The effect of caffeine on cue exposure responses in ex-smokers

The responses of ex-smokers to an experimental cue exposure trial, and the effect of caffeine on these responses, were compared with those of a matched group of control subjects in a placebo controlled single-blind cross-over design. In contrast to placebo, caffeine protected the ex-smokers from a surge of anxiety and rise in blood pressure associated with exposure to smoking-related cues. Caffeine had no significant effects on the control group at this dose (equivalent to a single cup of strong coffee). The results are discussed with reference to Stewart's conditioned appetitive motivational model of addiction. It is suggested that further work may identify caffeine as an adjunct to smoking relapse prevention measures.     

Contractile Responses and Structure of Small Bronchi Isolated from Rats after 20 Months' Exposure to Ozone

Short-term exposure to high concentrations of ozone has beenshown to increase airway responsiveness in normal humans andin all laboratory animal species studied to date. While ourknowledge concerning the pulmonary effects of single exposuresto ozone has increased rapidly over recent years, the effectsof repeated exposures are less understood. The goal of the presentstudy was to determine whether airway responsiveness is increasedafter near-lifetime exposure to ozone. Airway segments representingapproximately eighth generation airways were isolated from Fischer344 rats of both genders that had been exposed for 6 hr perday, 5 days per week for 20 months to 0, 0.12, 0.5, or 1.0 partsper million (ppm) ozone. Circtimferential tension developmentwas measured in isolated airways in response to bethanechol,acetylcholine, and electrical field stimulation. Responsivenessof the airways to the contractile stimuli was described by theeffective dose or frequency that elicited half-maximum contraction(ED50) and the maximum response. Since ozone exposure is associatedwith remodeling of peripheral airways, smooth muscle area wasdetermined and tension responses were normalized to the areameasurements. Before normalization of tension data to smoothmuscle area, neither the ED50 nor maximum response of smallbronchi to the contractile stimuli was altered after chronicozone exposure. Smooth muscle area was greater in airways isolatedfrom animals that had been exposed to 0.5 ppm ozone. After accountingfor smooth muscle area, maximum responses of the small bronchiisolated from male rats were significantly reduced after 0.12and 0.5 ppm ozone. Although not significant statistically, asimilar trend was observed in airways isolated from female rats.These results suggest that the increase in airway responsivenessassociated with acute ozone exposure does not persist duringnear-lifetime exposure. Although the mechanism responsible forthe adaptation to the effects of 03 on airway responsivenessis unknown, the results indicate that smooth muscle cell functionwas compromised by the chronic exposure. The mechanism(s) responsiblefor mediating this effect and the relevance of these resultsto humans remains to be determined.     

Subchronic Effects of Dieldrin and Phenobarbital on Hepatic DNA Synthesis in Mice and Rats

Dieldrin, an organochlorine pesticide, has been shown to behepatocarcinogenic in mice but not rats. Phenobarbital, in contrast,induces hepatic tumors in both mice and rats. Previous studieshave shown that acute dietary exposure of rats or mice to eitherdieldrin or phenobarbital produces several liver changes, includingcentrilobular hypertrophy, induction of hepatic cytochrome P450,and increased liver weight. The present study examined the subchroniceffect of dieldrin (0.1, 1.0, 3.0, 10.0 mg dieldrin/kg diet)and phenobarbital (10, 50, 100, 500 mg phenobarbital/kg diet)on the induction of hepatic DNA synthesis and hepatocyte lethalityin male B6C3F1 mice and male F344 rats. Eight-week-old animalswere treated as above and evaluated for hepatic DNA synthesisafter 7, 14, 21, 28, and 90 days of continual treatment to dieldrinor phenobarbital. Maximal induction of hepatic DNA synthesisin mice was seen at the 14-, 21-, and 28-day sampling times.In rats, no significant increase in hepatic DNA synthesis orhepatocyte lethality was observed at any dose of dieldrin investigated.Phenobarbital produced a significant increase in hepatic DNAsynthesis in both rat and mouse liver following 7 days of treatment.The induction of DNA synthesis in rat liver was transient, withthe labeling index returning to control levels by 14 days oftreatment. In contrast, mice treated with phenobarbital showeda significant increase in hepatic DNA synthesis throughout thetreatment. In both mice and rats, dieldrin and phenobarbitalinduced hepatic DNA synthesis selectively in the centrilobularregion of the hepatic lobule. The lack of an increase in serumenzymes indicative of hepatic damage and the absence of liverhistopathology in mice or rats fed dieldrin or phenobarbitalindicate that the induction of DNA synthesis was not mediatedby a cytolethal, compensatory hyperplastic response, suggestinga mitogenic mechanism. Therefore, the species-specific inductionof hepatic DNA synthesis by either dieldrin or phenobarbitalcorrelated with the previously observed species-specific inductionof hepatic cancer by these two compounds.     

