tbuckley/cabot-search huggingface dataset:
Protective effect and duration of action of formoterol aerosol on exercise-induced asthma
Authors: A Patessio, A Podda, M Carone, N Trombetta, CF Donner
Journal: European Respiratory Journal (1991)

The short-term protective effect on exercise-induced asthma (EIA) and the duration of action of formoterol, given by metered dose aerosol at a dose of 24 micrograms, were compared with salbutamol (200 micrograms) and placebo in twelve asthmatic EIA-positive patients in a double-blind, placebo-controlled, three period cross-over study. On each treatment day the patients were given one of the drugs or placebo and two exercise tests were performed at the second and at the eighth hour after dosing. Using a standard procedure, exercise was performed by treadmill in well-controlled environmental conditions. In the first test at 2 h a significant difference relative to placebo (p less than 0.001) at each incremental time after exercise (i.e. 5, 10, 15, 20, 30 min) was obtained with both formoterol and salbutamol, without any significant difference between formoterol and salbutamol. After the eighth hour test formoterol still protected against EIA in comparison to both salbutamol and placebo. The effect of salbutamol at this time was not different from placebo. No adverse effects were reported in any treatment group. Formoterol has a long duration of action in protecting against EIA that persisted for eight hours, removing the need to dose with beta 2-agonist before every exercise.
Heterogeneity of red blood cell perfusion in capillary networks supplied by a single arteriole in resting skeletal muscle.
Authors: C G Ellis, S M Wrigley, A C Groom
Journal: Circulation Research (1994)

Flow heterogeneity within capillary beds may have two sources: (1) unequal distribution of red blood cell (RBC) supply among arterioles and (2) unique properties of RBC flow in branching networks of capillaries. Our aim was to investigate the capillary network as a source of both spatial and temporal heterogeneity of RBC flow. Five networks, each supplied by a single arteriole, were studied in frog sartorius muscle (one network per frog) by intravital video microscopy. Simultaneous data on RBC velocity (millimeters per second), lineal density (RBCs per millimeter), and supply rate (RBCs per second) were measured continuously (10 samples per second) from video recordings in 5 to 10 capillary segments per network for 10 minutes by use of automated computer analysis. To quantify heterogeneity, mean values from successive 10-second intervals were tabulated for each flow parameter in each capillary segment (ie, portion of capillary between successive bifurcations), and percent coefficient of variation (SD/mean.100%) was calculated for (1) spatial heterogeneity among vessels (CVs) every 10 seconds and for the entire 10-minute sample and (2) temporal heterogeneity within vessels for every capillary segment and for the mean flow parameter. Analysis of these data indicates that (1) capillary networks are a significant source of both spatial and temporal flow heterogeneity, and (2) continuous redistributions of flow occur within networks, resulting in substantial temporal changes in CVs, although a persistent spatial heterogeneity of perfusion still exists on a 10-minute basis. In most networks, CVs decreased as supply rate within the network increased, thus indicating that rheology plays a significant role in determining the perfusion heterogeneity.
Sorafenib Overcomes TRAIL Resistance of Hepatocellular Carcinoma Cells through the Inhibition of STAT3
Authors: Kuen-Feng Chen, Wei-Tien Tai, Tsung-Hao Liu, Hsiang-Po Huang, Yu-Chin Lin, Chung-Wai Shiau, Pui-Kai Li, Pei-Jer Chen, Ann-Lii Cheng
Journal: Clinical Cancer Research (2010)

Recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising antitumor agent. However, many hepatocellular carcinoma (HCC) cells show resistance to TRAIL-induced apoptosis. Here, we report that sorafenib improves the antitumor effect of TRAIL-related agents in resistant HCC.HCC cell lines (PLC5, Huh-7, Hep3B, and Sk-Hep1) were treated with sorafenib and/or TRAIL-related agents (TRAIL or LBY135) and analyzed in terms of apoptosis and signal transduction. In vivo efficacy was determined in nude mice with PLC5 xenografts.Sorafenib, the only approved drug for HCC, sensitizes resistant HCC cells to an agonistic DR5 antibody (LBY135) and TRAIL-induced apoptosis in TRAIL-resistant HCC cells. We found that STAT3 played a significant role in mediating TRAIL sensitization. Our data showed that sorafenib downregulated phospho-STAT3 (pSTAT3) and subsequently reduced the expression levels of STAT3-related proteins (Mcl-1, survivin, and cyclin D1) in a dose- and time-dependent manner in TRAIL-treated HCC cells. Knockdown of STAT3 by RNA interference overcame apoptotic resistance to TRAIL in HCC cells, and ectopic expression of STAT3 in HCC cells abolished the TRAIL-sensitizing effect of sorafenib. Moreover, SHP-1 inhibitor reversed downregulation of pSTAT3 and apoptosis induced by sorafenib, and silencing of SHP-1 by RNA interference abolished the effects of sorafenib on pSTAT3. Notably, sorafenib increased SHP-1 activity in PLC5 cells. Finally, sorafenib plus LBY135 significantly suppressed PLC5 xenograft tumor growth.Sorafenib sensitizes resistant HCC cells to TRAIL-induced apoptosis at clinical achievable concentrations, and this effect is mediated via the inhibition of STAT3.
Home Drug Infusion Therapy Under Medicare
Authors: Elaine J. Power
Journal: JAMA (1993)

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
Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE)
Authors: Keith A A Fox, Omar H Dabbous, Robert J Goldberg, Karen S Pieper, Kim A Eagle, Frans Van de Werf, Álvaro Avezum, Shaun G Goodman, Marcus D Flather, Frederick A Anderson, Christopher B Granger
Journal: BMJ (2006)

<b>Objective</b> To develop a clinical risk prediction tool for estimating the cumulative six month risk of death and death or myocardial infarction to facilitate triage and management of patients with acute coronary syndrome. <b>Design</b> Prospective multinational observational study in which we used multivariable regression to develop a final predictive model, with prospective and external validation. <b>Setting</b> Ninety four hospitals in 14 countries in Europe, North and South America, Australia, and New Zealand. <b>Population</b> 43 810 patients (21 688 in derivation set; 22 122 in validation set) presenting with acute coronary syndrome with or without ST segment elevation enrolled in the global registry of acute coronary events (GRACE) study between April 1999 and September 2005. <b>Main outcome measures</b> Death and myocardial infarction. <b>Results</b> 1989 patients died in hospital, 1466 died between discharge and six month follow-up, and 2793 sustained a new non-fatal myocardial infarction. Nine factors independently predicted death and the combined end point of death or myocardial infarction in the period from admission to six months after discharge: age, development (or history) of heart failure, peripheral vascular disease, systolic blood pressure, Killip class, initial serum creatinine concentration, elevated initial cardiac markers, cardiac arrest on admission, and ST segment deviation. The simplified model was robust, with prospectively validated C-statistics of 0.81 for predicting death and 0.73 for death or myocardial infarction from admission to six months after discharge. The external applicability of the model was validated in the dataset from GUSTO IIb (global use of strategies to open occluded coronary arteries). <b>Conclusions</b> This risk prediction tool uses readily identifiable variables to provide robust prediction of the cumulative six month risk of death or myocardial infarction. It is a rapid and widely applicable method for assessing cardiovascular risk to complement clinical assessment and can guide patient triage and management across the spectrum of patients with acute coronary syndrome.
Recurrence of spontaneous bacterial peritonitis in cirrhosis: Frequency and predictive factors
Authors: Llúcia Titó, Antoni Rimola, Pere Ginès, Josep Llach, Vicente Arroyo, Joan Rodés
Journal: Hepatology (1988)

