Impact of salt on cardiac differential gene expression and coronary lesion in normotensive mineralocorticoid-treated mice

We previously reported that excess of deoxycorticosterone-acetate (DOCA)/salt-induced cardiac hypertrophy in the absence of hypertension in one-renin gene mice. This model allows us to study molecular mechanisms of high-salt intake in the development of cardiovascular remodeling, independently of blood pressure in a high mineralocorticoid state. In this study, we compared the effect of 5-wk low- and high-salt intake on cardiovascular remodeling and cardiac differential gene expression in mice receiving the same amount of DOCA. Differential gene and protein expression was measured by high-density cDNA microarray assays, real-time PCR and Western blot analysis in DOCA-high salt (HS) vs. DOCA-low salt (LS) mice. DOCA-HS mice developed cardiac hypertrophy, coronary perivascular fibrosis, and left ventricular dysfunction. Differential gene and protein expression demonstrated that high-salt intake upregulated a subset of genes encoding for proteins involved in inflammation and extracellular matrix remodeling (e.g., Col3a1, Col1a2, Hmox1, and Lcn2). A major subset of downregulated genes encoded for transcription factors, including myeloid differentiation primary response (MyD) genes. Our data provide some evidence that vascular remodeling, fibrosis, and inflammation are important consequences of a high-salt intake in DOCA mice. Our study suggests that among the different pathogenic factors of cardiac and vascular remodeling, such as hypertension and mineralocorticoid excess and sodium intake, the latter is critical for the development of the profibrotic and proinflammatory phenotype observed in the heart of normotensive DOCA-treated mice.

Infrapopliteal lesion morphology in patients with critical limb ischemia: implications for the development of anti-restenosis technologies

Purpose : To angiographically evaluate infrapopliteal arterial lesion morphology in a consecutive series of patients presenting with critical limb ischemia (CLI) and undergoing infrapopliteal angioplasty. Methods : A prospective analysis was undertaken of a consecutive series of CLI patients undergoing endovascular therapy in a tertiary referral center in the year 2011. Morphological assessment of baseline angiograms obtained prior to revascularization included lesion length, assessment of calcification using a semi-quantitative scoring system, and reference vessel diameter (RVD) measurement. Delta RVDs were assessed subtracting distal RVDs from proximal RVDs. A total of 197 infrapopliteal lesions in 105 CLI patients (n=106 limbs) were assessed. Of these, 136 lesions were treated by endovascular means. Results : The average length of treated lesions was 87.1±43.8 mm in stenoses and 124.0±78.3 mm in chronic occlusions (p<0.001). Mean RVD proximal to the lesions was 1.88 mm whereas it was 1.66 mm distal to the lesions (p≤0.03). Mean arterial calcification was 1.15. Conclusion : This prospective angiographic series underlines the complex nature and extensive longitudinal involvement of infrapopliteal lesions in CLI patients. These findings should be taken into consideration for anti-restenosis concepts in this challenging subgroup of peripheral artery disease patients.

Mild encephalopathy with splenial lesion and parainfluenza virus infection

Mild encephalopathy with reversible splenial lesions has mainly been associated with influenza A and B virus infection. Patients present with neurologic symptoms 1 to 3 days after a prodromal illness and recover completely within a few days. Magnetic resonance imaging typically shows reversible lesions with reduced diffusion in the corpus callosum, predominantly in the splenium. We report on a 5-year old Caucasian boy who was referred with recurrent seizures and decreased level of consciousness after a 2-day prodromal fever and cough. Magnetic resonance imaging showed cytotoxic edema of the entire corpus callosum and the adjacent periventricular white matter with diffusion restriction and faint T(2)-hyperintensity. Parainfluenza virus type 1-3 infection was documented by direct immunofluorescence in the initial nasopharyngeal swab, but polymerase chain reaction for parainfluenza virus type 1-4 in the cerebrospinal fluid remained negative. This is-to our knowledge-the first description of mild encephalopathy with reversible splenial lesions in association with parainfluenza virus infection. The pathogenesis of mild encephalopathy with reversible splenial lesions, however, still remains unclear, and further studies investigating detailed mechanisms that lead to the typical brain lesions are warranted.

Induction of the Neurokinin 1 Receptor by TNFα in Endometriotic Tissue Provides the Potential for Neurogenic Control Over Endometriotic Lesion Growth

Context: Endometriosis is characterized by the growth of ectopic endometrial tissue. Nerve fibers are frequently associated with ectopic lesions, and neurogenic inflammation may play a role in endometriosis. Objective: The purpose of this study was to determine the presence of tachykinin receptors in endometriotic lesions and the role of TNFα on their expression. Design: This study was an assessment of matching eutopic and ectopic endometrial tissue and peritoneal fluid from patients with endometriosis and an in vitro analysis of primary endometrial cells. Setting: The setting was a university hospital. Patients: Participants were premenopausal women undergoing laparoscopy. Interventions: Endometriotic lesions were removed surgically. Main Outcome Measures: Tachykinin mRNA (TACR1/2) and protein (neurokinin 1 receptor [NK1R]) expression in both eutopic and ectopic endometrial tissue from patients with endometriosis and the correlation to peritoneal fluid TNFα were measured. Primary endometrial epithelial and stromal cells were assessed in vitro to determine the induction of TACR1/2 and NK1R expression after TNFα treatment. Cell viability of endometrial stromal cells after substance P exposure was also assessed. Results: Expression of both TACR1 and TACR2 mRNA was significantly higher in the ectopic than in the eutopic tissue. Both TACR1 mRNA and NK1R protein expression was significantly correlated with peritoneal fluid TNFα, and in vitro studies confirmed that TNFα treatment induced both TACR1 mRNA and NK1R protein expression in endometrial stromal cells. In endometrial stromal cells, substance P treatment enhanced cell viability, which was inhibited by a specific NK1R antagonist. Conclusions: NK1R expression is induced in ectopic endometrial tissue by peritoneal TNFα. Induction of NK1R expression may permit endometriotic lesion maintenance via exposure to substance P.

