Cannabinoid effects on behaviors maintained by ethanol or food: a within-subjects comparison

The cannabinoid CB1 antagonist rimonabant (SR141716A) has been proposed as a therapeutic agent for several addictive disorders, including alcoholism. Rimonabant may selectively reduce responding for an ethanol solution compared with an alternative. While this could represent a specific effect of CB1 inhibition on ethanol reinforcement, this could also result from differences in the baseline rates of behavior or experiences between comparison groups. We developed a procedure in rats that allows a within-subject comparison of ethanol and food-maintained responding and provides well matched baseline response rates. We determined the effects of acute doses of rimonabant (0.3-5.6 mg/kg, intraperitoneal) and the CB1 agonist Delta-9-tetrahydrocannabinol (1.0-5.6 mg/kg, intraperitoneal) on responding for food and ethanol under a multiple fixed-ratio schedule. To confirm that rimonabant blocked cannabinoid receptors, the ability of rimonabant to antagonize Delta-9-tetrahydrocannabinol effects in the same subjects under the same reinforcement schedule was also determined. In contrast with previous reports, rimonabant did not significantly alter responding for ethanol or food. The effects of Delta-9-tetrahydrocannabinol on responding for food were completely antagonized by rimonabant, whereas Delta-9-tetrahydrocannabinol effects on responding for ethanol were not. These results suggest that there may be neuroadaptation of the cannabinoid system following aging or chronic self-administration of ethanol.     

Comparison of three different procedures for antireflux surgery

BACKGROUND: No long-term comparisons of the various open and laparoscopic antireflux procedures have been undertaken. The aim of this study was to compare symptomatic outcomes of three procedures for antireflux surgery performed at three specialist units. METHODS: Patients undergoing open Nissen fundoplication, laparoscopic Nissen fundoplication and laparoscopic anterior partial fundoplication between December 1993 and February 2001 were identified. Patient outcome was assessed by means of a postal questionnaire. This was a hypothesis-generating study. RESULTS: Three hundred and fifty-seven patients (80.0 per cent) completed the questionnaire, with no differences in response rate between centres. Overall, a mean of only 7.6 per cent of patients reported a poor outcome. Logistic regression revealed no significant differences amongst the three procedures for any symptoms, after allowing for the effect of time. There was a general increase in the DeMeester score with increasing time from operation. The incidence of revisional reflux surgery was similar in the three groups. CONCLUSION: Medium-term symptomatic outcome following all three procedures was similar. There was some recurrence of symptoms of gastro-oesophageal reflux with time for all procedures, suggesting that the effects of surgery diminish with time. The level of experience of the surgeon in a particular operation was more important than the procedure performed.     

Shaping smoking cessation using percentile schedules

Behavioral interventions that provide incentives contingent upon abstinence are effective addiction treatments. Nevertheless, these treatments often fail for individuals whose recent behaviors are very different from those reinforced. These hard-to-treat individuals may require shaping to achieve abstinence. We used percentile schedules to shape smokers' delivery of breath samples indicative of recent smoking abstinence (breath carbon monoxide (BCO) <4 ppm). Percentile schedules deliver incentives to current behaviors proximal to the target. Participants (N = 102) were assigned to treatments delivering incentives for breath COs at or below the 10th, 30th, 50th, or 70th percentile of recent breath COs. Each condition effectively ensured contact with available contingencies, and resulted in BCO <4 ppm in >90% of the 30th, 50th and 70th percentile groups versus 63% in the 10th percentile. The 30th, 50th and 70th percentiles were especially effective in a sub-sample of hard-to-treat participants who did not deliver a breath CO <4 ppm during an initial abstinence test or during a nine-visit baseline period, suggesting the value of shaping for this important sub-sample.     

Convergent and concurrent validity of the Contemplation Ladder and URICA scales

This study examined the convergent and concurrent validity of the Contemplation Ladder and the University of Rhode Island Change Assessment (URICA). Intake data of participants recruited into two concurrent studies were analyzed. One group (n=77) had no plans to quit smoking within the next 6 months, while a second group (n=106) had definite plans to quit. The groups did not differ on any demographic variables except employment status. Contemplation Ladder scores for the entire sample (n=183) correlated positively with the URICA Contemplation and Action subscale scores but negatively with Precontemplation subscale scores. The Contemplation Ladder also correlated positively with the URICA Composite score. Additionally, participants seeking to quit within the next 6 months had significantly higher Contemplation Ladder and URICA Contemplation, Action, and Composite scores, but lower Precontemplation scores than participants not seeking to quit. Controlling for employment status did not change the pattern of results. Our findings provide support for the convergent and concurrent validity of these two measures and suggest that the single-item Contemplation Ladder may be a practical alternative to the URICA in certain situations.     

