First time and repeat cardioversion of atrial tachyarrhythmias - a comparison of outcomes.

INTRODUCTION: Repeat cardioversion may be necessary in over 50% of patients with persistent atrial fibrillation (AF), but identifying responders remains challenging. This study evaluates the long-term success of direct current cardioversion (DCCV) and the clinical and echocardiographical parameters that influence them, in over 1000 sedation-cardioversion procedures undertaken at Eastbourne General Hospital between 1996 and 2006. METHODS: A total of 770 patients of mean age (SD) 70.1(10.1) underwent 1013 DCCVs (first n = 665, repeat n = 348) for atrial tachyarrhythmias from 1996 to 2006. Time to persistent arrhythmia recurrence was compared between first and multiple DCCV, and the effect of age, gender, presence of heart disease, left atrial size, fractional shortening, arrhythmia duration, anti-arrhythmic drug therapy (AAD) and other concomitant cardiac medication was evaluated using the Kaplan-Meier method and Cox's Proportional-hazards model. RESULTS: In all, 33% of first and 29% of repeat DCCVs were in sinus rhythm (SR) at 12 months (m). There was no difference in median time to arrhythmia recurrence (SE) between first and multiple procedures: 1.5 +/- 0.1 m (1.3-1.7) and 1.5 +/- 0.0 m (1.4-1.6) respectively, p = 0.45. AAD use was significantly higher, arrhythmia duration shorter and more diabetic patients underwent repeat procedures. Amiodarone, OR 0.56, p = 0.04, sotalol, OR 0.61, p = 0.02 and arrhythmia duration, < 6 m, OR 0.72, p = 0.03 were independent predictors of improved outcome in first procedures only. In patients undergoing first procedures on amiodarone or sotalol, median time to arrhythmia recurrence was longer and 12 m SR rates higher, 6.0 +/- 2.4 m (42%) than those who had a repeat procedure on the same medication, 1.5 +/- 0.1 m (33%), p = 0.06. CONCLUSIONS: The efficacy of first and subsequent DCCV procedures is similar, achieving a similar proportion of SR maintenance at 1 year. However, the benefits of AAD therapy are the greatest following first time procedures. Concomitant AAD therapy should be considered for all first time procedures for persistent AF.

Testosterone acts as an efficacious vasodilator in isolated human pulmonary arteries and veins: evidence for a biphasic effect at physiological and supra-physiological concentrations.

BACKGROUND: Testosterone is recognized to elicit vasodilatation in numerous vascular beds, however to date no study has investigated whether testosterone has this effect in the human pulmonary vasculature. AIM: To determine whether isolated human pulmonary arteries and veins dilate in response to testosterone and whether the response differs in relation to gender, endothelial function or location with the pulmonary vasculature. METHODS: Intralobar pulmonary arteries [no.=44, diameter =581 (349) microm] and veins [no.=27, diameter =573 (302) microm] were dissected from lobectomy samples obtained from male and female patients [no.=40, age =69 (8) yr]. Vessels were mounted in an automated wire myograph, bathed in physiological saline at 37 C and pH 7.4, and loaded to their in vivo pressure. Vessels were preconstricted with noradrenaline (10 microM) and exposed to acetylcholine (1 microM) to assess endothelial function, washed and then preconstricted with potassium chloride (1-100 mM) followed by either cumulative concentrations of testosterone (1 nM-100 microM) or ethanol vehicle (<0.1%). RESULTS: Significant marked vasodilatation was seen in all vessels, irrespective of size, gender and endothelial function at micromolar concentrations. Testosterone triggered significant vasodilatation at concentrations > or = 10 nM in pulmonary arteries obtained from males, a response which was not observed in vessels from females. The maximal response at 100 microM was also significantly greater in male pulmonary arteries. Significant vasodilatation was only observed at physiological (nM) concentrations in pulmonary resistance arteries and pulmonary arteries with good endothelial function. CONCLUSION: Testosterone acts as an efficacious vasodilator in the human pulmonary vasculature, with dilatation observed at physiological concentrations in the male arterial resistance bed, dependent on the presence of an intact endothelium.

