A group randomised trial of two methods for disseminating a smoking cessation programme to public antenatal clinics: effects on patient outcomes.

OBJECTIVE: To assess the differential effectiveness of two methods of disseminating a smoking cessation programme to public hospital antenatal clinics. DESIGN: Group randomised trial. SETTING: 22 antenatal clinics in New South Wales, Australia. INTERVENTION: Clinics were allocated to a simple dissemination (SD) condition (11 clinics) which received a mail-out of programme resources or to an intensive dissemination (ID) condition (11 clinics) which included the mail-out plus feedback, training, and ongoing support with midwife facilitator. MAIN OUTCOME MEASURES: Independent cross sectional surveys of women on a second or subsequent visit undertaken pre-dissemination and 18 months after dissemination. Outcomes were: (1) levels of smoking status assessment by clinic staff; (2) proportion of women identifying as having been smokers at their first visit who reported receiving cessation advice; (3) proportion of these women who had quit (self report and expired air carbon monoxide (CO)); and (4) smoking prevalence among all women (self report and CO). SUBJECTS: 5849 women pre-dissemination (2374 SD, 3475 ID) and weighted sample of 5145 women post-dissemination (2302 SD, 2843 ID). RESULTS: There were no significant differences between the groups on change on any outcome. Change in either group was minimal. In the post-dissemination survey, the cessation proportions were 6.4% (SD) and 10.5% (ID). CONCLUSIONS: Relatively modest strategies for encouraging incorporation of smoking cessation activities into antenatal care were not effective in the long term. Alternative strategies should be implemented and evaluated. The findings reinforce the importance of a whole population approach to tobacco control.

Direct telemarketing of smoking cessation interventions: will smokers take the call?

AIMS: Few smokers currently make use of available and effective cessation strategies, despite their expressed desire to quit and reported interest in cessation support. This study aimed to explore the feasibility of a telephone-based direct-marketing approach to delivering cessation strategies. DESIGN, SETTING, MEASUREMENTS AND PARTICIPANTS: A community survey was conducted to explore the views of current adult smokers regarding the acceptability, likely uptake and barriers to uptake of smoking cessation services offered by direct telephone marketing. FINDINGS: Three quarters (73.8%) of smokers contacted agreed to be surveyed. Of the 194 study participants, 75.3% reported that they would utilize vouchers for discount nicotine replacement therapy (NRT), 66.5% would use a mailed self-help booklet, 57.2% would take up the offer of regular mailings of personalized letters and self-help materials and 46.4% would utilize a 'we-call-you' telephone counselling service. The characteristics of those indicating likely uptake of these services were also explored. The two major barriers to uptake of services were preferring to quit without help and a belief that a particular service would not help the participant. CONCLUSIONS: The data suggest strong support for the direct marketing of smoking cessation strategies; they also highlight the need for further study of the cost-effectiveness of telephone-based direct marketing of smoking cessation strategies as a population-based strategy for reducing the prevalence of smoking in the community.

Src family kinase and adenosine differentially regulate multiple MAP kinases in ischemic myocardium: modulation of MAP kinases activation by ischemic preconditioning.

Recent studies suggest that ischemia activates Src and members of the mitogen-activated protein (MAP) kinase superfamily and their downstream effectors, including big MAP kinase 1 (BMK1) and p90 ribosomal S6 kinase (p90RSK). It has also been reported that adenosine is released during ischemia and involved in triggering the protective mechanism of ischemic preconditioning. To assess the roles of Src and adenosine in ischemia-induced MAP kinases activation, we utilized the Src inhibitor PP2 (4-Amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine) and the adenosine receptor antagonist 8-(p-sulfophenyl) theophylline (SPT) in perfused guinea pig hearts. PP2 (1 microm) inhibited ischemia-induced Src, BMK1 and JNK activation but not JAK2 and p38 activation. SPT inhibited ischemia-mediated p38 and JNK activation. These results demonstrate that Src family kinase and adenosine regulate MAP kinases by parallel pathways. Preconditioning significantly improved both recovery of developed pressure and dp/dt in isolated guinea pig hearts. Since the protective effect of preconditioning was blocked by PP2 (1 microm) and SPT (50 microm), we next investigated the regulation of Src, MAP kinases and p90RSK during preconditioning. The activity and time course of ERK1/2 was not changed, but p90RSK activation by reperfusion was completely inhibited by preconditioning. In contrast, the activation by ischemia of Src, BMK1, p38 and JNK was significantly faster in preconditioned hearts. Maximal BMK1 activation by ischemia was also significantly enhanced by preconditioning. These data suggest important roles for Src family kinases and adenosine in mediating preconditioning, and suggest specific roles for individual MAP kinases in preconditioning.

