Evaluation of the structures of agreement and disagreement in reliability studies

AIMS: To investigate, in healthy volunteers, the relationships between the plasma concentrations (C, ng ml(-1)) of zabiciprilat, the active metabolite of the angiotensin I-converting enzyme inhibitor (ACEI) zabicipril, and the effects (E) induced on plasma converting enzyme activity (PCEA, nmol ml(-1) min(-1)), brachial and femoral artery flows (BAF, FAF, ml min(-1)), and brachial and femoral vascular resistances (BVR, FVR, mmHg x s ml(-1)) after a single oral administration of two doses (0.5 and 2.5 mg) of zabicipril. METHODS: The study was placebo-controlled, randomized, double-blind and crossover. E was related to C by the Hill model, E = Emax x Cgamma/(CE50gamma + Cgamma), fitted to the data of both doses simultaneously. RESULTS: We obtained (mean +/- s.d.) Emax = -99 +/- 1%, CE50 = 2.2 +/- 1.0 ng ml(-1) and gamma = 1.0 +/- 0.4 for PCEA, Emax = 55 +/- 26 ml min(-1), CE50 = 5.1 +/- 4.0 ng ml(-1) and gamma = 2.4 +/- 1.6 for BAF, and Emax = -45 +/- 10%, CE50 = 2.0 +/- 1.3 ng ml(-1) and gamma = 2.3 +/- 1.4 for BVR. The parameters obtained for FAF and FVR were similar to those obtained for BAF and BVR, respectively. The CE95 (C required to induce 95% of Emax) varies from 7 to 17 ng ml(-1) for haemodynamic effects. CONCLUSIONS: As zabiciprilat peak plasma concentrations average 20 ng ml(-1) after the 2.5 mg dose of zabicipril, this dose of the drug should be sufficient to induce optimal haemodynamic effects.     

Genetic risk of neuropsychological impairment in schizophrenia: a study of monozygotic twins discordant and concordant for the disorder

We investigated the effect of the adenosine receptor agonist 5'-(N-ethylcarboxamido)adenosine (NECA) in catecholamine secretion from adrenal chromaffin cells that exhibit only the A2b subtype adenosine receptor. NECA reduced catecholamine release evoked by the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP) in a time-dependent manner. Inhibition reached 25% after 30-40-min exposure to NECA. This effect on DMPP-evoked catecholamine secretion was mirrored by a similar (27.7 +/- 3.3%), slowly developing inhibition of [Ca2+]i transients induced by DMPP that peaked at 30-min preincubation with NECA. The capacity of the chromaffin cells to buffer Ca2+ load was not affected by the treatment with NECA. Short-term treatment with NECA failed both to modify [Ca2+]i levels and to increase endogenous diacylglycerol production, showing that NECA does not activate the intracellular Ca2+/protein kinase C signaling pathway. The inhibitory effects of NECA were accompanied by a 30% increase of protein phosphatase activity in chromaffin cell cytosol. We suggest that dephosphorylation of a protein involved in DMPP-evoked Ca2+ influx pathway (e.g., L-type Ca2+ channels) could be the mechanism of the inhibitory action of adenosine receptor stimulation on catecholamine secretion from adrenal chromaffin cells.     

Significance of hemoptysis following thrombolytic therapy for acute myocardial infarction

