Hybrid Ablation for Atrial Fibrillation: Safety & Efficacy of Unilateral Epicardial Access.

Hybrid ablation combines thoracoscopic epicardial ablation with percutaneous catheter based endocardial ablation for the treatment of AF. The purpose of this study was to evaluate the safety and efficacy of hybrid ablation surgery for the treatment of atrial fibrillation (AF), and to compare outcomes of unilateral vs bilateral thoracoscopic epicardial ablation. Patients with documented AF who underwent hybrid ablation were followed post-operatively for major events. Major events were classified into 2 categories consisting of (1) safety, comprising all-cause mortality and major morbidities, and (2) efficacy, which included recurrence of atrial arrhythmia, cessation of antiarrhythmic drugs (AAD), and completeness of lesion set. A total of 84 consecutive patients were consented for hybrid ablation. Patients presented with an average AF duration of 85.9 months before hybrid ablation. 80 patients underwent successful thoracoscopic epicardial ablation. At 1-year, 87% (60/69) of patients were free from AF and 73% (50/69) were free from AF and off AAD. 63 patients completed both epicardial and endocardial hybrid ablation with posterior wall isolation achieved in 89% (56/63) of patients. Unilateral epicardial ablation was associated with significantly shorter hospital length of stay compared to bilateral surgical approached (3.9 vs 6.7 days, p = 0.002) with no difference in freedom from AF between groups at 1 year. Hybrid ablation for atrial fibrillation is effective for patients at high risk for recurrence after catheter ablation. The unilateral surgical approach may be associated with shorter hospital stay with no appreciable effect on procedure success rates.

Mapping Atrial Fibrillation After Surgical Therapy to Guide Endocardial Ablation.

BACKGROUND: Surgical ablation for atrial fibrillation (AF) can be effective, yet has mixed results. It is unclear which endocardial lesions delivered as part of hybrid therapy' will best augment surgical lesion sets in individual patients. We addressed this question by systematically mapping AF endocardially after surgical ablation and relating findings to early recurrence, then performing tailored endocardial ablation as part of hybrid therapy. METHODS: We studied 81 consecutive patients undergoing epicardial surgical ablation (stage 1 hybrid), of whom 64 proceeded to endocardial catheter mapping and ablation (stage 2). Stage 2 comprised high-density mapping of pulmonary vein (PV) or posterior wall (PW) reconnections, low-voltage zones (LVZs), and potential localized AF drivers. We related findings to postsurgical recurrence of AF. RESULTS: Mapping at stage 2 revealed PW isolation reconnection in 59.4%, PV isolation reconnection in 28.1%, and LVZ in 42.2% of patients. Postsurgical recurrence of AF occurred in 36 patients (56.3%), particularly those with long-standing persistent AF (P=0.017), but had no relationship to reconnection of PVs (P=0.53) or PW isolation (P=0.75) when compared with those without postsurgical recurrence of AF. LVZs were more common in patients with postsurgical recurrence of AF (P=0.002), long-standing persistent AF (P=0.002), advanced age (P=0.03), and elevated CHA2DS2-VASc (P=0.046). AF mapping revealed 4.4±2.7 localized focal/rotational sites near and also remote from PV or PW reconnection. After ablation at patient-specific targets, arrhythmia freedom at 1 year was 81.0% including and 73.0% excluding previously ineffective antiarrhythmic medications. CONCLUSIONS: After surgical ablation, AF may recur by several modes particularly related to localized mechanisms near low voltage zones, recovery of posterior wall or pulmonary vein isolation, or other sustaining mechanisms. LVZs are more common in patients at high clinical risk for recurrence. Patient-specific targeting of these mechanisms yields excellent long-term outcomes from hybrid ablation.

Elevated tumor LDLR expression accelerates LDL cholesterol-mediated breast cancer growth in mouse models of hyperlipidemia.

