tbuckley/cabot-search huggingface dataset:
Waking up to sleep-disordered breathing
Authors: J. A. Fleetham
Journal: Thorax (2010)

In 1997 Wright and colleagues1 published a systematic review on the health effects of obstructive sleep apnoea syndrome (OSA) and the effectiveness of treatment with continuous positive airway pressure (CPAP). They concluded that there was limited evidence of increased mortality or morbidity in patients with OSA, and that the evidence linking the condition to cardiovascular risk factors and motor vehicle crashes was conflicting and inconclusive. They also concluded that, although CPAP had been shown to improve daytime sleepiness, there were insufficient data to determine its effect on quality of life, morbidity or mortality. This review generated much controversy, but was a wake-up call to investigators in this field that all were not convinced that OSA was an important condition that always warranted treatment.2 At that time, our understanding of OSA and the impact of CPAP treatment was at a similar stage to where we were with cardiovascular risk factors such as systemic hypertension, diabetes and hypercholesterolaemia several decades ago. Considerable progress has been made since this review, and many of the issues which it raised have subsequently been addressed in papers published in Thorax .

Systemic hypertension has been reported in epidemiological and hospital-based studies of patients with OSA, and is independent of obesity and the other common risk factors for hypertension which are also frequently present in this patient population. There have been conflicting data as to whether nasal CPAP can effectively reduce blood pressure in patients with OSA. Hui and associates3 performed a randomised controlled study in 56 patients with moderate to severe OSA and daytime sleepiness which showed that 12 weeks of therapeutic CPAP reduced 24 h mean and diastolic blood pressure by 3.8 mmHg and 3.5 mmHg, respectively. No …
Potentiation of the bronchoprotective effects of vasoactive intestinal peptide, isoprenaline, and theophylline against histamine challenge in anaesthetised guinea pigs by adrenomedullin.
Authors: H. Kanazawa, T. Kawaguchi, T. Fujii, S. Shoji, K. Hirata, S. Kudoh, N. Kurihara, J. Yoshikawa
Journal: Thorax (1996)

BACKGROUND: Adrenomedullin is a hypotensive peptide recently discovered in human phaeochromocytoma which has been found to inhibit bronchoconstriction induced by histamine and acetylcholine. This study was designed to determine the manner in which adrenomedullin and other bronchodilators interact in modulating airway function. METHODS: A study was undertaken to determine whether adrenomedullin potentiated the bronchoprotective effects of isoprenaline, vasoactive intestinal peptide (VIP), and theophylline against histamine-induced bronchoconstriction in anaesthetised guinea pigs in vivo. RESULTS: Adrenomedullin in a concentration of 10(-9) M significantly inhibited histamine-induced bronchoconstriction but in a concentration of 10(-10) M it did not exhibit the bronchoprotective effect against histamine. VIP (10(-9) M) did not affect histamine-induced bronchoconstriction but it markedly inhibited the bronchoprotective effect against histamine in the presence of adrenomedullin (10(-10) M). VIP (10(-6) M) significantly inhibited histamine-induced bronchoconstriction but this effect was short lived. Adrenomedullin in a concentration of 10(-10) M potentiated bronchoprotection induced by VIP (10(-6) M) and prolonged it. Isoprenaline (10(-8) M) also significantly inhibited histamine-induced bronchoconstriction and this effect was enhanced in the presence of adrenomedullin (10(-10) M). Similarly, adrenomedullin (10(-10) M) significantly potentiated theophylline-induced bronchoprotection, and a sub-bronchoprotective dose of theophylline (20 mg/kg i.p.) was effective in preventing histamine-induced bronchoconstriction in the presence of adrenomedullin (10(-10) M). CONCLUSIONS: This study shows that adrenomedullin potentiates the bronchoprotective effects of different classes of bronchodilators against histamine challenge in anaesthetised guinea pigs.
A CASE OF TUBERCULAR SYPHILIS.From the Clinic of
Authors: JOHN V. SHOEMAKER
Journal: JAMA (1893)