Isolated mediotegmental lesion causing narcolepsy and rapid eye movement sleep behaviour disorder: a case evidencing a common pathway in narcolepsy and rapid eye movement sleep behaviour disorder

Narcolepsy is usually an idiopathic disorder, often with a genetic predisposition. Symptomatic cases have been described repeatedly, often as a consequence of hypothalamic lesions. Conversely, REM (rapid eye movement) sleep behaviour disorder (RBD) is usually a secondary disorder, often due to degenerative brain stem disorders or narcolepsy. The case of a hitherto healthy man is presented, who simultaneously developed narcolepsy and RBD as the result of an acute focal inflammatory lesion in the dorsomedial pontine tegmentum in the presence of normal cerebrospinal fluid hypocretin-1 levels and in the absence of human lymphocyte antigen haplotypes typically associated with narcolepsy and RBD (DQB1*0602, DQB1*05). This first observation of symptomatic narcolepsy with RBD underlines the importance of the mediotegmental pontine area in the pathophysiology of both disorders, even in the absence of a detectable hypocretin deficiency and a genetic predisposition.

Echinococcosis presenting as an otogenic brain abscess: an unusual lesion of the middle ear cleft and temporal lobe

This paper presents a case of a 28-year-old male with a seizure episode and a 4-year history of intermittent tinnitus on the left ear. On computed tomography and magnetic resonance imaging, a density with rim enhancement was found at the temporal lobe, associated with mastoid tegmen destruction and middle ear mass, indicating cholesteatoma with complicating brain abscess. Evacuation of the brain abscess was performed with a combined otolaryngologic and neurosurgical procedures (canal wall-down mastoidectomy and temporal craniotomy). The pathology turned out to be infestation with Echinococcus granulosus.

Rotational atherectomy followed by drug-eluting stent implantation (Rota-DES): a rational approach for complex calcified coronary lesions

Rotational atherectomy has been regaining interest over the last couple of years after it almost has disappeared from most interventional catheterization laboratories for several years due to failure to prove its original concept of improving long term results of percutaneous coronary interventions (PCI) as was repeatedly shown in studies in the 1990s. Its revival coupled the introduction of drug-eluting stents (DES); these devices have led to treating much more complex lesions and high-risk patients by PCI. However, real-world experience suggested that off-label use of DES is associated with a higher rate of early and late stent thrombosis. Therefore, more attention is now being paid to the initial implantation technique of DES including aggressive lesion preparation to facilitate stent delivery and expansion. The limited studies with rot-ablation and DES showed promising results with no long term safety concerns. In these studies, a subtle observation was made suggesting that rot-ablation prior to DES implantation in such lesions may have an add-on effect on long term outcome compared to DES alone. An ongoing multicenter study is investigating such effect among complex calcified coronary lesions. Even if this additive benefit does not prove true, rot-ablation remains an efficient tool for preparing certain lesions to facilitate effective and safe DES implantation. Therefore, interventional training programs should focus on this difficult technique to bridge the gap of experience which resulted from neglecting it for several years. In this regard, dedicated courses at experienced sites as well as medical simulation may be appropriate.

Prognostic value of the modified American College of Cardiology/American Heart Association lesion morphology classification for clinical outcome after sirolimus-eluting stent placement (results of the prospective multicenter German Cypher Registry)

The modified American College of Cardiology/American Heart Association (ACC/AHA) lesion morphology classification scheme has prognostic impact for early and late outcomes when bare-metal stents are used. Its value after drug-eluting stent placement is unknown. The predictive value of this lesion morphology classification system in patients treated using sirolimus-eluting stents included in the German Cypher Registry was prospectively examined. The study population included 6,755 patients treated for 7,960 lesions using sirolimus-eluting stents. Lesions were classified as type A, B1, B2, or C. Lesion type A or B1 was considered simple (35.1%), and type B2 or C, complex (64.9%). The combined end point of all deaths, myocardial infarction, or target vessel revascularization was seen in 2.6% versus 2.4% in the complex and simple groups, respectively (p = 0.62) at initial hospital discharge, with a trend for higher rates of myocardial infarction in the complex group. At the 6-month clinical follow-up and after adjusting for other independent factors, the composite of cumulative death, myocardial infarction, and target vessel revascularization was nonsignificantly different between groups (11.4% vs 11.2% in the complex and simple groups, respectively; odds ratio 1.08, 95% confidence interval 0.8 to 1.46). This was also true for target vessel revascularization alone (8.3% of the complex group, 9.0% of the simple group; odds ratio 0.87, 95% confidence interval 0.72 to 1.05). In conclusion, the modified ACC/AHA lesion morphology classification system has some value in determining early complications after sirolimus-eluting stent implantation. Clinical follow-up results at 6 months were generally favorable and cannot be adequately differentiated on the basis of this lesion morphology classification scheme.