tbuckley/cabot-search huggingface dataset:
Keeping up the Population
Authors: A. M. Toms
Journal: BMJ (1945)

<h3>BACKGROUND:</h3> The purpose of this study was to evaluate how factors (ambient temperature, shaking the inhaler before use, suspension of the inhaler in water, and the variation over the lifetime of the inhaler) affect the particle-size distributions from albuterol HFA inhalers. <h3>METHODS:</h3> We used a laser particle-size analyzer to measure the percentage of particles in the 1- to 5-μm range (fine-particle fraction) serially 2,500 times per second to obtain a window of useful measurements with each inhaler actuation. We compared the inhaler performance results as follows: cold versus hot, full versus partial versus empty inhaler actuations, shaken versus unshaken, and inhaler characteristics after water submersion. <h3>RESULTS:</h3> The effect of temperature was as follows: fine-particle fraction was 14.4% at 5°C, 37.9% at 24 - 25°C, and 38.1% at 45°C. The fine-particle fraction at the start, middle, end, and past the end of the inhaler’s rated lifetime were 37.9, 26.3, 27.9, and 22.0%, respectively. Shaking the inhaler did not improve the inhaler’s fine-particle fraction. Submerging the inhaler reduced the fine-particle fraction to 14.3% without purging and to 20.5% with purging compared with the 42.1% for the control inhaler, which was not submerged. <h3>CONCLUSIONS:</h3> Temperature made a difference, with cold inhalers producing a lower fine-particle fraction. The early portion of the inhaler had a better fine-particle fraction than the middle and end of the inhaler’s lifespan. We could not demonstrate that shaking the inhaler had a significant effect on the fine-particle fraction. Submerging the inhaler in water significantly reduced the fine-particle fraction.
AN APPEAL FOR BELGIAN AND FRENCH PHYSICIANS
Authors: W. W. Keen
Journal: JAMA (1918)

To the Editor:  —I am writing on the birthday of that splendid patriot and monarch, King Albert of Belgium. I beg to remind my colleagues of the profession that now we shall be able to assist our Belgian and French colleagues who will be going back to their homes—in fact, are now going back to their homes in the territory evacuated by the barbarous Hun.  Money is especially needed now. The large number of instruments that I have acknowledged inThe Journalfrom time to time have gone forward and more will be welcome; but, after all, the needs of these utterly destitute men can best be met by contributions in money. This money ought also to be forwarded as quickly as possible. I shall hope to send a large Christmas gift to Dr. Depage at LaPanne and the committee in Paris for the Belgian and French physicians, respectively. Bis
Real-time MRI of Orthotopic Ileal Neobladder Voiding: Preliminary Findings
Authors: Satoru Muto, Yutaka Kamiyama, Hisamitsu Ide, Hiroshi Okada, Keisuke Saito, Kojiro Nishio, Shino Tokiwa, Tatsuro Kaminaga, Shigeru Furui, Shigeo Horie
Journal: European Urology (2007)
Assessing exposure to air toxics relative to asthma.
Authors: Clifford P Weisel
Journal: Environmental Health Perspectives (2002)

Asthma is a respiratory disease whose prevalence has been increasing since the mid 1970s and that affects more than 14.6 million residents of the United States. Environmental triggers of asthma include air pollutants that are respiratory irritants. Air toxics emitted into the ambient air are listed in the 1990 Clean Air Act Amendments as hazardous air pollutants (HAPs) if they can adversely affect human health, including the respiratory tract. HAPs include particulate and gaseous-phase pollutants, individual organic compounds and metals, and mixtures. Associations between asthma exacerbation and both particles and indoor volatile organic compounds (VOCs), often referred to as indoor air quality, have been reported. Studies conducted in the United States, Canada, and Europe over the past two decades have shown that most people living in the developed countries spend the majority of their time indoors and that the air concentrations of many air toxics or HAPs are higher indoors than in the ambient air in urban, suburban, and rural settings. Elevated indoor air concentrations result from emissions of air toxics from consumer products, household furnishings, and personal activities. The Relationship of Indoor, Outdoor and Personal Air (RIOPA) study was designed to oversample homes in close proximity to ambient sources, excluding residences where smokers lived, to determine the contribution of ambient emissions to air toxics exposure. The ratios of indoor to outdoor air concentrations of some VOCs in homes measured during RIOPA were much greater than one, and for most other VOCs that had indoor-to-outdoor ratios close to unity in the majority of homes, elevated ratios were found in the paired samples with the highest concentration. Thus, although ambient emissions contribute to exposure of some air toxics indoors as well as outdoors, this was not true for all of the air toxics and especially for the higher end of exposures to most volatile organic air toxics examined. It is therefore critical, when evaluating potential effects of air toxics on asthma or other adverse health end points, to determine where the exposure occurs and the source contributions for each air toxic and target population separately and not to rely solely on ambient air concentration measurements.
S106 Polymorphisms in genes encoding RAGE or RAGE ligands predispose patients to adverse outcomes following surgery necessitating cardiopulmonary bypass
Authors: N. Zakeri, B. Creagh-Brown, L. R. Hector, R. J. Hewitt, A. L. Lagan, G. J. Quinlan, P. Pantelidis
Journal: Thorax (2010)

