tbuckley/cabot-search huggingface dataset:
Local Mechanisms Drive Genioglossus Activation in Obstructive Sleep Apnea
Authors: ATUL MALHOTRA, ROBERT B. FOGEL, JILL K. EDWARDS, STEVEN A. SHEA, DAVID P. WHITE
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Individuals with obstructive sleep apnea (OSA) require increased pharyngeal muscle dilator activation during wakefulness to maintain upper airway patency. Negative pressure is one potential stimulus for this neuromuscular compensation. Individuals with OSA who have previously undergone tracheostomy provide an opportunity to study upper airway physiology in both the presence and absence of upper airway respiratory stimuli. If negative pressure (or another local airway stimulus) were important in driving pharyngeal dilator muscle activation, one would predict that during nasal breathing, the pharynx of a tracheostomized patient would be exposed to negative pressure, and that high levels of muscle activation would therefore be measured. Conversely, during breathing by the patient through the tracheal stoma, one would expect low levels of muscle activation in the absence of local stimuli. We measured a number of respiratory variables, including genioglossus activation under both nasal and tracheal stomal breathing conditions, in five patients. In all five patients there was a significant and substantial decrease in both peak phasic (100 ± 0 to 53.4 ± 9.2 arbitrary units [mean ± SEM], p < 0.01) and tonic genioglossus activation (36.3 ± 5.3 to 20.7 ± 3.9 arbitrary units, p < 0.05) during stomal breathing as compared with nasal breathing. We conclude that local upper airway respiratory stimuli, possibly negative pressure, are important in mediating the increased pharyngeal dilator muscle activation seen in sleep apnea patients during wakefulness.
Addition of growth hormone to gonadotrophins in ovarian stimulation of poor responders treated by in-vitro fertilization: a systematic review and meta-analysis
Authors: E.M. Kolibianakis, C.A. Venetis, K. Diedrich, B.C. Tarlatzis, G. Griesinger
Journal: Human Reproduction Update (2009)

Whether the addition of growth hormone (GH) can improve the probability of pregnancy in poor responders undergoing ovarian stimulation for in-vitro fertilization (IVF) has been examined to date by several underpowered studies, which have not provided solid conclusions. A computerized literature search in MEDLINE, EMBASE, CENTRAL and randomized controlled trial (RCT) registries was performed independently by two reviewers, aiming to identify RCTs that evaluated the following research question: does GH addition increase the probability of pregnancy in poor responders undergoing ovarian stimulation with gonadotrophin releasing hormone (GnRH) analogues and gonadotrophins for IVF? Six relevant RCTs were identified, including a total of 169 patients. GH addition significantly increased clinical pregnancy (rate difference: +16%, 95% CI: +4 to +28; fixed effects model) (number-needed-to-treat (NNT) = 6, 95% CI: 4–25) and live birth rates (rate difference: +17%, 95% CI: +5 to +30; fixed effects model) (NNT = 6; 95% CI: 3–20). Furthermore, GH addition was associated with a significantly higher proportion of patients reaching embryo transfer (rate difference: +22%, 95% CI: +7 to +36; fixed effects model). The present meta-analysis provides evidence that GH addition increases the probability of clinical pregnancy and live birth in poor responders undergoing ovarian stimulation with GnRH analogues and gonadotrophins for IVF. However, the total number of patients analyzed is small and thus further RCTs are warranted to prove or disprove this finding.
Barriers to creating uniform chemotherapy practice at a university hospital: the Chemotherapy Council (CC)
Authors: A. J. Tevaarwerk, S. Attia, B. Campbell, R. C. Warren, S. D. Lentz, J. A. Stewart
Journal: Journal of Clinical Oncology (2008)