[REPORTED BY DR. GEO. HEWITT.] <i>Gentlemen</i>:—Mr. S., 35 years of age, a stonemason by trade, was admitted to the Medico-Chirurgical Hospital, Dec. 15, 1892. In the year 1878, the patient contracted gonorrhœa. Being at that time of wild and reckless habits, addicted to drink, he was careless as regards treatment. As a consequence the disease was not readily cured and he suffered from it for at least four months. During this period he was not aware of any chancre upon the penis or elsewhere, nor does he remember any enlargement of the inguinal glands. He at length recovered from the gonorrhœa and remained in good health for ten years. For the last six years he has been strictly temperate. During the interval he never had any eruption upon his body except small papules which came out upon the face especially after he had been drinking. He does not know that
Modulation of transforming growth factorβ response and signaling during transdifferentiation of rat hepatic stellate cells to myofibroblasts
Authors: Steven Dooley, Bert Delvoux, Birgit Lahme, Kerstin Mangasser-Stephan, Axel M. Gressner
Journal: Hepatology (2000)

Activation of hepatic stellate cells (HSCs) is the key step in liver fibrogenesis. Increased transforming growth factor beta (TGF-beta) expression and extracellular matrix production in patients with hepatic fibrosis and experimental models of liver fibrogenesis support implication of TGF-beta in the pathogenesis of this disease. However, a causative role for TGF-beta during transdifferentiation of HSCs has not been delineated in molecular detail. Using a rat cell culture model of HSC transdifferentiation, we analyzed TGF-beta signal transduction and identified changes between stellate cells and their transdifferentiated phenotype. Fully transdifferentiated myofibroblasts, opposed to HSCs, were not inhibited in proliferation activity on treatment with TGF-beta1. Furthermore, stimulation of alpha2 (I) collagen and Smad7 messenger RNA (mRNA) expression by TGF-beta1 was achieved in stellate cells but not in myofibroblasts. Northern and Western blot analyses indicated significant expression of TGF-beta receptors I and II in both cell types. In contrast, [(125)I]-TGF-beta1 receptor affinity labeling displayed strongly reduced types I, II, and III receptor presentation at the cell surface of myofibroblasts. Moreover, myofibroblasts did not display DNA-binding SMAD proteins in electrophoretic mobility shift assays with a CAGA box. These data indicate that stellate cells are responsive to TGF-beta1 treatment and transduce a signal that may play an important role in liver fibrogenesis. Myofibroblasts display decreased availability of surface receptors for TGF-beta, which could be based on autocrine stimulation. However, lack of activated SMAD complexes with DNA-binding activity and absence of alpha2 (I) collagen transcription inhibition by latency-associated peptide (LAP)/anti-TGF-beta antibody raise the possibility of TGF-beta signaling independent receptor down-regulation in myofibroblasts.
β-blocker therapy for prophylaxis of initial variceal hemorrhage: Has its time come?
Authors: Telfer B. Reynolds
Journal: Hepatology (1991)

In a double-blind randomized trial, the hemodynamic events following the administration of propranolol (n = 51) or a placebo (n = 51) were prospectively studied in cirrhotic patients with esophageal varices. The hepatic venous pressure gradient, heart rate, and variceal size were determined at the baseline and 3, 12, and 24 months after the beginning of therapy. Baseline values were similar in both groups. At 3 months, the hepatic venous pressure gradient decreased significantly in propranolol-treated patients (from 18.1 ± 4.2 to 15.7 ± 3.4 mm Hg; P &lt; 0.05) but not in patients receiving the placebo (19.6 ± 6.8 to 17.5 ± 5.3 mm Hg; NS). At subsequent time intervals this gradient decreased significantly from the baseline value in both groups. Heart rate decreased significantly in the propranolol-treated group at all times (P &lt; 0.001). Variceal hemorrhage occurred in 13 patients (11 placebo-, 2 propranolol-treated; P &lt; 0.01), all of whom had a hepatic venous pressure gradient &gt; 12 mm Hg. In 21 patients (14 propranolol-, 7 placebo-treated) the hepatic venous pressure gradient decreased to ≤12 mm Hg; none of them bled from esophageal varices, and their mortality rate also decreased. Because most of the bleeding events occurred during the first year (10 placebo-, 1 propranololtreated; P &lt; 0.01), propranolol seems to have its protective effect during the period associated with the largest reduction in the hepatic venous pressure gradient. Because a reduction in the hepatic venous pressure gradient to &lt; 12 mm Hg protects from variceal bleeding and increases the rate of survival, this should be the aim of the pharmacological therapy of portal hypertension.
Regional changes in hemodynamics and cardiac myocyte size in rats with aortocaval fistulas. 1. Developing and established hypertrophy.
Authors: Z Liu, D R Hilbelink, W B Crockett, A M Gerdes
Journal: Circulation Research (1991)