Two new species of Bargmannia (Pyrostephidae, Physonectae, Siphonophorae).

Two new deep-living species of the genus Bargmannia (Siphonophorae, Physonectae, Pyrostephidae) are described based, almost exclusively, on the nectophores of single specimens collected by ROVs off the west coast of California. The nectophores of B. stenotes sp. nov. were relatively small, up to 11.4 mm in length and, in the preserved condition had very narrow nectosacs. There was a marked bend in the distal part of the preserved nectophore, resulting in the ostium opening upwards. The mature nectophores of B. profunda sp. nov. were almost twice as long as those of B. stenotes and were characterised by the fact that the lower lateral ridges did not join, distally, with the meso-lateral ones. This feature also was present in smaller nectophores of B. amoena but those of B. stenotes, at that stage, did not have a mouth-plate.

A review of the siphonophore species mentioned in Haeckel's (1888b) Challenger Monograph.

In his Challenger Monograph Haeckel (1888b) listed a total of 204 species of siphonophores and 36 species of Porpitidae (Disconectae, according to Haeckel), which are now known not to belong to the Siphonophorae. In this paper the siphonophore species have been divided into four categories: a). species that had been described previously by an acknowledged authority other than Haeckel; b). species where Haeckel changed the generic or specific name of a previously described species by another authority, and then ascribed the authority to himself; c). species that Haeckel actually described and illustrated as what he believed to be new; and d). species that Haeckel mentioned in the text as a new species, but with the description deferred to a later publication or simply not given. The validity of the forty-three species that Haeckel actually described is then discussed. A full list of all these species is given in an Appendix.

A history of the sub-order Cystonectae (Hydrozoa: Siphonophorae).

The siphonophore sub-order Cystonectae presently comprises just five species in three genera and two families, and includes Physalia physalis, the Portuguese Man O'War. Despite the smallness of the group its history has been very chequered, particularly for P. physalis, which has been described under more than fifty different names. Haeckel (1888) was one of the worst offenders regarding the description of questionable species, but even Totton (1965) was uncertain as to the validity of some previously described cystonect species. Herein, an attempt has been made to review the history of the sub-order Cystonectae and to clarify its taxonomy. A list of synonyms for each recognised cystonect species is given in an appendix.

Nicotinic receptors that bind alpha-bungarotoxin on neurons raise intracellular free Ca2+.

Many populations of vertebrate neurons have a membrane component that binds alpha-bungarotoxin and cholinergic ligands. Despite the abundance of this component and its similarities to nicotinic receptors, its function has remained controversial. Using a fluorescence assay, we show here that activation of the component elevates the intracellular concentration of free Ca2+, demonstrating a receptor function for the toxin-binding component. Whole-cell voltage-clamp and intracellular recordings did not detect a significant current resulting from receptor activation, possibly because the currents were small or the receptors rapidly desensitized. The rise in intracellular free Ca2+ caused by the receptor was prevented by Ca2+ channel blockers. This suggests a signaling cascade likely to have important regulatory consequences for the neuron.

The alpha subunit of type II Ca2+/calmodulin-dependent protein kinase is highly conserved in Drosophila.

A monoclonal antibody against rat brain type II Ca2+/calmodulin-dependent protein kinase (CaM kinase) precipitates three proteins from Drosophila heads with apparent molecular weights similar to those of the subunits of the rat brain kinase. Fly heads also contain a CaM kinase activity that becomes partially independent of Ca2+ after autophosphorylation, as does the rat brain kinase. We have isolated a Drosophila cDNA encoding an amino acid sequence that is 77% identical to the sequence of the rat alpha subunit. All known autophosphorylation sites are conserved, including the site that controls Ca(2+)-independent activity. The gene encoding the cDNA is located between 102E and F on the fourth chromosome. The protein product of this gene is expressed at much higher levels in the fly head than in the body. Thus, both the amino acid sequence and the tissue specificity of the mammalian kinase are highly conserved in Drosophila.