We investigated whether spontaneous bacterial peritonitis in cirrhosis is a recurrent process and attempted to identify possible predictors of recurrence in 75 consecutive cirrhotics who had recovered from a first episode of spontaneous bacterial peritonitis between January, 1981 and December, 1984 and who were followed closely throughout their illness (follow-up period 10 +/- 13 months; mean +/- S.D.). Thirty-eight patients (51%) developed one or more episodes of spontaneous bacterial peritonitis during follow-up, the probability of recurrence (Kaplan-Meier's method) being 43% at 6 months, 69% at 1 year and 74% at 2 years. Twenty-three variables (age, sex, etiology of cirrhosis, standard liver and renal function tests and characteristics of the first spontaneous bacterial peritonitis) were analyzed as possible predictors of recurrence of spontaneous bacterial peritonitis. In univariate analysis (curves of Kaplan-Meier compared with Mantel-Cox's method), serum bilirubin greater than 4 mg per dl, prothrombin less than or equal to 45% and protein concentration in ascitic fluid less than or equal to 1 gm per dl were significantly (p less than 0.05) associated with a high risk or recurrence of spontaneous bacterial peritonitis. In multivariate analysis (Cox multiple regression model), only ascitic fluid protein concentration (p = 0.005) and prothrombin activity (p = 0.009) were found to be independent predictors of recurrence of spontaneous bacterial peritonitis. Fifty-nine patients (79%) died during follow-up, 18 of them (31%) secondary to spontaneous bacterial peritonitis. The 1-year survival probability in the whole series of patients was 38%.(ABSTRACT TRUNCATED AT 250 WORDS)
True, True, and Related
Authors: Gurpreet Dhaliwal, Katherine E. Schmidt, Daniel J. Gilden, Sanjay Saint
Journal: New England Journal of Medicine (2003)

A 51-year-old woman was admitted to a community hospital with a six-week history of progressive shortness of breath. She had initially noted dyspnea when climbing stairs at work, and by the time of admission it prevented her from walking approximately 4.6 m (15 ft).
Problems With Institutional Review Board Inconsistency
Authors: Robert M. Veatch
Journal: JAMA (1982)

An evaluation of inconsistent decision making by institutional review boards (IRBs) is discussed. Reasons for inconsistencies are explored; they include, for example, value differences between institutions and varying community attitudes. Implications of the uneven decision making are examined and suggestions are made for improving IRB consistency to assure the public that protection of subjects in human experimentation is adequate.
Clinical governance in primary care: Accountability for clinical governance: developing collective responsibility for quality in primary care
Authors: P. Allen
Journal: BMJ (2000)

This is the second in a series of five articles 

Accountability is at the heart of the concept of clinical governance. Not only must health professionals strive to improve the quality of care, they must also be able to show that they are doing so.

The notion of accountability is not new—clinicians have long been accountable to their professional regulatory bodies. However, recent scandals about dangerous practice by doctors have damaged confidence in the current system of peer-led self regulation and raised concerns about the limited accountability of doctors in particular. 1 2 The new requirement for primary care clinicians to be answerable to colleagues in their practice and their primary care group or trust can be seen as one of a range of responses to these concerns and is central to the notion of clinical governance.

This paper will discuss how the notion of accountability in clinical governance can be understood and operationalised within primary care. It will use the clinical governance work of a London primary care group as a case study to illustrate mechanisms of accountability and will show how there are different forms of accountability between health professionals and others, relating to various aspects of performance. The paper will also consider the barriers to improved accountability and highlight tensions that are likely to arise.

#### Summary points

Clinical governance will extend primary health care professionals' accountability beyond current forms of legal and professional accountability

Clinical governance in primary care is aimed at enhancing the collective responsibility and accountability of professionals in primary care groups or trusts

It is mainly concerned with increasing the accountability of primary health professionals to local communities (downwards accountability), the NHS hierarchy (upwards accountability), and their peers (horizontal accountability)

Primary care groups and trusts may find that, in addition to encouraging a …
Optimization of inhalation treatment – Evaluation of influence of PNEUMOlogic® and Optimiser® spacers on aerosol particle distribution from pMDI-EB
Authors: Zygmunt Podolec, Joanna Siekaniec
Journal: European Respiratory Journal (2011)

Introduction: PNEUMOlogic® \[PNL] is the first inhalation chamber [vol. 800 ml] integrated with the spirometer, used for the controlled drug delivery from pMDI-EB. Optimiser® [OPT\] \[vol. 50 ml\] is the aerosol chamber used for drug administration from pMDI-EB.

The aim of the study was to evaluate the influence of inhalation chamber and method of performing inhalation on the quality of aerosol.

