Knockout of ERK1 enhances cocaine-evoked immediate early gene expression and behavioral plasticity.

The ability of cocaine to produce lasting neural adaptations in mesocorticolimbic brain regions is thought to promote drug seeking and facilitate addiction in humans. The Ras-controlled Raf-MEK-ERK protein kinase signaling cascade has been implicated in the behavioral and neurobiological actions of cocaine in animals. However, these pharmacological studies have not been able to determine the specific role of the two predominant isoforms of ERK (ERK1 and ERK2) in these processes. We report here that deletion of the ERK1 isoform, which leads to increased ERK2 stimulus-dependent signaling, facilitates the development of cocaine-induced psychomotor sensitization and the acquisition of a cocaine conditioned place preference. Conversely, pharmacological blockade of ERK signaling attenuates the development of psychomotor sensitization to cocaine. Finally, cocaine-evoked gene expression in mesocorticolimbic brain regions is potentiated in ERK1-deficient mice. Thus, alterations in ERK signaling influence both the neurobiological impact of cocaine and its ability to produce enduring forms of drug experience-dependent behavioral plasticity. Our results suggest that enhanced ERK2 signaling following repeated drug exposure may facilitate the development of forms of cocaine-induced plasticity that contribute to addiction.     

Using Ontario's "Telehealth" health telephone helpline as an early-warning system: a study protocol

Background  

The science of syndromic surveillance is still very much in its infancy. While a number of syndromic surveillance systems are being evaluated in the US, very few have had success thus far in predicting an infectious disease event. Furthermore, to date, the majority of syndromic surveillance systems have been based primarily in emergency department settings, with varying levels of enhancement from other data sources. While research has been done on the value of telephone helplines on health care use and patient satisfaction, very few projects have looked at using a telephone helpline as a source of data for syndromic surveillance, and none have been attempted in Canada. The notable exception to this statement has been in the UK where research using the national NHS Direct system as a syndromic surveillance tool has been conducted.     

Pilot randomised controlled trial of community pharmacy administration of buprenorphine versus methadone

Objectives The established regime for opiate substitute prescribing for drug misusers is daily methadone administered under supervision in community pharmacies. Buprenorphine has recently been introduced as an alternative. However there is a lack of evidence of the effectiveness of buprenorphine maintenance therapy (BMT) in the UK treatment setting. This study aimed to assess methods for a randomised controlled trial (RCT) and the feasibility of pharmacy‐based supervised self‐administration (SSA) of buprenorphine compared to methadone. Setting Specialist substance misuse service, general practices and community pharmacies in Aberdeen, Scotland. Method The design was a pilot RCT. Opiate‐dependent drug misusers, newly referred for maintenance treatment were randomised to receive BMT or methadone maintenance therapy (MMT). Clients and pharmacists were interviewed at baseline and at the end of a 12‐week intervention period. Clients completed the quality of life measure EQ‐5D. Pharmacy activities were timed. Key findings Twenty‐one opiate‐dependent clients were recruited (BMT = 11, MMT = 10). Recruitment levels improved as the trial progressed. Clients' treatment preferences were evident. Withdrawals occurred early with BMT. Clients found SSA of buprenorphine acceptable, but found daily administration more manageable than three times weekly. Pharmacists found the dispensing of buprenorphine to be an acceptable role, but felt less certain of ensuring against diversion with buprenorphine than they were with methadone. Pharmacy activities associated with buprenorphine took longer than those associated with methadone (mean = 7 min 25 s versus mean = 3 min 27 s, respectively). Conclusion Recruitment to a trial comparing MMT to BMT for opiate‐dependent clients within a UK treatment setting is feasible. Clients and pharmacists found buprenorphine acceptable.     

The long-term effects of tibolone on aortic stiffness and endothelial function.

