BDNF over-expression increases olfactory bulb granule cell dendritic spine density in vivo.

Olfactory bulb granule cells (GCs) are axon-less, inhibitory interneurons that regulate the activity of the excitatory output neurons, the mitral and tufted cells, through reciprocal dendrodendritic synapses located on GC spines. These contacts are established in the distal apical dendritic compartment, while GC basal dendrites and more proximal apical segments bear spines that receive glutamatergic inputs from the olfactory cortices. This synaptic connectivity is vital to olfactory circuit function and is remodeled during development, and in response to changes in sensory activity and lifelong GC neurogenesis. Manipulations that alter levels of the neurotrophin brain-derived neurotrophic factor (BDNF) in vivo have significant effects on dendritic spine morphology, maintenance and activity-dependent plasticity for a variety of CNS neurons, yet little is known regarding BDNF effects on bulb GC spine maturation or maintenance. Here we show that, in vivo, sustained bulbar over-expression of BDNF in transgenic mice produces a marked increase in GC spine density that includes an increase in mature spines on their apical dendrites. Morphometric analysis demonstrated that changes in spine density were most notable in the distal and proximal apical domains, indicating that multiple excitatory inputs are potentially modified by BDNF. Our results indicate that increased levels of endogenous BDNF can promote the maturation and/or maintenance of dendritic spines on GCs, suggesting a role for this factor in modulating GC functional connectivity within adult olfactory circuitry.

Expansion of the dentate mossy fiber-CA3 projection in the brain-derived neurotrophic factor-enriched mouse hippocampus.

Structural changes that alter hippocampal functional circuitry are implicated in learning impairments, mood disorders and epilepsy. Reorganization of mossy fiber (MF) axons from dentate granule cells is one such form of plasticity. Increased neurotrophin signaling is proposed to underlie MF plasticity, and there is evidence to support a mechanistic role for brain-derived neurotrophic factor (BDNF) in this process. Transgenic mice overexpressing BDNF in the forebrain under the α-calcium/calmodulin-dependent protein kinase II promoter (TgBDNF mice) exhibit spatial learning deficits at 2-3months of age, followed by the emergence of spontaneous seizures at ∼6months. These behavioral changes suggest that chronic increases in BDNF progressively disrupt hippocampal functional organization. To determine if the dentate MF pathway is structurally altered in this strain, the present study employed Timm staining and design-based stereology to compare MF distribution and projection volumes in transgenic and wild-type mice at 2-3months, and at 6-7months. Mice in the latter age group were assessed for seizure vulnerability with a low dose of pilocarpine given 2h before euthanasia. At 2-3months, TgBDNF mice showed moderate expansion of CA3-projecting MFs (∼20%), with increased volumes measured in the suprapyramidal (SP-MF) and intra/infrapyramidal (IIP-MF) compartments. At 6-7months, a subset of transgenic mice exhibited increased seizure susceptibility, along with an increase in IIP-MF volume (∼30%). No evidence of MF sprouting was seen in the inner molecular layer. Additional stereological analyses demonstrated significant increases in molecular layer (ML) volume in TgBDNF mice at both ages, as well as an increase in granule cell number by 8months of age. Collectively, these results indicate that sustained increases in endogenous BDNF modify dentate structural organization over time, and may thereby contribute to the development of pro-epileptic circuitry.

Co-seeded Er3+:Yb3+ single frequency fiber amplifier with 60 W output power and over 90% TEM(00) content.

We report on the design and fabrication of an Er(3+):Yb(3+) triple clad fiber and on the power scaling of a single frequency fiber amplifier at 1.5 µm based on that fiber. In addition, we report on mode content measurements in order to reveal the overlap of the amplifier output with the TEM(00) mode. The triple clad design was used to enable high output power levels, a good slope efficiency and an excellent beam quality. A maximum single frequency output power of 61 W at 1.5 µm could be achieved with the aid of the co-seeding method, which was used to suppress parasitic processes at 1.0 µm. With a scanning ring cavity the mode content of the amplifier output was analyzed with respect to the TEM modes. For all output power levels the TEM(00) content was above 90%.

Usefulness of transoesophageal echocardiography before circumferential pulmonary vein ablation in patients with atrial fibrillation: is it really mandatory?

