OBJECTIVE: Asymmetric septal hypertrophy frequently coexists with severe aortic stenosis and can be unmasked after successful aortic valve replacement (AVR), jeopardizing the clinical and echocardiographic results. The aim of our study was to investigate, at 5 years postoperatively, the effectiveness of myectomy associated with AVR on left ventricular (LV) mass regression and LV diastolic function. METHODS: From 1997 and 2004, 86 patients with a diagnosis of severe aortic stenosis and asymmetric septal hypertrophy consecutively underwent AVR (group A) or AVR and concomitant myectomy (group B). To assess the improvement in LV mass and LV diastolic function, we studied the 52 survivors (23 in group A and 29 in group B) who had the same prosthesis type (beleaflet mechanical), the same size (21 mm), and the same follow-up length. RESULTS: In group A, the LV mass index regressed from 119.2 ± 22.0 to 113.8 ± 21.8, and in group B, it regressed from 121.6 ± 20.8 to 112.7 ± 20.0 (P < .0005). In group A, the E/E' ratio improved from 15.3 ± 3.0 to 11.8 ± 3.0, and in group B, it improved from 16.2 ± 3.2 to 12.1 ± 3.3 (P = .02). CONCLUSIONS: Surgeons should inspect the LV outflow tract at AVR. Concomitant myectomy at AVR is a safe and effective procedure that improves LV mass regression and LV diastolic function.

Pain, a homeostatic and protective mechanism which can go awry in disease states and therefore needs treatment, is a complex and differentiated sensorial perception which may be classified as physiological, inflammatory and neuropathic. Chronic pain represents a major health problem throughout the world, thus several companies and researchers have embarked on the search for new drugs and targets to treat the disease. The different types of receptors in the CNS involved in the mediation of analgesia include the cannabinoid receptors: in particular, CB2 modulators seem to represent a new potential class of analgesic. This review covers recent patents and advances in CB2 agonist studies in the management of pain.

The study was designed to demonstrate the need of accounting for respiration (R) when causality between heart period (HP) and systolic arterial pressure (SAP) is under scrutiny. Simulations generated according to a bivariate autoregressive closed loop model were utilized to assess how causality changes as a function of the model parameters. An exogenous (X) signal was added to the bivariate autoregressive closed loop model to evaluate the bias on causality induced when the X source was disregarded. Causality was assessed in the time domain according to a predictability improvement approach (i.e. Granger causality). HP and SAP variability series were recorded with R in 19 healthy subjects during spontaneous and controlled breathing at 10, 15 and 20 breaths/minute. Simulations proved the importance of accounting for X signals. During spontaneous breathing assessing causality without taking into consideration R lead to a significantly larger percentage of closed loop interactions and a smaller fraction of unidirectional causality from HP to SAP. This finding was confirmed during paced breathing and it was independent of the breathing rate. These results suggest that the role of baroreflex cannot be correctly assessed without accounting for R.

Aim: Different studies, carried out by us and others, have investigated the impact of carbon nanotubes (CNTs) in vitro and in animal models. To date, only a few studies have been performed on human cells ex vivo. There is also a lack of comparison between CNTs with varied functionalization and structural properties and their impact on different cell types. Materials & Methods: The present ex vivo human study focuses on the impact of a series of functionalized multiwalled CNTs on human T and B lymphocytes, natural killer (NK) cells and monocytes. Results: Smaller diameter nanotubes are internalized more efficiently. Viability assays displayed the absence of cytotoxicity of all multiwalled CNTs used. Activation assay demonstrated a strong effect on monocytes and NK cells. Conclusion: Our results, on human cells ex vivo, confirmed previous studies demonstrating appropriately functionalized CNTs are nontoxic. The effects on cell functionality were significant for the monocytes and NK cells. These findings encourage the possible use of CNTs for biomedical applications either as carriers of therapeutic molecules or as immune modulator systems.

The endoscopic endonasal approach is emerging as a feasible alternative to the trans-oral route for the resection of the odontoid process, when the latter produces a compression of the brainstem and cervicomedullary junction. This type of approach has some advantages, such as excellent pre-vertebral exposure of the cranio-vertebral junction in patients with small oral cavities and the possibility to avoid the use of mouth retractors. A typical case of a 24-year-old male patient with a previous diagnosis of type I Arnold-Chiari Malformation, suffering from a posterior dislocation of the odontoid process causing severe anterior compression of the brainstem, is presented to stress the potential of this technique. Trans-nasal endoscopic removal of the odontoid process was performed and resolution of the ventral compression of the brainstem was achieved. This report demonstrates that in selected cases, an endoscopic endonasal approach should now be considered an excellent alternative to the traditional trans-oral approach.

