The Histone Methyltransferase SETDB1 Controls T Helper Cell Lineage Integrity by Repressing Endogenous Retroviruses

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Chronic total occlusion treatment in post-CABG patients: saphenous vein graft versus native vessel recanalization-long-term follow-up in the drug-eluting stent era.

OBJECTIVE: To compare the postprocedural and long-term clinical outcomes of two groups of patients, all presenting with chronic saphenous vein graft (SVG) occlusion, who underwent either SVG or native vessel reopening. BACKGROUND: Chronic total occlusions (CTO) treatment in patients who underwent previous surgical revascularization is a dilemma and the choice of performing native vessel or SVG recanalization is not always easy. METHODS: Between July 2002 and October 2004, a total of 260 patients were successfully treated for a CTO. Of them, we selected all patients (n = 24) who had previous bypass surgery with graft occlusion. Of this final group, 13 patients underwent a percutaneous graft recanalization while 11 underwent native vessel reopening. RESULTS: Primary end points were in-hospital and 3-year rates of death, myocardial infarction, target lesion revascularization, and target vessel revascularization. No events occurred in either group during the in-hospital period. Cumulative 3-year event-free survival in the native vessel and SVG group was 81.8% and 83.9% respectively (P = NS). One death and one TVR occurred in each group. CONCLUSION: In selected cases, SVG reopening instead of the native vessel is feasible. In such a high-risk population, drug-eluting stent implantation in both SVG and native CTO lesions is associated with good long-term outcomes.     

Septal ablation in hypertrophic obstructive cardiomyopathy improves systolic myocardial function in the lateral (free) wall: a follow-up study using CMR tissue tagging and 3D strain analysis.

AIMS: Alcohol septal ablation (ASA) has been successful in the treatment of symptomatic hypertrophic obstructive cardiomyopathy (HOCM). The aim of this study is to evaluate the effects of ethanol-induced myocardial infarcts on regional myocardial function using cardiac magnetic resonance (CMR) tissue tagging and 3-dimensional (3D) strain analysis. METHODS AND RESULTS: In nine patients (age 52+/-15 years) who underwent ASA, CMR was performed prior to and 6 months after the procedure. Regional myocardial mass was evaluated using cine imaging. Myocardial tagging was used to calculate systolic 3D myocardial strain values. These strain values were used to calculate the shortening index (SI), a robust parameter for myocardial contraction. Maximum end-systolic (ES) SI and systolic SI rate were quantified in three circumferential segments: septum, adjacent, and remote (lateral) myocardium. Compared with baseline, septal and non-septal mass decreased at follow-up (from 72+/-27 to 59+/-21 g; P=0.008 and from 131+/-34 to 109+/-30 g; P=0.008, respectively). In the septum, maximum ES SI and SI rate remained unchanged after ASA. In adjacent myocardium, ES SI remained unchanged, whereas SI rate improved (from -56.5+/-21.1 to -70.0+/-16.7%/s; P=0.02). Both ES SI and SI rate improved significantly in remote myocardium (from -16.9+/-2.8 to -18.8+/-3.2%; P=0.02 and from -70.3+/-9.2 to -86.1+/-15.0%/s; P=0.01, respectively). CONCLUSION: Reduction of left ventricular (LV) outflow tract obstruction in symptomatic HOCM is associated with a significant reduction in myocardial mass and improvement of intramural systolic function in the lateral (remote) wall, indicating reversed LV remodelling.     

School and leisure activities in adolescents and young adults with chronic digestive disorders: Impact of burden of disease

First, we compared the nature of burden of disease (i.e., manifestations of the disease in daily life) in adolescents and young adults with various chronic digestive disorders with controls. After that, we investigated whether burden of disease is associated with difficulties in school and leisure activities of adolescents and young adults with various digestive disorders. For this purpose, we performed a multicenter study in 5 diagnostic groups (total N = 758; ages 12 to 25 years) including inflammatory bowel diseases (IBD), chronic liver diseases, congenital disorders, celiac disease, and food allergy and a population based control group (N = 306) using a self-report questionnaire. Especially adolescents and young adults with a chronic liver disease, IBD, and food allergy were found to experience daily manifestations of their disease. Several disease burden characteristics, of which especially depression, could be identified as important contributors to difficulties in school performance and leisure activities. This study was supported by a grant from the Foundation for Children’s Welfare Stamps Netherlands. We thank Nel Feijten, Ciska Mastenbroek, Ellen Kampman, Karin Wittebrood, and Maarten Sinaasappel for their support in this study.     

Meta-analysis urges the development of new strategies to treat depression in order to improve cardiac prognosis.