6614 Background: Increasing pressure for evidence-based, uniform prescribing practice and need for greater safety measures led to the creation of a CC at the University of Wisconsin Paul P. Carbone Comprehensive Cancer Center. CC membership included hematologist/oncologists, pharmacists and nurses. Prior to the CC physicians had autonomy for ordering a variety of chemotherapy regimens for like clinical situations. This internal regulatory body provides peer-review of cancer center chemotherapy prescribing. Challenges during implementation are described here. Methods: In December 2005, the CC requested from each disease-oriented working group (breast, lung, etc.) a list of core chemotherapy regimens anticipated for use in the adjuvant and metastatic setting. Applications for review included the regimen, a summary of the supporting literature/evidence, and the cost of drugs per cycle. Clinical fellows were active in preparing applications as part of a practice based improvement project. The CC would then “approve,” “approve with tracking,” or “deny” regimens. Monitoring of “tracked” regimens (expected low benefit/high cost) yielded feedback data for prescribers. Order sets were then created for approved core regimens. An ad hoc mechanism was developed for review of patient-specific regimens for rare cancers or unusual circumstances. Results: As of December 2007, the CC received 273 regimens, approved 234, denied nine and is tracking 30. Over a 10 month period 28 patient-specific regimens were reviewed and approved: 74% within 24 hours and 89% within 72 hours of submission. No regimen was denied based on cost alone. The dominant implementation barrier was physician concern with restricted prescribing autonomy and time burden for writing applications. For nursing and pharmacy considerable time was spent developing order sets, but enhanced safety and discussion of drug cost stimulated enthusiasm for the project. Conclusions: Major barriers to creation of uniform chemotherapy practice via the CC mechanism include loss of prescribing autonomy, challenges related to change in practice and time commitment. No significant financial relationships to disclose.
Domiciliary non-invasive ventilation in stable COPD?
Authors: M. W Elliott
Journal: Thorax (2009)

Chronic obstructive pulmonary disease (COPD) is the commonest indication for domiciliary non-invasive ventilation (NIV) in Europe.1 However, there is a paucity of evidence to support its use. A number of short-term randomised controlled trials (RCTs) failed to show any consistent benefit from NIV.2–5 In a crossover study comparing 3 months of bilevel ventilation plus long term oxygen therapy (LTOT) with LTOT alone,6 there were small improvements in arterial blood gas tensions during spontaneous breathing by day and in health-related quality of life (QOL) with NIV. In a longer term RCT,7 20 patients randomised to NIV were compared with 24 controls; there was a reduction in the need for hospitalisation in the first 3 months in the NIV group but this effect disappeared by 1 year. One-year survival (78%) was similar in both groups. Dyspnoea, measured using the Borg scale, was reduced in the NIV group. In a larger RCT from Italy,8 90 stable patients on oxygen for more than 6 months were randomly assigned to continuing oxygen alone or oxygen and bilevel ventilation. There was no change in survival, lung or inspiratory muscle function, exercise tolerance or sleep quality score in either group. By contrast, the arterial carbon dioxide tension (Paco2) measured on usual oxygen and resting dyspnoea scores improved. Health-related QOL, as assessed by the Maugeri Foundation Respiratory Failure Questionnaire (MRF 28), improved in the NIV plus oxygen group, but there was no difference in St George’s Respiratory Questionnaire (SGRQ) scores. NIV has also been used as an adjunct to pulmonary rehabilitation with two RCTs showing greater improvements in exercise capacity and QOL when NIV, used overnight, was added to a pulmonary rehabilitation programme.9 10

In this issue of Thorax McEvoy et al 11 report the results of an …
Clinical Impact of Prandial State, Exercise, and Site Preparation on the Equivalence of Alternative-Site Blood Glucose Testing
Authors: Dawn M. Bina, Robyn L. Anderson, Mary L. Johnson, Richard M. Bergenstal, David M. Kendall
Journal: Diabetes Care (2003)