<h3>Background</h3> Surgery necessitating cardiopulmonary bypass (snCPB) induces a systemic inflammatory response which can lead to organ dysfunction, including acute lung injury (ALI). Polymorphisms in inflammatory genes have been linked to adverse clinical outcomes following snCPB. The receptor for advanced glycation end products (RAGE) is an inflammation-perpetuating pattern recognition receptor. We investigated the hypothesis that polymorphisms in genes encoding RAGE or RAGE ligands predispose patients to a more severe systemic inflammatory response and the development of ALI after snCPB. <h3>Methods</h3> In a nested unmatched case–control study 187 UK Caucasian patients undergoing cardiac surgery necessitating CPB were genotyped for eight biallelic single nucleotide polymorphisms (SNPs) in the <i>RAGE</i>, <i>S100A8</i> and <i>HMGB1</i> genes using sequence-specific primer polymerase chain reactions. Intensive care unit length of stay, duration of level 3 care, post-operative neutrophil and white blood cell count (WCC), C-reactive protein (CRP) and PaO<sub>2</sub>:FiO<sub>2</sub> ratio were used as clinical outcome measures. <h3>Results</h3> All SNPs conformed to Hardy–Weinberg equilibrium. Patients carrying the C alleles of rs3795391 and rs3806232 SNPs, in linkage disequilibrium in the <i>S100A8</i> gene, had a higher neutrophil and WCC (p=0.019, p=0.039 respectively) and a lower PaO<sub>2</sub>:FiO<sub>2</sub> (p=0.01) on post-operative day 3. Median post-operative PiO<sub>2</sub>:FiO<sub>2</sub> of patients carrying the C alleles versus those not was 123.5 mm Hg vs 204.4 mm Hg. Patients carrying the GG genotype of the rs2070600 (Gly82Ser) SNP in the <i>RAGE</i> gene had a higher neutrophil count on post-operative day 2 (p=0.025). Patients carrying the T allele of the <i>RAGE</i> rs1800624 (−374T/A) SNP had higher CRP levels on post-operative day 1 (p=0.015). <h3>Conclusion</h3> SNPs in the <i>RAGE</i> and <i>S100A8</i> genes are associated with the intensity of the systemic inflammatory response and patient oxygenation levels in our cohort of patients following snCPB. Patients carrying the C alleles of the <i>S100A8</i> SNPs had significantly impaired oxygenation in the early post-operative period compared to patients carrying the TT genotype, suggesting a genetic influence on the degree of lung injury arising as a result of snCPB. Pre-operative genotyping for polymorphisms associated with adverse outcomes may be used to stratify patients9 risk from snCPB, allowing the development of interventions designed to reduce post-operative morbidity and mortality.
Noninvasive Imaging of Lipid Nanoparticle–Mediated Systemic Delivery of Small-Interfering RNA to the Liver
Authors: Weikang Tao, Joseph P Davide, Mingmei Cai, Guo-Jun Zhang, Victoria J South, Andrea Matter, Bruce Ng, Ye Zhang, Laura Sepp-Lorenzino
Journal: Molecular Therapy (2010)
Effect of hypercholesterolemia on vascular reactivity in the rabbit. II. Influence of treatment with dipyridamole on endothelium-dependent and endothelium-independent responses in isolated aortas of control and hypercholesterolemic rabbits.
Authors: T J Verbeuren, M C Coene, F H Jordaens, C E Van Hove, L L Zonnekeyn, A G Herman
Journal: Circulation Research (1986)

