Computer-aided mapping of the beta-adrenoceptor. 1. Explanation for effect of para substitution on blocking activity at the beta-1-adrenoceptor.

Anomalously low affinities for the beta-1-adrenoceptor are seen for members of a series of para-substituted N-isopropylphenoxypropanolamines in which the substituent is able to conjugate with the aromatic ring. The energy of conjugation was calculated using the AM1 semiempirical molecular orbital method and appears to correlate with the loss of binding energy, and hence affinity for the receptor. This suggests that binding is associated with movement of the substituent out of the plane of the aromatic ring due to steric interference with the receptor. A previously unrecognized binding site for aromatic groups off the para position is also identified.     

LK 204-545, a highly selective beta1-adrenoceptor antagonist at human beta-adrenoceptors

LK 204-545 ((+/-)-1-(2-(3-(2-cyano-4-(2-cyclopropyl-methoxy-ethoxy)phenoxy)-2-hydro xy-propyl-amino)-ethyl)-3-(4-hydrxy-phenyl) urea), an antagonist that possesses high beta1-/beta2-selectivity in the rat, and a range of cardio-selective and non-selective beta-adrenoceptor antagonists were examined to compare their radioligand binding affinities for human beta1-, beta2- and beta3-adrenoceptors transfected into CHO cells. LK 204-545 and CGP 20712A displayed the highest beta1-/beta2- (approximately 1800 and approximately 650, respectively) and beta1-/beta3-selectivity (approximately 17000 and approximately 2200, respectively) at human beta-adrenoceptors with LK 204-545 being approximately 2.75-fold more beta1-/beta2-selective and approximately 8-fold beta1-/beta3-selective than CGP 20712A. The high potency of LK 204-545 at transfected human beta1-adrenoceptors and in functional models of rat beta1-adrenoceptors together with its high selectivity, identify it as a useful ligand for studying beta1-adrenoceptors and suggest that it may be the preferred ligand for human beta-adrenoceptor studies.     

Provision of healthcare in the context of financial crisis: approaches to the Greek health system and international implications

Both healthcare professionals and the healthcare system must defend each patient's health individually while simultaneously seeking to protect the population's health in general. Nowadays, there is an important increase in the cost of healthcare supply, mainly due to the developments of medical science, the public's expectations and the demographic ageing. Since healthcare resources are not unlimited, it is obvious that immoderate consumption of them by certain patients limits the use of the same funds by others. Therefore, we have to seek an optimal distribution of the existing resources in order to manage a constriction of expenses, especially under the circumstances of the modern economic crisis. The criteria of effectiveness and efficiency should be used. Health policies focus on both the public's behaviour and the rules of medical practice. Under the modern challenges the physician's role is particularly important for the protection of the patient's health and the promotion of public health.     

Nasogastric aspiration/lavage in patients with gastrointestinal bleeding: a review of the evidence

Introduction: The usefulness of nasogastric aspiration and nasogastric lavage in patients with gastrointestinal bleeding is controversial, as evidenced by conflicting recommendations, both among and within society guidelines.

Areas covered: Considering these controversies, we reviewed the evidence regarding the following questions: 1) Can nasogastric lavage stop or slow down the bleeding and improve subsequent endoscopic visualization? 2) Is nasogastric aspiration helpful for the localization of bleeding? 3) Can nasogastric aspiration identify high risk patients that might benefit from earlier endoscopy? 4) Is there evidence for benefit in terms of outcomes from using nasogastric aspiration? 5) Is nasogastric intubation safe in patients with possible esophageal varices? Our review was conducted according to PRISMA guidelines.

Expert commentary: Based on the available literature, nasogastric lavage or aspiration cannot be routinely recommended unless a large properly designed randomized trial (which is currently lacking) proves otherwise. It is a painful and time-consuming procedure with no demonstrated benefit for the patient in terms of outcomes. Other clinical and laboratory parameters, and risk scores, are less invasive and are effective for guiding the stratification and management of patients, while pre-endoscopic erythromycin infusion is a good if not better alternative for improving visualization of the stomach.     

Administration of low-molecular-weight heparin in patients with two or more unsuccessful IVF/ICSI cycles: a multicenter cohort study

To compare the effects of the administration of low-molecular-weight heparin (LMWH) in subfertile patients with two or more unsuccessful IVF/ICSI cycles. In this six-center two-arm retrospective cohort study, the study population (230 women) underwent a GnRH-antagonist protocol and was classified into two groups, according to the couse of LMWH or not. Groups were compared regarding the clinical and IVF/ICSI cycle characteristics and reproductive outcomes, whereas clinical pregnancy and miscarriage constituted the primary endpoints. Logistic regression analysis was performed to determine the potential predictors of clinical pregnancy, miscarriage and live birth rates using the Enter method. Baseline characteristics were comparable in the two groups. There was no statistically significant difference between the two study groups with regard neither to clinical pregnancy and miscarriage rates (33/133 vs. 20/97, p?=?.456 and 15/133 vs. 9/97, p?=?.624, respectively), nor to the secondary outcomes preset for this study (all p values?>.05). Logistic regression revealed that age of the woman and ICSI and dose of gonadotrophins used were predictors of clinical pregnancy and live birth, respectively. In conclusion, there is no evidence to support the standard addition of LMWH in patients with two or more unsuccessful IVF/ICSI cycles.     

Eleven Patients With Testicular Leydig Cell Tumors

We present the sonographic and magnetic resonance imaging findings of Leydig cell tumors in a series of patients, along with a brief review of the literature. We evaluated the sonographic features of 11 cases of Leydig cell tumors, including echogenicity, size, margins, and patterns of vascularity. The magnetic resonance imaging characteristics of 9 patients were also assessed, with special attention to the appearance of the tumors on T2-weighted imaging and postcontrast T1-weighted imaging. Seven tumors were hypoechoic, and 4 were almost isoechoic. Ten patients showed various patterns of hypervascularity in the tumors, combined in some cases with feeding vessels. One case presented with a single feeding vessel. The tumors showed homogeneous or heterogeneous low signal intensity on T2-weighted imaging and marked enhancement on postcontrast T1-weighted imaging. The small size of these tumors, the various patterns of vascularity on color and power Doppler sonography, and the marked enhancement on postcontrast T1-weighted imaging are considered valuable but generally nonspecific for identification of these tumors.