tbuckley/cabot-search huggingface dataset:
P252 A physiological characterisation of injury, inflammation and resolution in murine aspiration pneumonitis
Authors: B. V. Patel, M. R. Wilson, M. Takata
Journal: Thorax (2010)

<h3>Introduction and Objectives</h3> Aspiration pneumonitis is an important risk factor for acute lung injury/acute respiratory distress syndrome (ALI/ARDS).1 Animals models of ALI should ideally mimic the human situation, although to date none fully reflect the complex pathophysiology involved. Our objective was to develop, optimise and characterise a model of acid aspiration that would closely resemble clinical ALI/ARDS including both inflammatory and recovery phases. While longer-term animal models of acid aspiration have been utilised, their clinical applicability has been limited by high mortality or use of unilateral pulmonary instillation2. <h3>Methods</h3> C57Bl6 mice were anaesthetized, orotracheally catheterised and instilled with 75 μl of 0.1 M hydrochloric acid. They were recovered with FiO<sub>2</sub> of 0.4 for 6 h and then placed in room air. At pre-determined time points they underwent tracheostomy, low tidal volume ventilation (8 ml/kg), and arterial catheter placement. Respiratory system mechanics and arterial oxygenation were determined, and following termination, bronchoalveolar lavage (BAL) was sampled for neutrophil infiltration and total protein concentration. <h3>Results</h3> Following acid aspiration mice showed significant weight loss, decreased PaO<sub>2</sub>:FiO<sub>2</sub> ratios and increased respiratory system elastance compared to untreated controls. There was significant pulmonary endothelial/epithelial leak as measured by BAL protein concentration, as well as substantial neutrophil influx. Changes in all of these parameters were transient, peaking on days 1–3 and then resolving to near baseline by day 10 (Abstract P252 Table 1). <h3>Conclusion</h3> In this study, we describe a translational model of acid-induced lung injury that shows significant injury and inflammation resolving over a 10-day period. It shows many characteristics of clinical ALI/ARDS including severe hypoxaemia, worsening respiratory mechanics, alveolar-capillary barrier permeability, and neutrophilic infiltration within the alveolar space. This resolving model of aspiration pneumonitis may allow further elucidation of the pathophysiological mechanisms of ALI/ARDS and its resolution, in particular oedema formation and inflammatory cell recruitment.
Hot Flushes in a 76-Year-Old Man-Reply
Authors: Emmanuel L. Bravo
Journal: JAMA (1986)

<h3>In Reply.—</h3> Thank you for giving me the opportunity to respond to the letters submitted by Drs Harris and Schwartz and Dr Kreider. Hot flushes as the only manifestation of panic disorder and somatization would be very unusual. Such patients usually exhibit a constellation of signs and symptoms representing several systems (principally related to the cardiovascular, gastrointestinal, neurological, and autonomic systems). Symptoms are often vague and sometimes bizarre and overlap with those of common disorders. Whether hot flushes are a manifestation of atypical depression is unclear. In this patient, a therapeutic trial was certainly warranted in view of a normal basic medical workup. However, it needs emphasizing that even when panic disorders or depression is a prime consideration, the physician must remain vigilant for the telltale signs and symptoms that portend the onset of serious organic disease. This will require periodic testing dependent on the clinical setting. All too often
In Vivo Cell Seeding With Anti-CD34 Antibodies Successfully Accelerates Endothelialization but Stimulates Intimal Hyperplasia in Porcine Arteriovenous Expanded Polytetrafluoroethylene Grafts
Authors: Joris I. Rotmans, Jan M.M. Heyligers, Hence J.M. Verhagen, Evelyn Velema, Machiel M. Nagtegaal, Dominique P.V. de Kleijn, Flip G. de Groot, Erik S.G. Stroes, Gerard Pasterkamp
Journal: Circulation (2005)