Description of Tottonophyes enigmatica gen. nov., sp. nov. (Hydrozoa, Siphonophora, Calycophorae), with a reappraisal of the function and homology of nectophoral canals.

A new species of calycophoran siphonophore, Tottonophyes enigmatica gen. nov, sp. nov., is described. It has a unique combination of traits, some shared with prayomorphs (including two rounded nectophores) and some with clausophyid diphyomorphs (the nectophores are dissimilar, with one slightly larger and slightly to the anterior of the other, and both possess a somatocyst). Molecular phylogenetic analyses indicate that the new species is the sister group to all other diphyomorphs. A new family, Tottonophyidae, is established for it. Its phylogenetic position and distinct morphology help clarify diphyomorph evolution. The function and homology of the nectophoral canals and somatocyst is also re-examined and further clarification is given to their nomenclature.

A synopsis of the Family Cordagalmatidae fam. nov. (Cnidaria, Siphonophora, Physonectae).

The genus Cordagalma is reviewed and a re-description given of one of the extant species, C. ordinatum (Haeckel). In addition, four new species are described in the genus Cordagalma, namely C. abyssorum sp. nov., C. bimaculatum sp. nov., C. isocarrei sp. nov. and C. rugosum sp. nov. All these species have similar larval-type tentilla. A fifth new species, which has extraordinary tentilla, with an involucrum forming two flaps, is placed in a new genus Cardianecta gen. nov. as C. parchelion sp. nov. The significant differences that all these species have from other physonects is considered to warrant the establishment of the family Cordagalmatidae fam. nov. for them. This family is diagnosed purely on the presence of heart-shaped nectophores budded on the ventral side of the nectosome.

A description of two new species of the genus Erenna (Siphonophora: Physonectae: Erennidae), with notes on recently collected specimens of other Erenna species.

Two new Erenna species, E. insidiator sp. nov. and E. sirena sp. nov., are described from specimens collected in the vicinity of Monterey Bay, California, and also, for E. sirena at the southern end of the Gulf of California, Mexico. Further information on the three extant Erenna species is given, based on specimens collected in the same areas. These have enabled, for instance, the identification of three types of tentilla on the tentacles of E. cornuta Pugh, 2001, rather than the two noted on the single previously known specimen. The genus is remarkable for the presence of bioluminescent lures on the tentilla of all five species. In E. sirena sp. nov. the tentilla are also covered by a red-fluorescent layer, which was briefly described by Haddock et al. (2005), and further details are given herein. Another extraordinary feature of the colonies E. sirena sp. nov. is that the main part of the tentacle, with its tentilla, can be extended away from the siphosomal stem on a long peduncle. This phenomenon also appears to occur in E. laciniata Pugh, 2001, and has not been observed before for other physonect species.

Early-life exposure to the SSRI paroxetine exacerbates depression-like behavior in anxiety/depression-prone rats.

Selective serotonin reuptake inhibitor (SSRI) antidepressants are the mainstay treatment for the 10-20% of pregnant and postpartum women who suffer major depression, but the effects of SSRIs on their children's developing brain and later emotional health are poorly understood. SSRI use during pregnancy can elicit antidepressant withdrawal in newborns and increase toddlers' anxiety and social avoidance. In rodents, perinatal SSRI exposure increases adult depression- and anxiety-like behavior, although certain individuals are more vulnerable to these effects than others. Our study establishes a rodent model of individual differences in susceptibility to perinatal SSRI exposure, utilizing selectively bred Low Responder (bLR) and High Responder (bHR) rats that were previously bred for high versus low behavioral response to novelty. Pregnant bHR/bLR females were chronically treated with the SSRI paroxetine (10 mg/kg/day p.o.) to examine its effects on offspring's emotional behavior and gene expression in the developing brain. Paroxetine treatment had minimal effect on bHR/bLR dams' pregnancy outcomes or maternal behavior. We found that bLR offspring, naturally prone to an inhibited/anxious temperament, were susceptible to behavioral abnormalities associated with perinatal SSRI exposure (which exacerbated their Forced Swim Test immobility), while high risk-taking bHR offspring were resistant. Microarray studies revealed robust perinatal SSRI-induced gene expression changes in the developing bLR hippocampus and amygdala (postnatal days 7-21), including transcripts involved in neurogenesis, synaptic vesicle components, and energy metabolism. These results highlight the bLR/bHR model as a useful tool to explore the neurobiology of individual differences in susceptibility to perinatal SSRI exposure.

