Evidence that the TRH-like peptide pyroglutamyl-glutamyl-prolineamide in human serum may not be secreted by the pituitary gland

A prospective, randomized, placebo-controlled, double-blind, parallel-group, 6-month study assessed the efficacy and safety of ropinirole, a nonergoline D2-dopamine agonist, in patients with early Parkinson's disease (n = 241; Hoehn & Yahr stages I to III) with limited or no prior dopaminergic therapy. Patients (mean age, 62.8 years), stratified by concomitant use of selegiline, were randomized to ropinirole (n = 116) or placebo (n = 125). The starting dose of ropinirole was 0.25 mg tid with titration to at least 1.5 mg tid (maximum dose, 8 mg tid). Primary efficacy endpoint was the percentage improvement in Unified Parkinson's Disease Rating Scale (UPDRS) motor score. Ropinirole-treated patients had a significantly greater percentage improvement in UPDRS motor score than patients who received placebo (+24% vs -3%; p < 0.001). Ropinirole was well tolerated and patient withdrawals were infrequent. Most adverse experiences were related to peripheral dopaminergic activity. Ropinirole monotherapy is an effective and well-tolerated therapeutic option for treatment of early Parkinson's disease.     

Necrotizing enterocolitis in horses: a retrospective study

OBJECTIVE: To evaluate awareness and knowledge of cigarette filter ventilation in a national probability sample of smokers of Ultra-light, Light, and regular cigarettes. DESIGN: Random-digit-dialling and computer-assisted telephone interviewing was used on a probability sample of daily cigarette smokers (ages 18 and above). SUBJECTS AND SETTING: 218 Smokers of Ultra-light cigarettes, 360 smokers of Light cigarettes, and 210 smokers of Regular cigarettes living in the continental United States. MAIN OUTCOME MEASURES: Percentage of respondents indicating knowledge of the presence of filter vents and the consequences of behavioural blocking of vents. RESULTS: Many smokers had not heard about or seen the filter holes: 43% (95% CI = 36 to 50%) of smokers of Ultra-lights, 39% (95% CI = 34 to 44%) of smokers of Lights, and 47% (95% CI = 40 to 54%) of smokers of Regulars. About two in three smokers either did not know of the existence of rings of small holes on the filters of some cigarettes, or did not know that blocking increases tar yields: 69% (95% CI = 63 to 75%) of Ultra-lights, 66% (95% CI = 61 to 71%) of Lights, and 69% (95% CI = 63 to 75%) of Regulars. CONCLUSIONS: Smokers are generally unaware of the presence and function of filter vents-a major design feature subject to behavioural blocking by smokers and now present on most cigarettes in the United States. Smokers and policy-makers need to be informed about the presence of filter vents and how vent blocking increases tar and nicotine yields from ostensibly very low-yield cigarettes.     

Transformational leadership, initiating structure, and substitutes for leadership: A longitudinal study of research and development project team performance.

Transformational leadership, initiating structure, and selected substitutes for leadership were studied as longitudinal predictors of performance in 118 research and development (R&D) project teams from 5 firms. As hypothesized, transformational leadership predicted 1-year-later technical quality, schedule performance, and cost performance and 5-year-later profitability and speed to market. Initiating structure predicted all the performance measures. The substitutes of subordinate ability and an intrinsically satisfying task each predicted technical quality and profitability, and ability predicted speed to market. Moderator effects for type of R&D work were hypothesized and found whereby transformational leadership was a stronger predictor of technical quality in research projects, whereas initiating structure was a stronger predictor of technical quality in development projects. Implications for leadership theory and research are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Obstructive sleep apnea in Schwartz-Jampel syndrome

Schwartz-Jampel syndrome (SJS) is a rare entity characterized by myotonia and skeletal abnormalities. Death and respiratory distress have previously been reported in newborns and young children with SJS. We describe a patient with SJS and snoring in whom polysomnography demonstrated obstructive sleep apnea and hypoxia. Although tonsillectomy with laser palatoplasty significantly widened the oropharyngeal introitus, obstructive sleep apnea persisted. Ultimate improvement occurred only after the institution of home therapy with bi-level positive airway pressure during the night. We also discuss the specific structural and neuromuscular features of SJS that may be responsible for upper airway obstruction.     

High affinity recognition of serotonin transporter antagonists defined by species-scanning mutagenesis. An aromatic residue in transmembrane domain I dictates species-selective recognition of citalopram and mazindol

Human and Drosophila melanogaster serotonin (5-HT) transporters (SERTs) exhibit similar 5-HT transport kinetics and can be distinguished pharmacologically by many, but not all, biogenic amine transporter antagonists. By using human and Drosophila SERT chimeras, major determinants of potencies of two transporter antagonists, mazindol and citalopram, were tracked to the amino-terminal domains encompassing transmembrane domains I and II. Species-scanning mutagenesis, whereby amino acid substitutions are made switching residues from one species to another, was employed on the eight amino acids that differ between human and Drosophila SERTs in this region, and antagonist potencies were reassessed in 5-HT uptake assays. A single mutation in transmembrane domain I of human SERT, Y95F, shifted both citalopram and mazindol to Drosophila SERT-like potencies. Strikingly, these potency changes were in opposite directions suggesting Tyr95 contributes both positive and negative determinants of antagonist potency. To gain insight into how the Y95F mutant might influence mazindol potency, we determined how structural variants of mazindol responded to the mutation. Our studies demonstrate the importance of the hydroxyl group on the heterocyclic nucleus of mazindol for maintaining species-selective recognition of mazindol and suggest that transmembrane domain I participates in the formation of antagonist-binding sites for amine transporters.     

