Endovascular brachytherapy in coronary arteries: the Rotterdam experience

Purpose: The use of endovascular coronary brachytherapy to prevent restenosis following percutaneous transluminal coronary angioplasty (PTCA) began in April 1997 at the Department of Interventional Cardiology of the Thoraxcenter at the University Hospital of Rotterdam. This article reviews the more than 250 patients that have been treated so far.Methods and Materials: The Beta-Cath System (Novoste), a manual, hydraulic afterloader with 12 90Sr seeds, was used in the Beta Energy Restenosis Trial (BERT-1.5, n=31), for compassionate use (n=25), in the Beta-Cath System trial (n=27) and in the Beta Radiation in Europe (BRIE, n=14). Since the Beta-Cath System has been commercialized in Europe, 57 patients have been treated and registered in RENO (Registry Novoste). In the Proliferation Reduction with Vascular Energy Trial (PREVENT), 37 patients were randomized using the Guidant-Nucletron remote control afterloader with a 32P source wire and a centering catheter. Radioactive 32P coated stents have been implanted in 102 patients. In the Isostent Restenosis Intervention Study 1 (IRIS 1), 26 patients received a stent with an activity of 0.75-1.5 μCi, and in the IRIS 2 (European 32P dose response trial), 40 patients were treated with an activity of 6-12 μCi. In two consecutive pilot trials, radioactive stents with non-radioactive ends (cold-end stents) and with ends containing higher levels of activity (hot-end stents) were implanted in 21 and 17 patients, respectively.Results: In the BERT-1.5 trial, the radiation dose, prescribed at 2 mm from the source train (non-centered), was 12 Gy (10 patients), 14 Gy (10 patients) and 16 Gy (11 patients). At 6-month follow-up, 8 out of 28 (29%) patients developed restenosis. The target lesion revascularization rate (TLR) was 7 out of 30 (23%) at 6 months and 8 out of 30 (27%) at 1 year. Two patients presented with late thrombosis in the first year. For compassionate use patients, a restenosis rate (RR) of 53% was observed. In the PREVENT trial, 34 of 37 patients underwent an angiographic 6-month follow-up. The doses prescribed at 0.5 mm depth into the vessel wall were 0 Gy (8), 28 Gy (9), 35 Gy (11) and 42 Gy (8). TLR was 14% in the irradiated patients and 25% in the placebo group. One patient developed late thrombosis. In the IRIS 1 trial, 23 patients showed an RR of 17% (in-stent). In the IRIS 2 trial, in-stent restenosis was not seen in 36 patients at 6-month follow-up. However, a high RR (44%) was observed at the stent edges.Conclusions: The integration of vascular brachytherapy in the catheterization laboratory is feasible and the different treatment techniques that are used are safe. Problems, such as edge restenosis and late thrombotic occlusion, have been identified as limiting factors of this technique. Solutions have been suggested and will be tested in future trials.     

ACS,myocardial bridging,Tako-tsubo syndrome and mitral regurgitation

Isolated systolic compression of the mid portion of the left anterior descending artery (LAD) by a bridge of overlying cardiac muscle is an infrequent but well-recognised angiographic anomaly that is often considered harmless. The long-term prognosis appears to be excellent, but occasional reports of patients with angina pectoris, myocardial infarction and sudden death indicate that this is not always true. The prevalence of the anomaly in the normal population is unknown, but the incidence is low and ischaemic events are rare.Tako-tsubo-like left ventricular dysfunction syndrome (TTS) is characterised by ischaemia, anterior ST-segment elevation, no significant coronary artery disease and reversible ampulla-like left ventricular ballooning in postmenopausal females after emotional or physical stress. Dynamic left ventricular outflow tract (LVOT) obstruction is a rare but potentially fatal complication of acute anterior wall infarction.We present a patient with an acute coronary syndrome (ACS) with ST-segment elevation in the anterior leads, transient TTS and transient LVOT obstruction with systolic anterior motion (SAM) of the mitral valve and severe mitral regurgitation. This is the first report of myocardial bridging associated with TTS, and the first report of TTS associated with dynamic LVOT obstruction with SAM and mitral regurgitation.     