The effects of cholesterol-feeding in the presence of dipyridamole (0.60 g daily) on contractile responses and on endothelium-dependent and endothelium-independent relaxations in isolated rabbit aortas are described. The investigations were performed simultaneously with those described in Part I (Circ Res 1986; 58:552-564), where the effects of cholesterol feeding on vascular reactivity in rabbit arteries (n = 8 in each group) selected at random from the same group of animals was studied. In the hypercholesterolemic rabbits treated with dipyridamole for 8 or 16 weeks, both the increases in plasma cholesterol and the formation of fatty streaks were significantly less pronounced than in the hypercholesterolemic rabbits not receiving the drug. Segments of the isolated arteries were mounted in organ chambers for isometric tension recording. The contractions caused by acetylcholine, prostaglandin F2 alpha, norepinephrine, clonidine, and serotonin and the endothelium-independent relaxations to nitroglycerin were not significantly altered by the hypercholesterolemia in rabbits treated with dipyridamole, even after 16 weeks of treatment. Thus, the decreased responses to norepinephrine, clonidine, and nitroglycerin and the augmented responses to serotonin noted in aortas of hypercholesterolemic rabbits in Part I were absent in the dipyridamole-treated hypercholesterolemic animals. The endothelium-dependent relaxations to ATP and acetylcholine were not affected after 8 weeks of hypercholesterolemia in presence of dipyridamole, while after 16 weeks the relaxations to ATP and acetylcholine were attenuated only in the more severely affected arteries. The effects of hypercholesterolemia + dipyridamole on endothelium-dependent relaxations were significantly less pronounced than those induced by hypercholesterolemia alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Treatment of Unresectable Pancreatic Carcinoma by Intraluminal Brachytherapy in the Duct of Wirsung
Authors: M. Mutignani, S. K. Shah, A. G. Morganti, V. Perri, G. Macchia, G. Costamagna
Journal: Endoscopy (2002)

Our aim was to evaluate the feasibility and clinical outcome of intraluminal brachytherapy (ILBT) in the duct of Wirsung in patients with unresectable pancreatic adenocarcinoma.Nine patients (eight men, one woman; mean age 72.4 +/- 9.1, range 52 - 80) with unresectable pancreatic adenocarcinoma of the head or body underwent ERCP for biliary and/or pancreatic stent placement and placement of a nasopancreatic drain with/without nasobiliary drain. The ILBT dose administered was 30 - 50 Gy calculated at 1 cm from the iridium-192 wire axis. Seven patients received ILBT from the duct of Wirsung whereas two patients received dual-duct ILBT (duct of Wirsung and the common bile duct). Three patients received combined-modality treatment (ILBT with external beam radiotherapy and 5-fluorouracil). The patients were prospectively followed up.No endoscopy-related complications occurred. No radiation-related toxicity occurred in patients treated with ILBT alone. One patient undergoing combined-modality treatment developed gastric bleeding. Intraluminal source dislodgement occurred in three patients. Obvious tumor mass reduction of greater than 50 % was seen in three patients at 8 weeks after brachytherapy. Median survival was 11 months (range 6 - 37 months) and the 1-year and 3-year actuarial survival rates were 44 % and 15 %, respectively.Intraluminal brachytherapy in the duct of Wirsung in patients with unresectable pancreatic carcinoma is safe and feasible. Further clinical trials are warranted.
Fluoride Induces Endoplasmic Reticulum Stress and Inhibits Protein Synthesis and Secretion
Authors: Ramaswamy Sharma, Masahiro Tsuchiya, John D. Bartlett
Journal: Environmental Health Perspectives (2008)

Exposure to excessive amounts of fluoride (F(-)) causes dental fluorosis in susceptible individuals; however, the mechanism of F(-)-induced toxicity is unclear. Previously, we have shown that high-dose F(-) activates the unfolded protein response (UPR) in ameloblasts that are responsible for dental enamel formation. The UPR is a signaling pathway responsible for either alleviating endoplasmic reticulum (ER) stress or for inducing apoptosis of the stressed cells.In this study we determined if low-dose F(-) causes ER stress and activates the UPR, and we also determined whether F(-) interferes with the secretion of proteins from the ER.We stably transfected the ameloblast-derived LS8 cell line with secreted alkaline phosphatase (SEAP) and determined activity and localization of SEAP and F(-)-mediated induction of UPR proteins. Also, incisors from mice given drinking water containing various concentrations of F(-) were examined for eucaryotic initiation factor-2, subunit alpha (eIF2alpha) phosphorylation.We found that F(-) decreases the extracellular secretion of SEAP in a linear, dose-dependent manner. We also found a corresponding increase in the intracellular accumulation of SEAP after exposure to F(-). These changes are associated with the induction of UPR proteins such as the molecular chaperone BiP and phosphorylation of the UPR sensor PKR-like ER kinase, and its substrate, eIF2alpha. Importantly, F(-)-induced phosphorylation of eIF2alphawas confirmed in vivo.These data suggest that F(-) initiates an ER stress response in ameloblasts that interferes with protein synthesis and secretion. Consequently, ameloblast function during enamel development may be impaired, and this may culminate in dental fluorosis.
Quantitative magnetic resonance imaging (MRI) in the evaluation of the degree of steatosis, iron accumulation and fibrosis in chronic liver diseases (MRKER STUDY)
Authors: C. L. Hoad, L. Marciani, P. Kaye, I. N. Guha, C. Costigan, A. Austin, R. C. Spiller, M. W. James, P. A. Gowland, S. Francis, G. P. Aithal
Journal: Gut (2011)