Background— The patency of AV expanded polytetrafluoroethylene (ePTFE) grafts for hemodialysis is impaired by intimal hyperplasia (IH) at the venous outflow tract. The absence of a functional endothelial monolayer on the prosthetic grafts is an important stimulus for IH. In the present study, we evaluated the feasibility of capturing endothelial progenitor cells in vivo using anti-CD34 antibodies on ePTFE grafts to inhibit IH in porcine AV ePTFE grafts. Methods and Results— In 11 pigs, anti-CD34–coated ePTFE grafts were implanted between the carotid artery and internal jugular vein. Bare ePTFE grafts were implanted at the contralateral side. After 3 (n=2) or 28 (n=9) days, the pigs were terminated, and the AV grafts were excised for histological analysis and SEM. At 3 and 28 days after implantation, 95% and 85% of the coated graft surface was covered by endothelial cells. In contrast, no cell coverage was observed in the bare graft at 3 days, whereas at 28 days, bare grafts were partly covered with endothelial cells (32%; P =0.04). Twenty-eight days after implantation, IH at the venous anastomosis was strongly increased in anti-CD34–coated grafts (5.96±1.9 mm 2 ) compared with bare grafts (1.70±0.4 mm 2 ; P =0.03). This increase in IH coincided with enhanced cellular proliferation at the venous anastomosis. Conclusions— Autoseeding with anti-CD34 antibodies results in rapid endothelialization within 72 hours. Despite persistent endothelial graft coverage, IH at the outflow tract is increased profoundly at 4 weeks after implantation. Further modifications are required to stimulate the protective effects of trapped endothelial cells.
Fabry's Disease With Cardiovascular Changes
Authors: George L. Kemp
Journal: JAMA (1969)

To the Editor:—  The recent letter concerning a case report of Fabry's disease ( 208 :1190, 1969) is of interest. When I reported the first case of Fabry's disease presenting cardiovascular manifestations without skin manifestations in 1967 there were only approximately 50 cases of the disease with skin manifestations reported in the world literature. 1 The first case reported in America was by Fessas et al in 1955 2 . The cardiovascular as well as renal involvement in this disease was described by Ruiter et al 3 placing this entity in a systemic disease order.  I saw two cases of proven Fabry's disease in 1967 and am sure that this disorder is not as rare as one would expect from the literature.
Analysis of candidate modifier loci for the severity of colonic familial adenomatous polyposis, with evidence for the importance of the N-acetyl transferases
Authors: M D Crabtree
Journal: Gut (2004)

<b>Background:</b> We have recently shown that the severity of human colonic familial adenomatous polyposis (FAP) varies in a manner consistent with the action of modifier genes. These modifier genes may harbour common alleles which increase the risk of colorectal cancer (CRC) in the general population. Analyses have suggested several common polymorphisms as risk alleles for CRC. <b>Methods:</b> We determined the association between the severity of colonic FAP (151 patients) and polymorphisms in <i>MTHFR</i>, <i>NAT1</i>, <i>NAT2</i>, <i>GSTM</i>, <i>GSTT</i>, cyclin D1, E-cadherin, and <i>APC</i>. All of these loci have been suggested as influencing the risk of CRC. Colonic FAP severity was quantitated as the number of polyps per colectomy specimen, standardised for colon size. We analysed the relationship between disease severity and genotype at the polymorphic site, making allowance for the position of the germline <i>APC</i> mutation. <b>Results:</b> We identified significant associations between more severe disease and the absence of the <i>NAT1*10</i> genotype in the whole group of patients. In a subset of patients with germline mutations in the so-called “mutation cluster region”, there was an association between more severe disease and the presence of <i>NAT2*fast</i> alleles. In the whole patient set, a relatively strong association existed between more severe disease and possession of both the <i>NAT1*non-10</i> and <i>NAT2*fast</i> genotypes. There was weak evidence for an association between the <i>APCT1493C</i> allele and more severe disease in the whole patient group. No consistent association with disease severity was found for the other polymorphisms. <b>Conclusion:</b> The severity of colonic FAP may be modified by alleles at the <i>NAT1</i> and/or <i>NAT2</i> loci. The identity of any functional variation remains unknown as <i>NAT1*10</i> appears to be non-functional and there is linkage disequilibrium between alleles at multiple sites within these loci which are adjacent on chromosome 8p22. While evidence from this study cannot be conclusive, our data suggest that <i>NAT1</i> and <i>NAT2</i> variants may explain an approximately twofold increase in polyp number in the FAP colon.
Cumulative effect of high radiation dose and prolonged antiplatelet therapy in improving outcomes of patients treated with vascular brachytherapy
Authors: Edouard F. Cheneau, Andrew E. Ajani, Roswitha Wolfram, Rebecca Torguson, Augusto D. Pichard, Lowell F. Satler, Regina Deible, Ellen Pinnow, Afework GebreEyesus, Joseph Lindsay, Ron Waksman
Journal: Journal of the American College of Cardiology (2003)
TECHNETIUM 99m HMPAO SPECT IN CHILDREN WITH VARIOUS SPEECH DISORDERS
Authors: Ilgin Nese, Gucuyener Kivilcim, Gokcora Nahide, Isik Sedat, Unlu M.
Journal: Clinical Nuclear Medicine (1994)