Testosterone as a protective factor against atherosclerosis--immunomodulation and influence upon plaque development and stability.

Inflammation plays a central pathogenic role in the initiation and progression of coronary atheroma and its clinical consequences. Cytokines are the mediators of cellular inflammation and promote local inflammation in the arterial wall, which may lead to vascular smooth muscle apoptosis, degradation of the fibrin cap and plaque rupture. Platelet adhesion and thrombus formation then occur, resulting clinically in unstable angina or myocardial infarction. Recent studies have suggested that cytokines are pathogenic, contributing directly to the disease process. 'Anti-cytokine' therapy may, therefore, be of benefit in preventing or slowing the progression of cardiovascular disease. Both oestrogens and testosterone have been shown to have immune-modulating effects; testosterone in particular appears to suppress activation of pro-inflammatory cytokines. Men with low testosterone levels are at increased risk of coronary artery disease. An anti-inflammatory effect of normal physiological levels of sex hormones may, therefore, be important in atheroprotection. In this Article, we discuss some of the mechanisms involved in atherosclerotic coronary artery disease and the putative link between testosterone deficiency and atheroma formation. We present the hypothesis that the immune-modulating properties of testosterone may be important in inhibiting atheroma formation and progression to acute coronary syndrome.

Different effects on learning ability after injection of the cholinergic immunotoxin ME20.4IgG-saporin into the diagonal band of Broca, basal nucleus of Meynert, or both in monkeys.

Immunotoxic lesions of the diagonal band of Broca (VDB) in monkeys disrupted cholinergic input to the hippocampus, producing impaired learning of visuospatial conditional discriminations but not simple visual discriminations. Immunotoxic lesions of the basal nucleus of Meynert (NBM) deprived the cortex of most of its cholinergic input, producing impaired learning of simple visual discriminations but not visuospatial conditional discriminations. Combined lesions of the NBM + VDB resulted in impaired learning of both types of task. The impairment after NBM lesions ameliorated with time but could be reinstated by a low dose of the glutamate blocking drug MK801, which, at this dose, did not impair simple visual discrimination learning in normal monkeys. The cholinergic projections from the NBM and VDB may sustain the function of the glutamatergic pyramidal cell pathways within the cortex and hippocampus, respectively.

Written patient information about triple-marker screening: a randomized, controlled trial.

OBJECTIVE: To investigate to what extent a newly revised educational pamphlet on triple-marker screening improves patient knowledge and to identify subgroups of women who may not benefit from these materials. METHODS: Women in six geographically and demographically diverse Ontario sites were allocated randomly to receive the pamphlet on triple-marker screening or a similar-appearing educational pamphlet on daily activities during pregnancy. The primary outcome measure was the Maternal Serum Screening Knowledge Questionnaire, a previously validated 14-item scale. RESULTS: Baseline demographic, obstetric, and medical factors were comparable in the intervention and control groups, as were measures of previous exposure to triple-marker screening. Knowledge scores were significantly higher among the 133 women receiving the intervention pamphlet than among 64 women who received the control pamphlet (0.89 versus 0.52 on a scale from -2 to +2, P < .001). Subgroups not benefiting from the pamphlet on triple-marker screening were women age 25 and younger and those not speaking English at home. Those who had completed university or postgraduate education had high levels of knowledge with and without the pamphlet. CONCLUSION: Written patient information can contribute in an important way to patient knowledge about triple-marker screening. Providers of antenatal care should be made aware of the value of written patient information as well as the limitations for some subgroups of women. These subgroups are likely to require additional educational materials and resources. It would be appropriate to make these materials available to the general public and pregnant women in their physicians' offices.