Diet and Physical Activity Behaviors among Americans Trying to Lose Weight: 2000 Behavioral Risk Factor Surveillance System

Objective: To examine the prevalence and correlates of trying to lose weight among U.S. adults, describe weight loss strategies, and assess attainment of recommendations for weight control (eating fewer calories and physical activity). Research Methods and Procedures: This study used the Behavioral Risk Factor Surveillance System, a state‐based telephone survey of adults ≥18 years of age (N = 184, 450) conducted in the 50 states, the District of Columbia, and Puerto Rico in 2000. Results: The prevalence of trying to lose weight was 46% (women) and 33% (men). Women reported trying to lose weight at a lower BMI than did men; 60% of overweight women were trying to lose weight, but men did not reach this level until they were obese. Adults who had a routine physician checkup in the previous year and reported medical advice to lose weight vs. checkup and no medical advice to lose weight had a higher prevalence of trying to lose weight (81% women and 77% men vs. 41% women and 28% men, respectively). The odds of trying to lose weight increased as years of education increased. Among respondents who were trying to lose weight, ～19% of women and 22% of men reported using fewer calories and ≥150 min/wk leisure‐time physical activity. Discussion: A higher percentage of women than men were trying to lose weight; both sexes used similar weight loss strategies. Education and medical advice to lose weight were strongly associated with trying to lose weight. Most persons trying to lose weight were not using minimum recommended weight loss strategies.     

Angiotensin II-induced changes of calcium sparks and ionic currents in human atrial myocytes: potential role for early remodeling in atrial fibrillation

AIMS: Atrial angiotensin II (ANG II) levels have been shown to be increased in atrial fibrillation (AF). The purpose of the study was to evaluate a potential role of ANG II in the early remodeling and susceptibility to chronicization of AF. METHODS AND RESULTS: Isolated human atrial myocytes were incubated in ANG II and/or angiotensin type 1 receptor blocker candesartan. ANG II markedly increased the frequency of spontaneous Ca(2+) sparks, spark full duration, time to peak Ca(2+) fluorescence and decay time measured by confocal imaging. Sarcoplasmic reticulum calcium content estimated by caffeine-evoked calcium release did not differ between ANG II-treated cells and controls. Patch-clamp recordings revealed that ANG II significantly decreased I(to) and increased I(Ca,L) current densities. Candesartan blocked these ANG II-mediated alterations. ANG II exhibited no effect on I(K1), I(Kur) and I(f) current size. Expression of connexin 40 and connexin 43 was not significantly changed by ANG II as assessed by immunohistochemistry and Western blot analysis. CONCLUSION: ANG II-induced alterations of calcium handling and electrophysiological changes in human atrial cells similar to those previously observed in the onset of AF. Prevention of these alterations by candesartan might constitute a useful pharmacological strategy for the treatment of AF.     

K+ channel regulator KCR1 suppresses heart rhythm by modulating the pacemaker current If

Hyperpolarization-activated, cyclic nucleotide sensitive (HCN) channels underlie the pacemaker current I(f), which plays an essential role in spontaneous cardiac activity. HCN channel subunits (HCN1-4) are believed to be modulated by additional regulatory proteins, which still have to be identified. Using biochemistry, molecularbiology and electrophysiology methods we demonstrate a protein-protein interaction between HCN2 and the K(+) channel regulator protein 1, named KCR1. In coimmunoprecipitation experiments we show that KCR1 and HCN2 proteins are able to associate. Heterologously expressed HCN2 whole-cell current density was significantly decreased by KCR1. KCR1 profoundly suppressed I(HCN2) single-channel activity, indicating a functional interaction between KCR1 and the HCN2 channel subunit. Endogenous KCR1 expression could be detected in adult and neonatal rat ventriculocytes. Adenoviral-mediated overexpression of KCR1 in rat cardiomyocytes (i) reduced I(f) whole-cell currents, (ii) suppressed most single-channel gating parameters, (iii) altered the activation kinetics, (iv) suppressed spontaneous action potential activity, and (v) the beating rate. More importantly, siRNA-based knock-down of endogenous KCR1 increased the native I(f) current size and single-channel activity and accelerated spontaneous beating rate, supporting an inhibitory action of endogenous KCR1 on native I(f). Our observations demonstrate for the first time that KCR1 modulates I(HCN2)/I(f) channel gating and indicate that KCR1 serves as a regulator of cardiac automaticity.     