The effects of a large arteriovenous fistula on left and right ventricular hemodynamics and cardiac myocyte size were examined in adult rats at 1 week and 1 month after surgery. Cardiac output, left ventricular function, and right ventricular function were evaluated before obtaining isolated myocytes for cell size measurements. Average heart weight increased 35% at 1 week and 86% at 1 month in rats with fistulas. In general, myocyte hypertrophy was due to a proportional increase in length and width (length/width ratio remained constant). This change was more evident in the large hearts from rats with 1-month fistulas. At both the 1-week and 1-month intervals, the hypertrophic response of right ventricular myocytes was slightly greater than that observed in the left ventricle or interventricular septum. Left ventricular systolic pressure and dP/dtmax were significantly reduced at 1 week but returned to normal after 1 month of overloading. Left ventricular end-diastolic pressure was increased approximately fivefold and twofold at 1 week and 1 month, respectively. Right ventricular systolic pressure and dP/dtmax were increased at both intervals examined. We conclude that severe volume overloading from a large aortocaval fistula in the rat is characterized by 1) depressed left ventricular function at 1 week followed by a large compensatory hypertrophy and near normal function at 1 month, 2) right ventricular pressure overload, and 3) changes in myocyte shape that resemble normal physiological growth.
The Periprostatic Autonomic Nerves—Bundle or Layer?
Authors: Karl-Dietrich Sievert, Jörg Hennenlotter, Ines Laible, Bastian Amend, David Schilling, Aristotelis Anastasiadis, Ursula Kuehs, Udo Nagele, Arnulf Stenzl
Journal: European Urology (2008)
Medicine and Politics in Australia
Authors: DEREK MEYERS
Journal: Annals of Internal Medicine (1973)

Abroad1 October 1973Medicine and Politics in AustraliaDEREK MEYERS, M.D., F.R.A.C.P.DEREK MEYERS, M.D., F.R.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-79-4-602 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptMedicine, said the late Aneurin Bevan, architect of the British National Health Service, is at the heart of politics—a statement just as true for Australia.There are two major political forces in Australia—Labor and non-Labor—the latter has used various names over the years but at present is constituted in the federal sphere by the Liberal and Country parties. Since the first federal parliament was elected in 1901, there have been fewer Labor than Liberal—Country party governments. In the last 30 years Labor held office from 1941 to 1949, the Liberal—Country Coalition from 1949 to 1972, and now Labor is back... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Brisbane, Australia PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1973Volume 79, Issue 4Page: 602-603 ePublished: 13 March 2020 Issue Published: 1 October 1973 PDF downloadLoading ...
The Cost of Gastrointestinal Endoscopy
Authors: STEPHEN L. TALLER
Journal: Annals of Internal Medicine (1985)