PURPOSE: To describe the occurrence, cause, and significance of hemoptysis following thrombolytic therapy for acute myocardial infarction. PATIENTS AND METHODS: We retrospectively reviewed 2,634 patients presenting with acute myocardial infarction who received thrombolytic therapy to determine the incidence of hemoptysis. Chart and radiographic review included the type, dose, and route of thrombolytic therapy. In addition, the onset, duration, and severity of hemoptysis were recorded and correlated with radiographic and bronchoscopic findings. RESULTS: Eleven patients (0.4%) developed hemoptysis following administration of thrombolytic therapy for an acute myocardial infarction. The duration and severity had a wide range, although no patient had significant hemodynamic compromise. The source of hemoptysis was identified in only one patient who had a tongue laceration following cardiopulmonary resuscitation, and blood was seen within the oropharynx and trachea. No definitive cause was identified in all other patients. There was no correlation between the different types or doses of thrombolytic therapy and the duration or severity of hemoptysis. Chest radiographs were nonspecific and demonstrated resolution within 11 days following hemoptysis. CT of the thorax in one patient and bronchoscopy in two patients confirmed chest radiographic findings and in no patient was an underlying pulmonary abnormality identified. CONCLUSIONS: Pulmonary hemorrhage and hemoptysis are unusual complications of thrombolytic therapy in patients with acute myocardial infarction. Although hemoptysis may be the first indicator of an underlying pulmonary abnormality, we found no case in which a significant abnormality was unmasked. This study suggests that follow-up chest radiographs are recommended and further evaluation may be unnecessary if complete resolution is demonstrated.     

Osteonecrosis of the knee following arthroscopic laser meniscectomy

An unusual case of osteonecrosis of the knee following an arthroscopic laser meniscectomy is presented. The unusual presentation of the osteonecrosis and the chronology suggest that the osteonecrosis of the knee resulted from damage to the articular cartilage and subchondral bone at the time of the arthroscopic laser meniscectomy.     

Anandamide- and delta9-tetrahydrocannabinol-evoked arachidonic acid mobilization and blockade by SR141716A [N-(Piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4 -methyl-1H-pyrazole-3-carboximide hydrochloride]

The purpose of this study was to investigate whether anandamide induces cannabimimetic responses, mainly mobilization of arachidonic acid, in primary cultures of rat brain cortical astrocytes. Confluent monolayer cultures of astrocytes, prelabeled with [3H]arachidonic acid, were incubated with anandamide or delta9-tetrahydrocannabinol (delta9-THC) in the presence or absence of thimerosal, a fatty acid acyl CoA transferase inhibitor and phenylmethylsulfonyl fluoride, an amidohydrolase inhibitor. Anandamide and delta9-THC induced a time- and concentration-dependent release of arachidonic acid in the presence, but not in the absence, of thimerosal. Anandamide- and delta9-THC-stimulated arachidonic acid release was pertussis toxin-sensitive, indicating a receptor/G-protein involvement. A novel and selective cannabinoid receptor antagonist, SR141716A [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazole-3-carboximide hydrochloride], blocked the arachidonic acid release, suggesting a cannabinoid receptor-mediated pathway. In astrocytes, the magnitude of anandamide-induced arachidonic acid release was equal to that released by equimolar concentrations of delta9-THC. Furthermore, direct assay of amidohydrolase activity indicated that degradation of anandamide into arachidonic acid and ethanolamine was negligible in cortical astrocytes. Our results suggest that anandamide stimulates receptor-mediated release of arachidonic acid, and the receptor may be the cannabinoid receptor. Astrocytes, containing a cannabinoid receptor and lower or negligible amidohydrolase activity, may be an important brain cell model in which to study the cannabimimetic effects of anandamide at a cellular and molecular level.     

American College of Sports Medicine position stand. Exercise and fluid replacement