Quitting smoking in pregnancy.

Smoking doubles the risk of having a low-birthweight baby and significantly increases the rate of perinatal mortality and several other adverse pregnancy outcomes. The mean reduction in birthweight for babies of smoking mothers is 200 g. High quality interventions to help pregnant women quit smoking produce an absolute difference of 8.1% in validated late-pregnancy quit rates. If abstinence is not achievable, it is likely that a 50% reduction in smoking would be the minimum necessary to benefit the health of mother and baby. Healthcare providers perform poorly in antenatal interventions to stop women smoking. Midwives deliver interventions at a higher rate than doctors. The efficacy of nicotine replacement therapy has not been established in pregnancy. Currently, its use should only be considered in women smoking more than 10 cigarettes per day who have made a recent, unsuccessful attempt to quit and who are motivated to quit. Relapse prevention programs have shown little success in the postpartum period.

Sarcoplasmic reticulum Ca(2+) atpase (SERCA) 1a structurally substitutes for SERCA2a in the cardiac sarcoplasmic reticulum and increases cardiac Ca(2+) handling capacity.

Ectopic expression of the sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA) 1a pump in the mouse heart results in a 2.5-fold increase in total SERCA pump level. SERCA1a hearts show increased rates of contraction/relaxation and enhanced Ca(2+) transients; however, the cellular mechanisms underlying altered Ca(2+) handling in SERCA1a transgenic (TG) hearts are unknown. In this study, using confocal microscopy, we demonstrate that SERCA1a protein traffics to the cardiac SR and structurally substitutes for the endogenous SERCA2a isoform. SR Ca(2+) load measurements revealed that TG myocytes have significantly enhanced SR Ca(2+) load. Confocal line-scan images of field-stimulated SR Ca(2+) release showed an increased rate of Ca(2+) removal in TG myocytes. On the other hand, ryanodine receptor binding activity was decreased by approximately 30%. However, TG myocytes had a greater rate of spontaneous ryanodine receptor opening as measured by spark frequency. Whole-cell L-type Ca(2+) current density was reduced by approximately 50%, whereas the time course of inactivation was unchanged in TG myocytes. These studies provide important evidence that SERCA1a can substitute both structurally and functionally for SERCA2a in the heart and that SERCA1a overexpression can be used to enhance SR Ca(2+) transport and cardiac contractility.

Differential uptake of a smoking cessation programme disseminated to doctors and midwives in antenatal clinics.

AIMS: Two methods of dissemination (simple and intensive) were used to disseminate a smoking cessation programme to doctors and midwives working in antenatal clinics. This paper describes the differential uptake of the smoking cessation programme by doctors and midwives. It investigates whether the number of smoking cessation interventions used differ due to the type of dissemination. It also examines the frequency with which doctors and midwives provide smoking cessation interventions after dissemination. DESIGN: Clinics were randomized to the method of dissemination (simple or intensive). Pre-post test design was used to examine the relationship between dissemination method and professional status at baseline and follow-up. A baseline survey collected data on the use of smoking cessation intervention in the clinics prior to dissemination. A follow-up survey was conducted 18 months after the dissemination. SETTING: Twenty-three public hospital antenatal clinics in NSW. PARTICIPANTS: All clinical staff (midwives and doctors) working in the clinic during the 1-2-week survey period prior to dissemination and 18 months after the dissemination were asked to participate. The response rate was 63% (223) at baseline and 64% (182) at follow-up. Only 48% of midwives and doctors at follow-up were working in the original clinic. MEASURES: The proportion of clinicians who initially adopted the programme; the proportion of clinicians who had used one or more programme components in the last week); the number of types of smoking cessation intervention provided (maximum = 13), and the estimated proportion of clients offered smoking cessation intervention. FINDINGS: More midwives than doctors "ever used" the programme (76% vs. 25%) and continued to implement (58% vs. 22%) the programme 18 months after dissemination. Both midwives and doctors increased the number of types of smoking cessation intervention offered at follow-up compared to baseline (mean difference 2.8). Midwives provided more smoking cessation interventions than doctors at baseline (mean difference 0.9) and at follow-up (1.6), regardless of method used to disseminate the programme. Midwives' mean estimates of the proportion of clients offered interventions were greater than doctors' (midwives' 59% vs. doctors' 35%) at follow-up. CONCLUSION: The dissemination of a smoking cessation programme increased the level of smoking cessation interventions used by doctors and midwives. Doctors and midwives differ in their uptake of smoking cessation programmes. This information can be used to plan programme dissemination strategies in the future.