<h3>Introduction</h3> Approximately 12 500 liver biopsies are performed annually in England and Wales. Liver biopsies are associated with sampling errors, observer variability and complications. In contrast, use of ultrasound and MR elastography may be limited by inter-operator variability, cost and access. Fat, iron accumulation and fibrosis are critical contributors to the pathogenesis of major chronic liver disease. <h3>Aim</h3> To correlate quantitative multimodal MRI parameters with histological grading of fat, iron accumulation and fibrosis. <h3>Methods</h3> MRI relaxation time data (T<sub>1</sub>, T<sub>2</sub> and T<sub>2</sub>*) were acquired using a novel Echo Planar Imaging technique with a respiratory-triggered (r.t.) rapid acquisition method, repeated multiple times with different contrast to generate accurate voxel-by-voxel (3×3×8 mm<sup>3</sup> voxel) relaxation time maps of the liver tissue. 1H MR spectra were acquired (r.t.) using a multiple echo PRESS acquisition which allowed for individual T<sub>2</sub> correction to the spectrum for accurate quantification of the fat fraction in a 30×30×30mm<sup>3</sup> voxel. <h3>Results</h3> Sixty two subjects (range 23–72 years) were included in the study based on the adequacy of liver biopsy. Liver biopsies were (mean ±SD) 28.7±7.3 mm long and 0.96±0.2 mm wide. Histology revealed non-alcoholic fatty liver in 50%, chronic viral hepatitis (HCV and HBV) in 24%, alcoholic liver disease in 11%, normal in 11% and haemochromatosis in 3%. There was significant correlation between MR measures of fat fraction and percentage of fat on histology (r =0.81; p&lt;0.001), T<sub>2</sub>* with hepatic iron content (r = − 0.65, p&lt;0.001) and T<sub>1</sub> with percentage of fibrosis on histology (r=0.48, p&lt;0.001). Performance characteristic of T<sub>1</sub> MR parameter in the detection of different histological stages of fibrosis is listed in table 1. <h3>Conclusion</h3> In chronic liver diseases, MR measures of fat fraction, hepatic iron content and fibrosis correlate well with histological grading. Quantitative MR techniques allow accurate distinction of different stages of fibrosis on liver biopsy. If these are replicated in independent cohorts, these techniques can be translated into clinical applications.
Fibroblast growth factor stimulates angiotensin converting enzyme expression in vascular smooth muscle cells. Possible mediator of the response to vascular injury.
Authors: R S Fishel, V Thourani, S J Eisenberg, S Y Shai, M A Corson, E G Nabel, K E Bernstein, B C Berk
Journal: Journal of Clinical Investigation (1995)

Angiotensin converting enzyme (ACE) activity contributes to the vascular response to injury because ACE inhibition limits neointima formation in rat carotid arteries after balloon injury. To investigate the mechanisms by which ACE may contribute to vascular smooth muscle cell (VSMC) proliferation, we studied expression of ACE in vivo after injury and in vitro after growth factor stimulation. ACE activity 14 d after injury was increased 3.6-fold in the injured vessel. ACE expression, measured by immunohistochemistry, became apparent at 7 d in the neointima and at 14 d was primarily in the most luminal neointimal cells. To characterize hormones that induce ACE in vivo, cultured VSMC were exposed to steroids and growth factors. Among steroids, only glucocorticoids stimulated ACE expression with an 8.0 +/- 2.1-fold increase in activity and a 6.5-fold increase in mRNA (30 nM dexamethasone for 72 h). Among growth factors tested, only fibroblast growth factor (FGF) stimulated ACE expression (4.2 +/- 0.7-fold increase in activity and 1.6-fold increase in mRNA in response to 10 ng/ml FGF for 24 h). Dexamethasone and FGF were synergistic at the indicated concentrations inducing 50.6 +/- 12.4-fold and 32.5-fold increases in activity and mRNA expression, respectively. In addition, when porcine iliac arteries were transfected with recombinant FGF-1 (in the absence of injury), ACE expression increased in neointimal VSMC, to the same extent as injured, nontransfected arteries. The data suggest a temporal sequence for the response to injury in which FGF induces ACE, ACE generates angiotensin II, and angiotensin II stimulates VSMC growth in concert with FGF.
Recurrent Incapacitating Mucosal Ulcerations
Authors: Kristin M. Leiferman, J. Desmond O'Duffy, Harold O. Perry, Philip R. Greipp, Emilio R. Giuliani, Gerald J. Gleich
Journal: JAMA (1982)