Severe learning impairment caused by combined immunotoxic lesion of the cholinergic projections to the cortex and hippocampus in monkeys.

Monkeys with immunotoxic lesions of both the basal nucleus of Meynert and the vertical limb of the diagonal band of Broca (NBM+VDB) lost cholinergic innervation throughout the cortex and hippocampus. They were impaired at learning discriminations between objects differing in either few, or many, attributes and at learning visuospatial conditional discriminations. Monkeys with immunotoxic lesions of the NBM lost cholinergic innervation of the neocortex only. Initially, they were unable to learn a simple visual discrimination where the stimuli differed in a limited number of attributes but they were unimpaired at learning discriminations between objects that differed in more attributes. They were mildly impaired at learning a visuospatial conditional task. The impairment exhibited by monkeys with lesions of the NBM alone ameliorated with time but that following NBM+VDB lesions did not. Previous experiments have shown that monkeys with immunotoxic lesions of the VDB alone are impaired at learning visuospatial conditional discriminations but are unimpaired at learning simple visual discriminations. When monkeys with NBM lesions were given excitotoxic lesions of the CA1 field of the hippocampus the learning impairment on discriminations between objects which differed in few attributes was reinstated. Pretreatment with a cholinergic agonist improved learning ability on visual discrimination learning in all monkeys but this improvement was significantly greater in monkeys with lesions of the NBM. On conditional discrimination learning, which is particularly sensitive to hippocampal damage, pilocarpine produced a significant improvement in monkeys with NBM+VDB lesions (where the hippocampal dysfunction was cholinergic) but not in monkeys with NBM+CA1 lesions (where the hippocampal damage was structural).

Metabolism of pyruvate by pre-elongation sheep embryos and effect of pyruvate and lactate concentrations during culture in vitro.

In the first of two experiments, utilization of [1-14C]pyruvate by 8-cell and blastocyst-stage embryos derived in vivo was examined during a 3-h incubation in HEPES-buffered synthetic oviduct fluid (SOF) medium in the presence or absence of other substrates. In the second, a factorial design examined the effect of pyruvate (0, 0.33, 1.0 and 3.3 mM) and lactate (3.3, 10 and 33 mM) on development of 1- and 2-cell sheep embryos cultured in vitro in a modified SOF medium (containing glucose, glutamine and modified Eagle's medium non-essential amino acids). Peak utilization of [1-14C]pyruvate was unaffected by the presence or absence of other energy substrates. In contrast, rate of utilization was affected by the addition of other energy substrates, with half maximal utilization occurring at either 0.4 +/- 0.2 mM or 1.2 +/- 0.2 mM for 8-cells and either 0.2 +/- 0.2 mM or 1.3 +/- 0.3 mM for blastocysts when incubated in the absence or presence of other energy substrates respectively. In the second experiment the proportion of embryos developing to blastocysts was inhibited by high lactate levels (P < 0.001), but was generally not affected by pyruvate concentration. However, there was a significant interaction (P < 0.001) between pyruvate and lactate when both were present in the medium. At 0.33 mM pyruvate, 3.3 mM lactate supported good development (83 +/- 8% blastocysts) whereas 10 mM lactate supported less development (50 +/- 11%). However, at the higher levels of pyruvate this effect was lost.(ABSTRACT TRUNCATED AT 250 WORDS)

Exogenous protein affects developmental competence and metabolic activity of bovine pre-implantation embryos in vitro.