Catheter Ablation of Typical Atrial Flutter in Severe Pulmonary Hypertension

Atrial Flutter and Pulmonary Hypertension. Background: Radiofrequency ablation is first‐line therapy for atrial flutter (AFL). There are no studies of ablation in patients with severe pulmonary arterial hypertension (PAH). Methods: Consecutive patients with severe PAH (systolic pulmonary artery pressure >60 mmHg) and AFL referred for ablation were evaluated. Patients with complex congenital heart disease were excluded. Results: A total of 14 AFL ablation procedures were undertaken in 12 patients. A total of 75% of patients were female; mean age 49 ± 12 years. SPAP prior to ablation was 99 ± 35 mmHg. Baseline 6‐minute walk distance was 295 ± 118 m. ECG demonstrated a typical AFL pattern in only 42% of cases. Baseline AFL cycle length was longer in PAH patients compared to controls (295 ± 53 ms vs 252 ± 35 ms, P = 0.006). Cavotricuspid isthmus dependence was verified in 86% of cases. Acute success was obtained in 86% of procedures. SPAP decreased from 114 ± 44 mmHg to 82 ± 38 mmHg after ablation (P = 0.004). BNP levels were lower postablation (787 ± 832 pg/mL vs 522 ± 745 pg/mL, P = 0.02). Complications were seen in 14%. A total of 80% (8/10) of patients were free of AFL at 3 months; 75% (6/8) at 1 year. Conclusion: Ablation of AFL in severe PAH patients is feasible, with good short‐ and intermediate‐term success rates. The ECG pattern is not a reliable marker of isthmus dependence. The SPAP and BNP levels may decrease postablation. AFL may be a marker of poor outcomes in patients with PAH with a 1‐year mortality rate of 42% in this study. This rate is higher than expected in the general PAH population. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1185–1190, November 2012)     

The Psychostimulant Check‐Up: A pilot study of a brief intervention to reduce illicit stimulant use

Introduction and Aims. This study is to test the acceptability of a single‐session ‘check‐up’ intervention for psychostimulant users and document participants' subsequent progress in reducing psychostimulant use and related harms. Design and Methods. The design was pre‐experimental single‐group repeated measures. Eighty participants received the Psychostimulant Check‐Up, with 62% completing a 3 month follow up. Results. Participants were predominantly young adult methamphetamine users. The majority indicated that the Check‐Up answered their questions, increased their awareness of services, and they would recommend it to their friends. At follow up, there was a significant reduction in self‐reported methamphetamine use, the number of self‐reported psychostimulant‐related negative consequences experienced in the previous month and rates of injecting: 62% self‐reported at least a 1 g reduction in methamphetamine use. Discussion and Conclusions. The intervention was well accepted and the majority of those who received it subsequently made meaningful reductions in psychostimulant use and related harm. The intervention offers sufficient promise to warrant a randomised trial to establish whether improvements were specific to the intervention.[Smout MF, Longo M, Harrison S, Minniti R, Cahill S, Wickes W, White JM. The Psychostimulant Check‐Up: A pilot study of a brief intervention to reduce illicit stimulant use. Drug Alcohol Rev 2009]     

Measuring the Complexity of Atrial Fibrillation Electrograms

AF Electrogram Complexity. Introduction: Complex fractionated atrial electrograms (CFAE) have been identified as targets for atrial fibrillation (AF) ablation. Robust automatic algorithms to objectively classify these signals would be useful. The aim of this study was to evaluate Shannon's entropy (ShEn) and the Kolmogorov‐Smirnov (K‐S) test as a measure of signal complexity and to compare these measures with fractional intervals (FI) in distinguishing CFAE from non‐CFAE signals. Methods and Results: Electrogram recordings of 5 seconds obtained from multiple atrial sites in 13 patients (11 M, 58 ± 10 years old) undergoing AF ablation were visually examined by 4 independent reviewers. Electrograms were classified as CFAE if they met Nademanee criteria. Agreement of 3 or more reviewers was considered consensus and the resulting classification was used as the gold standard. A total of 297 recordings were examined. Of these, 107 were consensus CFAE, 111 were non‐CFAE, and 79 were equivocal or noninterpretable. FIs less than 120 ms identified CFAEs with sensitivity of 87% and specificity of 79%. ShEn, with optimal parameters using receiver‐operator characteristic curves, resulted in a sensitivity of 87% and specificity of 81% in identifying CFAE. The K‐S test resulted in an optimal sensitivity of 100% and specificity of 95% in classifying uninterpretable electrogram from all other electrograms. Conclusions: ShEn showed comparable results to FI in distinguishing CFAE from non‐CFAE without requiring user input for threshold levels. Thus, measuring electrogram complexity using ShEn may have utility in objectively and automatically identifying CFAE sites for AF ablation. (J Cardiovasc Electrophysiol, Vol. 21, pp. 649‐655, June 2010)