AIMS: Transoesophageal echocardiography (TEE) is recommended prior to circumferential pulmonary vein ablation (CPVA) in patients with atrial fibrillation (AF) to identify left atrial (LA) or left atrial appendage (LAA) wall thrombi. It is not clear whether all patients undergoing CPVA should receive pre-procedural TEE. We wanted to assess the incidence of LA thrombus in these patients and to identify factors associated with its presence. METHODS AND RESULTS: Consecutive patients referred for CPVA from 2004 to 2009 underwent TEE within 48 h prior to the procedure. Of 408 patients included in the study, 6 patients (1.47%) had LA thrombi, persistent AF, and LA dilation. Compared with patients without thrombus, these six patients had larger LA diameter (P = 0.0001) and more frequently were women (P = 0.002), had persistent AF (P = 0.04), and had underlying structural cardiac disease (P = 0.014). The likelihood of presenting LA thrombus increased with the number of these four risk factors present (P < 0.001). None of the patients with paroxysmal AF and without LA dilation had LA thrombus. A cut-off value of 48.5 mm LA diameter yielded 83% sensitivity, 92% specificity, and a 10.1 likelihood ratio to predict LA thrombus appearance. CONCLUSION: The incidence of LA thrombus prior to CPVA is low. Persistent AF, female sex, structural cardiopathy, and LA dilation were associated with the presence of LA thrombus. Our data suggest that the use of TEE prior to CPVA to detect LA thrombi might not be needed in patients with paroxysmal AF and no LA dilation or structural cardiopathy.

Estudio piloto de la utilidad de la tomografía computarizada cardiaca para descartar síndrome coronario agudo en urgencias / Utility of coronary computed tomography to rule out acute coronary syndrome in the emergency department: a pilot study

Objetivo: Analizar, en pacientes con dolor torácico de bajo riesgo, las aportaciones de la coronariografía por tomografía computarizada multidetector (TCMD) en el diagnóstico de síndrome coronario agudo (SCA). Método: Subestudio piloto descriptivo y retrospectivo de un estudio prospectivo que comparaba la rentabilidad diagnóstica de la ecografía de estrés con la angiografía por TCMD. Se realizó en una unidad de dolor torácico (UDT) que atiende a pacientes con dolor torácico no traumático. Se incluyeron, en 2008, pacientes sin coronariopatía conocida y con al menos 2 factores de riesgo coronario y dolor torácico con estudio habitual (historia clínica, electrocardiogramas, troponinas seriadas y ergometría) negativo para SCA. Se registraron datos clínicos, epidemiológicos y se les realizó una coronariografía por TCMD y, si era patológica, un cateterismo. Resultados: De los 502 pacientes con posible SCA atendidos durante la disponibilidad de la prueba, 54 (10,7%) cumplían criterios para la TCMD. La TCMD mostró coronarias normales en 35 (64,8%); en 3 (5,5%), no interpretables por artefactos; y en 16(29,6%) la TCMD fue patológica. En estos últimos, se practicaron 15 cateterismos, de los que 10 fueron patológicos. Así, la TCMD permitió el diagnóstico de SCA en un 2,0% adicional de los pacientes incluidos inicialmente en el grupo de posible SCA y el18,5% de los 54 pacientes finalmente incluidos. Conclusiones: La TCMD cardiaca aumentó el rendimiento diagnóstico de un protocolo estándar (historia clínica, electrocardiogramas y troponinas seriadas y ergometría) en los pacientes con dolor torácico (AU)

Objective: To analyze the diagnostic contribution of coronary multidetector computed tomography (CMCT) in low-riskchest pain patients. Methods: Retrospective, descriptive substudy as part of a prospective study of the diagnostic yield of stress echocardiography in comparison with CMCT angiography. The setting was a non-traumatic chest pain unit. Patients with chest pain but without diagnosed coronary artery disease and fewer than 2 coronary risk factors in 2008 were included if the information usually gathered to diagnose acute coronary syndrome (ACS) (ie, medical history, electrocardiogram, troponin series, and ergometry) was negative. Clinical and patient data were recorded and CMCT was performed; if abnormalities were detected, heart catheterism was undertaken. Results: Of the 502 patients suspected of having ACS while CMCT was available to the department, 54 (10.7%) met the criteria for performing the procedure. CMCT demonstrated normal coronary arteries in 35 (64.8%). In 3 (5.5%) the findings could not be interpreted due to artifacts and in 16 (29.6%), abnormalities were detected. Catheterization was performed in 15 of the 16 patients; the test was positive in 10. CMCT led to a diagnosis of ACS in an additional 2% of the group of patients in whom the diagnosis was initially suspected and in 18.5% of the 54 patients included in the CMCT study (AU)

Quantification of left ventricular asynchrony throughout the whole cardiac cycle with a computed algorithm: application for optimizing resynchronization therapy.

