Involvement of tobacco in alcoholism and illicit drug use

Survey data from the United States indicate that tobacco use is associated with the initiation of use of other addicting substances, and that increasing levels of tobacco use are associated with increasing levels of use of other psychoactive substances. Furthermore, factors affecting initiation, abstinence, and relapse to the use of tobacco, alcohol, and opioids are similar in nature. In addition, there are similarities in the addictive processes underlying the use of these substances. Taken together, these data suggest that tobacco use is involved, possibly more than by simple association, in the use of other substances containing psychoactive chemicals. In the present paper we discuss the involvement of tobacco in the use of alcohol, opioids, cocaine, and other substances, as well as some of the implications of these observations for researchers and clinicians. One such implication is that it may be possible to use tobacco and nicotine as models for phenomena of interest to other substance use researchers. For example, drug abuse treatment and prevention strategies could be explored using tobacco use as a target behavior, and biological phenomena such as the development of tolerance and physical dependence may be more readily studied with nicotine than with many other drugs. Certain pharmacologic differences across substances are also discussed in tight of their implications for development of treatment and drug control policies.     

Enhanced Predictive Power of Quantitative TWA during Routine Exercise Testing in the Finnish Cardiovascular Study

Introduction: We examined whether quantification of T-wave alternans (TWA) enhances this parameter's capacity to evaluate the risk for total and cardiovascular mortality and sudden cardiac death (SCD).
Methods and Results: The Finnish Cardiovascular Study (FINCAVAS) enrolled consecutive patients (n = 2,119; 1,342 men and 777 women) with a clinically indicated exercise test with bicycle ergometer. TWA (time domain-modified moving average method) was analyzed from precordial leads, and the results were grouped in increments of 10 μV. Hazard ratios (HR) for total and cardiovascular mortality and SCD were estimated for preexercise, routine exercise, and postexercise stages. Cox regression analysis was performed. During follow-up of 47.1 ± 12.9 months (mean ± standard deviation [SD]), 126 patients died: 62 were cardiovascular deaths, and 33 of these deaths were sudden. During preexercise, TWA ≥ 20 μV predicted the risk for total and cardiovascular mortality (maximum HR >4.4 at 60 μV, P < 0.02 for both). During exercise, HRs of total and cardiovascular mortality were significant when TWA measured ≥50 μV, with 90 μV TWA yielding maximum HRs for total and cardiovascular death of 3.1 (P = 0.03) and 6.4 (P = 0.002), respectively. During postexercise, TWA ≥60 μV indicated risk for total and cardiovascular mortality, with maximum HR of 3.4 at 70 μV (P = 0.01) for cardiovascular mortality. SCD was strongly predicted by TWA levels ≥60 μV during exercise, with maximum HR of 4.6 at 60 μV (P = 0.002), but was not predicted during pre- or postexercise.
Conclusion: Quantification of TWA enhances its capacity for determination of the risk for total and cardiovascular mortality and SCD in low-risk populations. Its prognostic power is superior during exercise compared to preexercise or postexercise.     

Cesarean Section Prophylaxis: Comparison of Two Doses With Three Doses of Mezlocillin

ABSTRACT: A prospective randomized double-blind comparison of two doses, with three doses of mezlocillin for nonelective cesarean section prophylaxis was performed. One hundred seven (107) patients were evaluated. Mezlocillin (4 g) was given post-cord clamping and then at 4-h intervals for a total of two doses or three doses. The incidence of febrile morbidity was lower in the three-dose group (2 of 46, 4%) than the two-dose group (14 of 61, 23%) (P<0.02). However, the incidence of infectious morbidity was not different between the three-dose group (3 of 46, 7%) and the two-dose group (10 of 61, 16%), and the incidence of endomyometritis was similar in the two groups (6.5% vs 9.8%). Among failures of prophylaxis there were no differences compared to successes in the number of potential commensals or potential pathogens cultured from amniotic fluid. However, the proportion of failures among patients with both commensals and potential pathogens isolated (10/58) was significantly greater than among patients with none or only commensals isolated (1/37) (P<0.03). We found mezlocillin to be an effective agent for perioperative cesarean section prophylaxis with two doses as effective as three doses. The presence of clinically important organisms in the amniotic fluid at the time of operation typified patients with postoperative infectious complications despite perioperative prophylaxis.     