Preventive and other interactional skills of general practitioners, surgeons, and physicians: perceived competence and endorsement of postgraduate training.

BACKGROUND: Perceived competencies and support for formal postgraduate training across a range of preventive and other interactional skills were examined in three medical groups. METHODS: All eligible final year students and recent graduates of the three major Australian medical colleges (n = 767) were mailed a questionnaire examining communication skills in four domains: preventive, educational, therapeutic, and general. RESULTS: Overall consent rate was 45%. For most items, at least one-third of each group reported low competence. On preventive items, low competence ratings ranged from 5 to 39% in general practice, 38 to 67% in surgery, and 33 to 51% in the speciality physician group. Significant intergroup differences occurred on eight competence items. Agreement with training on preventive topics ranged from 80 to 91% in general practice, 48 to 69% in surgery, and 72 to 82% in the specialty physician group. On all 11 training items where significant differences occurred, the general practice group reported the highest level and the surgeon group the lowest level of endorsement for formal training and assessment. CONCLUSIONS: Substantial proportions in the general practice, surgery, and the physician specialty report lack of competence in common interactional skills. There were high levels of support for formal training in preventive and other interactional skills. The strong endorsement supports the development of effective, tailored interactional skills training programs.

Effect of angiotensin type I-receptor blockade on left ventricular remodeling in pressure overload hypertrophy.

BACKGROUND: The renin-angiotensin system is involved in cardiac remodeling. In contrast to the well-recognized salutary effects of angiotensin-converting enzyme inhibition, the value of angiotensin II type I (AT(1))-receptor blockade on left ventricular (LV) hypertrophy and dysfunction is controversial. METHODS AND RESULTS: Descending thoracic aorta-banded and sham-operated guinea pigs were given either losartan (30 mg x kg(-1) x day(-1) intraperitoneally) or vehicle for 8 weeks (n = 7 in each group). LV end-diastolic and end-systolic dimensions and wall thicknesses were measured echocardiographically, and LV fractional shortening, relative wall thickness, and LV mass normalized by body weight were calculated. Isolated heart function (Langendorff perfusion) was studied 8 weeks after surgery, and LV performance was assessed by maximum LV pressure and +/-dP/dt normalized by LV mass. Eight weeks after banding guinea pigs developed concentric LV hypertrophy and had decreased maximum LV pressure and +/-dP/dt normalized by LV mass; LV end-diastolic dimension and LV fractional shortening were unchanged. In band-operated guinea pigs treatment with losartan had no significant effects on any of these measurements. CONCLUSIONS: In guinea pigs with descending aortic banding, treatment with losartan for 8 weeks neither attenuates progression of pressure overload hypertrophy nor significantly improves impaired mass-normalized pressure-derived indices of LV contraction and relaxation.

Process measures in an antenatal smoking cessation trial: another part of the picture.