OBJECTIVE—To determine whether clinically significant differences exist in fasting blood glucose (BG) at the forearm, palm, and thigh relative to the fingertip; to assess the impact of prandial status by comparing BG between alternative sites and the fingertip at several time intervals after carbohydrate intake; to assess the effects of moderate brief exercise on site-to-site differences in BG; to evaluate the impact of site preparation by local rubbing on alternative-site testing (AST) equivalence; and to determine levels of perceived pain and satisfaction associated with AST. RESEARCH DESIGN AND METHODS—Fasting BG was measured using the One Touch Ultra (LifeScan, Milpitas, CA) at the fingertip, palm, thigh, and each forearm (with local rubbing) in 86 patients with type 2 diabetes. A 40-g carbohydrate meal was consumed and BG was again measured from each site at 60, 90, and 120 min postmeal, with an additional forearm test at 90 min without local rubbing. Patients then exercised for 15 min with repeat BG at each site. Differences in BG between sites were assessed using repeated-measures ANOVA and regression analyses. RESULTS—Significant differences in BG at alternative sites were found 60 min postmeal (P = 0.0003) and postexercise (P = 0.037). Specifically, clinically significant differences (expressed as percent difference from the fingertip) at 60 min include −8.8 ± 10.8% at the forearm and −13.7 ± 10.7% at the thigh, and postexercise +19.1 ± 19.1% at the forearm and +15.6 ± 22.6% at the thigh. However, no significant differences were observed between sites in either the fasting state or at 90 and 120 min postmeal. The dynamic results suggest a time lag in equilibration of forearm and thigh BG during periods of rapid glucose change. Palm and fingertip BG test results were similar at all time points. CONCLUSIONS—AST results are consistent with fingertip BG results in both the fasting state and 2 h postmeal; no benefit from site preparation by local rubbing was noted. However, testing at sites other than the hand cannot be recommended 1 h postmeal or immediately after exercise. AST is equivalent and appropriate for use at testing times commonly used in clinical practice.
Overexpression of the Anti-Adhesin Podocalyxin Is an Independent Predictor of Breast Cancer Progression
Authors: Aruna Somasiri, Julie S. Nielsen, Nikita Makretsov, Marcia L. McCoy, Leah Prentice, C. Blake Gilks, Stephen K. Chia, Karen A. Gelmon, David B. Kershaw, David G. Huntsman, Kelly M. McNagny, Calvin D. Roskelley
Journal: Cancer Research (2004)

Abstract Podocalyxin is a CD34-related cell surface molecule with anti-adhesive qualities. We probed a tissue microarray (n = 272) linked to long-term outcome data and found that podocalyxin was highly overexpressed in a distinct subset of invasive breast carcinomas (n = 15; 6%). Univariate disease-specific (P &amp;lt; 0.01) and multivariate regression (P &amp;lt; 0.0005) analyses indicated that this overexpression is an independent indicator of poor outcome. Forced podocalyxin expression perturbed cell junctions between MCF-7 breast carcinoma cells, and it caused cell shedding from confluent monolayers. Therefore, podocalyxin overexpression is a novel predictor of breast cancer progression that may contribute to the process by perturbing tumor cell adhesion.
Controlled delivery of PDGF-BB for myocardial protection using injectable self-assembling peptide nanofibers
Authors: P. C.H. Hsieh
Journal: Journal of Clinical Investigation (2005)

Endothelial cells can protect cardiomyocytes from injury, but the mechanism of this protection is incompletely described. Here we demonstrate that protection of cardiomyocytes by endothelial cells occurs through PDGF-BB signaling. PDGF-BB induced cardiomyocyte Akt phosphorylation in a time- and dose-dependent manner and prevented apoptosis via PI3K/Akt signaling. Using injectable self-assembling peptide nanofibers, which bound PDGF-BB in vitro, sustained delivery of PDGF-BB to the myocardium at the injected sites for 14 days was achieved. A blinded and randomized study in 96 rats showed that injecting nanofibers with PDGF-BB, but not nanofibers or PDGF-BB alone, decreased cardiomyocyte death and preserved systolic function after myocardial infarction. A separate blinded and randomized study in 52 rats showed that PDGF-BB delivered with nanofibers decreased infarct size after ischemia/reperfusion. PDGF-BB with nanofibers induced PDGFR-β and Akt phosphorylation in cardiomyocytes in vivo. These data demonstrate that endothelial cells protect cardiomyocytes via PDGF-BB signaling and that this in vitro finding can be translated into an effective in vivo method of protecting myocardium after infarction. Furthermore, this study shows that injectable nanofibers allow precise and sustained delivery of proteins to the myocardium with potential therapeutic benefits.
Changing Physical Activity Participation for the Medical Profession
Authors: Antronette K. Yancey, Robert E. Sallis, Roshan Bastani
Journal: JAMA (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Intracoronary Ultrasound Assessment Late After the Arterial Switch Operation for Transposition of the Great Arteries
Authors: Simone R.F.F. Pedra, Carlos A.C. Pedra, Alexandre A. Abizaid, Sérgio L.N. Braga, Rodolfo Staico, Raul Arrieta, J. Ribamar Costa, Vinicius D. Vaz, Valmir F. Fontes, J. Eduardo R. Sousa
Journal: Journal of the American College of Cardiology (2005)
THE CULTURAL AND STAINING REACTIONS OF A STRAIN OF THE TUBERCLE BACILLUS PRODUCING PARALYSIS IN GUINEA PIGS
Authors: Paul A. Lewis, Richard E. Shope
Journal: The Journal of Experimental Medicine (1929)

