Chronic-alcohol exposure alters IGF1 signaling in H9c2 cells via changes in PKC delta.

Previously, we have demonstrated that chronic-alcohol exposure alters insulin-like growth factor 1 (IGF1) signaling in adult rat heart cells. This report examines the effects of alcohol in vitro on the expression of protein kinase C (PKC) alpha, delta, and epsilon using the embryonic heart cell line, H9c2, and how this may be linked to changes in IGF1 signal transduction. Western blot analyses of H9c2 protein preparations demonstrate that there are significant increases in the total protein levels of PKC delta and epsilon after 4 days exposure to alcohol, and similar increases were found after 2 and 6 days exposure. In addition, there was a significant increase in PKC delta and epsilon in the membranal fractions and a decrease in the cytosolic fractions. No change was found in the expression or activity levels for PKC alpha. Chronic-alcohol exposure (100 mM, 4 days) increased the basal tyrosine kinase activity of the IGF1 receptor (IGF1R), and altered its rate of activation. Chronic-alcohol exposure also reduced the rate of Erk1/Erk2 activation by IGF1. Chronic alcohol blocked the proliferative effects of IGF1 on cell growth and reduced cell viability both in the presence and absence of IGF1, and this alcohol-induced reduction in cell viability was blocked using siRNA to inhibit PKC delta. In addition, a reduction in the amount of myosin light chain 2 was found in the alcohol-exposed cells. In conclusion, chronic alcohol alters PKC delta and epsilon expression and activity, and suppresses the IGF1 signaling pathway in embryonic heart cell culture. Blockage of PKC delta expression using siRNA inhibits the suppressive effects of alcohol on cell viability.     

Postoperative Analgesic Effects of Continuous Wound Infiltration with Diclofenac after Elective Cesarean Delivery

Background: Postoperative pain mostly results from sensitization of afferent fibers at injury sites driving central sensitization. Recently, peripheral processes have gained attention as mechanisms of hyperalgesia, and prostaglandins are among highly sensitizing agents. To date, perioperative administration of a single local dose of nonsteroidal antiinflammatory drugs has shown inconclusive efficacy. Rather than a single bolus, the current study evaluates the postoperative analgesic effect of diclofenac continuous intrawound infusion after elective cesarean delivery.

Methods: Ninety-two parturients were randomly allocated to receive a 48-h continuous intrawound infusion with 240 ml containing 300 mg diclofenac, 0.2% ropivacaine, or saline. In the ropivacaine and saline groups, patients also received 75 mg intravenous diclofenac every 12 h for 48 h. Postoperative evaluation included intravenous morphine consumption by patient-controlled analgesia and visual analog pain scores. Punctate mechanical hyperalgesia surrounding the wound and presence of residual pain after 1 and 6 months were also assessed.

Results: Continuous diclofenac infusion significantly reduced postoperative morphine consumption (18 mg; 95% confidence interval, 12.7-22.2) in comparison with saline infusion and systemic diclofenac (38 mg; 95% confidence interval, 28.8-43.7) (P = 0.0009) without unique adverse effects. Postoperative analgesia produced by local diclofenac infusion was as effective as local ropivacaine infusion with systemic diclofenac.     

Small proportions: what to report for confidence intervals?

The original article to which this Erratum refers was published in Pharmacoepidemiology and Drug Safety 2005; 14: 239–247.     

How does a Belgian health care provider deal with a request for emergency contraception?

OBJECTIVE: To evaluate how Belgian health care providers deal with a request for emergency contraception. METHOD: In 2002-2003 we conducted 12 focus groups with pharmacists, general practitioners and school physicians. A skilled moderator accompanied by an observer conducted the focus groups using a semi-structured screenplay. RESULTS: All these health care providers agree with the free access to emergency contraception (EC), but experience considerable frustration with regard to the practical aspects and the legal framework. General practitioners (GPs) claim to spend a lot of time on requests for EC and they are concerned about the quality of the counselling provided in pharmacies. Pharmacists are creative when giving counselling in the pharmacy, but there is, nevertheless, a problem with a lack of privacy. School physicians are frustrated that there is no legal possibility to respond to a request for EC when they feel they are ideally placed to advise adolescents. CONCLUSION: The over-the-counter sale of EC offers women better access, but many barriers still interfere with optimal care. Pharmacists experience a lack of skills to communicate with adolescents and a lack of privacy to give counselling. GPs have good intentions, but are confronted with a lack of willingness on the part of the patients and also financial barriers. School physicians want more possibilities to help adolescents.     