Data on provider and patient compliance can be crucial in understanding the degree of a health education program's effectiveness, as well as in identifying areas where the program requires modification. However, such data are rarely systematically reported in randomized trials. This report assesses the degree to which doctors and midwives complied with intervention protocols in a hospital antenatal smoking cessation trial, and also examines the program's acceptability to patients. Provider compliance was assessed principally via consultation audiotapes and provider-completed checklists. The audiotape analysis identified substantial compliance problems. For example, in relation to six specific smoking-related pregnancy risks, the proportions of Experimental Women informed about each individual risk ranged from 26 to 38% and the proportions receiving counselling items ranged from 52 to 79%. Doctors only informed a minority of Experimental Women of the increased risk of Sudden Infant Death Syndrome (28%) and of the presence of toxic chemicals in tobacco (21%). Comparison of compliance data from audiotapes and provider checklists revealed there was no significant agreement in three of four cases tested. Experimental Patients completed questionnaires to assess recall of smoking advice and to rate 12 program features. Of specific Experimental Program elements, the videotape (85%) received the highest level of positive patient ratings and the lottery (42%) the lowest. The process evaluation indicated that the Experimental Program needed some modification to increase its suitability for routine application. The findings also support the value of including an objective measure of provider compliance.

Disruption of a single copy of the SERCA2 gene results in altered Ca2+ homeostasis and cardiomyocyte function.

A mouse model carrying a null mutation in one copy of the sarcoplasmic reticulum (SR) Ca(2+)-ATPase isoform 2 (SERCA2) gene, in which SERCA2 protein levels are reduced by approximately 35%, was used to investigate the effects of decreased SERCA2 level on intracellular Ca(2+) homeostasis and contractile properties in isolated cardiomyocytes. When compared with wild-type controls, SR Ca(2+) stores and Ca(2+) release in myocytes of SERCA2 heterozygous mice were decreased by approximately 40-60% and approximately 30-40%, respectively, and the rate of myocyte shortening and relengthening were each decreased by approximately 40%. However, the rate of Ca(2+) transient decline (tau) was not altered significantly, suggesting that compensation was occurring in the removal of Ca(2+) from the cytosol. Phospholamban, which inhibits SERCA2, was decreased by approximately 40% in heterozygous hearts, and basal phosphorylation of Ser-16 and Thr-17, which relieves the inhibition, was increased approximately 2- and 2.1-fold. These results indicate that reduced expression and increased phosphorylation of phospholamban provides compensation for decreased SERCA2 protein levels in heterozygous heart. Furthermore, both expression and current density of the sarcolemmal Na(+)-Ca(2+) exchanger were up-regulated. These results demonstrate that a decrease in SERCA2 levels can directly modify intracellular Ca(2+) homeostasis and myocyte contractility. However, the resulting deficit is partially compensated by alterations in phospholamban/SERCA2 interactions and by up-regulation of the Na(+)-Ca(2+) exchanger.

Single scrotal incision orchiopexy for the palpable undescended testicle.

PURPOSE: We prospectively evaluated the Bianchi single high scrotal incision technique for orchiopexy in boys with palpable undescended testis distal to the external inguinal ring. MATERIALS AND METHODS: A total of 60 Bianchi orchiopexies were performed in 48 patients. We identified a group with primary undescended and secondary ascended testis, and a trapped testicle associated with previous inguinal surgery, respectively. Testicular position and size were assessed at 6 weeks of followup. RESULTS: We evaluated group 1-34 patients with bilateral (8), right (17) and left (9) primary undescended testis, group 2-3 with secondary ascended testis and group 3-11 with bilateral (4), right (4) and left (3) trapped testis. Average surgical time was 15, 35 and 35 minutes, respectively. Four patients required conversion to a traditional inguinal incision to achieve adequate cord length. All but 2 patients had a palpable testicle of acceptable size compared with the contralateral mate in the dependent scrotum at the end of the operation and 6 weeks postoperatively. Those returning for 1-year followup had identical findings. In groups 1 and 2 a single testicle normal to palpation resided in a high scrotal position and 1 testis required secondary orchiectomy for infarction, respectively. Scrotal hematoma resolved spontaneously without injury to the testis in 1 case. No hernias were evident. CONCLUSIONS: A single high scrotal incision for palpable primary, secondary ascended or even trapped testis is well tolerated, cosmetically pleasing and associated with a short operative time. The complication rate is acceptably low.