Tarsal attachment devices of the southern green stink bug Nezara viridula (Heteroptera: Pentatomidae)

Based on analyses with cryo‐scanning and transmission electron microscopy, the present study reports on the morphology and ultrastructure of the attachment structures of the green stinkbug Nezara viridula L. (Heteroptera: Pentatomidae), a cosmopolitan pest of different crops in most areas of the world. In addition, the presence and distribution of large proportions of the elastic protein resilin in these structures was revealed by confocal laser scanning microscopy. The attachment structures of each leg comprise two sclerotised claws, a pair of smooth flexible pulvilli and a hairy adhesive pad located at the ventral side of the basitarsus. No sexual dimorphism is evident. Contact areas of resting individuals on a smooth surface show that N. viridula creates contact to the substrate with the ventral surface of (a) the distal portions of the pulvilli, (b) the setae of the hairy adhesive pad, (c) the two paraempodia representing mechanosensory setae, and (d) the tips of the claws. Each pulvillus is a sac‐like structure formed by complex cuticular layers that vary in their structure and resilin content. The dorsal side consists of sclerotised chitinous material, while the ventral cuticle consists mainly of resilin and shows a very thin epicuticle and a thick exocuticle. The setae of the hairy adhesive pad are pointed and socketed. They exhibit a pronounced longitudinal gradient in the material composition, with large proportions of resilin being present in the setal tips. In most of these setae, especially in those of the distal‐most part of the pad, also a transverse gradient in the material composition is visible.     

Tumor Necrosis Factor-α +489G/A gene polymorphism is associated with chronic obstructive pulmonary disease

Background  

Chronic obstructive pulmonary disease (COPD) is characterized by a chronic inflammatory process, in which the pro-inflammatory cytokine Tumor Necrosis Factor (TNF)-α is considered to play a role. In the present study the putative involvement of TNF-α gene polymorphisms in pathogenesis of COPD was studied by analysis of four TNF-α gene polymorphisms in a Caucasian COPD population.     

The multifunctional isopropyl alcohol dehydrogenase of Phytomonas sp. could be the result of a horizontal gene transfer from a bacterium to the trypanosomatid lineage

Isopropyl alcohol dehydrogenase (iPDH) is a dimeric mitochondrial alcohol dehydrogenase (ADH), so far detected within the Trypanosomatidae only in the genus Phytomonas. The cloning, sequencing, and heterologous expression of the two gene alleles of the enzyme revealed that it is a zinc-dependent medium-chain ADH. Both polypeptides have 361 amino acids. A mitochondrial targeting sequence was identified. The mature proteins each have 348 amino acids and a calculated molecular mass of 37 kDa. They differ only in one amino acid, which can explain the three isoenzymes and their respective isoelectric points previously found. A phylogenetic analysis locates iPDH within a cluster with fermentative ADHs from bacteria, sharing 74% similarity and 60% identity with Ralstonia eutropha ADH. The characterization of the two bacterially expressed Phytomonas enzymes and the comparison of their kinetic properties with those of the wild-type iPDH and of the R. eutropha ADH strongly support the idea of a horizontal gene transfer event from a bacterium to a trypanosomatid to explain the origin of the iPDH in Phytomonas. Phytomonas iPDH and R. eutropha ADH are able to use a wide range of substrates with similar Km values such as primary and secondary alcohols, diols, and aldehydes, as well as ketones such as acetone, diacetyl, and acetoin. We speculate that, as for R. eutropha ADH, Phytomonas iPDH acts as a safety valve for the release of excess reducing power.