Obesity is associated with an increase in cancer-specific mortality in women with breast cancer. Elevated cholesterol, particularly low-density lipoprotein cholesterol (LDL-C), is frequently seen in obese women. Here, we aimed to determine the importance of elevated circulating LDL, and LDL receptor (LDLR) expression in tumor cells, on the growth of breast cancer using mouse models of hyperlipidemia. We describe two novel immunodeficient mouse models of hyperlipidemia (Rag1-/-/LDLR-/- and Rag1-/-/ApoE (apolipoprotein E)-/- mice) in addition to established immunocompetent LDLR-/- and ApoE-/- mice. The mice were used to study the effects of elevated LDL-C in human triple-negative (MDA-MB-231) and mouse Her2/Neu-overexpressing (MCNeuA) breast cancers. Tumors derived from MCNeuA and MDA-MB-231 cells had high LDLR expression and formed larger tumors in mice with high circulating LDL-C concentrations than in mice with lower LDL-C. Silencing the LDLR in the tumor cells led to decreased growth of Her2/Neu-overexpressing tumors in LDLR-/- and ApoE-/- mice, with increased Caspase 3 cleavage. Additionally, in vitro, silencing the LDLR led to decreased cell survival in serum-starved conditions, associated with Caspase 3 cleavage. Examining publically available human data sets, we found that high LDLR expression in human breast cancers was associated with decreased recurrence-free survival, particularly in patients treated with systemic therapies. Overall, our results highlight the importance of the LDLR in the growth of triple-negative and HER2-overexpressing breast cancers in the setting of elevated circulating LDL-C, which may be important contributing factors to the increased recurrence and mortality in obese women with breast cancer.

Occurrence of viral pathogens in Penaeus monodon post-larvae from aquaculture hatcheries.

Viral pathogens appear to exert the most significant constraints on the growth and survival of crustaceans under culture conditions. The prevalence of viral pathogens White Spot Syndrome Virus (WSSV), Hepatopancreatic Parvo Virus (HPV), Monodon Baculo Virus (MBV) and Infectious Hypodermal and Hematopoietic Necrosis Virus (IHHNV) in Penaeus monodon post-larvae was studied. Samples collected from different hatcheries and also samples submitted by farmers from Kerala were analyzed. Out of 104 samples collected, WSSV was detected in 12.5% of the post-larvae samples. Prevalence of concurrent infections by HPV, MBV and WSSV (either dual or triple infection) was present in 60.6% of the total post-larvae tested. Out of the 51 double positives, 98% showed either HPV or IHHNV infection. HPV or IHHNV was detected in 11 post-larval samples showing triple viral infection. This is the first report of IHHNV from India. Result of this study reveals the lack of efficient screening strategies to eradicate viruses in hatchery reared post-larvae.

Screening for MRSA in ICU patients. How does PCR compare with culture?

BACKGROUND: The polymerase chain reaction (PCR) for the detection of methicillin-resistant Staphylococcus aureus (MRSA) has the potential to reduce the time before the identification of nasal carriage, and therefore help in the control and prevention of spread. OBJECTIVE: In a pilot study in a general intensive care unit (ICU) we compared culture with PCR for MRSA detection. METHODS: Between October and November 2005, 170 swabs taken from 63 patients on admission, and then twice weekly were cultured on Columbia Blood Agar, CHROMagar MRSA (CHROMagar Microbiology, Paris, France) and by enrichment and swaps were also tested for MRSA by real-time PCR, using the IDI-MRSA assay. RESULTS: Five patients, previously not know to be positive for MRSA, were detected, but PCR detected only three of these initially. The quickest time to detection using culture was with CHROMagar MRSA, which detected 80% of MRSA. Real-time PCR was rapid (2.25 h) and facilitated the optimization of antibiotic therapy in two of three positive PCR patients, but PCR was less specific and more expensive than CHROMagar MRSA. CONCLUSIONS: PCR facilitates the rapid detection of MRSA and has the potential to contribute to preventing spread, but should continue to be used in conjunction with culture.

Postnatal support for mothers living in disadvantaged inner city areas: a randomised controlled trial.