With interest, we read the meta-analysis by Nicholson et al.¹on depression as an aetiological and prognostic factor in coronaryheart disease (CHD). Focusing on the prognostic risk associatedwith depression,     

Effects of preoperative treatment with diltiazem on diastolic ventricular function after coronary artery bypass graft surgery

OBJECTIVE: To examine whether preoperative treatment with diltiazem could ameliorate left ventricular (LV) diastolic dysfunction in patients after coronary artery bypass graft (CABG) surgery. DESIGN: Prospective, nonrandomized clinical study. SETTING: University hospital. PARTICIPANTS: Thirty-four patients with preserved LV function undergoing elective CABG surgery. INTERVENTIONS: According to medical history, patients were divided into 2 groups: patients not receiving diltiazem (n = 17) and patients treated with once-daily oral diltiazem for at least 2 weeks (n = 17). All patients received preoperative beta-blockers. MEASUREMENTS AND MAIN RESULTS: After induction of anesthesia, after sternal closure, and 4 hours after cardiopulmonary bypass (CPB), mitral and pulmonary venous flow velocities were measured with pulsed Doppler. LV short-axis end-diastolic area by Doppler transesophageal echocardiography (TEE) and hemodynamic variables were obtained simultaneously at comparable pulmonary capillary wedge pressures. Postoperatively, increased peak E and A velocities were observed in patients with diltiazem and controls and returned to baseline 4 hours post-CPB in controls. Changes in these velocities did not result in a decreased E/A ratio. Peak A velocity, E/A ratio, and E wave deceleration time were significantly dependent on heart rate, not peak E velocity. End-diastolic area at comparable pulmonary capillary wedge pressure remained unchanged. In relation to diltiazem, only peak A velocity and time velocity integral of the A wave (TVI-A) at 4 hours post-CPB differed from controls. CONCLUSION: Diastolic function is preserved after CABG surgery and is not altered by diltiazem in patients with preserved LV systolic function. The persistence of increased peak A velocity and TVI-A into the postoperative period suggests improved atrial systolic function with diltiazem.     

Comparison of coumarin-induced toxicity between sandwich-cultured primary rat hepatocytes and rats in vivo: a toxicogenomics approach.

Sandwich-cultured primary rat hepatocytes are often used as an in vitro model in toxicology and pharmacology. However, loss of liver-specific functions, in particular, the decline of cytochrome P450 (P450) enzyme activity, limits the value of this model for prediction of in vivo toxicity. In this study, we investigated whether a hepatic in vitro system with improved metabolic competence enhances the predictability for coumarin-induced in vivo toxicity by using a toxicogenomics approach. Therefore, primary rat hepatocytes were cultured in sandwich configuration in medium containing a mixture of low concentrations of P450 inducers, phenobarbital, dexamethasone, and beta-naphthoflavone. The toxicogenomics approach used enabled comparison of similar mechanistic end-points at the molecular level between in vitro and in vivo conditions, namely, compound-induced changes in multiple genes and signaling pathways. Toxicant-induced cytotoxic effects and gene expression profiles observed in hepatocytes cultured in modified medium and hepatocytes cultured in standard medium (without inducers) were compared with results from a rat in vivo study. Coumarin was used as a model compound because its toxicity depends on bioactivation by P450 enzymes. Metabolism of coumarin toward active metabolites, coumarin-induced cytotoxicity, and gene expression modulation were more pronounced in hepatocytes cultured in modified medium compared with hepatocytes cultured in standard medium. In addition, more genes and biological pathways were similarly affected by coumarin in hepatocytes cultured in modified medium and in vivo. In conclusion, these experiments showed that for coumarin-induced toxicity, sandwich-cultured hepatocytes maintained in modified medium better represent the situation in vivo compared with hepatocytes cultured in standard medium.     

How to Avoid Underdiagnosed Asthma/Chronic Obstructive Pulmonary Disease?

The prevalence of asthma and chronic obstructive pulmonary disease (COPD) is rising in most countries, including the Netherlands. It has been suggested that a majority of these cases of (self-reported) symptoms related to asthma/COPD are not diagnosed in general practice. We compared a population screening for underdiagnosed asthma/COPD with a high-risk approach by a questionnaire form with specified questions about asthma/COPD-related symptoms. A case-controlled study including a record review was performed of cases and controls. The results of a population screening were used to classify patients as (a) asthma/COPD, (b) at risk for asthma/COPD, or (c) no asthma/COPD. Eleven hundred fifty-five patients were screened. One hundred fifty-five patients reported previous asthma/COPD-related care (cases). The difference between number of cases and controls in asthma/COPD diagnosis was chosen as main outcome measure. The population screening revealed 85 subjects with a diagnosis of asthma/COPD and 154 subjects with an increased risk. Nineteen diagnoses could be made in cases, and eight diagnoses in controls. The chart review showed that only seven cases and two controls were known to the general practitioner. From this study it can be concluded that in order to reduce the number of un- and underdiagnosed patients, all listed patients in general practice should be screened. However, if screening of all patients is not feasible, active case finding by asking a few questions about shortness of breath or wheezing to all patients in the group of listed individuals is recommended.