Occult lung malignancy presenting with finger pain: a case report

<p>Abstract</p> <p>Introduction</p> <p>Lung cancer is currently one of the most common malignancies in the world. Early detection is an important prognostic factor. Unfortunately, initial symptoms may be vague and a substantial proportion of cases present with the effects of metastases.</p> <p>Case presentation</p> <p>We discuss a case of occult lung malignancy in a 61-year-old man. The only symptom at presentation was pain in the right ring finger due to metastasis from the lung primary.</p> <p>Conclusion</p> <p>This case highlights the need for vigilance when a patient presents with unusual or unexplained symptoms, especially if they have known risk factors for cancer.</p

Specification of a foxj1-dependent lineage in the forebrain is required for embryonic-to-postnatal transition of neurogenesis in the olfactory bulb

Establishment of a neural stem cell niche in the postnatal subependymal zone (SEZ) and the rostral migratory stream (RMS) is required for postnatal and adult neurogenesis in the olfactory bulbs (OB). We report the discovery of a cellular lineage in the SEZ-RMS-OB continuum, the specification of which is dependent on the expression of the forkhead transcription factor Foxj1 in mice. Spatially- and temporally- restricted Foxj1+ neuronal progenitors emerge during embryonic periods, surge during perinatal development, and are active only for the first few postnatal weeks. We show that the development of the unique Foxj1-derived lineage is dependent on Foxj1 expression, and is required for overall postnatal neurogenesis in the OB. Strikingly, the production of neurons from Foxj1+ progenitors significantly declines after the early postnatal weeks, but Foxj1-derived neurons in the OB persist during adult periods. Our study for the first time identifies the time-and region-specific activity of a perinatal progenitor domain that is required for transition and progression of OB neurogenesis from the embryonic-to-postnatal periods

Differential Regulation of PDE5 Expression in Left and Right Ventricles of Feline Hypertrophy Models

Though long known to affect smooth muscle biology, recent studies indicate that phosphodiesterase 5 (PDE5) is also expressed in myocardium. Recognizing that the regulation of PDE5 in hypertrophy is not well understood, we assessed the response of PDE5 expression and the level of cGMP-dependent kinase I (cGKI) in the left and right ventricles of feline hypertrophy models.Using a cDNA library of feline aortic smooth muscle cells, we identified and cloned PDE5 cDNA for the first time in this species. The sequence shares 98% identity with its human orthologue at the amino acid level. E. coli expression of the cloned allele allowed selection of antibodies with appropriate specificity, facilitating the analysis of PDE5 expression in feline models created by selective proximal aortic (Ao) or pulmonary artery (PA) banding that resulted in hypertrophy of the left ventricle (LV) and right ventricle (RV), respectively. We demonstrated that PDE5 expression responded differentially with a decreased expression in the LV and an increased expression in the RV in the Ao-banded model. Similarly, in the PA-banded model, LV showed reduced expression while the RV expression was unaltered. In addition, the expression of cGKI was significantly decreased in the RV of Ao-banded group, correlating inversely with the increase in PDE5 expression.The differential regulation of PDE5 and cGKI expression suggests that the mechanisms involved in hypertrophy could be different in RV vs. LV. Reciprocal PDE5 and cGKI expression in the RV of Ao-banded model suggests functional significance for PDE5 up-regulation

Concomitant ablation of atrial fibrillation in octogenarians: an observational study

<p>Abstract</p> <p>Background</p> <p>Cardiac surgery is increasingly required in octogenarians. These patients frequently present atrial fibrillation (AF), a significant factor for stroke and premature death. During the last decade, AF ablation has become an effective procedure in cardiac surgery. Because the results of concomitant AF ablation in octogenarians undergoing cardiac surgery are still not clear, we evaluated the outcome in these patients.</p> <p>Methods</p> <p>Among 200 patients undergoing concomitant AF ablation (87% persistent AF), 28 patients were ≥ 80 years (82 ± 2.4 years). The outcome was analysed by prospective follow up after 3, 6, 12 months and annually thereafter. Freedom from AF was calculated according to the Kaplan-Meier method.</p> <p>Results</p> <p>Octogenarians were similar to controls regarding AF duration (48 ± 63.2 versus 63 ± 86.3 months, n.s.) and left atrial diameter (49 ± 6.1 versus 49 ± 8.8 mm, n.s.), but differed in EuroSCORE (17.3 ± 10.93 versus 7.4 ± 7.31%, p < 0.001), prevalence of paroxysmal AF (25.0 versus 11.0%, p = 0.042) and aortic valve disease (67.8 versus 28.5%, p < 0.001). ICU stay (8 ± 16.9 versus 4 ± 7.2 days, p = 0.027), hospital stay (20 ± 23.9 versus 14 ± 30.8 days, p < 0.05), and 30-d-mortality (14.3 versus 4.6%, p = 0.046) were increased. After 12 ± 6.1 months of follow-up (95% complete), 14 octogenarians (82%) and 101 controls (68%, n.s.) were in sinus rhythm; 59% without antiarrhythmic drugs in either group (n.s.). Sinus rhythm restoration was associated with improved NYHA functional class and renormalization of left atrial size. Cumulative freedom from AF demonstrated no difference between groups. Late mortality was higher in octogenarians (16.7 versus 6.1%, p = 0.065).</p> <p>Conclusion</p> <p>Sinus rhythm restoration rate and functional improvement are satisfactory in octogenarians undergoing concomitant AF ablation. Hence, despite an increased perioperative risk, this procedure should be considered even in advanced age.</p