STUDY OBJECTIVE: To evaluate the effect of two forms of postnatal social support for disadvantaged inner city mothers on maternal and child health outcomes. DESIGN: Randomised controlled trial with economic and process evaluations and follow up at 12 and 18 months. The two intervention groups received either the offer of a year of monthly supportive listening home visits by a support health visitor (SHV), or a year of support from community groups providing drop in sessions, home visiting and/or telephone support (CGS). Each was compared with a control group that received standard health visitor services. SETTING: Two disadvantaged boroughs of London, United Kingdom. PARTICIPANTS: 731 women from culturally diverse backgrounds with infants. MAIN RESULTS: At 12 and 18 months, there was little impact for either intervention on the main outcomes: child injury (SHV: relative risk 0.99; 95% confidence intervals 0.68 to 1.45, CGS: 0.91; 0.61 to1.36), maternal smoking (SHV: 0.86; 0.62 to 1.19, CGS: 0.97; 0.72 to 1.33) or maternal depression (SHV: 0.86; 0.62 to1.19, CGS: 0.93; 0.69 to 1.27). SHV women had different patterns of health service use (with fewer taking their children to the GP) and had less anxious experiences of motherhood than control women. User satisfaction with the SHV intervention was high. Uptake of the CGS intervention was low: 19%, compared with 94% for the SHV intervention. CONCLUSIONS: There was no evidence of impact on the primary outcomes of either intervention among this culturally diverse population. The SHV intervention was associated with improvement in some of the secondary outcomes.

The Social Support and Family Health Study: a randomised controlled trial and economic evaluation of two alternative forms of postnatal support for mothers living in disadvantaged inner-city areas.

OBJECTIVES: To determine whether increased postnatal support could influence maternal and child health outcomes. DESIGN: This was a randomised controlled trial comparing maternal and child health outcomes for women offered either of the support interventions with those for control women receiving standard services only. Outcome data were collected through questionnaires distributed 12 and 18 months postrandomisation. Process data were also collected. There was also an integral economic evaluation. SETTING AND PARTICIPANTS: Women living in deprived enumeration districts in selected London boroughs were eligible for the trial if they gave birth between 1 January and 30 September 1999. RESULTS: The 731 participants were found to be well matched in terms of socio-economic characteristics and health and support variables (14% of the participants were non-English speaking). Response rates at the two follow-up points were 90% and 82%. At both points there were no differences that could not be attributed to chance on the primary outcomes of maternal depression, child injury or maternal smoking. At the first follow-up, there was reduced use of general practitioners by support health visitor (SHV) children, but increased use of NHS health visitors and social workers by mothers. At the second follow-up, both community group support (CGS) and SHV mothers had less use of midwifery services (fewer were pregnant), and SHV mothers were less worried about their child's health and development. Uptake of the CGS intervention was low: 19%, compared with 94% for the SHV intervention. Satisfaction with the intervention among women in the SHV group was high. Based on the assumptions and conditions of the costing methods, the economic evaluation found no net economic cost or benefit of choosing either of the two interventions. CONCLUSIONS: There was no evidence of impact on the primary outcomes of either intervention. The SHV intervention was popular with women, and was associated with improvement in some of the secondary outcomes. This suggests that greater emphasis on the social support role of health visitors could improve some measures of family well-being. Possible areas for future research include a systematic review of social support and its effect on health; developing and testing other postnatal models of support that match more closely the age of the baby and the changing patterns of mothers' needs; evaluating other strategies for mobilising 'non-professional' support; developing and testing more culturally specific support interventions; developing more culturally appropriate standardised measures of health outcomes; providing longer term follow-up of social support interventions; and exploring the role of social support on the delay in subsequent pregnancy.

What retroviruses teach us about the involvement of c-Myc in leukemias and lymphomas.

Overexpression of the cellular oncogene c-Myc frequently occurs during induction of leukemias and lymphomas in many species. Retroviruses have enhanced our understanding of the role of c-Myc in such tumors. Leukemias and lymphomas induced by retroviruses activate c-Myc by: (1) use of virally specified proteins that increase c-Myc transcription, (2) transduction and modification of c-Myc to generate a virally encoded form of the gene, v-Myc, and (3) proviral integration in or near c-Myc. Proviral integrations elevate transcription by insertion of retroviral enhancers found in the long terminal repeat (LTR). Studies of the LTR enhancer elements from these retroviruses have revealed the importance of these elements for c-Mycactivation in several cell types. Retroviruses also have been used to identify genes that collaborate with c-Myc during development and progression of leukemias and lymphomas. In these experiments, animals that are transgenic for c-Mycoverexpression (often in combination with the overexpression or deletion of known proto-oncogenes) have been infected with retroviruses that then insertionally activate novel co-operating cellular genes. The retrovirus then acts as a molecular 'tag' for cloning of these genes. This review covers several aspects of c-Myc involvement in retrovirally induced leukemias and lymphomas.

The c-myc locus is a common integration site in type B retrovirus-induced T-cell lymphomas.

