Background: Robot-assisted pelvic lymph node dissection (rPLND) has been reported in heterogenous groups of patients with melanoma, including macroscopic or at-high-risk-for microscopic metastasis. With changing indications for surgery in melanoma, and availability of effective systemic therapies, pelvic dissection is now performed for clinically detected bulky lymph node metastasis followed by adjuvant drug therapy. rPLND has not been compared with open pelvic lymph node dissection (oPLND) for modern practice.
View Article and Find Full Text PDFJAMA
July 2017
Importance: Less than one-third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant.
Objective: To determine the relative effectiveness and safety of 3 common alternate treatments for MDD.
Design, Setting, And Participants: From December 2012 to May 2015, 1522 patients at 35 US Veterans Health Administration medical centers who were diagnosed with nonpsychotic MDD, unresponsive to at least 1 antidepressant course meeting minimal standards for treatment dose and duration, participated in the study.
Proc Natl Acad Sci U S A
February 2011
The vasculature of the CNS is structurally and functionally distinct from that of other organ systems and is particularly prone to developmental abnormalities and hemorrhage. Although other embryonic tissues undergo primary vascularization, the developing nervous system is unique in that it is secondarily vascularized by sprouting angiogenesis from a surrounding perineural plexus. This sprouting angiogenesis requires the TGF-β and Wnt pathways because ablation of these pathways results in aberrant sprouting and hemorrhage.
View Article and Find Full Text PDFAm J Health Syst Pharm
November 2010
Purpose: The effects of varenicline treatment for smoking cessation on mental health (MH) stability in veterans with posttraumatic stress disorder (PTSD) was studied.
Methods: Data were collected by retrospective chart review at a Veterans Affairs medical center. Patients with PTSD who were prescribed varenicline for smoking cessation between May 2006 and July 2008 were included; all patients had failed previous attempts to quit using nicotine replacement therapy, bupropion, or both.
Background & Aims: Peptide YY (PYY) and pancreatic polypeptide (PPY) are members of the neuropeptide Y peptide family. The neuropeptide Y receptor signaling pathway has been implicated in a number of physiologic processes, including the regulation of energy balance and bone mass. To investigate the contribution of endogenous PYY and PPY to these processes, we generated both Pyy- and Ppy-deficient mice.
View Article and Find Full Text PDFNeuromedin U (NMU) has recently been reported to have a role in nociception and inflammation. To clarify the function of the two known NMU receptors, NMU receptor 1 (NMUR1) and NMU receptor 2 (NMUR2), during nociception and inflammation in vivo, we generated mice in which the genes for each receptor were independently deleted. Compared to wild type littermates, mice deficient in NMUR2 showed a reduced thermal nociceptive response in the hot plate, but not in the tail flick, test.
View Article and Find Full Text PDFEndogenous modulators of the central melanocortin system, such as the agouti-related protein (AgRP), should hold a pivotal position in the regulation of energy intake and expenditure. Despite this, AgRP-deficient mice were recently reported to exhibit normal food intake, body weight gain, and energy expenditure. Here we demonstrate that 2- to 3-month-old Agrp null mice do in fact exhibit subtle changes in response to feeding challenges (fasting and MCR agonists) but, of more significance and magnitude, exhibit reduced body weight and adiposity after 6 months of age.
View Article and Find Full Text PDFAm J Physiol Heart Circ Physiol
February 2006
Unlike during development, blood vessels in the adult are generally thought not to require VEGF for normal function. However, VEGF is a survival factor for many tumor vessels, and there are clues that some normal blood vessels may also depend on VEGF. In this study, we sought to identify which, if any, vascular beds in adult mice depend on VEGF for survival.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2005
We identified a glycoprotein hormone beta-subunit (OGH, also called GPB5) that, as a heterodimer with the alpha-subunit GPA2, serves as a second ligand for the thyroid-stimulating hormone receptor. Mice in which the OGH gene is deleted (OGH-/-) are indistinguishable from WT littermates in body weight, response to high-fat diet, metabolic parameters, body composition, and insulin tolerance. Mice engineered to transgenically globally overexpress OGH (OGH-TG) develop approximately 2-fold elevations in their basal thyroid levels and weigh slightly less than WT littermates despite increased food intake because of an increase in their metabolic rates.
View Article and Find Full Text PDFGhrelin is a recently identified growth hormone (GH) secretogogue whose administration not only induces GH release but also stimulates food intake, increases adiposity, and reduces fat utilization in mice. The effect on food intake appears to be independent of GH release and instead due to direct activation of orexigenic neurons in the arcuate nucleus of the hypothalamus. The effects of ghrelin administration on food intake have led to the suggestion that inhibitors of endogenous ghrelin could be useful in curbing appetite and combating obesity.
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