Agents increasing cyclic GMP amplify 5-HT4-elicited positive inotropic response in failing rat cardiac ventricle

Activation of 5-HT4 receptors in failing ventricles elicits a cAMP-dependent positive inotropic response which is mainly limited by the cGMP-inhibitable phosphodiesterase (PDE) 3. However, PDE4 plays an additional role which is demasked by PDE3 inhibition. The objective of this study was to evaluate the effect of cGMP generated by particulate and soluble guanylyl cyclase (GC) on the 5-HT4-mediated inotropic response. Extensive myocardial infarctions were induced by coronary artery ligation in Wistar rats, exhibiting heart failure 6 weeks after surgery. Contractility was measured in left ventricular preparations. Cyclic GMP was measured by EIA. In ventricular preparations, ANP or BNP displayed no impact on 5-HT4-mediated inotropic response. However, CNP increased the 5-HT4-mediated inotropic response as well as the β1-adrenoceptor (β1-AR)-mediated response to a similar extent as PDE3 inhibition by cilostamide. Pretreatment with cilostamide eliminated the effect of CNP. Inhibition of nitric oxide (NO) synthase and soluble GC by l-NAME and ODQ, respectively, attenuated the 5-HT4-mediated inotropic response, whereas the NO donor Sin-1 increased this response. The effects were absent during PDE3 inhibition, suggesting cGMP-dependent inhibition of PDE3. However, in contrast to the effects on the 5-HT4 response, Sin-1 inhibited whereas l-NAME and ODQ enhanced the β1-AR-mediated inotropic response. cGMP generated both by particulate (NPR-B) and soluble GC increases the 5-HT4-mediated inotropic response in failing hearts, probably through inhibition of PDE3. β1-AR and 5-HT4 receptor signalling are subject to opposite regulatory control by cGMP generated by soluble GC in failing hearts. Thus, cGMP from different sources is functionally compartmented, giving differential regulation of different Gs-coupled receptors

Therapeutic efficacy of TBC3711 in monocrotaline-induced pulmonary hypertension

Background: Endothelin-1 signalling plays an important role in pathogenesis of pulmonary hypertension. Although different endothelin-A receptor antagonists are developed, a novel therapeutic option to cure the disease is still needed. This study aims to investigate the therapeutic efficacy of the selective endothelin-A receptor antagonist TBC3711 in monocrotaline-induced pulmonary hypertension in rats. Methods: Monocrotaline-injected male Sprague-Dawley rats were randomized and treated orally from day 21 to 35 either with TBC3711 (Dose: 30 mg/kg body weight/day) or placebo. Echocardiographic measurements of different hemodynamic and right-heart hypertrophy parameters were performed. After day 35, rats were sacrificed for invasive hemodynamic and right-heart hypertrophy measurements. Additionally, histologic assessment of pulmonary vascular and right-heart remodelling was performed. Results: The novel endothelin-A receptor antagonist TBC3711 significantly attenuated monocrotaline-induced pulmonary hypertension, as evident from improved hemodynamics and right-heart hypertrophy in comparison with placebo group. In addition, muscularization and medial wall thickness of distal pulmonary vessels were ameliorated. The histologic evaluation of the right ventricle showed a significant reduction in fibrosis and cardiomyocyte size, suggesting an improvement in right-heart remodelling. Conclusion: The results of this study suggest that the selective endothelin-A receptor antagonist TBC3711 demonstrates therapeutic benefit in rats with established pulmonary hypertension, thus representing a useful therapeutic approach for treatment of pulmonary hypertension

Recommendations for cardiovascular magnetic resonance in adults with congenital heart disease from the respective working groups of the European Society of Cardiology

This paper aims to provide information and explanations regarding the clinically relevant options, strengths, and limitations of cardiovascular magnetic resonance (CMR) in relation to adults with congenital heart disease (CHD). Cardiovascular magnetic resonance can provide assessments of anatomical connections, biventricular function, myocardial viability, measurements of flow, angiography, and more, without ionizing radiation. It should be regarded as a necessary facility in a centre specializing in the care of adults with CHD. Also, those using CMR to investigate acquired heart disease should be able to recognize and evaluate previously unsuspected CHD such as septal defects, anomalously connected pulmonary veins, or double-chambered right ventricle. To realize its full potential and to avoid pitfalls, however, CMR of CHD requires training and experience. Appropriate pathophysiological understanding is needed to evaluate cardiovascular function after surgery for tetralogy of Fallot, transposition of the great arteries, and after Fontan operations. For these and other complex CHD, CMR should be undertaken by specialists committed to long-term collaboration with the clinicians and surgeons managing the patients. We provide a table of CMR acquisition protocols in relation to CHD categories as a guide towards appropriate use of this uniquely versatile imaging modality