When a strain of human tuberculosis was carried from guinea pig to guinea pig by intracerebral inoculation the bacillus of tuberculosis could be readily recovered in the semisolid "Leptospira" medium of Noguchi simply modified by the substitution of guinea pig for rabbit serum. Whether even this modification is required remains to be determined. The tubercle bacillus in these cultures and possibly in the nervous tissue as well differed from the classical type in that it was less acid-fast and quite lacking in alcohol fastness. However, it retained the Gram stain as modified by Much. Staining reactions, as this culture of the tubercle bacillus shows, are not absolute qualities but are variable with conditions, a consideration which it may be important to recognize. Efforts to define these conditions more precisely are likely to be productive.
Altered inotropic and chronotropic effects of noradrenaline on isolated rat atria exposed to chagasic sera. Influences of cocaine, normetanephrine and U-0521 (3'-4'-dihydroxy-2-methyl propiophenone
Authors: A L GIMENO, M F GIMENO, L STERIN-BORDA, P M COSSIO, N STERIN-SPEZIALE, C DIEZ, S M SEARA, R M ARANA
Journal: Cardiovascular Research (1979)

The effects of chagasic sera containing an antibody (EVI antibody), which reacts with the plasma membrane of striated muscle fibres and endothelial cells, on the inotropic and chronotropic influences of noradrenaline upon isolated rat atria suspended in different media, were explored. Also explored were the action of cocaine, normetanephrine and U-0521 (3′-4′-dihydroxy-2- methyl propiophenone) on the atrial effects of the agonist in preparations immersed in Krebs-Ringer bicarbonate, alone and with the addition of normal human sera or EVI positive human chagasic sera (EVI(+)S). The positive inotropic action of a single dose of noradrenaline (3.0 x 10−7 mol·litre−1) was significantly smaller in spontaneously beating auricles exposed to the EVI(+)S. Cumulative dose-response curves for the agonist showed depression and reduced slope suggesting that EVI(+)S may nihilate the effect of the amine by means of a "noncompetitive-like" mechanism. A similar diminished reactivity towards noradrenaline was found regarding atrial contractile rate. Incubation in a solution with U-0521 enhanced the maximal augmentation of atrial isometric tension evoked by the amine in the three media whereas cocaine failed to elicit significant changes. However, normal human sera not only restored but actually potentiated the inotropic influence of noradrenaline although only in auricles bathed with a solution containing EVI(+)S. None of these three agents altered the reduced chronotropic effect of the agonist exposed to the EVI antibody. Contractile influences on atria paced at single fixed rates were similar to those observed in spontaneously beating preparations. The experimental findings suggest that: a) at the contractile frequencies in the present studies neuronal uptake is neither an important mechanism for terminating the contractile effect of exogenously added noradrenaline, nor a factor involved in the altered action of the agonist in the presence of EVI(+)S; and b) the importance of extraneuronal uptake of noradrenaline became clear after the incubation in a media containing EVI(+)S. It is, therefore plausible to suggest that the EVI antibody might influence the contractile effect of the agonist through a reversible enhancement of extraneuronal uptake. This would in turn modify the interaction between the amine and adrenoceptive sites needed for the full positive inotropic effectiveness of noradrenaline. The possible significance of these findings in the alterations observed in chronic Chagas heart disease is discussed.
Diuretic induced gout: a multifactorial condition.
Authors: J T Scott, C S Higgens
Journal: Annals of the Rheumatic Diseases (1992)