Benzodiazepines remain the most frequently used psychotropic drugs for the treatment of anxiety spectrum disorders; however their use is associated with development of tolerance and dependence. Another major hindrance is represented by their lack of efficacy in many patients, including patients with posttraumatic stress disorder (PTSD). For these non-responders, the use of selective serotonin reuptake inhibitors (SSRIs) has been the therapy of choice. In the past decade, clinical studies have suggested that the pharmacological action of SSRIs may include the ability of these drugs to normalize decreased brain levels of neurosteroids in patients with depression and PTSD, in particular the progesterone derivative allopregnanolone, which potently and allosterically modulates the action of GABA at GABAA receptors. Preclinical studies using the socially isolated mouse as an animal model of PTSD have demonstrated that fluoxetine and congeners ameliorate anxiety-like behavior, fear responses, and aggressive behavior expressed by such mice by increasing corticolimbic levels of allopregnanolone. This is a novel and more selective mechanism than 5-HT reuptake inhibition, which for half a century has been thought to be the main molecular mechanism for the therapeutic action of SSRIs. Importantly, this finding may shed light on the high rates of SSRI resistance among patients with PTSD and depression, disorders in which there appears to be a block in allopregnanolone synthesis. There are several different mechanisms by which such a block may occur, and SSRIs may only be corrective under some conditions. Thus, upregulation of allopregnanolone biosynthesis in corticolimbic neurons may offer a novel non-traditional pharmacological target for a new generation of potent non-sedating, anxiolytic medications for the treatment of anxiety, depression, and PTSD: selective brain steroidogenic stimulants (SBSSs).

Intersectin 1 (ITSN1) is a human chromosome 21 (HSA21) gene product encoding a multidomain scaffold protein that functions in endocytosis, signal transduction, and is implicated in Down's syndrome, Alzheimer's Disease, and potentially other neurodegenerative diseases through activation of c-Jun N-terminal kinase. We report for the first time that ITSN1 proteins are elevated in individuals with Down's syndrome of varying ages. However, ITSN1 levels decreased in aged cases with Down's syndrome with Alzheimer's disease-like neuropathology. Analysis of a novel ITSN1 transgenic mouse reveals that ITSN1 overexpression results in a sex-dependent decrease in locomotor activity. This study reveals a link between overexpression of specific ITSN1 isoforms and behavioral phenotypes and has implications for human neurodegenerative diseases such as Down's syndrome and Alzheimer's disease.

An unusual reaction involving ninhydrin and aminothiols was exploited to set an indirect method for the chiral recognition of stereoisomers of penicillamine. Separation of diastereoisomers was achieved on a C18 column in isocratic mode by using a mixture of propionic acid (pH 3.0)/acetonitrile/water (10:10:80, v/v/v) as a mobile phase. Diastereoisomers were detected by a fluorescence detector in fairly short times (about 7min) and with a good resolution. The lowest detectable amount of toxic isomer of penicillamine (l-enantiomer) in samples of the d-enantiomer, was around 0.01%. The method was also suitable for the indirect chiral recognition of other aminothiols such as cysteine and cysteinylglycine.

BACKGROUND: Atrial fibrillation is the most frequent arrhythmia, but few data are available on patients' characteristics and management in the context of Internal Medicine wards. METHODS: Data were collected at the beginning of 2010 in 18 Internal Medicine units of the regions Liguria and Piemonte (Italy). Each centre reviewed the hospital charts of the last 50 patients discharged during the year 2009 in whom a diagnosis of atrial fibrillation had been made (patient's history or during the hospitalization). RESULTS: A total of 903 atrial fibrillation patients were evaluated. Prevalence of atrial fibrillation among patients hospitalized in Internal Medicine units was 18.2%. More than 85% of patients had at least two diseases other than atrial fibrillation, and 'lone' atrial fibrillation was rare (1.3%). During hospital stay, 80.5% of the patients received at least one treatment for atrial fibrillation: 55.5% received an antithrombotic and 61.8% a drug for arrhythmia, mostly aimed at rate control (47.2%). In-hospital all-cause mortality was 13.4%. At discharge, 70.2 and 68.9% of the patients received prescription of a drug for arrhythmia and for antithrombotic treatment, respectively. Prescription of oral anticoagulants was significantly associated with hypertension, while previous bleeding, age above 75 years, paroxysmal atrial fibrillation, male sex and a number of concomitant drugs of more than four were strong negative predictors. CONCLUSION: Data from our study confirm that atrial fibrillation is a common finding in patients hospitalized in Internal Medicine units, and this population is characterized by multiple comorbidities and severe prognosis. Discrepancies exist between recommendations by guidelines and real-world management, owing to the complexity of patients and limits of existing treatment strategies.

Anabolic androgenic steroid (AAS) replacement therapy is standard care for patients with low testosterone, including HIV-related conditions. These medications have been associated with development of aggressiveness, anxiety disorders, and depression, but only in short-term clinical trials. We conducted an anonymous street survey at a gay and lesbian community event and a survey in a clinic-based setting to study the wider prevalence of psychiatric side-effects associated with androgenic steroids. In the street-based survey, almost half of those prescribed AAS reported psychological side-effects, most commonly aggression (29%) followed by depression (21%). In the clinic survey of mostly HIV+ male patients, changes in sex drive were the most commonly reported effect of treatment while impulsive aggression, anxiety and depression were reported at levels similar to those in the street fair survey. These findings suggest that AAS therapy may be more frequently associated with distress than has been reported in the clinical literature.