Effect of Growth Hormone (hGH) Replacement Therapy on Physical Work Capacity and Cardiac and Pulmonary Function in Patients with hGH Deficiency Acquired in Adulthood.

The effects of 6 months of replacement therapy with recombinant human GH (hGH) on physical work capacity and cardiac structure and function were investigated in 20 patients with hGH deficiency of adult onset in a double blind, placebo-controlled trial. The GH dose of 12.5 micrograms/kg BW was self-administered daily sc. Oxygen consumption (VO2), CO2 production, and ventilatory volumes were measured during exercise on a bicycle spiroergometer. M-Mode echocardiography was performed using standard techniques. The VO2 max data, expressed per kg BW (mL/min.kg BW) showed a significant increase from 23.2 +/- 2.4 to 30.0 +/- 2.3 (P < 0.01) in the hGH-treated group, whereas the VO2 max data, expressed per lean body mass (milliliters per min/kg lean body mass) did not change significantly in either group. Maximal O2 pulse (milliliters per beat) increased significantly from 15.2 +/- 5.6 to 19.6 +/- 3.3 mL/beat (P < 0.01), but remained constant in the placebo group. The maximal power output (watts +/- SE) increased significantly (P < 0.01) from 192.5 +/- 13.5 to 227.5 +/- 11.5 in the hGH-treated group, but remained constant in the placebo group. Cardiac structure (left ventricular posterior wall, interventricular septum thickness, left ventricular mass, left ventricular end-systolic dimension, and left ventricular end-diastolic dimension) as well as echocardiographically assessed cardiac function did not change significantly after 6 months of treatment in either group. We conclude that hGH replacement in hGH-deficient adults improves oxygen uptake and exercise capacity. These improvements in pulmonary parameters might be due to an increase in respiratory muscle strength and partly to the changes in muscle volume per se observed during hGH replacement therapy. Furthermore, an increased cardiac output might contribute to the improvement in exercise performance during hGH treatment. According to our data, hGH replacement therapy leads to an improvement of exercise capacity and maximal oxygen uptake, but has no significant effect on cardiac structure

A covalently bound photoisomerizable agonist. Comparison with reversibly bound agonists at electrophorus electroplaques

After disulphide bonds are reduced with dithiothreitol, trans-3-(alpha-bromomethyl)-3’-[alpha-(trimethylammonium)methyl]azobenzene (trans-QBr) alkylates a sulfhydryl group on receptors. The membrane conductance induced by this “tethered agonist” shares many properties with that induced by reversible agonists. Equilibrium conductance increases as the membrane potential is made more negative; the voltage sensitivity resembles that seen with 50 [mu]M carbachol. Voltage- jump relaxations follow an exponential time-course; the rate constants are about twice as large as those seen with 50 mu M carbachol and have the same voltage and temperature sensitivity. With reversible agonists, the rate of channel opening increases with the frequency of agonist-receptor collisions: with tethered trans-Qbr, this rate depends only on intramolecular events. In comparison to the conductance induced by reversible agonists, the QBr-induced conductance is at least 10-fold less sensitive to competitive blockade by tubocurarine and roughly as sensitive to “open-channel blockade” bu QX-222. Light-flash experiments with tethered QBr resemble those with the reversible photoisomerizable agonist, 3,3’,bis-[alpha-(trimethylammonium)methyl]azobenzene (Bis-Q): the conductance is increased by cis {arrow} trans photoisomerizations and decreased by trans {arrow} cis photoisomerizations. As with Bis-Q, ligh-flash relaxations have the same rate constant as voltage-jump relaxations. Receptors with tethered trans isomer. By comparing the agonist-induced conductance with the cis/tans ratio, we conclude that each channel’s activation is determined by the configuration of a single tethered QBr molecule. The QBr-induced conductance shows slow decreases (time constant, several hundred milliseconds), which can be partially reversed by flashes. The similarities suggest that the same rate-limiting step governs the opening and closing of channels for both reversible and tethered agonists. Therefore, this step is probably not the initial encounter between agonist and receptor molecules

SDSS J124602.54+011318.8: A Highly Variable AGN, Not an Orphan GRB Afterglow

The optically variable source SDSS J124602.54+011318.8 first appears in Sloan Digital Sky Survey (SDSS) data as a bright point source with nonstellar colors. Subsequent SDSS imaging and spectroscopy showed that the point source declined or disappeared, revealing an underlying host galaxy at redshift 0.385. Based on these properties, the source was suggested to be a candidate ``orphan afterglow'': a moderately beamed optical transient, associated with a gamma-ray burst (GRB) whose highly beamed radiation cone does not include our line of sight. We present new imaging and spectroscopic observations of this source. When combined with a careful re-analysis of archival optical and radio data, the observations prove that SDSS J124602.54+011318.8 is in fact an unusual radio-loud AGN, probably in the BL Lac class. The object displays strong photometric variability on time scales of weeks to years, including several bright flares, similar to the one initially reported. The SDSS observations are therefore almost certainly not related to a GRB. The optical spectrum of this object dramatically changes in correlation with its optical brightness. At the bright phase, weak, narrow oxygen emission lines and probably a broader H$\alpha$ line are superposed on a blue continuum. As the flux decreases, the spectrum becomes dominated by the host galaxy light, with emerging stellar absorption lines, while both the narrow and broad emission lines have larger equivalent widths. We briefly discuss the implications of this discovery on the study of AGNs and other optically variable or transient phenomena.Comment: 14 pages, 5 figures, AASTEX 5.0.2, slight modifications following referee's report, PASP, in pres

A simple quality improvement program improves cardiovascular preventive care offered by medical housestaff at a large, urban hospital treating a high-risk inpatient population

L'edifici fou construït l'any 1850, aproximadament.Primer pla, contrapicat, d'un edifici d'habitatges entre mitgeres. Consta de planta baixa, cinc plantes pis i coberta terrat. La composició de la façana té un eix de simetria vertical central, que coincideix amb la posició de l'escala de veïns

Challenges and Opportunities to Updating Prescribing Information for Longstanding Oncology Drugs.

A number of important drugs used to treat cancer-many of which serve as the backbone of modern chemotherapy regimens-have outdated prescribing information in their drug labeling. The Food and Drug Administration is undertaking a pilot project to develop a process and criteria for updating prescribing information for longstanding oncology drugs, based on the breadth of knowledge the cancer community has accumulated with the use of these drugs over time. This article highlights a number of considerations for labeling updates, including selecting priorities for updating; data sources and evidentiary criteria; as well as the risks, challenges, and opportunities for iterative review to ensure prescribing information for oncology drugs remains relevant to current clinical practice