Curriculum factors influencing knowledge of communication skills among medical students

Background  

Communication training builds on the assumption that understanding of the concepts related to professional communication facilitates the training. We know little about whether students' knowledge of clinical communication skills is affected by their attendance of communication training courses, or to what degree other elements of the clinical training or curriculum design also play a role. The aim of this study was to determine which elements of the curriculum influence acquisition of knowledge regarding clinical communication skills by medical students.     

Artificial dermis for major burns. A multi-center randomized clinical trial.

This communication presents an 11-center prospective randomized trial using the artificial dermis invented by Burke and Yannas. Patients with life-threatening burns who underwent primary excision and grafting within 7 days of injury had comparable sites randomized to receive either the artificial dermis (study site) or the investigator's usual skin grafting material (control site). Control materials were autograft, allograft, xenograft, or a synthetic dressing. Epidermal grafts were applied to the study site during a second operation, and surviving patients were followed for 1 year after grafting. One hundred thirty-nine sites on 106 patients were studied. Mean burn size was 46.5 +/- 15% mean total body surface (TBSA). Overall mortality was 13%, and mean hospital stay was 68 +/- 45 days. Median artificial dermis take was 80% compared with 95% for all comparative sites, but the take was equivalent to that of all nonautograft control materials. Results with the artificial dermis improved slightly as the investigators became more familiar with the material. Donor site thickness for the study site averaged .006' +/- .002' compared to .013' +/- .018' for control (p less than .0001) and the epidermal donor site healed an average of 4 days sooner (10 +/- 6 vs. 14 +/- 8 days) (p less than .0001). As the wounds matured during the first year, both patients and surgeons felt that both sites became more comparable in appearance and function. At the completion of the study, there was less hypertrophic scarring of the artificial dermis, and more patients preferred the artificial dermis to the control graft. Artificial dermis with an epidermal graft provides a permanent cover that is at least as satisfactory as currently available skin grafting techniques, and uses donor grafts that are thinner and donor sites that heal faster.     

Tunica media of aorta and pulmonary trunk in relation to internal calibres in transposition of great arteries,in aortic and pulmonary atresia and in normal hearts

Summary In a post mortem material of 17 cases of transposition of the great arteries (TGA) from patients with an age range from birth to two years and ten months after birth, the internal calibres of the great arteries and the ostia of the heart proved to be the same as in normal hearts. Furthermore, the media of the ascending aorta and pulmonary trunk showed no adaptation to the abnormal circulatory conditions in 15 cases of TGA with an age range from birth up to 51/2 months: in both great arteries the thickness of the tunica media and the packing density of its elastic fibres were the same as in normal hearts. However, adaptation of the tunica media of the pulmonary trunk to the abnormal circulatory conditions: increased media thickness, was found in the two remaining cases, older than 12 months.In 7 cases of pulmonary atresia (age from 1 day to 12 months) and in 9 cases of aortic atresia (age from 2 days to 37 days) the following observations were made. Vessels with reduced or absent function (ascending aorta in aortic atresia and pulmonary trunk in pulmonary atresia) showed a markedly different structure. In aortic atresia the internal calibre and thickness of the media of the ascending aorta were markedly reduced, whereas the packing density of the elastic fibres of the media remained the same as in normal hearts. In pulmonary atresia the pulmonary trunk showed large variations in internal calibre, whereas both media thickness and the packing density of its elastic fibres remained the same as in normal hearts. When the markedly enlarged single functional vessels (the pulmonary trunk in aortic atresia and the ascending aorta in pulmonary atresia) were compared no significant differences between their internal calibre, media thickness and the packing density of the elastic fibres were found indicating similar adaptation to the abnormal but comparable functional load of acting as sole arterial trunk.We are indebted to Prof. Dr. J. Moll for his help, to Dr. J.J. Willemse for statistical calculations, to Mr. P. Zondervan, M.D. (Dept. of Pathology I), for supply of material and to Mrs. L. Silvis for histo-technical assistance     