INTRODUCTION: Measurement of left ventricular (LV) asynchrony is usually determined on single time points from spectral tissue Doppler imaging (TDI) scans that are frequently difficult to identify or not representative of the whole cardiac cycle. Our aim was to validate a new asynchrony index that evaluates the motion of the LV walls throughout the whole cardiac cycle. METHODS AND RESULTS: Ten healthy volunteers and 50 patients undergoing cardiac resynchronization therapy (CRT) were studied with TDI. Wall displacement tracings from the septal and lateral LV walls were analyzed. Cross-correlation was calculated and 2 indices were obtained to assess LV asynchrony: the time delay and the superposition index (SI) between wall displacements. These results were compared between healthy volunteers and CRT patients, and between responders and nonresponders to CRT. Also, the optimal interventricular (VV) interval was based upon the best matching level. Volunteers showed lower asynchrony indices (83 +/- 2% SI, 17 +/- 8 ms time delay) as compared with CRT patients (63 +/- 15% SI, 73 +/- 60 ms time delay, P < 0.05). Responders also had more LV dyssynchrony than nonresponders (58 +/- 15% SI and 92 +/- 66 ms vs 68 +/- 12% and 48 +/- 34 ms, P < 0.05). The optimum VV interval selected by the computed algorithm showed an excellent concordance (Kappa = 0.90, P < 0.05) with that determined by other validated methods for optimizing the programming of CRT devices. CONCLUSIONS: This approach allows measurement of LV intraventricular asynchrony throughout the cardiac cycle, being useful to determine the optimum VV interval and to select candidates for CRT.

Transoesophageal echocardiography accurately detects cardiac output variation: a prospective comparison with thermodilution in cardiac surgery.

BACKGROUND AND OBJECTIVE: Intraoperative Doppler ultrasound can be used to measure cardiac output by transoesophageal echocardiography. Recently, its reliability, when compared to the thermodilution technique, has been questioned. The purpose of this study was to compare intraoperative changes in cardiac output measured by echo-Doppler and by thermodilution in cardiac surgery. We also assessed the agreement between the techniques. METHODS: Fifty cardiac surgical patients (38 male, 12 female, mean age of 63.4 +/- 14.3 yr) were prospectively included after approval by the Ethics Committee of the Institution. Cardiac output was assessed by thermodilution, with 10 mL saline at 12 degrees C, and simultaneously and blindly by echo-Doppler in deep transgastric view with pulsed wave Doppler at the level of the left ventricular outflow tract. Matched thermodilution cardiac output and echo-Doppler cardiac output measurements were taken three times at the end of expiration, both pre- and post-cardiopulmonary bypass. RESULTS: Echo-Doppler measurements were obtained in 44 patients (88%). In three patients, Doppler recordings could not be obtained adequately, and three developed left ventricular outflow tract obstruction after bypass. Bland-Altman analysis revealed a bias of 0.015 L min(-1), with narrow limits of agreement (-1.21 to 1.22 L min(-1)) and 29.1% error. Echo-Doppler was accurate (92% sensitivity and 71% specificity, P = 0.008 by receiver operating characteristic curves) for detecting more than 10% of change in thermodilution cardiac output. There were no complications related to the study. CONCLUSIONS: The agreement between cardiac output by echo-Doppler and by thermodilution is clinically acceptable and transoesophageal echocardiography is a reliable tool to assess significant cardiac output changes in a population of selected patients.

Clinical implications of late mitral valve regurgitation appearance in the follow-up of heart transplantation.