Type B leukemogenic virus (TBLV) induces rapidly appearing T-cell leukemias. TBLV insertions near the c-myc gene were detectable in 2 of 30 tumors tested, whereas 80% of the tumors showed c-myc overexpression. TBLV insertions on chromosome 15 (including a newly identified locus, Pad7) may cause c-myc overexpression by cis-acting effects at a distance.

Mouse mammary tumor virus: a virus that exploits the immune system.

Mouse mammary tumor virus (MMTV) causes mammary carcinomas and T-cell tumors in mice. MMTV variants that induce T-cell tumors have a large deletion within the U3 region of the long terminal repeat (LTR) compared to MMTV strains that induce mammary tumors. We provide evidence here that T-cell tropic MMTV strains lack a redundant binding site for a cellular protein called NBP (negative regulatory element binding protein). The lack of NBP-binding sites in T-cell tropic MMTV strains presumably leads to higher levels of transcription in T-cells during the MMTV life cycle and an increased incidence of mutagenic integration events.

Supporting vulnerable families: an evaluation of Newpin.

Newpin (the New Parent Infant Network) was set up in 1980 to provide support for vulnerable families. But according to a new study, while nearly half the women referred to four Newpin centres went on to make use of its services, a larger proportion did not: either the support package offered was felt to be inappropriate, or the referral was inappropriate, or the women were simply lost to the system. Ann Oakley et al argue that voluntary sector initiatives should be subjected to the same rigorous scrutiny for cost-effectiveness as the statutory sector.

Ca2+ signaling in Sf9 insect cells and the functional expression of a rat brain M5 muscarinic receptor.

The purpose of the present study was to examine Ca2+ signaling mechanisms in Sf9 cells and to demonstrate expression and functional linkage of a mammalian receptor to changes in cytosolic free Ca2+ concentration ([Ca2+]i). Addition of p-octopamine (50 microM to fura 2-loaded Sf9 cells produced a small transient increase in [Ca2+]i from a basal level of 58 +/- 10 to 194 +/- 7.6 (SD) nM. The response to octopamine was inhibited by both cyproheptadine and chlorpromazine and was mimicked by clonidine. In contrast, [Ca2+]i did not change in response to dopamine (50 microM), substance P (50 nM), histamine (50 microM), ATP (50 microM), acetylcholine (10 or 100 microM), carbachol (10 or 100 microM), serotonin (50 microM), epinephrine (10 microM), or bradykinin (50 nM). The Ca(2+)-adenosinetriphosphatase inhibitors thapsigargin (200 nM) and 2,5-di-tert-butylhydroquinone (BHQ; 10 microM) increased [Ca2+]i to 307 +/- 13 and 137 +/- 20 nM, respectively. In contrast to BHQ, the response to thapsigargin was attenuated by La3+ or removal of extracellular Ca2+ and increased by elevation of extracellular Ca2+. These results suggest that thapsigargin but not BHQ stimulates Ca2+ influx. The rat brain muscarinic receptor (subtype M5) was incorporated into the baculovirus by homologous recombination. Addition of carbachol (100 microM) increased [Ca2+]i from 92.7 +/- 6.4 to 480 +/- 26 nM in Sf9 cells infected with recombinant virus containing the M5 receptor cDNA. The effect of carbachol on [Ca2+]i was concentration dependent with a 50% effective concentration of approximately 30 microM and was blocked by atropine (10 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Depletion of the inositol 1,4,5-trisphosphate-sensitive intracellular Ca2+ store in vascular endothelial cells activates the agonist-sensitive Ca(2+)-influx pathway.

