily life. Future research should focus on the possible mechanisms of reduction of SERCA activity in Brody syndrome and other genetic causes, and on evaluation of treatment options.

Surfing the data tsunami, a bioinformatic dissection of the proangiogenic monocyte.

In this review we compare expression studies on monocyte subsets as an example to show the integrated possibilities of molecular databases and bioinformatic analysis tools. Monocytes have been recognized as cells with great plasticity and differentiation potential that play a pivotal role in revascularization processes, i.e. angiogenesis and arteriogenesis. To gain more insight in the relevant developmental programs, we compared the full-genome mRNA expression profiles of several distinct human monocyte subpopulations previously identified based on surface marker expression. These included classical and non-classical, M1 and M2 macrophages, circulating angiogenic cells (CAC), and non-monocyte-derived endothelial colony-forming cells (ECFC). Their transcriptional profiles revealed distinct and overlapping gene expression signatures and pathways reminiscent of utilization of transcription factors driving polarization into the different monocytic phenotypes. Hierarchical cluster analysis revealed that CAC are most related to M2 macrophages and unstimulated macrophages, and to a lesser extent to classical monocytes, and are quite distinct from M1 macrophages and ECFC. Analysis of the promoter region of CAC-expressed genes suggests that in particular the ETS family of transcription factors is important in CAC development. These analyses show the power of combining multiple datasets with existing databases on biological knowledge, to interpret full genome expression data.

Intracoronary infusion of mononuclear cells after PCI-treated myocardial infarction and arrhythmogenesis: is it safe?

To reduce long-term morbidity after revascularised acute myocardial infarction, different therapeutic strategies have been investigated. Cell therapy with mononuclear cells from bone marrow (BMMC) or peripheral blood (PBMC) has been proposed to attenuate the adverse processes of remodelling and subsequent heart failure. Previous trials have suggested that cell therapy may facilitate arrhythmogenesis. In the present substudy of the HEBE cell therapy trial, we investigated whether intracoronary cell therapy alters the prevalence of ventricular arrhythmias after 1 month or the rate of severe arrhythmogenic events (SAE) in the first year. In 164 patients of the trial we measured function and infarct size with cardiovascular magnetic resonance (CMR) imaging. Holter registration was performed after 1 month from which the number of triplets (3 successive PVCs) and ventricular tachycardias (VT, ≥4 successive PVCs) was assessed. Thirty-three patients (20%) showed triplets and/or VTs, with similar distribution amongst the groups (triplets: control n = 8 vs. BMMC n = 9, p = 1.00; vs. PBMC n = 10, p = 0.67. VT: control n = 9 vs. BMMC n = 9, p = 0.80; vs. PBMC n = 11, p = 0.69). SAE occurred in 2 patients in the PBMC group and 1 patient in the control group. In conclusion, intracoronary cell therapy is not associated with an increase in ventricular arrhythmias or SAE.

Intraoperative near-infrared fluorescence imaging of colorectal metastases targeting integrin α(v)ß(3) expression in a syngeneic rat model.

AIM: Near-infrared (NIR) fluorescence optical imaging is a promising technique to assess the extent of colorectal metastases during curative-intended surgery. However, NIR fluorescence imaging of liver metastases is highly challenging due to hepatic uptake and clearance of many fluorescent dyes. In the current study, the biodistribution and the ability to demarcate liver and peritoneal metastases were assessed during surgery in a syngeneic rat model of colorectal cancer using an integrin α(v)ß(3)-directed NIR fluorescence probe. METHODS: Liver tumors and peritoneal metastases were induced in 7 male WAG/Rij rats by subcapsular inoculation of 0.5 × 10(6) CC531 colorectal cancer rat cells into three distinct liver lobes. Intraoperative and ex vivo fluorescence measurements were performed 24 (N = 3 rats, 7 tumors) and 48 h (N = 4 rats, 9 tumors) after intravenous administration of the integrin α(v)ß(3)-directed NIR fluorescence probe. RESULTS: Colorectal metastases had a minimal two-fold higher NIR fluorescence signal than healthy liver tissue and other abdominal organs (p < 0.001). The tumor-to-background ratio was independent of time of imaging (24 h vs. 48 h post-injection; p = 0.31), which facilitates flexible operation planning in future clinical applications. Total fluorescence intensity was significantly correlated with the size of metastases (R(2) = 0.92 for the 24 h group, R(2) = 0.96 for the 48 h group). CONCLUSION: These results demonstrate that colorectal intra-abdominal metastases can be clearly demarcated during surgery using an integrin α(v)ß(3) targeting NIR fluorescence probe. Translating these findings to the clinic will have an excellent potential to substantially improve the quality of cancer surgery.