BACKGROUND: Tricuspid regurgitation is frequently observed after orthotopic heart transplantation (OHT), in association with severe pulmonary hypertension. However, the incidence of left-sided valvular disease has not been addressed. AIM: We analyzed the incidence and prognostic implications of left-sided valve disease in 141 patients after OHT. METHODS: Echocardiography was performed with every endomyocardial biopsy during the first year after OHT and every 6 months thereafter. Mitral regurgitation (MR) grade II or III was considered significant. Graft vasculopathy was assessed using coronary angiography. RESULTS: Eight patients (6%) developed significant left-sided valvular disease, namely, MR in 6 (4%) and aortic regurgitation (AR) in 2 (1.4%). The 2 cases with AR were diagnosed the first week after OHT, whereas significant MR was diagnosed at mean follow- up of 34 +/- 6 months. Mean regurgitant orifice and volume were 34 +/- 14 mm2 and 41 +/- 15 mL/beat, respectively. Patients with significant MR had experienced a greater number of acute rejection episodes >or=3A, (1.8 +/- 1.7 vs 0.8 +/- 1.05; P = .02) and were associated with allograft vasculopathy in 83% vs 6% among unaffected patients (P = .0001). Four of 6 patients with significant MR died during follow-up (67%) and 1 of the living patients underwent reparative mitral valve surgery. The probability of survival using Kaplan-Meier curves was significantly lower when patients developed late significant MR (54% vs 76%; P = .0001). CONCLUSIONS: The incidence of significant left-sided valvular disease after OHT was low. MR was associated with a higher degree of previous acute rejection, of graft vasculopathy, and mortality. The presence of moderate or severe MR of late appearance identified a group of OHT patients with poor outcomes.

Long-lasting sport practice and lone atrial fibrillation.

AIMS: To analyse whether the proportion of patients with lone atrial fibrillation engaged in chronic sport practice was higher than that observed in the general population. METHODS AND RESULTS: The records of 1160 patients, seen at the arrhythmia outpatient clinic, were reviewed. A total of 70 patients (6%) suffered lone atrial fibrillation and were younger than 65 years. Thirty two of them had been engaged in long-term sport practice. All patients in the sport group were men as compared to only 50% in the sedentary group (P<0 x 0001). To avoid the confounding effect of sex distribution, women were excluded. Sportsmen started their episodes of atrial fibrillation at a younger age, they had a lower incidence of mild hypertension and their episodes of atrial fibrillation were predominantly vagal in contrast to the sedentary patients. The echocardiographic parameters were similar to those observed in the sedentary patients, but when compared with 20 healthy controls, they showed greater atrial and ventricular dimensions and a higher ventricular mass. The proportion of sportsmen among patients with lone atrial fibrillation is much higher than that reported in the general population of Catalonia: 63% vs 15% (P<0 x 05). CONCLUSION: Long-term vigorous exercise may predispose to atrial fibrillation.

Sudden death in Staphylococcus aureus-associated infective endocarditis due to perforation of a free-wall myocardial abscess.

Free-wall myocardial abscess perforation with hemopericardium and sudden death is an extremely infrequent complication of infective endocarditis (IE). We describe a case of Staphylococcus aureus-associated native aortic and tricuspid valve endocarditis complicated by a septic myocardial infarction and abscess formation of embolic origin, with fatal rupture into the pericardium. To our knowledge, only 2 cases of myocardial abscess rupture have previously been reported in relation to IE.

[Intracardial thrombosis and primary antiphospholipid syndrome. A familial case report]. / Trombosis intracardíaca y síndrome antifosfolípido primario. Un caso familiar.

The main clinical manifestation of antiphospholipid syndrome is repeated thrombotic events in young patients without cardiovascular risk factors. There are several clinical features but the most frequent ones are repeated fetal losses and acute cerebral ischemic events. Cardiac involvement is less frequent. We present a family case with intracardiac thrombosis and secondary cerebral embolism.

Genomic scan for genes affecting body composition before and after training in Caucasians from HERITAGE.