Stress-Specific Influences of Opioids on Cardiac Electrical Stability

Opioids and Arrhythmias. Evidence is provided indicating that the action of opioids on cardiac electrical stability is contingent on the nature of the stress that impinges on the myocardium. This concept is illustrated by the studies of three clinically relevant conditions, namely, acute behavioral stress, hemorrhage, and myocardial ischemia. During aversive conditioning in dogs, morphine sulfate has been found to prevent the stress-induced reduction in cardiac electrical stability. This protective effect is significantly blunted by administration of atropine, indicating that enhanced vagal activity plays a major role. However, there is a remaining component of morphine's action, which is probably due to reduced perception of the aversive stress. In the context of hemorrhage, the mu-selective agonist fentanyl substantially reduces the profibrillatory effect of this physiological stress. The main mechanism involved in this condition is amplification of baroreceptor sensitivity leading to inhibition of cardiac sympathetic drive. Full activation of mu receptors with fentanyl is also effective in reducing vulnerability to fibrillation during acute coronary artery occlusion. This effect was due to vagal efferent activation and not to enhanced baroreceptor responsiveness as in the case of hemorrhage. Administration of the partial mu-agonist buprenorphine does not exert an antifibrillatory action. Collectively, these results not only demonstrate the potent stabilizing influence of opioids on cardiac rhythm but also the stress specificity of the intermediary mechanisms.     

Voluntary involvement in community health promotion: the Pawtucket Heart Health Program

The Pawtucket Heart Health Program employs a community activationapproach aimed at reducing cardiovascular morbidity and mortality.This approach is put into operation through the recruitmentof lay volunteers from the community to assist in planning,implementing, evaluating and managing various components ofthe Program. This unique approach of voluntary delivery of programmesis presented in this report. Strategies for the recruitment,interview and placement, training, maintenance and evaluationof volunteers are discussed. The characteristics of people whohave volunteered for specific administrative and service deliveryjobs with the Pawtucket Heart Health Program are also described.The volunteer delivery focus of the Program provides a modelfor adaptation by other public health projects.     

Visualisation of the gastrin receptor within rat mucosa using a biotinylated gastrin antagonist

We have previously demonstrated that the peptide Boc-l -Trp-l -Leu-β-Ala is a potent and specific antagonist of pentagastrin-stimulated acid secretion in both the rat and the dog. Using conventional solution phase methodology, the analogue biotinyl-l -Trp-l -Leu-β-Ala was prepared in reasonable yield and purity and applied to cryostat sections of rat intestinal and other tissues. The sections were exposed to 5–10 μg of peptide and the bound analogue was visualised using streptavidin-fluorescein. The binding of the analogue was demonstrated in sections from fundus, duodenum, ileum, colon, and lung. However, the analogue failed to bind to tissue from the pancreas, heart, kidney, or liver. The binding of the probe was greatly reduced or completely inhibited by preincubation with Boc-l -Trp-l -Leu-β-Ala, pentagastrin, or gastrin 1–17. The distribution of the cells recognised by the probe was consistent with the distribution of histamine-containing enterochromaffin-like cells. The results of this study may have some bearing on current theories of the mechanism of gastrin-stimulated acid release.     

Structural and functional changes of the gastric mucosa in rats with portal hypertension

Structural and functional changes of the gastric mucosa were studied in rats made portal hypertensive by partially ligating the portal vein. Studies were carried out at either 3 or 12 days after ligation or sham operation. At 3 days, structural changes were greater than at 12 days, the major effects being vascular congestion in the lamina propria, muscularis mucosa, submucosa, and submucosal oedema. Transmission electron microscopy showed only a mild hyperplasia in the muscularis mucosa. Gastric blood flow appeared to decrease at 3 days post-ligation compared to sham-operated control rats, but was significantly increased by 12 days after ligation (P less than 0.01). Cardiac output also appeared to increase in the portal hypertensive rats by 12 days post-ligation but this was not statistically significant. Portal venous inflow was significantly increased by 12 days (P less than 0.05) but after correction for collateral circulation liver blood flow had returned to normal values by 12 days post-ligation.     