Donor work-up and transport of bone marrow--recommendations and requirements for a standardized practice throughout the world from the Donor Registries and Quality Assurance Working Groups of the World Marrow Donor Association (WMDA)

In October 1995 the World Marrow Donor Association (WMDA) was restructured in order to facilitate its primary function of establishing guidelines in relation to international bone marrow and blood stem cell transplants -- transplants in which the donor is in one country and the patient is in another country. Five new working groups were established -- Donor Registries, Ethics, Quality Assurance, Finances, and Stem Cells. This paper, prepared by members of the Donor Registries Working Group, in consultation with the Quality Assurance Working Group, provides recommendations for the 'donor work-up'. This term covers events that start when the definitive donor has been identified, includes the harvesting (collection) and transportation of the stem cell product and ends when the product reaches the transplant centre. The paper includes examples of the documentation intended to ensure compliance with the recommendations at all key points in the sequence.     

The sympathetic nerves of the parasellar region: pathways to the orbit and the brain

Sympathetic nerves innervate targets in the orbit and the brain. They issue from the superior cervical ganglion and reach the parasellar region via the internal carotid nerve. Information on their further parasellar course and distribution is scant and contradictory. In this study the parasellar sympathetic pathways of 30 human infants and 6 human fetuses were investigated by microdissection and histologically. A common parasellar sympathetic trunk, which reunites all the nerve fibers emanating from the lateral and medial internal carotid plexus, is described as well as its further divisions. It was found that the posterior knee of the infant carotid siphon is free of large sympathetic nerve bundles. In addition a ganglion is described, which is situated in the parasellar adipose body. It is reached by nerve fibers coming from the parasellar sympathetic pathways. Fibers that issue from this ganglion join the periorbita and the orbital muscle of Müller. These anatomical facts are of immediate importance for preventing nerve damage during cavernous sinus surgery. Furthermore, the study improves the anatomical knowledge of the parasellar region and suggests a new concept for the innervation of the orbital muscle.     

Role of nitric oxide in tubuloglomerular feedback: effects of dietary salt

1. The tubuloglomerular feedback (TGF) response operates primarily by vasoconstriction of the afferent arteriole and a fall in glomerular capillary pressure (PGC) and single-nephron glomerular filtration rate (SNGFR) during increased NaCl reabsorption in the macula densa (MD). Numerous studies have suggested that nitric oxide (NO) is synthesized by the MD and acts to suppress TGF. As a high-salt (HS) diet has been found to blunt TGF, we tested the effects of salt intake on NO-dependent changes in TGF. 2. In the first series of experiments, values of SNGFR were contrasted from samples of tubular fluid taken from the proximal tubule (PT; MD delivery interrupted) and the distal tubule DT; MD delivery intact). Compared with HS rats, the difference between PT and DT values of SNGFR was increased in low-salt (LS) diet rats (4.3 +/- 0.4 vs 10.3 +/- 1.2 nL/min, respectively; P < 0.001). Intravenous infusion of NG-monomethyl-L-arginine (L-NMMA), in pressor doses increased the difference between PT and DT values of SNGFR of HS rats (4.3 +/- 0.4 vs 9.5 +/- 1.2 nL/min before and during L-NMMA, respectively; P < 0.001) without significantly affecting values in LS rats (10.3 +/- 1.2 vs 12.3 +/- 1.4 nL/min before and during L-NMMA, respectively; NS). 3. A second series of experiments assessed TGF responses directly. Changes in stop-flow pressure (PSF; an index of PGC) were measured in response to graded perfusion of the loop of Henle (LH) with artificial tubular fluid. Loop perfusion with 10(-3) mol/L L-NMMA did not affect the PSF responses of LS rats but did reduce (P < 0.01) the PSF of HS rats during perfusion at 20 nL/min (-1.5 +/- 0.4 mmHg; P < 0.01), 30 nL/min (-1.8 +/- 0.5 mmHg; P < 0.01) and 40 nL/min (-2.2 +/- 0.5 mmHg; P < 0.001). 4. We conclude that the TGF response is increased by suppression of NOS activity during HS but not LS intake.     

Analysis of the major mercapturic acid pathway metabolites of benzo[a]pyrene found in rat urine by nano-electrospray mass spectrometry

Nano-electrospray has been used in combination with high resolution and tandem mass spectrometry in the analysis of the major mercapturic acid pathway metabolites of benzo[a]pyrene (BP). Accurate mass measurements indicate that the [M-H]- ion of the major metabolite has a chemical formula C25H22NO6S, which corresponds to the deprotonated form of tetrahydro-trihydroxy-BP-S-N-acetylcysteine. Tandem mass spectrometry of this [M-H]- ion results in a collision induced dissociation spectrum identical to that of synthetic 7,8,9,10-tetrahydro-8,9,10-trihydroxy-BP-7-S-N-acetylcysteine.     

Protein solution structure calculations in solution: solvated molecular dynamics refinement of calbindin D9k

Data were collected on the drinking behavior of 415 pregnant adolescents from 1990 to 1994. The relationships between knowledge and attitudes about drinking and drinking behavior were examined. Knowledge about drinking was not related to average daily volume of alcohol before or during pregnancy. Those with specific knowledge about fetal alcohol effects drank less before pregnancy, and in the first trimester, and were also less likely to drink to intoxication. Among drinkers, general knowledge about drinking was significantly related to a decrease in drinking between pre-pregnancy and first trimester, as well as between first and third trimesters. Those with more intolerant attitudes about drinking drank less before and during pregnancy. They had fewer episodes of binge drinking, intoxication, negative consequences, and problem drinking during pregnancy. They were more likely to decrease drinking from the first to third trimesters. These relationships are relevant to developing effective education programs for the high-risk group of pregnant teenagers who drink.