Changes in Ca(2+) cycling proteins underlie cardiac action potential prolongation in a pressure-overloaded guinea pig model with cardiac hypertrophy and failure.

Ventricular arrhythmias are common in both cardiac hypertrophy and failure; cardiac failure in particular is associated with a significant increase in the risk of sudden cardiac death. We studied the electrophysiologic changes in a guinea pig model with aortic banding resulting in cardiac hypertrophy at 4 weeks and progressing to cardiac failure at 8 weeks using whole-cell patch-clamp and biochemical techniques. Action potential durations (APDs) were significantly prolonged in banded animals at 4 and 8 weeks compared with age-matched sham-operated animals. APDs at 50% and 90% repolarization (APD(50) and APD(90) in ms) were the following: 4 week, banded, 208+/-51 and 248+/-49 (n = 15); 4 week, sham, 189+/-68 and 213+/-69 (n = 16); 8 week, banded, 197+/-40 and 226+/-40 (n = 21); and 8 week, sham, 156+/-42 and 189+/-45 (n = 22), respectively; P<0.05 comparing banded versus sham-operated animals. We observed no significant differences in the K(+) currents between the 2 groups of animals at 4 and 8 weeks. However, banded animals exhibited a significant increase in Na(+) and Na(+)-Ca(2+) exchange current densities compared with controls. Furthermore, we have found a significant attenuation in the Ca(2+)-dependent inactivation of the L-type Ca(2+) current in the banded compared with sham-operated animals, likely as a result of the significant downregulation of the sarcoplasmic reticulum Ca(2+) ATPase, which has been documented previously in the heart failure animals. Our data provide an alternate mechanism for APD prolongation in cardiac hypertrophy and failure and support the notion that there is close interaction between Ca(2+) handling and action potential profile.

Alterations in Ca2+ cycling proteins and G alpha q signaling after left ventricular assist device support in failing human hearts.

OBJECTIVE: Left ventricular assist device support mechanically unloads the failing ventricle with resultant improvement in cardiac geometry and function in patients with end-stage heart failure. Activation of the G alpha q signaling pathway, including protein kinase C, appears to be involved in the progression of heart failure. Similarly down-regulation of Ca2+ cycling proteins may contribute to contractile depression in this clinical syndrome. Thus we examined whether protein kinase C activation and decreased Ca2+ cycling protein levels could be reversed by left ventricular assist device support. METHODS: Left ventricular myocardial specimens were obtained from seven patients during placement of left ventricular assist device and heart transplantation. We examined changes in protein levels of G alpha q, phospholipase C beta 1, regulators of G protein signaling (RGS), sarcoplasmic reticulum Ca2+ ATPase, phospholamban and translocation of protein kinase C isoforms (alpha, beta 1, and beta 2). RESULTS: The paired pre- and post-left ventricular assist device samples revealed that RGS2, a selective inhibitor of G alpha q, was decreased (P < 0.01), while the status of G alpha q, phospholipase C beta 1, RGS3 and RGS4 were unchanged after left ventricular assist device implantation. Translocation of protein kinase C isoforms remained unchanged. Left ventricular assist device support increased sarcoplasmic reticulum Ca2+ ATPase protein level (P < 0.01), while phospholamban abundance was unchanged. CONCLUSIONS: We conclude that altered protein expression and stoichiometry of the major cardiomyocyte Ca2+ cycling proteins rather than reduced phospholipase C beta 1 activation may contribute to improved mechanical function produced by left ventricular assist device support in human heart failure.

Influence of transgenic overexpression of phospholamban on postextrasystolic potentiation.