Fluvoxamine and desipramine on fixed-ratio responding: effects of reinforcement magnitude

Fluvoxamine, a serotonin reuptake blocker, was previously shown to decrease ethanol-maintained behavior at doses lower than those needed to decrease food-maintained behavior. While these effects could have been due to different response rates and histories of the two groups being compared, a subsequent study found differential effects using a within-subjects design, in which rates of responding were well equated. Another explanation for such differential effects is that food and ethanol reinforcement differ in a quantitative fashion. This is difficult to resolve when comparing between behaviors maintained by different events. To examine how such quantitative differences in reinforcement magnitude might influence the effects of fluvoxamine, we used a multiple schedule of fixed-ratio 30 responding in the pigeon. In each of the three fixed-ratio 30 components, behavior was maintained by a different duration of grain presentation (2, 4, and 8 s). The effects of fluvoxamine and also desipramine were examined. Both dose-dependently decreased fixed-ratio responding. Their effects were independent of the duration of grain presentation maintaining responding. These results do not support the idea that the differential effects of fluvoxamine on ethanol-maintained behavior, as compared with food-maintained behavior, are a result of quantitative differences in reinforcement magnitude.     

Blockade of beta-adrenergic receptors prevents amphetamine-induced behavioural sensitization in rats: a putative role of the bed nucleus of the stria terminalis

Recent findings have given evidence a role for noradrenergic transmission in the mechanisms underlying behavioural sensitization to psychostimulants. This work was undertaken to investigate the possible role of beta-adrenergic receptors in amphetamine-induced behavioural sensitization in rats. Rats were sensitized by a single administration of amphetamine (1 mg/kg s.c.) and challenged with the same dose 7 d later. The beta(1) /beta(2) -adrenergic receptor antagonists timolol (10 mg/kg i.p.) and nadolol (10 mg/kg i.p.), which respectively cross or do not readily cross the blood-brain barrier, were injected prior to the first or second amphetamine administration. Timolol, but not nadolol, prevented the initiation of behavioural sensitization without interfering with the expression of the sensitized response or the acute locomotor response to amphetamine. Since we found amphetamine-induced fos-activated cells closely associated with dopamine beta-hydroxylase immunoreactive varicosities in the bed nucleus of the stria terminalis (BNST), we investigated the effect of a bilateral micro-injection of timolol into this nucleus. Similarly to systemic administration, intra-BNST timolol (2.5 microg/side) prevented the development of behavioural sensitization. These results suggest that central beta-adrenergic receptors could specifically modulate early neuronal changes leading to the development of behavioural sensitization to psychostimulants, and that the BNST could be an important part of the brain circuitry involved in these long-term neuroadaptations.     

The shift of psychiatric inpatient care from hospitals to jails and prisons

Far-reaching structural changes have been made in the mental health system. Many severely mentally ill persons who come to the attention of law enforcement now receive their inpatient treatment in jails and prisons, at least in part, because of a dramatic reduction of psychiatric inpatient beds. While more high-quality community treatment, such as intensive case management and assertive community treatment, is needed, the authors believe that for many, 24-hour structured care is needed in the mental health system for various lengths of time to decrease criminalization. Another central theme of this article is that when a mentally ill individual is arrested, that person now has a computerized criminal record, which is easily accessed by the police and the courts in subsequent encounters. This may influence their decisions and reinforce the tendency to choose the criminal justice system over the mental health system.     