The hypereosinophilic syndrome is a multisystem disease characterized by infiltration of eosinophils in bone marrow, heart, and other organs. Cutaneous involvement occurs, but usually it appears late in the disease and is of less importance than the cardiac and other organ involvement. We describe two patients with the hypereosinophilic syndrome (HES) in whom the initial manifestations of the disease were recurrent, severe mucosal ulcers involving the mouth and genitalia. In both patients, the mucosal involvement antedated the cardiac manifestations of the disease, and in both, the disease was refractory to treatment.
Natural History of More Than 20 Years of Node-Positive Primary Breast Carcinoma Treated With Cyclophosphamide, Methotrexate, and Fluorouracil–Based Adjuvant Chemotherapy: A Study by the Cancer and Leukemia Group B
Authors: Raymond B. Weiss, Susan H. Woolf, Erin Demakos, James F. Holland, Donald A. Berry, Geoffrey Falkson, Constance T. Cirrincione, Alice Robbins, Sandra Bothun, I. Craig Henderson, Larry Norton
Journal: Journal of Clinical Oncology (2003)

Breast cancer heterogeneity dictates lengthy follow-up to assess outcomes. Efficacy differences for three regimens that are based on adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) are presented in this article, but cancer recurrence sites, time of relapse, subsequent primary cancers, and causes of death in the natural history of node-positive breast cancer are emphasized.Beginning in 1975, 905 patients with node-positive cancer were randomly assigned to receive CMF or two regimens of CMF plus other agents. Median follow-up is 22.6 years. The natural-history analysis was performed on a subset of 814 patients.Eighty percent of the 599 women known to have died, died of metastatic breast cancer. Only 8.5% of the deceased women died of a cause other than breast cancer, a second or third cancer, or adjuvant chemotherapy toxicity. One hundred five women (12.8%) developed other primary cancers, with 49 (46.6%) occurring in the contralateral breast. Therapeutic efficacy differences of the CMF regimens reported earlier have been maintained more than 20 years later. For certain subsets, the five-drug regimen had advantages over CMF. Bone was the most common recurrence site. The longest interval to relapse has been 23.5 years, and 18% of those who relapsed did so more than 10 years later.Despite adjuvant chemotherapy, a large majority (80%) of women with node-positive breast cancer die of the disease, and many recurrences develop more than 10 years later. CMF plus vincristine and prednisone provides a benefit compared with CMF, but the magnitude varies with the number of involved nodes. Outcome trends in earlier analyses of this study were maintained even years later.
Management of Chronic Stable Angina: Medical Therapy, Percutaneous Transluminal Coronary Angioplasty, and Coronary Artery Bypass Graft Surgery: Lessons from the Randomized Trials
Authors: Allen J. Solomon
Journal: Annals of Internal Medicine (1998)

Purpose: To review the available data on the treatment of chronic stable angina and formulate a rational approach to the use of pharmacologic therapy, percutaneous transluminal coronary angioplasty (PTCA), and coronary artery bypass graft surgery (CABG). Data Sources: A MEDLINE search of the English-language literature published between 1976 and 1996 and the bibliographies of relevant articles. Study Selection: Primary research articles, meta-analyses, and meeting abstracts related to the management of chronic stable angina with an emphasis on comparisons of medical therapy, PTCA, and CABG. Data Extraction: Three trials comparing medical therapy with PTCA, seven trials comparing medical therapy with CABG, and nine trials comparing PTCA with CABG. Data Synthesis: Low-risk patients with single-vessel coronary artery disease and normal left ventricular function had greater alleviation of symptoms with PTCA than with medical treatment; mortality rates and rates of myocardial infarction were unchanged. In high-risk patients (risk was defined by severity of ischemia, number of diseased vessels, and presence of left ventricular dysfunction), improvement of survival was greater with CABG than with medical therapy. In moderate-risk patients with multivessel coronary artery disease (most had two-vessel disease and normal left ventricular function), PTCA and CABG produced equivalent mortality rates and rates of myocardial infarction. Conclusions: In low-risk patients, a strategy of initial medical therapy is reasonable. In moderate-risk patients, PTCA and CABG produce similar mortality rates and rates of myocardial infarction but PTCA-treated patients require more revascularization procedures. In high-risk patients, CABG is usually preferred.