An autosomal genomewide search for genes related to body composition and its changes after a 20-wk endurance-exercise training program has been completed in the HERITAGE Family Study. Phenotypes included body mass index (BMI), sum of eight skinfold thicknesses, fat mass (FM), fat-free mass, percent body fat (%Fat), and plasma leptin levels. A maximum of 364 sib-pairs from 99 Caucasian families was studied with the use of 344 markers with single-point and multipoint linkage analyses. Evidence of significant linkage was observed for changes in fat-free mass with the S100A and the insulin-like growth factor I genes (P = 0.0001). Suggestive evidence (2.0 < or = Lod < 3.0; 0.0001 < P < or = 0.001) was also observed for the changes in FM and %Fat at 1q31 and 18q21-q23, in %Fat with the uncoupling protein 2 and 3 genes, and in BMI at 5q14-q21. At baseline, suggestive evidence was observed for BMI at 8q23-q24, 10p15, and 14q11; for FM at 14q11; and for plasma leptin levels with the low-density lipoprotein receptor gene. This is the first genomic scan on genes involved in exercise-training-induced changes in body composition that could provide information on the determinants of weight loss.

Aortocardiac fistulas complicating infective endocarditis.

This study sought to determine the clinical and echocardiographic features, surgical approach, and outcome of patients with infective endocarditis complicated with aortocardiac fistulas among a series of 346 consecutive cases between 1988 and 1998. Nine patients (2%) were found to have aortocardiac fistulas complicating infective endocarditis caused by highly pyogenic pathogens (4 patients had ruptured abscesses of the right sinus of Valsalva, 3 had fistulous communications from the left coronary sinus, and 1 had a fistulized abscess in the noncoronary sinus). Mortality in these patients was very high (55%), even when surgery was attempted early in the course of the disease and reconstructive procedures were implemented.

Differential scanning calorimetry and (2)H nuclear magnetic resonance and Fourier transform infrared spectroscopy studies of the effects of transmembrane alpha-helical peptides on the organization of phosphatidylcholine bilayers.

We have studied the effects of the incorporation of the alpha-helical transmembrane peptides Ac-K(2)-L(24)-K(2)-amide (L(24)) and Ac-K(2)-(L-A)(12)-K(2)-amide ((LA)(12)) on the thermotropic phase behavior of 1,2-dipalmitoyl-d(62)-sn-glycero-3-phosphocholine (DPPC-d(62)) and 1-palmitoyl-d(31)-2-oleoyl-sn-glycero-3-phosphocholine (POPC-d(31)) lipid bilayer model membranes by differential scanning calorimetry (DSC) and the conformational and orientational order of the phospholipid chains by Fourier transform infrared (FTIR) spectroscopy and (2)H nuclear magnetic resonance ((2)H-NMR) spectroscopy, respectively. Our DSC and FTIR spectroscopic studies indicate that the peptides L(24) and (LA)(12) both decrease the temperature and enthalpy of the gel/liquid-crystalline phase transition of DPPC-d(62) bilayers, with (LA)(12) having the greater effect in this regard. An examination of the frequencies of the CH(2) and CD(2) symmetric stretching bands of the infrared spectra of liquid-crystalline states of the peptide-free and peptide-containing DPPC-d(62) and POPC-d(31) samples, and a comparison with the orientational order as measured by (2)H-NMR spectroscopy as well as with the chain order as measured by electron spin resonance spectroscopy, lead us to conclude that the CH(2) (or CD(2)) stretching frequencies of lipid hydrocarbon chains are not a reliable measure of chain conformational order in lipid bilayers containing significant amounts of peptides or other lipophilic inclusions. In contrast, the results of our (2)H-NMR spectroscopic studies present a consistent picture in which both L(24) and (LA)(12) increased in a similar way the time-averaged orientational order of the lipid chains of their liquid-crystalline lipid bilayer hosts. The comparison of the effects L(24) and (LA)(12) on phosphatidylcholine bilayers indicates that the gel-to-liquid-crystalline phase transition appears to be more sensitive to small changes in transmembrane peptide surface topology than hydrocarbon carbon chain orientational order in the liquid-crystalline state.

Dobutamine stress echocardiography and exercise electrocardiography for risk stratification in medically treated unstable angina.

