Mechanistic Studies on the Base-Promoted Ring Opening of Glycal-Derived -Dibromocyclopropanes.

In the presence of a nucleophilic base, ring-fused -dibromocyclopropanes derived from d-glycals undergo ring opening to give 2-deoxy-2-(-bromomethylene)glycosides. Such cleavage of an exocyclic cyclopropane bond contrasts with the more usual silver-promoted ring-expansion reactions in which endocyclic bond cleavage occurs. Experimental and theoretical studies are reported which provide insights into the reaction mechanism and the origin of its kinetic selectivity for -configured bromoalkene products.

The use and misuse of the Dix-Hallpike test in the emergency department.

Objectives: A simple bedside test, the Dix-Hallpike test (DHT), can reliably diagnose benign paroxysmal positional vertigo (BPPV) in patients with acute onset dizziness or vertigo. We evaluated patterns of DHT use by emergency physicians in patients presenting with dizziness and vertigo. Our objective was to assess the frequency and clinically appropriate use of the DHT in an emergency department.

Diagnostic Accuracy of the HINTS Exam in an Emergency Department: A Retrospective Chart Review.

Introduction: The HINTS exam is a series of bedside ocular motor tests designed to distinguish between central and peripheral causes of dizziness in patients with continuous dizziness, nystagmus, and gait unsteadiness. Previous studies, where the HINTS exam was performed by trained specialists, have shown excellent diagnostic accuracy. Our objective was to assess the diagnostic accuracy of the HINTS exam as performed by emergency physicians on patients presenting to the emergency department (ED) with a primary complaint of vertigo or dizziness.

Catalytic Asymmetric Staudinger-aza-Wittig Reaction for the Synthesis of Heterocyclic Amines.

Many natural products and medicinal drugs are heterocyclic amines possessing a chiral quaternary carbon atom in their heterocyclic ring. Herein, we report the first catalytic and asymmetric Staudinger-aza-Wittig reaction for the desymmetrization of ketones. This highly enantioselective transformation proceeds at room temperature to provide high yields-even on multigram scales-of nitrogen heterocycles featuring a chiral quaternary center.

Asymmetric synthesis of multiple quaternary stereocentre-containing cyclopentyls by oxazolidinone-promoted Nazarov cyclizations.

Carbometalation of oxazolidinone ()-substituted ynamides is used to generate highly substituted -divinyl (and aryl vinyl) ketones for use in Nazarov cyclizations. The -group serves as a remarkably effective chiral activating group, enabling the torquoselective Nazarov cyclization of these sterically congested substrates to be performed under mild conditions. It also serves as a charge-stabilizing group in the intermediate oxyallyl cation, suppressing undesired [1,2]-sigmatropic shifts of neighboring substituents and facilitating the regio- and stereoselective incorporation of nucleophiles to yield cyclopentanoids containing up to three contiguous all-carbon quaternary (4°) stereocentres.

Synthesis of spirocyclic orthoesters by 'anomalous' rhodium(ii)-catalysed intramolecular C-H insertions.

A tetrahydropyranyl acetal bearing a proximal phenyl diazoketone substituent underwent Rh(ii)-catalysed C-H insertion via an 'anomalous' C-O bond-forming, rather than C-C bond-forming, transformation, giving spirocyclic orthoesters. Density functional theory calculations with M06 show that the formation of these anomalous products involves hydride transfer to the rhodium carbene, giving an intermediate zwitterion which undergoes C-O bond formation in preference to C-C bond formation.

Associations Between Neural Reward Processing and Binge Eating Among Adolescent Girls.

Purpose: Neuroimaging studies suggest that altered brain responses to food-related cues in reward-sensitive regions characterize individuals who experience binge-eating episodes. However, the absence of longitudinal data limits the understanding of whether reward-system alterations increase vulnerability to binge eating, as theorized in models of the development of this behavior.

Methods: Adolescent girls (N = 122) completed a functional magnetic resonance imaging monetary reward task at age 16 years as part of an ongoing longitudinal study.