Fifteen patients with clinical gout occurring after long term treatment with diuretics were studied retrospectively. In all 15 patients one or more additional factors were present which might have contributed to the hyperuricaemia and gout. The most common of these was the impairment of the glomerular filtration rate. Twenty five other patients receiving long term treatment with diuretics who did not have gout were also studied. The concentrations of uric acid, urea, and creatinine were, in general, markedly lower in these patients than in those who had developed gout. It is concluded that diuretic induced gout occurs in patients in whom there is an additional cause of hyperuricaemia, usually impaired renal function.
Impact of physical deconditioning on ventricular tachyarrhythmias in trained athletes
Authors: Alessandro Biffi, Barry J. Maron, Luisa Verdile, Fredrick Fernando, Antonio Spataro, Giuseppe Marcello, Roberto Ciardo, Fabrizio Ammirati, Furio Colivicchi, Antonio Pelliccia
Journal: Journal of the American College of Cardiology (2004)
Cyclin D1 Induction of Cellular Migration Requires p27KIP1
Authors: Zhiping Li, Xuanmao Jiao, Chenguang Wang, Xiaoming Ju, Yinan Lu, Liangping Yuan, Michael P. Lisanti, Sanjay Katiyar, Richard G. Pestell
Journal: Cancer Research (2006)

Abstract The cyclin D1 gene is amplified and overexpressed in human breast cancer, functioning as a collaborative oncogene. As the regulatory subunit of a holoenzyme phosphorylating Rb, cyclin D1 promotes cell cycle progression and a noncatalytic function has been described to sequester the cyclin-dependent kinase inhibitor protein p27. Cyclin D1 overexpression correlates with tumor metastasis and cyclin D1–deficient fibroblasts are defective in migration. The genetic mechanism by which cyclin D1 promotes migration and movement is poorly understood. Herein, cyclin D1 promoted cellular migration and cytokinesis of mammary epithelial cells. Cyclin D1 enhanced cellular migratory velocity. The induction of migration by cyclin D1 was abolished by mutation of K112 or deletion of NH2-terminal residues 46 to 90. These mutations of cyclin D1 abrogated physical interaction with p27KIP1. Cyclin D1−/− cells were p27KIP1 deficient and the defect in migration was rescued by p27KIP1 reintroduction. Conversely, the cyclin D1 rescue of cyclin D1−/− cellular migration was reversed by p27KIP1 small interfering RNA. Cyclin D1 regulated p27KIP1 abundance at the posttranslational level, inhibiting the Skp2 promoter, Skp2 abundance, and induced p27KIP1 phosphorylation at Ser10. Together, these studies show cyclin D1 promotes mammary epithelial cell migration. p27KIP1 is required for cyclin D1–mediated cellular migration. (Cancer Res 2006; 66(20): 9986-94)
Bradykinin B <sub>2</sub> -Receptor Activation Augments Norepinephrine Exocytosis From Cardiac Sympathetic Nerve Endings
Authors: Nahid Seyedi, Terrance Win, Harry M. Lander, Roberto Levi
Journal: Circulation Research (1997)

Abstract We determined whether local bradykinin production modulates cardiac adrenergic activity. Depolarization of guinea pig heart sympathetic nerve endings (synaptosomes) with 1 to 100 mmol/L K + caused the release of endogenous norepinephrine (10% to 50% above basal level). This release was exocytotic, because it depended on extracellular Ca 2+ , was inhibited by the N-type Ca 2+ -channel blocker ω-conotoxin and the protein kinase C inhibitor Ro31-8220, and was potentiated by the neuronal uptake-1 inhibitor desipramine. Typical of adrenergic terminals, norepinephrine exocytosis was enhanced by activation of prejunctional angiotensin AT 1 -receptors and attenuated by adrenergic α 2 -receptors, adenosine A 1 -receptors, and histamine H 3 -receptors. Exogenous bradykinin enhanced norepinephrine exocytosis by 7% to 35% (EC 50 , 17 nmol/L), without inhibiting uptake 1. B 2 -receptor, but not B 1 -receptor, blockade antagonized this effect. The kininase II/angiotensin-converting enzyme inhibitor enalaprilat and the addition of kininogen or kallikrein enhanced norepinephrine exocytosis by ≈6% to 40% (EC 50 , 20 nmol/L) and ≈25% to 60%, respectively. This potentiation was prevented by serine protease inhibitors and was antagonized by B 2 -receptor blockade. Therefore, norepinephrine exocytosis is augmented when bradykinin synthesis is increased or when its breakdown is inhibited. This is the first report of a local kallikrein-kinin system in adrenergic nerve endings capable of generating enough bradykinin to activate B 2 -receptors in an autocrine/paracrine fashion and thus enhance norepinephrine exocytosis. This amplification process may operate in disease states, such as myocardial ischemia, associated with severalfold increases in local kinin concentrations.