Method: Aerosol particle distribution and mass of aerosol was measured using particle counter with constant flow of 28,3L/min.

Results: Results are shown in Table 1 and Table 2.

View this table:

Table 1





View this table:

Table 2





Our study demonstrated statistically significant influence of chamber's size and the air exhaled into the chamber on quality and mass of aerosol.

Conclusion: Application of the chamber integrated with the spirometer opens up new possibilities for optimization of inhalation treatment.
Geographic Variation and Positive Selection on M7 Lysin, an Acrosomal Sperm Protein in Mussels (Mytilus spp.)
Authors: Cynthia Riginos, Duane Wang, A. Jeanine Abrams
Journal: Molecular Biology and Evolution (2006)

Successful fertilization in free-spawning marine organisms depends on the interactions between genes expressed on the surfaces of eggs and sperm. Positive selection frequently characterizes the molecular evolution of such genes, raising the possibility that some common deterministic process drives the evolution of gamete recognition genes and may even be important for understanding the evolution of prezygotic isolation and speciation in the marine realm. One hypothesis is that gamete recognition genes are subject to selection for prezygotic isolation, namely, reinforcement. In a previous study, positive selection on the gene coding for the acrosomal sperm protein M7 lysin was demonstrated among allopatric populations of mussels in the Mytilus edulis species group (M. edulis, Mytilus galloprovincialis, and Mytilus trossulus). Here, we expand sampling to include M7 lysin haplotypes from populations where mussel species are sympatric and hybridize to determine whether there is a pattern of reproductive character displacement (RCD), which would be consistent with reinforcement driving selection on this gene. We do not detect a strong pattern of RCD; neither are there unique haplotypes in sympatry nor is there consistently greater population structure in comparisons involving sympatric populations. One distinct group of haplotypes, however, is strongly affected by natural selection, and this group of haplotypes is found within M. galloprovincialis populations throughout the Northern Hemisphere concurrent with haplotypes common to M. galloprovincialis and M. edulis. We suggest that balancing selection, perhaps resulting from sexual conflicts between sperm and eggs, maintains old allelic diversity within M. galloprovincialis.
Two gut intraepithelial CD8+ lymphocyte populations with different T cell receptors: a role for the gut epithelium in T cell differentiation.
Authors: D Guy-Grand, N Cerf-Bensussan, B Malissen, M Malassis-Seris, C Briottet, P Vassalli
Journal: The Journal of Experimental Medicine (1991)

Mouse gut intraepithelial lymphocytes (IEL) consist mainly (90%) of two populations of CD8+ T cells. One bears heterodimeric alpha/beta CD8 chains (Lyt-2+, Lyt-3+), a T cell receptor (TCR) made of alpha/beta chains, and is Thy-1+; it represents the progeny of T blasts elicited in Peyer's patches by antigenic stimulation. The other bears homodimeric alpha/alpha CD8+ chains, contains no beta chain mRNA, and is mostly Thy-1- and TCR-gamma/delta + or -alpha/beta +; it is thymo-independent and does not require antigenic stimulation, as shown by its presence: (a) in nude and scid mice; (b) in irradiated and thymectomized mice repopulated by T-depleted bone marrow cells bearing an identifiable marker; (c) in thymectomized mice treated by injections of monoclonal anti-CD8 antibody, which lead to total depletion of peripheral CD8+ T lymphocytes; and (d) in germ-free mice and in suckling mice. In young nude mice, alpha/alpha CD8 chains, CD3-TCR complexes, and TCR mRNAs (first gamma/delta) are found on IEL, while they are not detectable on or in peripheral or circulating lymphocytes or bone marrow cells. IEL, in contrast to mature T cells, contain mRNA for the RAG protein, which is required for the rearrangement of TCR and Ig genes. We propose that the gut epithelium (an endoderm derivative, as the thymic epithelium) has an inductive property, attracting progenitors of bone marrow origin, and triggering their TCR rearrangement and alpha/alpha CD8 chains expression, thus giving rise to a T cell population that appears to belong to the same lineage as gamma/delta thymocytes and to recognize an antigenic repertoire different from that of alpha/beta CD8+ IEL.
Acceleration in colorectal carcinogenesis: the hare, the tortoise or myth?: Table 1
Authors: Finlay Macrae, Dennis J Ahnen
Journal: Gut (2012)

