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.     

Changing Trends in Therapy Delivery with a Third Generation Noncommitted Implantable Defibrillator: Results of a Large Single Center Clinical Trial

Thirty-four patients underwent implantation of a third generation ICD, the 4210 ATP, for sudden cardiac death or ventricular tachycardia. This device incorporates significant telemetry logs as well as a detailed analysis of each arrhythmia episode detected. During the period of clinical follow-up, a mean of 12.2 months, a total of 26,569 VT or VF detections were made. The vast majority of these were either due to atrial fibrillation, nonsustained VT, or "noise" detection, and only 6% led to device therapy. ATP was successful in 86.3% of episodes, with 3.5% accelerations and 2.4% failure of ATP trains. The majority of inappropriate therapy episodes were clustered in seven patients, and all were easily diagnosed with the aid of the extensive telemetry Jogs and sense histories. Of five late deaths, three were from congestive heart failure, one from cerebrovascular accident, and one unknown. These data reveal that this "tiered" therapy noncommitted ICD performs to expectations; the stored data is of significant value in diagnosing the cause of ICD therapy. In addition, ATP is an effective modality for termination of VT.     

Diabetes and Multiple Stents Independently Double the Risk of Short-term Revascularization

Several studies show worse outcome for diabetic patients after percutaneous transluminal coronary angioplasty (PTCA). There are relatively few studies evaluating outcome in the modern era of coronary stenting. We compared the incidence of death, myocardial infarction (MI), and repeat target lesion revascularization (RTLR) by PTCA or coronary artery bypass grafting (CABG) over a 6-month follow-up in 110 diabetic and 400 nondiabetic patients receiving Palmaz-Schatz stents. All patients received aspirin/ticlopidine and stents were deployed using high-pressure inflations. Seventy-five (68.2%) diabetic patients and 272 (68%) nondiabetic patients had single stents, while 35 (31.8%) diabetic and 128 (32%) nondiabetic patients had multiple stents (≥ 2stents in the same vessel). The success rate and acute major complications were not significantly different between diabetic and nondiabetic patients. There was also no significant difference in death, MI, and repeat PTCA between these two groups. Diabetic patients underwent CABG more frequently than nondiabetic patients (12.7% vs 3.2%, respectively, P =0.001) and diabetic patients also had RTLR more frequently than nondiabetic patients (25.5% vs 12.8%, respectively, P = 0.002) during 6-month follow-up. Multivariate analysis showed that diabetes and multiple stents independently contributed to the 6-month RTLR rate. Coronary stenting in diabetic patients can be carried out with a high success rate and low incidence of acute major complications. The presence of diabetes mellitus and multiple stent placement significantly increase the incidence of repeat target lesion revascularization.     

Plasma concentrations of cyclic 3',5'-guanosine monophosphate in patients with cirrhosis: Relationship with atrial natriuretic peptide and haemodynamics

Little is known about the plasma concentrations of cyclic 3',5'-guanosine monophosphate (cGMP) in patients with cirrhosis. However, plasma cGMP concentrations provide information on cellular cGMP production by particulate guanylyl cyclases (which are stimulated by natriuretic peptides, such as atrial natriuretic peptide; ANP). In contrast, because intracellular cGMP elicits vasorelaxant mechanisms, plasma cGMP concentrations may be related to haemodynamic alterations in patients with cirrhosis. The aim of the present study was to measure plasma cGMP concentrations in patients with cirrhosis and controls and to examine the relationship between cGMP levels and plasma ANP concentrations and haemodynamic values. Plasma concentrations of cGMP and ANP and splanchnic and systemic haemodynamics were measured in 23 subjects; 13 subjects had cirrhosis and 10 were controls. All subjects had normal glomerular filtration. Plasma cGMP concentrations were significantly higher in patients (6.5±0.8 pmol/mL) than in controls (2.7±0.4 pmol/mL), while plasma ANP concentrations did not significantly differ between the two groups (127±22 and 123±27 pg/mL, respectively). In patients with cirrhosis, no significant correlation was found between plasma cGMP concentrations and plasma ANP concentrations, hepatic venous pressure gradient, cardiac output or systemic vascular resistance. In conclusion, in patients with cirrhosis, increased plasma cGMP concentrations may be due to an activation of particulate guanylyl cyclases by natriuretic peptides other than ANP. The present study suggests that plasma cGMP concentrations are not related to cirrhosis-induced haemodynamic alterations.     