Letters and Corrections1 March 1985The Cost of Gastrointestinal EndoscopySTEPHEN L. TALLER, M.D.STEPHEN L. TALLER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-102-3-415_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The article by Dooley and coworkers (1) is an important discussion of the comparative diagnostic value of upper gastrointestinal radiography and endoscopy. I will not enter into the dispute concerning which is the better study (2), but Dooley and coworkers make one statement that cannot remain unchallenged. After pointing out that "In the United States, endoscopy is two to three times more expensive than the upper gastrointestinal series . . ." they state ". . . it appears that in a system in which there is no cost differential between endoscopy and the barium study (such as...References1. DOOLEY C, LARSON A, and STACE N. Double-contrast barium meal and upper gastrointestinal endoscopy: a comparative study. Ann Intern Med. 1984;101:538-45. LinkGoogle Scholar2. GELFAND D, OTT D, MUNITZ H, and CHEN Y. Radiology and endoscopy: a radiologic viewpoint [Editorial]. Ann Intern Med. 1984;101:550-2. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: STEPHEN L. TALLER, M.D. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1985Volume 102, Issue 3Page: 415-415KeywordsDiagnostic radiologyEndoscopy ePublished: 1 December 2008 Issue Published: 1 March 1985 PDF downloadLoading ...
Relationship of Small Airway Chymase-Positive Mast Cells and Lung Function in Severe Asthma
Authors: Silvana Balzar, Hong Wei Chu, Matthew Strand, Sally Wenzel
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Distal lung inflammation may be important in asthma pathophysiology. The goal of this study was to measure cellular inflammation in the large airway and four distal lung regions (small airway inner and outer wall, alveolar attachments, and peripheral alveolar tissue) and to correlate the specific inflammatory cells with several lung function parameters. Sections of concurrently obtained endobronchial and transbronchial/surgical biopsy tissue from 20 individuals with severe asthma were immunostained for T-lymphocyte, eosinophil, monocyte/macrophage, neutrophil, and two mast cell markers (tryptase and chymase). Specific cell distributions were determined and correlated with lung function measures. The number of inflammatory cells generally increased toward the periphery, but the percentage of T-lymphocytes, eosinophils, monocytes/macrophages, and neutrophils remained similar or decreased from large to small airways. In contrast, mast cell number, percentage, and the chymase-positive phenotype increased in small airway regions. After the analysis was adjusted for multiple comparisons, only chymase-positive mast cells significantly and positively correlated with lung function. Such a relationship was seen only in the small airway/alveolar attachments lung region (r(s) = 0.61-0.89; p </= 0.001 for all correlations). These data suggest that induction of chymase-positive mast cells, particularly in the small airway outer wall/alveolar attachments region, may be protective for lung function in severe asthma.
277 Epimorphin, a mesenchymal cell surface-associated molecule, is involved in differentiation of hepatic stem-like cells through cell contact with hepatic stellate cells
Authors: K MIURA, T GOTO, K MIKAMI, K NAKANE, K YONEYAMA, H NAGAI, K TERADA, T SUGIYAMA, K IMAI, H SENOO
Journal: Hepatology (2003)

We investigated the effect of KL and IGF-I, alone or in combination, on the in vitro survival, growth and antrum formation of sheep preantral follicles, and subsequent oocyte developmental competence. Preantral follicles ∼200 μm were isolated and cultured for 18 days in basic medium (control) added or not by KL, IGF-I or both. Every six days follicular survival, growth and antrum formation was evaluated. At the end of the culture period, the oocytes underwent in vitro maturation (IVM) and their viability and chromatin configuration were assessed. To evaluate oocyte quality and its developmental competence, parthenogenetic activation and in vitro fertilization (IVF) of the oocytes recovered from in vitro grown preantral follicles were performed. Medium supplementation with KL improved follicular integrity and antrum formation. IGF-I promoted the increase in follicular diameter at the end of the in vitro culture when compared to control, but not differently from KL. Follicles cultured in the presence of KL presented the highest percentages of meiosis resumption (92.3%). Therefore, these oocytes were submitted to parthenogenetic activation and IVF resulting in a percentage of 35.6% of parthenotes and 23.1% of 2- or 4-cells embryos. Medium supplementation with KL results in increased rates of antrum formation, as well as in meiosis resumption, resulting in the production of embryos using parthenogenetic activation or IVF.
Risk Factors for 5-Year Mortality in Older Adults&lt;SUBTITLE&gt;The Cardiovascular Health Study&lt;/SUBTITLE&gt;
Authors: Linda P. Fried
Journal: JAMA (1998)