UNLABELLED: Previous reports have demonstrated the superiority of exercise echocardiography over exercise electro-cardiography (ex-ECG) for risk stratification in patients with medically stabilized unstable angina (UA). We sought to analyze the prognostic value of dobutamine stress echocardiography (DSE) compared with ex-ECG for risk stratification in patients with UA. METHODS: Ninety-two patients with medically treated UA were studied (mean age 65 +/- 11 years, 24 women, 42% of patients had electrocardiographic abnormalities on admission). Dobutamine stress echocardiography and treadmill ex-ECG were performed on the third day after hospital admission. End points were recurrent UA, myocardial infarction (MI), or cardiac death. RESULTS: Mean follow-up was 24 +/- 7 months. During follow-up, 22 patients had cardiac events (18 recurrent UA, 2 MI, 2 cardiac deaths). The event-free survival rate was 80% for patients with negative DSE results for ischemia and 52% for those with positive DSE results (log rank 9.57; P =.002), compared with an event-free survival rate of 79% for patients with negative ex-ECG results and 66% for those with positive ex-ECG results (log rank 2.06; P = not significant). Left ventricular dysfunction (P =.01) and a positive dobutamine stress echocardiogram (P =.03), but not a positive exercise electrocardiogram, were independent predictors of cardiac events during follow-up. CONCLUSIONS: Dobutamine stress echocardiography performed early in medically treated patients with UA predicts cardiac events during follow-up more accurately and with more specificity than ex-ECG does in this population.

[Guidelines of the Spanish Society of Cardiology on valve heart disease]. / Guías de práctica clínica de la Sociedad Española de Cardiología en valvulopatías.

Valvular heart diseases, which continue to be a major cause of morbidity and mortality world wide, have undergone radical changes since the first valve prostheses were implanted 40 years ago. These changes have been the result of both scientific progress and improved standard of living in developed countries. The availability of penicillin to treat streptococcal pharyngitis and less crowded living conditions have now made rheumatic fever uncommon in these countries. However, other forms of valve impairment have appeared over the past several years. The etiology of some of these valvular diseases remains obscure (e. g. myxomatous mitral valve); others, such as the senile type of calcific aortic valve stenosis, seem to be the price to be paid for the extension of life expectancy. With regard to diagnosis, echocardiography has constituted a formidable tool for visualizing anatomic valve changes, interpreting complex hemodynamic derangements, and evaluating repercussion on the left ventricle. In addition, the iteration of this non-invasive examination has allowed a much better understanding of the natural history of non-severe valvular disease and therefore of the precise timing for surgical intervention, without awaiting, in most cases, the appearance of advanced symptomatology. This has also been possible because of the great advances in cardiac surgery which can be summarised as: a) the improvement in extracorporeal circulation and myocardial preservation techniques; b) the greatly improved biologic and mechanic valve substitutes; c) the introduction of imaginative mitral valve repair procedures, and d) the use of intraoperative transesophageal echocardiography to assess the adequacy of valve repair. At the same time, percutaneous catheter balloon valvuloplasty has emerged as a valid alternative to mitral surgical commissurotomy for mitral stenosis. All these changes, and many more that can not be described in this brief summary, make a review of the management of patients with valve heart disease appropriate.

Feasibility and prognostic value of dobutamine-atropine stress echocardiography early in unstable angina.

BACKGROUND AND AIM: Because unstable angina has always been considered a contraindication for dobutamine-atropine stress echocardiography (DSE), the role of dobutamine-atropine stress echocardiography in unstable angina is unknown. Our aim was to assess the safety and prognostic value of dobutamine-atropine stress echocardiography in unstable angina. METHODS: One hundred and thirty-two patients were studied (mean age 64+/-12 years, 29 women). Dobutamine-atropine stress echocardiography was performed on the third day after hospital admission. End-points were unstable angina, myocardial infarction or cardiac death at 1 year follow-up. RESULTS: No major complications occurred during dobutamine-atropine stress echocardiography. Ninety-six (78%) patients were on beta-blocker therapy during the test; mean maximum heart rate achieved was 106+/-23 beats x min(-1). Nine of the 21 patients (43%) with a positive dobutamine-atropine stress echocardiography presented cardiac events during follow-up: two patients died, one had a myocardial infarction and six had recurrent class III-IV angina. Among 80 patients with negative dobutamine-atropine stress echocardiography, one (1%) had myocardial infarction and six patients (7.5%) had recurrent angina. Event-free survival after 1 year for patients with a negative dobutamine-atropine stress echocardiography for ischaemia was 91% compared to 57% for those with a positive dobutamine-atropine stress echocardiography (P<0. 0001). Left ventricular dysfunction (P=0.01), prior myocardial infarction (P=0.03) and a positive dobutamine-atropine stress echocardiography (P=0.004) were independent predictors of cardiac events during follow-up. CONCLUSIONS: Dobutamine-atropine stress echocardiography is safe in unstable angina if it is performed when patients remain asymptomatic for at least 48 h. A negative dobutamine-atropine stress echocardiogram for ischaemia predicts a good prognosis in medically treated patients with unstable angina and may allow their early discharge from hospital. Good prognostic information was obtained despite the use of beta-blockers and low heart rates during dobutamine-atropine stress echocardiography.