Shorter AV Delays Provide Improved Echocardiographic Hemodynamics during Exercise in Patients Receiving Cardiac Resynchronization Therapy

Background: Although atrial ventricular (AV) intervals are often optimized at rest in patients receiving cardiac resynchronization therapy (CRT), there are limited data on the impact of exercise on optimal AV interval.
Methods: In 15 patients with CRT, AV intervals were serially programmed while patients were supine and at rest, and during exercise with heart rates that averaged 20 and 40 beats per minute above their resting rates. Echocardiographic Doppler images were acquired at each programmed AV interval and each rate. Three independent echocardiographic criteria were retrospectively used to determine each patient's optimal AV interval as a function of exercise-induced increased heart rates: the duration of left ventricular filling, stroke volume, and a clinical assessment of left ventricular function.
Results: A negative correlation between the optimal AV interval and heart rate was observed across all patients using all three independent criterion: the maximum left ventricular filling time (slope =–0.77, intercept = 151.9, r = 0.55, P < 0.001), maximum stroke volume (slope =–0.93, intercept = 183.3, r = 0.50, P = 0.002), or the subjective clinical assessment (slope =–1.06, intercept = 182.0, r = 0.72, P < 0.001). Consistent trends were observed between all three parameters for 12 out of the 15 patients.
Conclusions: These results suggest that in patients indicated for CRT, rate-adaptive functions may be useful to shorten AV intervals with increased rate, in order to maximize left ventricular filling, stroke volume, and clinical left ventricular function. Further studies are necessary to determine the clinical impact of these rate-adaptive algorithms.     

Initial Experience with Transvenous Implantable Cardioverter Defibrillator Lead Systems: Operative Morbidity and Mortality

Introduction of non-thoracotomy lead systems™ (Medtronic, Inc.) for the implantable cardioverter defibrillator (ICD) has expanded the indications for use of this mode of therapy. Patients previously considered "too ill" to undergo a thoracotomy as well as patients who are at a high risk for developing sudden death but without previous cardiac arrest, are now considered candidates. The initial experience with the non-thoracotomy lead system at our institution was analyzed for morbidity and mortality. Thirty-four patients underwent attempted intravascular lead implantation, with 30 having initial successful implantation (88.2%). There were 23 males; average ejection fraction (EF) was 38.6%. Three patients developed pulmonary edema and low output immediately after the procedure. Three patients developed electromechanical dissociation during defibrillation threshold testing. A prolonged testing time for the non-thoracotomy lead system was noted when compared to the thoracotomy system (57.39 vs 32.30 min; P < 0.0000). There were more intraoperative morbidities with the non-thoracotomy leads than with the thoracotomy system. There were no perioperative deaths. The potential consequences of prolonged anesthesia time and extensive defibrillation threshold testing should be considered when choosing the route of ICD implant, the type of anesthesia, and the intraoperative testing protocol for each patient.     

Management of corticosteroid-induced osteoporosis

Abstract. Corticosteroid therapy results in osteoporosis. There is a doubling in the risk of fracture in patients taking more than the equivalent of 7.5 mg day^?1. The bone loss is most rapid from the axial skeleton, particularly during the 1st year of therapy. The most important mechanism for the bone loss is a decrease in osteoblastic activity. Preventative strategies should be targeted to patients with low bone-mineral density, especially if the dose of corticosteroids is likely to be high. Treatment strategies agreed on by the Consensus Panel included hormone replacement therapy and bisphosphonates, with monitoring of efficacy by bone densitometry.     

Activation Times for "Emergency Backup" Programs

A bench study was performed on 42 different pulse generators (PGs) to evaluate the time required to actuate an "emergency backup" (EBU) program. PGs were programmed to loss of capture before the EBU programming key was activated. Activation times for the EBU pause were measured on an ECG strip from the first noncaptured beat to the first recaptured beat while the total pause was measured between the two captured beats. Each test was performed five times. Special features for temporary threshold testing were also evaluated. Mean activation times for EBU pauses ranged from 1.46–11.90 seconds with total pauses of 2.18–12.94 seconds. Significant differences were observed for EBU activation times from the same PG but utilizing older and newer generation programmers, e.g., 10.90 (old) versus 4.54 seconds (new) for a mean EBU pause. Extreme variations existed in EBU activation times for programmers with multiple "EBU keys" for the same PG, e.g., 12.94 versus 4.96 seconds for the mean total pause. The special features for temporary threshold testing resulted in mean EBU pauses measuring 0.62–2.88 seconds and mean total pauses of 1.21–3.76 seconds. The special features were significantly faster than manual activation of the "EBU key" for regaining capture with few exceptions. Activation times were complicated by multiple programmers for the same PG and several "EBU keys" on the same programmer.