Pacemaker-Mediated Tachycardia: Engineering Solutions

This discussion summarizes the interaction of refractory periods and upper rate behaviors in modern dual-chamber demand (DDD) devices, the data regarding and nine events initiating VA conduction and engineering solutions proposed and/or implemented to address the problem of pacemaker-mediated tachycardia (PMT). Among the causes of PMT are premature atrial depolarization, loss of atrial capture, a return to the demand mode after asynchronous magnet mode pacing, programming from a mode that does not guarantee AV synchrony to a mode in which atrial tracking can occur, noise, certain situations involving Wenckebach behavior, loss of sensing, and the inability of a rate-smoothing algorithm to allow a rapid change in ventricular rate. Engineering solutions to prevent the occurrence of PMT include a programmable postventricular atrial refractory period (PVARP), differential AV delay, adaptive AV delay, and the ability to discriminate between P waves of atrial origin and those resulting from retrograde conduction from the ventricle. Features such as the ability to lengthen the PVARP for one cycle after exiting the magnet or noise reversion modes or programming to a new mode, lengthen the PVARP for a single cycle following a PVC or revert to DVI pacing for one cycle following a PVC have been developed to recognize initiating events. A third solution. a tachycardia termination algorithm, can recognize and terminate PMT; varying the AV delay to determine whether P waves move in a corresponding manner and using a metabolic sensor to confirm the need for a fast heart rate are other possibilities in the detection of PMT. Diagnostic data features may also be used to evaluate the appropriateness of programmed settings. This discussion concludes that PMT is no longer a significant clinical entity when more advanced DDD pacemakers are utilized.     

Inability of the Signal-Averaged Electrocardiogram to Determine Risk of Arrhythmia Recurrence in Patients with Implantable Cardioverter Defibrillators

Signal-averaged electrocardiography has been used to identify patients at risk for arrhythmic death after myocardial infarction. Since patients with implantable cardioverter defibrillators (ICDs) are at high risk for arrhythmic events, they should also be expected to have a high incidence of abnormal signal-averaged electrocardiograms (SAECGs). However, whether the SAECG can discriminate patients who will have arrhythmia recurrence and receive appropriate ICD shocks from those who will have no recurrence and no shocks is unknown. This study examines the usefulness of the SAECG to separate appropriate users from non-users of the ICD. Fifty patients with ICDs participated in this study. Those who received a shock preceded by symptoms, a shock without preceding symptoms but with electrocardiographic documentation of ventricular fibrillation or ventricular tachycardia, or a shock while asleep were classified as ICD users. All other patients were classified as nonusers. The SAECG was classified as normal if the QRS duration on the standard electrocardiogram was less than or equal to 110 msec and if the total filtered QRS duration was less than 120 msec, the root-mean square voltage of the terminal 40 msec was greater than 25 muV, and the terminal low amplitude signal duration measured less than 38 msec. The SAECG was classified as abnormal if the QRS duration on the standard electrocardiogram was less than or equal to 110 msec and any one of these three criteria were outside the "normal range." The SAECG was classified as indeterminate if the QRS duration on the standard 12-lead electrocardiogram was greater than 110 msec. For the entire group of 50 patients, 8 (16%), 12 (24%), and 30 (60%) had normal, abnormal, and indeterminate SAECGs, respectively. Of the 22 ICD users, 1 (5%), 5 (23%), and 16 (73%) patients had normal, abnormal, and indeterminate SAECGs, respectively. Of the 28 ICD nonusers, 7 (25%), 7 (25%), and 14 (50%) patients had normal, abnormal, and indeterminate SAECGs, respectively. ICD users had lower left ventricular ejection fractions (P = 0.0002), a higher incidence of ventricular tachycardia (P = 0.04), prior exposure to a greater number of antiarrhythmic drugs (P = 0.04), and a lower likelihood for survival (P = 0.02) compared to the ICD nonusers. There was no statistically significant difference between the ICD users and nonusers as stratified by SAECG classification regardless of whether or not the interminate studies were included or excluded from the analysis.(ABSTRACT TRUNCATED AT 400 WORDS)