Nese, Ilgin MD; Kivilcim, Gucuyener MD; Nahide, Gokcora MD; Sedat, Isik MD; M., Unlu Author Information
Vascular function in preeclampsia
Authors: M VanWijk
Journal: Cardiovascular Research (2000)

Preeclampsia is a multisystem disorder peculiar to human pregnancy. It occurs in 4–5% of all pregnancies and remains a leading cause of maternal and neonatal mortality and morbidity. The pathophysiology of this syndrome is not fully understood. Two stages of vascular dysfunction seem to be involved. In the early stage suboptimal development of the placenta and a hemodynamic maladaptation to pregnancy exist. At this stage maternal constitutional factors such as genetic and immunological factors and pre-existing vascular diseases may play a role. Due to this defective placentation a factor is released from the placenta, supposedly under the influence of ischemia. This factor then results in the late vascular dysfunction characterised mainly by a generalised endothelial dysfunction, leading to the clinical syndrome of preeclampsia. This review attempts to unravel the mechanisms that may contribute to preeclampsia-associated changes in vascular function and to indicate the research needed to improve our understanding of this disease.
Orphan nuclear receptor NR4A1 regulates transforming growth factor-β signaling and fibrosis
Authors: Katrin Palumbo-Zerr, Pawel Zerr, Alfiya Distler, Judith Fliehr, Rossella Mancuso, Jingang Huang, Dirk Mielenz, Michal Tomcik, Barbara G Fürnrohr, Carina Scholtysek, Clara Dees, Christian Beyer, Gerhard Krönke, Daniel Metzger, Oliver Distler, Georg Schett, Jörg H W Distler
Journal: Nature Medicine (2015)
Intracellular Po <sub>2</sub> and Its Regulation in Resting Skeletal Muscle of the Guinea Pig
Authors: WILLIAM J. WHALEN, PANKAJAM NAIR
Journal: Circulation Research (1967)

Intracellular Po 2 in the gracilis muscle of lightly anesthetized guinea pigs was measured by means of an O 2 microelectrode to see (a) whether the Po 2 was low enough that it might limit O 2 consumption, and (b) whether it would increase with high O 2 breathing. The resting cell membrane potential was used to localize the electrode tip. Of 184 cells tested in 26 animals, 70 cells had a Po 2 of less than 1 mm Hg. Mean intracellular Po 2 was about 4 mm Hg. When 100% O 2 or 98% O 2 -2% CO 2 was administered while the electrode was in a cell, 60 of 89 cells tested (20 animals) showed no change in Po 2 . In the other 29 cells, the Po 2 increased by 5% or more. We have concluded that blood flow in resting skeletal muscle in the anesthetized guinea pig is regulated so as to maintain a low Po 2 -low enough that it could limit O 2 consumption.
Relation of left ventricular filling dynamics to alterations in load and compliance in patients with and without pressure-overload hypertrophy.
Authors: T Wisenbaugh, E Harlamert, A N DeMaria
Journal: Circulation (1990)