OBJECTIVE: To investigate the effect of 10 years of treatment with tibolone on aortic stiffness and endothelial function. DESIGN: Cross-sectional study of women currently participating in an open-label, non-randomized study of the long-term efficacy of tibolone. A total of 113 recently postmenopausal women were recruited in 1988. Fifty-eight agreed to take tibolone 2.5 mg daily and 55 were followed during the study as matched controls (who chose not to take any form of hormone replacement therapy (HRT) for the duration of the study). The groups were matched for age, weight and time since last menstrual period. SETTING: A Central London Teaching Hospital. SUBJECTS: After 10 years, 60 women remained in the study, 32 in the tibolone group and 28 in the control group. All of these women were invited to participate in this pilot study and attend the Menopause Research Unit. Fourteen women from each group agreed to attend. The main outcome measures were aortic stiffness, measured by pulse wave velocity, and endothelial function, as assessed by flow-mediated dilatation of the brachial artery. RESULTS: Pulse wave velocity was significantly lower in the tibolone group (10.4 +/- 1.2) than in the control group (11.6 +/- 1.2), p = 0.042. The flow-mediated dilatations were similar in both groups. CONCLUSION: In this study, long-term use of tibolone over 10 years has a beneficial effect on aortic stiffness. The differences seen in brachial artery vasoreactivity failed to reach statistical significance. Whether this is a true indication of the effects of long-term tibolone on brachial artery vasoreactivity will only be determined by performing a larger, placebo-controlled, randomized study.     

Application of draft European Commission reference levels to a regional CT dose survey

A survey of CT doses in Northern Ireland in the period between October 1995 and March 1997 was carried out. The survey included all but one of the 10 scanners in use at the time, and, additionally, two others that were replacement machines. The method used was to study standard protocols and calculate doses to the NRPB mathematical phantom, so that a direct comparison could be made with other surveys carried out in a similar fashion elsewhere. The survey addressed the patient radiation dose but not image quality or clinical outcomes. It is estimated that in Northern Ireland the contribution to collective dose to the population from CT is about 40% of that from all medical X-rays. The proposed European Commission reference quantities, weighted CT dose index and dose-length product were computed and their potential use evaluated. A full study of mean values of effective dose per examination revealed the average dose per examination was not significantly different from that found in the 1989 UK survey, although several procedures gave rise to doses that were high enough to be investigated with a view to justification or reduction. One of the scanners was found to give consistently high doses. It is likely that a revision of the mAs values used on this scanner will produce a significant reduction in patient doses without compromising image quality. When compared with the draft EC reference levels, fewer procedures were found to have excessively high dose values. The proposed EC reference levels would therefore be useful for continual monitoring of CT dose status, but do not appear to provide as comprehensive an assessment of patient exposure as that given by consideration of effective doses.     

Double posterior labyrinthotomy technique: results in three Med-El patients with common cavity.

HYPOTHESIS: This study reports on the use of the double posterior labyrinthotomy surgical technique and a custom-designed electrode to ensure better positioning of stimulating electrodes within the common cavity and thus demonstrate suitable outcomes in patients. BACKGROUND: Cochlear implantation has proven beneficial for numerous children with congenital malformations of the inner ear. Several studies show good auditory perception outcomes in children with common cavity. However, there have been risks involved with surgical techniques used in the actual implantation. These include possible aberrant facial nerve and the strong potential for a cerebrospinal fluid gusher. Improved surgical techniques and electrode design could allow for better electrode contact and avoid electrode placement in the internal auditory meatus. METHOD: The double posterior labyrinthotomy technique was carried out in three cases using a custom made MED-EL COMBI 40+ electrode. RESULTS: Surgery was carried out with no complications and is no more technically demanding than other standard surgical approaches. The speech processor program remains stable over time, and auditory perception results are similar to those obtained from children with no cochlear abnormalities. CONCLUSION: These results demonstrate the success of the double posterior labyrinthotomy approach with modified cochlear implant, and this could be recommended as the procedure of choice in children presenting to an implant team with a common cavity.