Twelve mice with PLB overexpression (PLBOE), and 11 isogenic FVB/N wild-type (WT) controls, were anesthetized and instrumented with a 1.4 F Millar catheter in the LV and a 1 F pacemaker in the right atrium. At a cycle length of 200 ms and a fixed extrastimulus of 120 ms, extrastimuli with increasing intervals (PESI) up to 1000 ms were introduced, and the peak rates of LV isovolumic contraction (+/- dP/dtmax) were normalized and fit to monoexponential equations. In a subset of animals, the protocols were repeated after ryanodine (4 ng/g) was given to deplete SR Ca2+ stores. The time constant and the plateau of the exponential curve fits were significantly greater in PLBOE than WT (107.8 +/- 7.0 v 75.2 +/- 5.5 ms and 1.39 +/- 0.03 v 1.08 +/- 0.02, both P < 0.05). At 200, 600 and 1000 ms, the normalized dP/dt was significantly greater in PLBOE than WT. After ryanodine, normalized dP/dt was significantly decreased in PLBOE, but unchanged in WT. The protein levels of the sodium-calcium exchanger normalized to calsequestrin were increased 3.7 +/- 0.3-fold in PLBOE compared to controls. In conclusion, the phospholamban level is a critical determinant of postextrasystolic potentiation in this transgenic model, and is differentially impaired by ryanodine at long diastolic intervals in PLBOE v controls. These differences may be due in part to changes in the protein level and resultant activity of the sodium calcium exchanger.

The effects of levosimendan on the left ventricular function and protein phosphorylation in post-ischemic guinea pig hearts.

The widely accepted theories for the decreased function in the stunned myocardium relate to Ca2+ desensitization and free radical-mediated tissue damage of the myofilaments. The aim of the present study was to examine whether the depressed contractile function and Ca2+ responsiveness of the stunned myocardium may be restored by a new Ca2+ sensitizer (levosimendan), which has been shown to improve the Ca2+ response of the myofilaments. The effects of levosimendan on the left ventricular function and the in vivo protein phosphorylation were examined in both the non-ischemic and the stunned myocardium. Myocardial stunning was induced in Langendorff-perfused guinea pig hearts by suspending the circulation for 8 min, followed by a 20-min reperfusion period. Perfusion of post-ischemic guinea pig hearts with levosimendan (0.03-0.48 microM, 6 min) was associated with dose- and time-dependent increases in both dP/dtmax (contractility) and dP/dtmin (speed of relaxation). When the effectiveness of levosimendan was compared in non-ischemic and post-ischemic hearts, no significant differences were noted in the relative stimulatory effects on contractility and relaxation, at any given time point (time-response curve) or concentration (dose-response curve). Perfusion of the guinea pig hearts with a high (0.3 microM) levosimendan concentration did not reveal any qualitative or quantitative difference in the phosphodiesterase inhibitory potential of the compound (elevation of tissue cyclic AMP levels and characteristics of protein phosphorylation) between the non-ischemic and the post-ischemic myocardium. However, when isoproterenol was administered to induce maximal in vivo phosphorylation of cardiac phosphoproteins, an attenuation of the 32P-incorporation into troponin I was noted in the post-ischemic hearts. The decrease in isoproterenol-induced 32P-incorporation into troponin I was associated with similar alterations in the tissue level of this protein. We conclude that the Ca2+ sensitizer levosimendan exerts dose- and time-dependent positive inotropic and lusitropic effects on the post-ischemic myocardium, lending support to the hypothesis tha Ca2+ desensitization of the myofibrils is involved in myocardial stunning.

Identification of a specific role for the Na,K-ATPase alpha 2 isoform as a regulator of calcium in the heart.

It is well accepted that inhibition of the Na,K-ATPase in the heart, through effects on the Na/Ca exchanger, raises the intracellular Ca2+ concentration and strengthens cardiac contraction. However, the contribution that individual isoforms make to this calcium regulatory role is unknown. Assessing the phenotypes of mouse hearts with genetically reduced levels of Na,K-ATPase alpha 1 or alpha 2 isoforms clearly demonstrates different functional roles for these isoforms in vivo. Heterozygous alpha 2 hearts are hypercontractile as a result of increased calcium transients during the contractile cycle. In contrast, heterozygous alpha 1 hearts are hypocontractile. The different functional roles of these two isoforms are further demonstrated since inhibition of the alpha 2 isoform with ouabain increases the contractility of heterozygous alpha 1 hearts. These results definitively illustrate a specific role for the alpha 2 Na,K-ATPase isoform in Ca2+ signaling during cardiac contraction.