The role of exogenous protein during bovine pre-implantation embryo development in two in vitro production systems was investigated. Morphological development, survival after vitrification and metabolic activity before and after vitrification were recorded in blastocysts generated in vitro in synthetic oviduct fluid (SOF) medium in the presence of either bovine serum albumin (BSA) or polyvinyl-alcohol (PVA). Metabolic activity was determined by measuring oxygen consumption, glucose and pyruvate uptake as well as lactate production. Development to blastocysts and survival after vitrification were reduced significantly in medium lacking protein. Of the metabolic parameters measured, only pyruvate uptake was increased significantly in embryos cultured in medium supplemented with PVA. Whereas in BSA-supplemented medium pyruvate uptake was correlated with lactate production, in PVA-supplemented medium glucose uptake was correlated with lactate production. Lactate production increased significantly after vitrification as compared with fresh embryos. Thus, exogenously added protein significantly alters oxidative metabolism. In medium lacking protein, the additional pyruvate may be used for the maintenance of intracellular amino acid pools. Vitrification appears to alter glycolytic metabolic profiles indicating a stress-response. In conclusion, the perturbed metabolism corresponding to reduced developmental capacity of embryos produced under protein-free conditions emphasizes the ambiguity between maximum development, technical and hygienic requirements and physiological demands of the early bovine embryo in vitro. The use of well-defined recombinant proteins might assist in closing this gap.

Glucose utilization by sheep embryos derived in vivo and in vitro.

Embryos were collected from superovulated donors at various intervals from onset of oestrus, ranging from Day 1.5 to Day 6. In addition, blastocysts obtained from the culture of 1-cell embryos collected in vivo or of oocytes matured and fertilized in vitro were used to assess the effects of in vitro manipulation and culture on glucose utilization. Glycolytic activity was determined by the conversion of [5-3H]glucose to 3H2O, and oxidation of glucose was determined by the conversion of [U-14C]glucose to 14CO2. Glucose utilization increases significantly from the 8-cell stage and during compaction and blastulation. Glucose oxidation was at a relatively low level (5-12% of total utilization) compared with glycolysis. No difference was observed between the glycolytic activity of blastocysts derived from in vivo or in vitro sources. However, glucose oxidation was lower (P less than 0.05) in blastocysts derived from the culture of 1-cell embryos or from oocytes matured and fertilized in vitro. Exogenous tricarboxylic acid cycle substrates (i.e. pyruvate and lactate supplied in the medium) affected the level of glucose oxidation.

Effect of 2,4-dinitrophenol on the energy metabolism of cattle embryos produced by in vitro fertilization and culture.

In cattle embryos, the proportion of ATP produced by glycolysis increases following the major activation of the embryonic genome, and development to the blastocyst stage is improved in the presence of 10 microM 2,4-dinitrophenol (DNP), an uncoupler of oxidative phosphorylation, from Day 5 to Day 7 of culture. In Experiment 1 of the present study, culture of cattle embryos in the presence of 10 microM DNP from Day 5 to Day 7 stimulated development to the blastocyst stage, but had no significant effects on oxygen, pyruvate or glucose uptake, or on lactate production. In Experiment 2, culture of cattle embryos in the presence of 10 microM DNP from Day 5 to Day 7, stimulated the metabolism of [2-14C]pyruvate (a measure of Krebs cycle activity) on all of Days 5, 6 and 7, and stimulated metabolism of [5-3H]glucose (a measure of glycolysis) on Day 7 only. The results show that 10 microM DNP stimulates oxidative and glycolytic metabolism in Day-5 to Day-7 cattle embryos, but this does not fully explain the observed increase in developmental competence. We propose that partial inhibition or uncoupling of oxidative phosphorylation may reduce the level of intracellular reactive oxygen species production, thereby facilitating development.

Splenic size on routine chest films in AIDS: diagnostic and prognostic significance.

Sixty-nine percent of AIDS patients show evidence of splenomegaly on their plain chest film. This splenomegaly is not related to severity of AIDS, to intravenous drug abuse or to any specific infection or neoplasm but correlates well with severity of anemia, pancytopenia, and thrombocytopenia. Increasing splenomegaly usually indicates worsening of AIDS. The triad of splenomegaly, interstitial lung disease sparing the bases, and very thin chest wall soft tissues is highly specific for the diagnosis of AIDS. The sensitivity of the plain film for diagnosing AIDS can be increased by including AIDS in the differential diagnosis of all patients with splenomegaly, intrathoracic lymphadenopathy, cachexia, or bilateral interstitial lung disease of unknown cause.