Blocking interferon {beta} stimulates vascular smooth muscle cell proliferation and arteriogenesis.

Increased interferon (IFN)-ß signaling in patients with insufficient coronary collateralization and an inhibitory effect of IFNß on collateral artery growth in mice have been reported. The mechanisms of IFNß-induced inhibition of arteriogenesis are unknown. In stimulated monocytes from patients with chronic total coronary artery occlusion and decreased arteriogenic response, whole genome expression analysis showed increased expression of IFNß-regulated genes. Immunohistochemically, the IFNß receptor was localized in the vascular media of murine collateral arteries. Treatment of vascular smooth muscle cells (VSMC) with IFNß resulted in an attenuated proliferation, cell-cycle arrest, and increased expression of cyclin-dependent kinase inhibitor-1A (p21). The growth inhibitory effect of IFNß was attenuated by inhibition of p21 by RNA interference. IFNß-treated THP1 monocytes showed enhanced apoptosis. Subsequently, we tested if collateral artery growth can be stimulated by inhibition of IFNß-signaling. RNA interference of the IFNß receptor-1 (IFNAR1) increased VSMC proliferation, cell cycle progression, and reduced p21 gene expression. IFNß signaling and FAS and TRAIL expression were attenuated in monocytes from IFNAR1(-/-) mice, indicating reduced monocyte apoptosis. Hindlimb perfusion restoration 1 week after femoral artery ligation was improved in IFNAR1(-/-) mice compared with wild-type mice as assessed by infusion of fluorescent microspheres. These results demonstrate that IFNß inhibits collateral artery growth and VSMC proliferation through p21-dependent cell cycle arrest and induction of monocyte apoptosis. Inhibition of IFNß stimulates VSMC proliferation and collateral artery growth.

Experts' opinions on ethical issues of genetic research into Alzheimer's disease: results of a Delphi study in the Netherlands.

Most publications on the ethical aspects of genetic research into Alzheimer's Disease (AD) concentrate on the differences between the opinions of professionals and non-professionals. Differences in rating of morally relevant issues between groups of professionals have not yet been described. A modified Delphi study in two rounds was held to identify differences between groups of experts (i.e. clinicians, representatives of patient organisations, ethicists and persons with a commercial background). The strongest correlation was found between the opinions of ethicists and representatives of patient organisations (0.67) and between clinicians and ethicists (0.62). Moderate correlation (0.55) was found between the opinions of clinicians and representatives of patient organisations. Persons with a commercial background showed a weak correlation with clinicians (0.41), ethicists (0.35) and representatives of patient organisations (0.30). These differences in rating of morally relevant issues between various professional groups are relevant for clinical practice and dementia care, particularly the different rating of prenatal diagnosis found between clinicians and representatives of patient organisations. Interdisciplinary consultations between various professional groups -including at least researchers, clinicians and ethicists -are recommended to guarantee that all considerations will be incorporated into the debate on ethical issues of genetic research into AD.

Cell cycle effects of fatty acid derivatives of cytarabine, CP-4055, and of gemcitabine, CP-4126, as basis for the interaction with oxaliplatin and docetaxel.