Multiple factors contribute to mortality in older adults, but the extent to which subclinical disease and other factors contribute independently to mortality risk is not known.To determine the disease, functional, and personal characteristics that jointly predict mortality in community-dwelling men and women aged 65 years or older.Prospective population-based cohort study with 5 years of follow-up and a validation cohort of African Americans with 4.25-year follow-up.Four US communities.A total of 5201 and 685 men and women aged 65 years or older in the original and African American cohorts, respectively.Five-year mortality.In the main cohort, 646 deaths (12%) occurred within 5 years. Using Cox proportional hazards models, 20 characteristics (of 78 assessed) were each significantly (P<.05) and independently associated with mortality: increasing age, male sex, income less than $50000 per year, low weight, lack of moderate or vigorous exercise, smoking for more than 50 pack-years, high brachial (>169 mm Hg) and low tibial (< or = 127 mm Hg) systolic blood pressure, diuretic use by those without hypertension or congestive heart failure, elevated fasting glucose level (>7.2 mmol/L [130 mg/dL]), low albumin level (< or = 37 g/L), elevated creatinine level (> or = 106 micromol/L [1.2 mg/dL]), low forced vital capacity (< or = 2.06 mL), aortic stenosis (moderate or severe) and abnormal left ventricular ejection fraction (by echocardiography), major electrocardiographic abnormality, stenosis of internal carotid artery (by ultrasound), congestive heart failure, difficulty in any instrumental activity of daily living, and low cognitive function by Digit Symbol Substitution test score. Neither high-density lipoprotein cholesterol nor low-density lipoprotein cholesterol was associated with mortality. After adjustment for other factors, the association between age and mortality diminished, but the reduction in mortality with female sex persisted. Finally, the risk of mortality was validated in the second cohort; quintiles of risk ranged from 2% to 39% and 0% to 26% for the 2 cohorts.Objective measures of subclinical disease and disease severity were independent and joint predictors of 5-year mortality in older adults, along with male sex, relative poverty, physical activity, smoking, indicators of frailty, and disability. Except for history of congestive heart failure, objective, quantitative measures of disease were better predictors of mortality than was clinical history of disease.
Abstract 3604: Preclinical antitumor study of famitinib, an orally available multi-targeted kinase inhibitor of VEGFR/PDGFR/c-Kit in phase I clinical trials
Authors: Liguang Lou, Yi Mi, Yongping Xu, Chengying Xie, Hongbing Zhao
Journal: Cancer Research (2011)

Abstract Angiogenesis plays a key role in tumor progression and anti-angiogenic agents including sunitinib and sorafenib that target VEGF/VEGFR signaling pathway have been proved to an effective therapy for cancer in the clinic. However, severe side effects such as hypertension and bone marrow toxicity limit their clinical application. Thus, development of novel anti-angiogenic agents with fewer side effects is still an unmet challenge. In this study, we characterized the in vitro and in vivo antitumor activity of famitinib, an orally active multi-targeted kinase inhibitor. Famitinib inhibited the activity of c-kit, VEGFR-2, PDGFRα and PDGFRβ with IC50 values of 2.3 nM, 4.7 nM and 6.6 nM, respectively. In addition, Famitinib inhibited the VEGF-induced proliferation, migration and tubule formation of human umbilical vein endothelial cells, and micro-vessel spouting from matrigel-embedded rat aortic rings. In vivo, famitinib exhibited broad and potent anti-tumor activity, leading to regression or growth arrest of various established xenografts derived from human tumor cell lines. Moreover, famitinib significantly enhanced the efficacy of oxaliplatin or 5-fluorouracil when they were combined. In summary, famitinib has potent preclinical antitumor activity which supports its further evaluation in clinic. Famitinib is currently in phase I clinical trials in China. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3604. doi:10.1158/1538-7445.AM2011-3604
Percentage of Left Ventricular Stroke Work Loss
Authors: JOHN R. TOBIN, SHAHBUDIN H. RAHIMTOOLA, PETER E. BLUNDELL, H. J. C. SWAN
Journal: Circulation (1967)

The ratio of the mean systolic transaortic valvular gradient to the mean systolic left ventricular pressure times 100 yields a percentage that represents the portion of left ventricular pressure-volume work per stroke lost because of outflow-tract obstruction. The percentage of the left ventricular stroke work loss and the area of the aortic orifice have been estimated in 49 patients with aortic valvular stenosis and two open-chest dogs with varying degrees of supravalvular aortic constriction. Left ventricular stroke work loss of 30% or greater was associated with calculated aortic valve areas of 1.0 cm 2 (or 0.60 cm 2 /m 2 ) or less. These values are representative of serious obstruction to left ventricular outflow, that is, approximately 75% or greater reduction of normal orifice size. The calculation of the percentage of left ventricular stroke work loss, besides being simple, is based upon the most reliable measurements obtainable at left heart catheterization, that of the pressure pulses.