Colonoscopic screening and surveillance is routinely recommended for patients at risk for colorectal cancer (CRC) and these endoscopic procedures are a major source of healthcare costs in the developed world. Screening and surveillance guidelines vary greatly usually depending on the estimates of risk.1–4 But, what is the logic and evidence for determining colonoscopy frequency as a function of risk? Biologically, risk can relate to initiation of colon carcinogenesis (the risk of an initiating event occurring or number of initiating events that have already occurred) or to increased velocity of carcinogenesis (how long it takes to develop a new adenoma and for that adenoma to progress to a serious lesion, for example). Alternatively, future risk of colonic neoplasia may be due to a pseudo-risk factor, but the chance of missing adenomas or cancers at screening, due to procedural or patient identifiable factors that are not related to the biology of carcinogenesis. Elevated risk of initiation, without acceleration of carcinogenesis, should not per se dictate increased frequency, as the lesions, when initiated (even if frequently), will not develop rapidly. Similarly, if colonoscopy and polypectomy were perfect (all polyps seen and totally removed), the pseudo-risk factors would not be relevant and the interval between screening or surveillance examinations could be based solely on an understanding of the velocity of colon carcinogenesis. Unfortunately, colonoscopy is not perfect and we do not have ways of predicting the velocity of colon carcinogenesis in individual patients.

Currently, colonoscopy surveillance intervals are stratified based on age, prior colonic neoplasia, family history and known hereditary colon cancer syndromes (see table 1). For the non-hereditary syndrome groups, which make up the large majority of people undergoing colonoscopic screening and surveillance, very little is known about the velocity of carcinogenesis. There is no clear evidence that it varies among individuals …
Treatment of anthracycline extravasation with Savene (dexrazoxane): results from two prospective clinical multicentre studies
Authors: H.T. Mouridsen, S.W. Langer, J. Buter, H. Eidtmann, G. Rosti, M. de Wit, P. Knoblauch, A. Rasmussen, K. Dahlstrøm, P.B. Jensen, G. Giaccone
Journal: Annals of Oncology (2006)
A Lifetime of Allograft Function with Kidneys from Older Donors
Authors: Caren Rose, Elke Schaeffner, Ulrich Frei, Jagbir Gill, John S. Gill
Journal: Journal of the American Society of Nephrology (2015)

Strategies to increase expanded criteria donor (ECD) transplantation are needed. We quantified the extent to which ECD kidneys provide recipients with a lifetime of allograft function by determining the difference between patient survival and death-censored allograft survival (graft survival). Initial analyses compared 5-year outcomes in the Eurotransplant Senior Program (European) and the United States Renal Data System. Among European recipients ≥65 years, patient survival exceeded graft survival, and ECD recipients returned to dialysis for an average of 5.2 months after transplant failure. Among United States recipients ≥60 years, graft survival exceeded patient survival. Although patient survival in elderly recipients in the United States was low (49% at 5 years), the average difference in patient survival at 10 years in elderly recipients in the United States with an ECD versus non-ECD transplant was only 7 months. The probability of patient survival with a functioning allograft at 5 years was higher with ECD transplantation within 1 year after activation to the waiting list than with delayed non-ECD transplantation ≥3 years after activation to the waiting list. Subsequent analyses demonstrated that ECD transplants do not provide a lifetime of allograft function in recipients <50 years in the United States. These findings should encourage ECD transplantation in patients ≥60 years, demonstrate that rapid ECD transplantation is superior to delayed non-ECD transplantation, and challenge the policy in the United States of allowing patients <50 years to receive an ECD transplant.
Long-term endometrial effects in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES)—a randomised controlled trial of exemestane versus continued tamoxifen after 2–3 years tamoxifen
Authors: G. Bertelli, E. Hall, E. Ireland, C.F. Snowdon, J. Jassem, K. Drosik, H. Karnicka-Mlodkowska, R.C. Coombes, J.M. Bliss
Journal: Annals of Oncology (2009)