Multistereocenter-Containing Cyclopentanoids from Ynamides via Oxazolidinone-Controlled Nazarov Cyclization.

Achieving ready-enantioselective access to multistereocenter-containing cyclopentyl rings is an area of great significance to organic synthesis. In this work, we describe a general protocol for accessing multistereocenter-containing cyclopentanoids from simple N-alkynyloxazolidinones (Ox-ynamides). This protocol involves conversion of Ox-ynamides into Ox-activated divinyl and aryl vinyl ketones that undergo facile Nazarov cyclization with excellent chemo-, regio-, and stereocontrol.

Abnormality of standing posture improves in patients with bilateral spastic cerebral palsy following lower limb surgery.

Objectives: The degree of abnormality of the gait pattern of children with bilateral spastic cerebral palsy (BSCP) can be reduced by lower limb orthopaedic surgery. However, little attention is paid to the effects of surgery on standing posture. Here, we investigated the abnormality of standing posture in young people with BSCP as well as the effects of surgery on standing posture.

A bidirectional synthesis of spiroacetals via Rh(ii)-catalysed C-H insertion.

Acyclic methylene acetals bearing two diazoester subunits have been converted to [5,5]-spiroacetals via bidirectional C-H insertion under Rh(ii) catalysis. Using a chiral Rh(ii) catalyst, the major diastereomer can be produced in high enantiomeric excess (89%).

Probing function and structure of trehalose-6-phosphate phosphatases from pathogenic organisms suggests distinct molecular groupings.

The trehalose biosynthetic pathway is of great interest for the development of novel therapeutics because trehalose is an essential disaccharide in many pathogens but is neither required nor synthesized in mammalian hosts. As such, trehalose-6-phosphate phosphatase (TPP), a key enzyme in trehalose biosynthesis, is likely an attractive target for novel chemotherapeutics. Based on a survey of genomes from a panel of parasitic nematodes and bacterial organisms and by way of a structure-based amino acid sequence alignment, we derive the topological structure of monoenzyme TPPs and classify them into 3 groups.

A Case Study: Proton Therapy for Male Breast Cancer with Previous Irradiation.

This is a case report of a male patient with previous radiation for a thymic carcinoma (20 years ago) who presented with a left breast cancer. He underwent a partial mastectomy followed by proton radiation therapy with a dose of 5040 cGy to the whole breast in 28 fractions with simultaneous boost to 5800 cGy to the lumpectomy cavity. Proton beam therapy was used instead of conventional photon radiation therapy to spare the heart and lung and to avoid any previously irradiated areas.

Mechanisms of renal phosphate loss in liver resection-associated hypophosphatemia.

Objective: To determine precisely the role of parathyroid hormone (PTH) and of phosphatonins in the genesis of posthepatectomy hypophosphatemia.

Background: Posthepatectomy hypophosphatemia has recently been related to increased renal fractional excretion of phosphate (FE P). To address the cause of hypophosphatemia, we measured serum concentrations of PTH, various phosphatonins, and the number of removed hepatic segment in patients with this disorder.

Bone turnover markers in the management of postmenopausal osteoporosis.

Osteoporosis is the most common cause of fragility fractures. Bone remodelling is essential for repairing damaged areas within bone to preserve bone strength and for assisting in mineral homeostases. In young adults, bone remodelling is usually balanced with approximately as much bone replaced as is removed during each remodelling cycle.

Functional testosterone: biochemical assessment of hypogonadism in men--report from a multidisciplinary workshop hosted by the Ontario Society of Clinical Chemists.

Objectives: In 2004, the Ontario Society of Clinical Chemists (OSCC) held an invitational multidisciplinary workshop to establish the most reliable, cost-effective approach to the biochemical assessment of hypogonadism in men.