To bypass resistance due to limited entry into the cell derivatives of cytarabine (CP-4055, elacytarabine) and gemcitabine (CP-4126) containing a fatty acid chain at the 5' position of the nucleoside were developed. CP-4055 showed an increased retention of the active metabolite, the triphosphate. This characteristic was supposed to favor combinations, such as with the tubulin antagonist docetaxel, the platinum oxaliplatin and the antifolate pemetrexed. The role of the cell cycle effects of CP-4055 and CP-4126 on the efficacy of the combination with docetaxel or pemetrexed was determined. The combination of CP-4055 with oxaliplatin and docetaxel was also evaluated in a mouse xenograft model. CP-4055 induced a G2/M and S phase accumulation and CP-4126 an S phase accumulation. Both analogs induced a dose-dependent cell kill (apoptosis and necrosis). None of the docetaxel combinations induced a synergistic effect. The combination of docetaxel with CP-4055 or CP-4126 induced a G2/M accumulation in the A549 (lung cancer) cell line, but a G0/G1 accumulation in the WiDR (colon cancer) cell line. Preincubation with docetaxel induced an increased cell kill in both cell lines. The combination with oxaliplatin showed a synergistic effect in both cell lines. Combinations with pemetrexed were antagonistic in both cell lines. In the A549 cell line pemetrexed with CP-4055 led to an increase of the G0/G1 phase and the S phase. In WiDR the combination of pemetrexed with CP-4055 increased the G0/G1 phase and increased the cell kill. Pemetrexed with CP-4126 induced an increase in the G0/G1 phase and the S phase in the A549 cell line. In the xenograft study, on a colon cancer and a lung metastasis model, the combination of CP-4055 with docetaxel showed the best results. Treatment with CP-4055 followed by docetaxel after 4 h resulted in a reduction in metastasis in a lung metastasis model, and a favorable toxicity profile was observed. In conclusion, the combinations with oxaliplatin showed a synergistic effect in the combination studies. Although the combinations with docetaxel did not show an enhanced effect in the in vitro studies, this combination revealed an increased effect in the xenograft model.

Hotlines and clinical trial updates presented at the European Society of Cardiology Meeting 2009: data from RE-LY, PLATO, MADIT-CRT, PROTECT, SYNTAX, TRITON and more.

This summary article provides an update on novel clinical trials in the field of cardiovascular (CV) medicine which were presented at the annual meeting of the European Cardiac Society, held in Barcelona, Spain, in August-September 2009. The data were presented by leading experts in the field with relevant positions in the trials and registries. Unpublished reports should be considered as preliminary data as the analysis may change in the final publications. This article provides the reader with comprehensive summaries of the most recent diagnostic and therapeutic developments in CV medicine as previously reported (Kindermann et al. in Clin Res Cardiol 96:767-786, 2007; Müller et al. in Clin Res Cardiol 97:851-864, 2008).

A phase I and pharmacokinetic study of gemcitabine given by 24-h hepatic arterial infusion.

PURPOSE: This study was performed to assess the toxicities, the maximum-tolerated dose (MTD), the pharmacokinetics and the anti-tumour activity of gemcitabine given by 24-h hepatic arterial infusion (HAI). PATIENTS AND METHODS: Patients with liver malignancies received gemcitabine by 24-h HAI, weekly x 3, every 4 weeks. On day 1 or day 8 of the first cycle, patients received one administration by 24-h intravenous infusion for pharmacokinetic comparison and to determine hepatic extraction. RESULTS: Thirteen patients received gemcitabine at the dose levels of 75, 135 and 180 mg/m(2). The MTD was 180 mg/m(2) with thrombocytopaenia as the dose-limiting toxicity. Pharmacokinetic analysis showed a significantly lower maximum gemcitabine plasma concentration (C(max): HAI, 26, 80 and 128 nM, respectively; IV, 229, 264 and 293 nM, respectively) and area under the plasma-concentration-versus-time curve (AUC(0-24h): HAI, 386, 1247 and 2033 nmol x h/L, respectively; IV, 3526, 4818 and 5363 nmol x h/L, respectively) during HAI, compared with intravenous infusion (both P<0.001). Additionally, the mean hepatic extraction ratios of gemcitabine at the 75, 135 and 180 mg/m(2) dose level were 0.89, 0.75 and 0.55, respectively. Hepatic extraction decreased linearly with increasing dose. The C(max) and AUC(0-24h) of 2',2'-difluoro-2'-deoxyuridine, the deaminated product of gemcitabine, were similar for HAI and intravenous infusion. Seven patients had stable disease for a median duration of 9 months (range: 2-11 months). CONCLUSIONS: Gemcitabine given by 24-h HAI was well tolerated and resulted in significantly lower systemic gemcitabine plasma concentrations than intravenous infusion due to a relatively high hepatic extraction.

Gemcitabine uptake in glioblastoma multiforme: potential as a radiosensitizer.