A large atrial contribution to left ventricular (LV) filling (%A) in patients with LV hypertrophy has been assumed by some to indicate abnormal LV compliance. We tested this assumption by examining the influence of short- and long-term changes in load on compliance and filling dynamics using nitroprusside to decrease load in 11 patients with severe aortic stenosis (AS) and ergonovine to increase load in nine normal subjects. LV angiographic volume was analyzed frame-by-frame simultaneous with micromanometer pressure recordings. Operative LV chamber compliance (dV/VdP) and a time constant for isovolumic relaxation rate were computed using three-constant exponential equations fit to the data. Compared with normal subjects, resting left ventricular end-diastolic pressure was increased and dV/VdP was reduced in AS, but %A was not different. %A was inversely related to left ventricular end-diastolic pressure (r = -0.48, p = 0.02) and positively correlated with dV/VdP (r = 0.90, p less than 0.001) within the AS group. Nitroprusside infusion reduced LV peak systolic pressure by 11%, end-diastolic pressure by 38%, and end-diastolic volume by 12% (p less than or equal to 0.004 for each) and tended to increase dV/VdP by 26% (p = 0.23). These alterations in load resulted in a 21% decrease (-16 ml) in the early filling volume (p less than 0.05) and variable increases (mean, +7 ml; p = NS) in the late atrial filling volume and in the percent atrial contribution to ventricular filling (26 +/- 19% to 35 +/- 25% for the AS group, p = NS) that were related to changes in compliance.(ABSTRACT TRUNCATED AT 250 WORDS)
Specific immunity in patients suffering from recurring warts before and after repetitive intradermal tests with human papilloma virus
Authors: J. VIAC, J. THIVOLET, Y. CHARDONNET
Journal: British Journal of Dermatology (1977)

The specific humoral and cellular immunity of 22 patients with multiple or recurring warts was studied. After repeated intradermal tests, using an inactivated, purified viral antigen, the responses obtained could be classed into two groups. The first group (10 patients) was characterized immunologically by the acquisition of a specific cellular immunity and the appearance of circulating IgG antibodies, and clinically by a total regression of resolution of the warts two to three weeks after the final intradermal test. The second group (12 patients) was characterized immunologically by a weak or non-existent specific immune response, and clinically by the unmodified persistence of the warts.
Alzheimer Disease Experts Advise a 'Wait for the Data' Response to New Diagnostic Test
Authors: Joan Stephenson
Journal: JAMA (1997)

HIGH ON the wish list of Alzheimer disease (AD) researchers and clinicians is a reliable test for diagnosing the disease. But while a number of methods for doing so have been proposed in recent years, none has yet panned out as the answer clinicians have been looking for. "A recurring theme for most new Alzheimer's disease diagnostics is that they tend to get marketed and hyped before the data are available in large populations," said Creighton Phelps, PhD, director of the Alzheimer Disease Research Centers Program at the National Institute on Aging, Bethesda, Md. Now, a recent advertising campaign for a new diagnostic test that claims to be "the first test proven to help physicians be certain in the diagnosis of Alzheimer's disease" in symptomatic patients has a number of experts concerned that the procedure is being marketed before adequate data substantiating such claims have been reported in peer-reviewed journals
Impact of covert duplicate publication on meta-analysis: a case study
Authors: M. R Tramer, D J. M Reynolds, R A. Moore, H. J McQuay
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objective:</b> To quantify the impact of duplicate data on estimates of efficacy. <b>Design:</b> Systematic search for published full reports of randomised controlled trials investigating ondansetron9s effect on postoperative emesis. Abstracts were not considered. <b>Data sources:</b> Eighty four trials (11 980 patients receiving ondansetron) published between 1991 and September 1996. <b>Main outcome measures:</b> Percentage of duplicated trials and patient data. Estimation of antiemetic efficacy (prevention of emesis) of the most duplicated ondansetron regimen. Comparison between the efficacy of non-duplicated and duplicated data. <b>Results:</b> Data from nine trials had been published in 14 further reports, duplicating data from 3335 patients receiving ondansetron; none used a clear cross reference. Intravenous ondansetron 4 mg versus placebo was investigated in 16 reports not subject to duplicate publication, three reports subject to duplicate publication, and six duplicates of those three reports. The number needed to treat to prevent vomiting within 24 hours was 9.5 (95% confidence interval 6.9 to 15) in the 16 non-duplicated reports and 3.9 (3.3 to 4.8) in the three reports which were duplicated (P&lt;0.00001). When these 19 were combined the number needed to treat was 6.4 (5.3 to 7.9). When all original and duplicate reports were combined (n=25) the apparent number needed to treat improved to 4.9 (4.4 to 5.6). <b>Conclusions:</b> By searching systematically we found 17% of published full reports of randomised trials and 28% of the patient data were duplicated. Trials reporting greater treatment effect were significantly more likely to be duplicated. Inclusion of duplicated data in meta-analysis led to a 23% overestimation of ondansetron9s antiemetic efficacy. <h3>Key messages</h3> Although publishing the same data more than once is strongly discouraged, there is no evidence of the impact of duplicate data on meta-analysis Re-analysing an important trial, and cross referencing to original reports (overt duplication), may be necessary and valuable in some circumstances Covert duplication, masked by change of authors, of language, or by adding extra data, causes problems. One danger is that patient data are analysed more than once in meta-analysis 17% of systematically searched randomised trials of ondansetron as a postoperative antiemetic were covert duplicates and resulted in 28% of patient data being duplicated. None of these reports cross references the original source. Duplication lead to an overestimation of ondansetron9s antiemetic efficacy of 23%. Trials reporting greater treatment effect were significantly more likely to be duplicated Covert duplication of data has major implications for the assessment of drug efficacy and safety
Tetraspan microdomains distinct from lipid rafts enrich select peptide–MHC class II complexes
Authors: H. Kropshofer, S. Spindeldreher, T. A. Röhn, N. Platania, C. Grygar, N. Daniel, A. Wölpl, H. Langen, V. Horejsi, A. B. Vogt
Journal: Nature Immunology (2001)
Phorbol myristate acetate and catechol as skin cocarcinogens in SENCAR mice.
Authors: B L Van Duuren, S Melchionne, I Seidman
Journal: Environmental Health Perspectives (1986)