Methods: Specialists across Canada in clinical biochemistry, endocrinology, family medicine and urology were invited to participate in this workshop which included individual presentations and a consensus component addressing two challenge statements: 1) 'Determinations for total testosterone (TT) are equivalent to those for bioavailable testosterone (BAT) or calculated BAT (cBAT) or free testosterone (FT) (by analogue radioimmunoassay or equilibrium dialysis) or calculated FT (cFT)'; 2) 'There is no good evidence that borderline low testosterone concentrations in men should be treated'. The main outcomes were to identify what agreement exists in Canada, what issues were still controversial, and what research remains to be addressed.

Fifty years of development in the endocrinology laboratory.

The hormone assay laboratory has seen incredible changes over the last 50 years. In this historical review, we describe how the evolution of fundamental concepts in endocrinology and in hormone assay technology have faceted the laboratory as we know it today. The discovery of neurohormones, hormone receptors and the evolution of the concept of free hormones had a very significant impact on our understanding of the mechanisms of hormone action in health and disease and therefore on how physicians currently prescribe endocrine tests.

The first preclinical pharmacotoxicological safety assessment of CGS 35601, a triple vasopeptidase inhibitor, in chronically instrumented, conscious, and unrestrained spontaneously hypertensive rats.

CGS 35601 is a triple vasopeptidase inhibitor (VPI) of angiotensin-converting enzyme, neutral endopeptidase, and endothelin-converting enzyme-1 with respective IC50 values of 22, 2, and 55 nM. We characterized the safety profile and toxicity of escalating doses of CGS 35601 over a 20-day period in chronically instrumented, unrestrained, conscious, male, spontaneously hypertensive rats (SHR). Once instrumented with an arterial catheter, the SHR were placed in metabolic cages allowing daily assessment of hemodynamics and blood sampling for biochemical and hematological measurements.

Measurement of testosterone and its sub-fractions in Canada.

Interest in measuring bioactive testosterone in aging males has increased considerably in the last 5 years in Canada. Emerging andropause clinics have submerged our laboratories with requests for bioavailable testosterone (BAT) testing in replacement or addition to the traditional total testosterone (TT) and direct free testosterone (FT) assays. Beginning with a brief explanation of the bioavailability concept of Pardridge, this review examines the technical characteristics of various approaches currently available to measure TT and its sub-fractions.

When is bioavailable testosterone a redundant test in the diagnosis of hypogonadism in men?

Objectives: Total testosterone (TT) is frequently prescribed with an SHBG and/or free or bioavailable testosterone measurement. Our objective was to identify a TT range for which subsequent SHBG measurement/calculation adds no additional clinical information.

Design And Methods: Study data were composed of 3955 sets of TT, SHBG and calculated bioavailable testosterone (cBAT) results from unscreened ambulatory male subjects, aged 18-99.

Profile of endothelin isopeptides and markers of oxidative stress alongside the onset of streptozotocin-type I diabetes in rats.

Type I diabetes is associated with vascular endothelial abnormalities. Vasoactive mediators such as endothelins and reactive oxygen species are modulated in diabetic patients. We studied the hemodynamic profile and the release of mediators alongside the onset of streptozotocin-induced type I diabetes in rats.

Origin of parathyroid hormone (PTH) fragments detected by intact-PTH assays.

Background: Intact parathyroid hormone (I-PTH) assays react with non-(1-84)PTH, large carboxyl-terminal (C) fragments with a partially preserved amino-terminal (N) structure. They account for up to 50% of I-PTH in renal failure and may be implicated in PTH resistance. We wanted to know if they were secreted by the parathyroid glands and generated by peripheral metabolism of PTH(1-84).

Automatic P-wave analysis of patients prone to atrial fibrillation.

A method is presented for automatic analysis of the P-wave, based on lead II of a 12-lead standard ECG, in resting conditions during a routine examination for the detection of patients prone to atrial fibrillation (AF), one of the most prevalent arrhythmias. First, the P-wave was delineated, and this was achieved in two steps: the detection of the QRS complexes for ECG segmentation, using a wavelet analysis method, and a hidden Markov model to represent one beat of the signal for P-wave isolation. Then, a set of parameters to detect patients prone to AF was calculated from the P-wave.