Previous studies in non-excitable cells have suggested that depletion of internal Ca2+ stores activates Ca2+ influx from the extracellular space via a mechanism that does not require stimulation of phosphoinositide hydrolysis. To test this hypothesis in vascular endothelial cells, the effect of the Ca(2+)-ATPase/pump inhibitor 2,5-di-t-butylhydroquinone (BHQ) on cytosolic free Ca2+ concentration ([Ca2+]i) was examined. BHQ produced a dose-dependent increase in [Ca2+]i, which remained elevated over basal values for several minutes and was substantially inhibited in the absence of extracellular Ca2+. Application of bradykinin after BHQ demonstrated that the BHQ-sensitive compartment partially overlapped the bradykinin-sensitive store. Similar results were obtained with thapsigargin and cyclopiazonic acid, two other Ca(2+)-ATPase inhibitors. Although BHQ had no effect on phosphoinositide hydrolysis, both 45Ca2+ influx and efflux were stimulated by this agent. These results suggest that depletion of the agonist-sensitive Ca2+ store is sufficient for activation of Ca2+ influx. Several characteristics of the Ca(2+)-influx pathway activated by internal store depletion were compared with those of the agonist-activated pathway. Bradykinin-stimulated Ca2+ influx was increased at alkaline extracellular pH (pHo), and was inhibited by extracellular La3+, by depolarization of the membrane, and by the novel Ca(2+)-influx blocker 1-(beta-[3-(4-methoxyphenyl)propoxy]-4- methoxyphenethyl)-1H-imidazole hydrochloride (SKF 96365). Additionally, bradykinin stimulated influx of both 45Ca2+ and 133Ba2+, consistent with the hypothesis that the agonist-activated influx pathway is permeable to both of these bivalent cations. Likewise, activation of Ca2+ influx by BHQ, thapsigargin and cyclopiazonic acid was blocked by La3+, membrane depolarization and SKF 96365, but was unaffected by nitrendipine or BAY K 8644. Furthermore, Ca2+ influx stimulated by BHQ was increased at alkaline pHo and BHQ stimulated the influx of both 45Ca2+ and 133Ba2+ to the same extent. These results demonstrate that the agonist-activated Ca(2+)-influx pathway and the pathway activated by depletion of the agonist-sensitive internal Ca2+ store are indistinguishable.

A comparison of different sources of information about pregnancy and childbirth.

Different methods of obtaining information in medical and social research present problems of interpretation for the researcher. However, there are few systematic studies on the extent of the lack of concordance yielded by different methods. This paper uses data from a randomized controlled trial of social support in pregnancy to examine this issue in relation to three methods of data collection--medical records, home interviews and a postal questionnaire--on the following topics: obstetric history; smoking, alcohol use, number of antenatal hospital visits, bleeding and depression in pregnancy; length of labour; baby's sex, birthweight and neonatal health problems; and ethnicity. Considerable discrepancies are found comparing the different data sources. These suggest that mothers may be more reliable sources of information than medical records, and that the anonymity of a postal questionnaire may provide higher estimates than home interviews on some sensitive topics, such as smoking in pregnancy.

Low birth weight babies: the mother's point of view.

Women's feelings and beliefs about low birth weight (LBW) were obtained by postal questionnaire completed postnatally by 467 women who had participated in a randomised controlled trial of social support in pregnancy. All the women in the study had previously given birth to a LBW baby. Differences were found between beliefs about causes of LBW in general and in the women's explanations for their own LBW baby. These ambiguities were particularly noticeable in relation to smoking beliefs. The women's views on medical care; the practical and emotional problems of low birth weight; and the solutions to some of those problems are discussed. The need for more support from health professionals was given top priority. The main needs of women with a 'high risk' pregnancy were more reassurance and information, recognition of the economic hardships that can be caused, and more attention to their feelings and opinions.

Social support and pregnancy outcome.

A total of 509 women with a history of a low-birthweight (LBW, less than 2500 g) baby were recruited from the antenatal booking clinics of four hospitals and randomized to receive either a social support intervention in pregnancy in addition to standard antenatal care (the intervention group) or standard antenatal care only (the control group). At recruitment to the study, mean gestational age was 6 weeks, mean maternal age was 28.0 years, 86% of the women had one previous LBW baby, 11% had two and 2% had had three or more. The study population was socially disadvantaged: 77% of the women were working class, 18% had unemployed partners and 41% were smoking at booking. Social support was given by four research midwives in the form of 24-h contact telephone numbers and a programme of home visits, during which the midwives provided a listening service for the women to discuss any topic of concern to them, gave practical information and advice when asked, carried out referrals to other health professionals and welfare agencies as appropriate, and collected social and medical information. Pregnancy outcomes were assessed using obstetric case-note data (obtained for 507 women) and a postal questionnaire sent to all mothers 6 weeks after delivery (94% replied). Babies of intervention group mothers had a mean birthweight 38 g higher than that of control group babies; there were fewer very low-birthweight babies in the intervention group.(ABSTRACT TRUNCATED AT 250 WORDS)