Subcellular localization of Bic-D::GFP is linked to an asymmetric oocyte nucleus.

Bicaudal-D (Bic-D) is essential for the establishment of oocyte fate and subsequently for polarity formation within the developing Drosophila oocyte. To find out where in the germ cells Bic-D performs its various functions we made transgenic flies expressing a chimeric Bic-D::GFP fusion protein. Once Bic-D::GFP preferentially accumulates in the oocyte, it shows an initial anterior localization in germarial region 2. In the subsequent egg chamber stages 1-6 Bic-D::GFP preferentially accumulates between the oocyte nucleus and the posterior cortex in a focus that is consistently aligned with a crater-like indentation in the oocyte nucleus. After stage 6 Bic-D::GFP fluorescent signal is predominantly found between the oocyte nucleus and the dorso-anterior cortex. During the different phases several genes have been found to be required for the establishment of the new Bic-D::GFP distribution patterns. Dynein heavy chain (Dhc), spindle (spn) genes and maelstrom (mael) are required for the re-localization of the Bic-D::GFP focus from its anterior to its posterior oocyte position. Genes predicted to encode proteins that interact with RNA (egalitarian and orb) are required for the normal subcellular distribution of Bic-D::GFP in the germarium, and another potential RNA binding protein, spn-E, is required for proper transport of Bic-D::GFP from the nurse cells to the oocyte in later oogenesis stages. The results indicate that Bic-D requires the activity of mRNA binding proteins and a negative-end directed microtubule motor to localize to the appropriate cellular domains. Asymmetric subcellular accumulation of Bic-D and the polarization of the oocyte nucleus may reflect the function of this localization machinery in vectorial mRNA localization and in tethering of the oocyte nucleus. The subcellular polarity defined by the Bic-D focus and the nuclear polarity marks some of the first steps in antero-posterior and subsequently in dorso-ventral polarity formation.

Prognostic value of serum cytokines in patients with congestive heart failure.

BACKGROUND: Increased levels of circulating cytokines have been previously reported in patients with congestive heart failure; however, whether they have prognostic implications is still unknown. The aim of this study was to assess the prognostic implications of elevated serum cytokines in patients with heart failure and to identify the predictors of cytokine activation. METHODS AND RESULTS: We assessed neurohormonal determinations, circulating cytokines, ejection fraction (EF) and end-diastolic and end-systolic left ventricular lengths in 87 patients (aged 57 +/- 9 years) with left ventricular dysfunction (EF 24% +/- 6%). In 48 patients, we also assessed cytokine receptors. During follow-up (mean, 14 +/- 9 months), 8 patients died and 12 had new heart failure episodes that required hospital admission, 5 of whom underwent heart transplantation. The univariate predictors of these events were serum interleukin-6 (IL-6) (p = 0.00001), New York Heart Association (NYHA) functional class (p = 0.0004), tumor necrosis factor-soluble receptor I (p = 0. 001), atrial natriuretic peptide (p = 0.002), tumor necrosis factor-soluble receptor II (p = 0.004), angiotensin II (p = 0.006), serum interleukin-1 beta (p = 0.01), and plasma renin activity (p = 0.02). Increased serum interleukin-6 (>10 pg/ml) was a significant predictor of death or new heart failure episodes according to the Kaplan-Meier survival method by log-rank test (p = 0.004). By Cox regression analysis, serum IL-6 (p = 0.0005) and the NYHA functional class (p = 0.005) were identified as independent predictors of prognosis. CONCLUSIONS: In patients with congestive heart failure, increased serum IL-6 was identified as a powerful independent predictor of the combined end point: death, new heart failure episodes, and need for heart transplantation.