Glioblastoma multiforme (GBM), the most frequent malignant brain tumor, has a poor prognosis, but is relatively sensitive to radiation. Both gemcitabine and its metabolite difluorodeoxyuridine (dFdU) are potent radiosensitizers. The aim of this phase 0 study was to investigate whether gemcitabine passes the blood-tumor barrier, and is phosphorylated in the tumor by deoxycytidine kinase (dCK) to gemcitabine nucleotides in order to enable radiosensitization, and whether it is deaminated by deoxycytidine deaminase (dCDA) to dFdU. Gemcitabine was administered at 500 or 1000 mg/m(2) just before surgery to 10 GBM patients, who were biopsied after 1-4 h. Plasma gemcitabine and dFdU levels varied between 0.9 and 9.2 microM and 24.9 and 72.6 microM, respectively. Tumor gemcitabine and dFdU levels varied from 60 to 3580 pmol/g tissue and from 29 to 72 nmol/g tissue, respectively. The gene expression of dCK (beta-actin ratio) varied between 0.44 and 2.56. The dCK and dCDA activities varied from 1.06 to 2.32 nmol/h/mg protein and from 1.51 to 5.50 nmol/h/mg protein, respectively. These enzyme levels were sufficient to enable gemcitabine phosphorylation, leading to 130-3083 pmol gemcitabine nucleotides/g tissue. These data demonstrate for the first time that gemcitabine passes the blood-tumor barrier in GBM patients. In tumor samples, both gemcitabine and dFdU concentrations are high enough to enable radiosensitization, which warrants clinical studies using gemcitabine in combination with radiation.

The role of platelet-derived endothelial cell growth factor/thymidine phosphorylase in tumor behavior.

Platelet-derived endothelial cell growth-factor (PD-ECGF) is similar to the pyrimidine enzyme thymidine phosphorylase (TP). A high TP expression at tumor sites is correlated with tumor growth, induction of angiogenesis, and metastasis. Therefore, high TP is most likely associated with a poor prognosis. TP is not only expressed in tumor cells but also in tumor surrounding tissues, such as tumor infiltrating macrophages. TP catalyzes the conversion of thymidine to thymine and doxyribose-1-phosphate (dR-1-P). The latter in its parent form or in its sugar form, deoxyribose (dR) may play a role in the induction of angiogenesis. It may modulate cellular energy metabolism or be a substrate in a chemical reaction generating reactive oxygen species. L-deoxyribose (L-dR) and thymidine phosphorylase inhibitor (TPI) can reverse these effects. The mechanism of TP induction is not yet completely clear, but TNF, IL10 and other cytokines have been clearly shown to induce its expression. The various complex interactions of TP give it an essential role in cellular functioning and, hence, it is an ideal target in cancer therapy.

Correlation between cytidine deaminase genotype and gemcitabine deamination in blood samples.

Cytidine deaminase (CDA) is the major enzyme of gemcitabine inactivation. The aim of this study was to determine whether the CDA Lys27Gln polymorphism influenced gemcitabine deamination in blood samples from 90 lung cancer patients. The polymorphism was studied with Taqman probes-based assay; CDA activity was evaluated by HPLC in cytoplasmic extracts from red blood cells. Mean enzymatic activity was significantly lower in patients carrying the CDA Lys27Lys than in patients with the Lys27Gln or Gln27Gln protein (P < 0.05). CDA genotyping may be useful in screening patients before gemcitabine treatment, in order to identify subjects with lower CDA activity and potentially better clinical outcomes after gemcitabine-based chemotherapy.

Bone marrow cell therapy after acute myocardial infarction: the HEBE trial in perspective, first results.

During the last decennium, the role of bone marrow mononuclear cells (BMMC) has been underscored in the healing process after acute myocardial infarction (AMI). Although these cells improve left ventricular recovery after AMI in experimental studies, results from large-scale randomised trials investigating BMMC therapy in patients with AMI have shown contradictory results. To address this issue the HEBE study was designed, a multicentre, randomised trial, evaluating the effects of intracoronary infusion of BMMCs and the effects of intracoronary infusion of peripheral blood mononuclear cells after primary percutaneous coronary intervention. The primary endpoint of the HEBE trial is the change in regional myocardial function in dysfunctional segments at four months relative to baseline, based on segmental analysis as measured by magnetic resonance imaging. The results from the HEBE trial will provide detailed information about the effects of intracoronary BMMC therapy on post-infarct left ventricular recovery. In addition, further analysis of the data and material obtained may provide important mechanistic insights into the contribution of BMMCs to natural recovery from AMI as well as the response to cell therapy. This may significantly contribute to the development of improved cell-based therapies, aiming at optimising post-infarct recovery and preventing heart failure. (Neth Heart J 2008;16:436-9.).