It is the position of the American College of Sports Medicine that adequate fluid replacement helps maintain hydration and, therefore, promotes the health, safety, and optimal physical performance of individuals participating in regular physical activity. This position statement is based on a comprehensive review and interpretation of scientific literature concerning the influence of fluid replacement on exercise performance and the risk of thermal injury associated with dehydration and hyperthermia. Based on available evidence, the American College of Sports Medicine makes the following general recommendations on the amount and composition of fluid that should be ingested in preparation for, during, and after exercise or athletic competition: 1) It is recommended that individuals consume a nutritionally balanced diet and drink adequate fluids during the 24-hr period before an event, especially during the period that includes the meal prior to exercise, to promote proper hydration before exercise or competition. 2) It is recommended that individuals drink about 500 ml (about 17 ounces) of fluid about 2 h before exercise to promote adequate hydration and allow time for excretion of excess ingested water. 3) During exercise, athletes should start drinking early and at regular intervals in an attempt to consume fluids at a rate sufficient to replace all the water lost through sweating (i.e., body weight loss), or consume the maximal amount that can be tolerated. 4) It is recommended that ingested fluids be cooler than ambient temperature [between 15 degrees and 22 degrees C (59 degrees and 72 degrees F])] and flavored to enhance palatability and promote fluid replacement. Fluids should be readily available and served in containers that allow adequate volumes to be ingested with ease and with minimal interruption of exercise. 5) Addition of proper amounts of carbohydrates and/or electrolytes to a fluid replacement solution is recommended for exercise events of duration greater than 1 h since it does not significantly impair water delivery to the body and may enhance performance. During exercise lasting less than 1 h, there is little evidence of physiological or physical performance differences between consuming a carbohydrate-electrolyte drink and plain water. 6) During intense exercise lasting longer than 1 h, it is recommended that carbohydrates be ingested at a rate of 30-60 g.h(-1) to maintain oxidation of carbohydrates and delay fatigue. This rate of carbohydrate intake can be achieved without compromising fluid delivery by drinking 600-1200 ml.h(-1) of solutions containing 4%-8% carbohydrates (g.100 ml(-1)). The carbohydrates can be sugars (glucose or sucrose) or starch (e.g., maltodextrin). 7) Inclusion of sodium (0.5-0.7 g.1(-1) of water) in the rehydration solution ingested during exercise lasting longer than 1 h is recommended since it may be advantageous in enhancing palatability, promoting fluid retention, and possibly preventing hyponatremia in certain individuals who drink excessive quantities of fluid. There is little physiological basis for the presence of sodium in n oral rehydration solution for enhancing intestinal water absorption as long as sodium is sufficiently available from the previous meal.     

Reaction and total cross sections for low energy pi + and pi - on isospin zero nuclei

We calculated the electrostatic force between a planar interface, such as a planar-supported lipid bilayer membrane, and the tip of a stylus on which another lipid bilayer or some other biomacromolecular system might be deposited. We considered styli with rounded tips as well as conical tips. To take into account the effect of dynamical hydrogen-bonded structures in the aqueous phase, we used a theory of nonlocal electrostatics. We used the Derjaguin approximation and identified the systems for which its use is valid. We pointed out where our approach differs from previous calculations and to what extent the latter are inadequate. We found that 1) the nonlocal interactions have significant effects over distances of 10-15 A from the polar zone and that, at the surface of this zone, the effect on the calculated force can be some orders of magnitude; 2) the lipid dipoles and charges are located a distance L from the hydrophobic layer in the aqueous medium and this can have consequences that may not be appreciated if it is ignored; 3) dipoles, located in the aqueous region, can give rise to forces even though the polar layer is unchanged, and if this is ignored the interpretation of force data can be erroneous if an attempt is made to rationalize an observed force with a knowledge of an uncharged surface; 4) the shape of the stylus tip can be very important, and a failure to take this into account can result in incorrect conclusions, a point made by other workers; and 5) when L is nonzero, the presence of charges and dipoles can yield a force that can be nonmonotonic as a function of ionic concentration.     

Ozonation of unstretched natural rubber film from Hevea brasiliensis studied by ozone consumption and 13C NMR

Unstretched films of natural rubber (NR) from Hevea brasiliensis were exposed to ozone flow of 15 ml min^?1 from 4 to 300 min. The efficiency of reaction was determined by ozone consumption of NR films. Plots of reacted ozone mass versus film thickness show that the ozone penetration and the ozone reaction progressed into deeper layers (170 µm) than described in the literature (～0.5 µm). The previous proposed model based on viscometry measurements was corroborated by ozone consumption results. The effect of thickness on the O₃/NR stoichiometric ratio indicated that the diffusion process that controls the ozonation in unstretched film does not consist of the boundary progression behind which all reactive sites have been saturated. Ozonation in unstretched rubber film, while being less efficient than ozonolysis in solution, does have a reaction efficiency of the same order of magnitude. NMR spectroscopy was used to characterise the products formed by ozonation. Copyright © 2004 Society of Chemical Industry