Genetic linkage between erm(B) and vanA in Enterococcus hirae of poultry origin

Vancomycin-resistant enterococci (VRE) have frequently been isolated from Norwegian poultry production following the prohibition of the glycopeptide growth promoter avoparcin since 1995. In the present study, a close genetic linkage between the vanA and erm(B) determinants in an Enterococcus hirae isolate of poultry origin is demonstrated, a result that indicates a mechanism for co-selection and maintenance of vancomycin resistance in absence of selective pressure from avoparcin. A total of 36 vanA-positive enterococci of poultry origin, also phenotypically resistant to erythromycin and/or tetracycline, were analyzed by PCR for identification of erm and tet resistance determinants. An E. hirae isolate harbored erm(B) and tet(K), and in this isolate vanA and erm(B) were located on a BamHI fragment of an approximately 50-kb plasmid. Approximately 3 kb of this fragment was amplified by PCR with vanA and erm(B) primers. Sequence analysis of the region between erm(B) and vanZ of Tn1546 showed a truncated IS1216V inserted downstream of the erm(B) stop codon, aligned with a conserved copy of the 3'-inverted terminal repeat of Tn1546. Mating experiments with the E. hirae isolate as donor and E. faecalis JH2-2 as recipient did not result in any transconjugants, indicating that the vanA/erm(B)-carrying plasmid was nonconjugative under the given experimental conditions.     

Interaction analysis of physician-patient communication: the influence of trait anxiety on communication and outcome

Little attention has been paid to how patients' personality traits interfere with the communication and the outcome of physician-patient interaction. We performed an experimental study with students with high and low trait anxiety as patients. One physician conducted a single consultation with 41 students applying two beforehand-specified consultation styles. Patients completed questionnaires concerning emotional state and satisfaction. The actual content of the consultations was analyzed by Roter interaction analysis system (RIAS). The physician gave more biomedical information to low-anxiety students than high-anxiety students. Students who provided a lot of biomedical information themselves were less tense after the consultation. However, students with high anxiety were more dependent on the physician actively asking biomedical questions for them to be able to deliver that same information. In contrast to low-anxiety students, those with high anxiety were less satisfied after consultations involving many psychosocial questions posed by the physician and a good deal of emotional talk on their own part. Compared to low-anxiety students, students with high anxiety were less satisfied and tenser after consultations with much positive emotional talk on the part of the physician. We conclude that physicians and educators should be aware that psychological and emotional communication may be experienced as intrusive and inappropriate by patients with high trait anxiety when they present minor somatic problems.     

The effects of levetiracetam on objective and subjective sleep parameters in healthy volunteers and patients with partial epilepsy

Levetiracetam is a novel antiepileptic drug which has recently been released as an adjunctive treatment for partial epilepsy. In the two studies reported here we examined the objective and subjective effects of levetiracetam on sleep in 12 healthy volunteers and 17 patients [16 who could be evaluated for electroencephalogram (EEG) recordings] with a history of partial epilepsy on stable carbamazepine monotherapy. The studies were of a similar double-blind crossover placebo-controlled design with subjects' sleep being recorded in their own homes. The results from the two studies showed considerable similarities. In both, levetiracetam produced an increase in the time spent in stage 2 sleep, which in the patient study was accompanied by a decrease in the time spent in stage 4 sleep and in the volunteer study an increase in rapid eye movement (REM) latency. The subjective changes included reports that sleep was of a better quality with fewer awakenings and patients also reported that their sleep was more restful. Volunteers and patients did, however, feel less alert on waking in the morning. Therefore, both groups reported a decrease in awakenings after levetiracetam despite the finding from the EEG of no change in the actual number of awakenings. It may be concluded from both studies that levetiracetam does affect some indicators of subjective sleep perception, but does not influence objective sleep measures of sleep continuity. The results from the patient study during placebo add-on treatment also showed that patients on carbamazepine had a marked increase in SWS, an increase in stage 2 sleep and an increase in REM latency compared with healthy volunteers. Interestingly, levetiracetam also reduced bilateral epileptiform EEG activity, particularly in patients with more discharges.