Multiview active appearance models for simultaneous segmentation of cardiac 2- and 4-chamber long-axis magnetic resonance images

RATIONALE AND OBJECTIVES: Long-axis cardiac magnetic resonance (MR) views enable a rapid, online evaluation of cardiac function from only 2 views. In this article, we aimed to evaluate a model-based method for the simultaneous detection of 2- and 4-chamber endocardial and epicardial contours in end-diastolic and end-systolic phases of MR images. METHODS: We introduce multiview Active Appearance Models for the automated segmentation of long-axis cardiac MR images of the left ventricle. Two modes of initialization were used to test the accuracy of the model with minimal user interaction and the best-obtainable accuracy with this model. The segmentation was initialized by annotating 2 points in the base and one in the apex. We tested the method's performance by comparing the point-to-curve errors, ejection fractions, and biplane area-length volumes calculated with the automatically detected contours to those calculated from contours that were annotated manually by experts. Leave-one-out experiments were performed with 2- and 4-chamber long axis MR images of 59 subjects in end-diastolic and end-systolic phases. RESULTS: When initializing in all 4 frames, 97% of the segmentations were successful, and the standard deviation in the volume-errors with respect to the average manually identified volume was 9.0% for the end-diastolic volumes and 15% for the end-systolic volumes. When the method was initialized in the end-systolic frames only, 92% of the segmentations were successful, and the standard deviation in the errors in the volumes with respect to the average manually identified volume was 13.3% for the end-diastolic volumes and 16.7% for the end-systolic volumes. Bland-Altman plots showed that the errors were distributed randomly around 0, and by using a paired t test comparing manual and computer-determined volumes, we were able to detect that the volume differences were not significant. Simultaneous detection of the endocardial and epicardial contours in 2- and 4-chamber views and end-diastolic and end-systolic phases for one subject takes approximately 3 seconds. CONCLUSIONS: The accuracy of the reported method is comparable with the interobserver variability for initialization in all frames and slightly worse than the interobserver variability with initialization in the end-systolic frames only. However, in both cases the errors were not significant. Initialization in end-systolic frames only leads to a statistically insignificantly lower model accuracy; however, it requires only half the user interaction. Therefore, we can conclude that this method enables rapid analysis of the cardiac left ventricular function with little user interaction.     

The effects of a high carbohydrate diet on cortisol and salivary immunoglobulin A (s-IgA) during a period of increase exercise workload amongst Olympic and Ironman triathletes

The present study observed the effects of a 6-day high carbohydrate (H-CHO) diet on salivary cortisol and IgA during a period of increased exercise workload. Thirty-two competitively trained male triathletes were randomly allocated into a self-selected (SS), or an H-CHO (12 g CHO kgbm (-1) . day (-1)) dietary group. In addition to their training regimes, all subjects performed a 1-hour running exercise bout at 70 % V.O (2max) . d (-1), for six days. Saliva samples were taken pre, immediately post, and morning post-exercise bout on days 1, 4, and 6. The concentrations of s-IgA and cortisol were determined by ELISA assays. There was a significant (p < 0.001) interaction between Group x Time for cortisol, with a marked increase in concentrations occurring in the SS dietary group pre to post exercise, and pre to morning post-exercise (p < 0.01). Conversely, a significant (p = 0.009) Group x Time interaction reflected higher post exercise s-IgA concentrations (p < 0.005) than pre exercise in the H-CHO diet group. Blood glucose concentration decreased pre to post exercise in the SS diet group (p < 0.01), whilst remaining stable in the H-CHO group. It is concluded that the consumption of a high CHO diet throughout a 6-day period of overtraining had a favourable effect on markers of immune activity and thereby reduced the susceptibility of these endurance athletes to upper respiratory tract infection URTI.     

Development of a common outcome data set for fall injury prevention trials: the Prevention of Falls Network Europe consensus

The prevention of injury associated with falls in older people is a public health target in many countries around the world. Although there is good evidence that interventions such as multifactorial fall prevention and individually prescribed exercise are effective in reducing falls, the effect on serious injury rates is unclear. Historically, trials have not been adequately powered to detect injury endpoints, and variations in case definition across trials have hindered meta-analysis. It is possible that fall-prevention strategies have limited effect on falls that result in injuries or are ineffective in populations who are at a higher risk of injury. Further research is required to determine whether fall-prevention interventions can reduce serious injuries. Prevention of Falls Network Europe (ProFaNE) is a collaborative project to reduce the burden of fall injury in older people through excellence in research and promotion of best practice (www.profane.eu.org). The European Commission funds the network, which links clinicians, members of the public, and researchers worldwide. The aims are to identify major gaps in knowledge in fall injury prevention and to facilitate the collaboration necessary for large-scale clinical research activity, including clinical trials, comparative research, and prospective meta-analysis. Work is being undertaken in a 4-year program. As a first step, the development of a common set of outcome definitions and measures for future trials or meta-analysis was considered.