The enhancement of the carcinogenicity of benzo(a)pyrene (B[a]P) and beta-propiolactone (BPL) by the mouse skin cocarcinogens phorbol myristate acetate (PMA) and catechol were examined in female SENCAR mice, 30 per group. The carcinogen and cocarcinogen were applied simultaneously, three times weekly for 490-560 days. B(a)P and BPL were used at constant doses of 5 and 50 micrograms, respectively, in all experiments. PMA was used at three doses, 2.5, 1.0, and 0.5 micrograms per application, and catechol was used at one dose, 2 mg per application. Control groups included animals that received carcinogen only, cocarcinogen only, acetone only, and no treatment. The carcinogenicity of B(a)P and BPL were enhanced by the cocarcinogens, particularly in terms of tumor multiplicity. For both carcinogens, the most marked cocarcinogenic effects were observed at the lowest dose of PMA used (0.5 microgram per application). This observation applied for days to first tumor, animals with tumors, tumor multiplicity, and incidence of malignant skin tumors. Catechol applied alone did not induce any tumors; with PMA alone there were significant incidences of benign and malignant tumors, e.g., at a dose of only 0.5 microgram per application, 15 of 30 animals had 28 tumors, 5 of which were squamous carcinomas. In two-stage carcinogenesis experiments with 7,12-dimethylbenz(a)anthracene (DMBA) as initiator and PMA as promoter, SENCAR mice showed a greater susceptibility to tumor induction when compared to ICR/Ha mice used in earlier work. This susceptibility was most notable in terms of rate of tumor appearance and tumor multiplicity.
Regulation and Function of Epithelial Secreted Phospholipase A<sub>2</sub> Group X in Asthma
Authors: Teal S. Hallstrand, Ying Lai, William A. Altemeier, Cara L. Appel, Brian Johnson, Charles W. Frevert, Kelly L. Hudkins, James G. Bollinger, Prescott G. Woodruff, Dallas M. Hyde, William R. Henderson, Michael H. Gelb
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Indirect airway hyperresponsiveness (AHR) is a fundamental feature of asthma that is manifest as exercise-induced bronchoconstriction (EIB). Secreted phospholipase A2 group X (sPLA2-X) plays a key role in regulating eicosanoid formation and the development of inflammation and AHR in murine models.
Daily use of a lactobacilli probiotic prevented antibiotic-associated diarrhea in hospitalized patients
Authors: John C. Marshall
Journal: Annals of Internal Medicine (2008)

Source Citation Beausoleil M, Fortier N, Guénette S, et al. Effect of a fermented milk combining Lactobacillus acidophilus CL 1285 and Lactobacillus casei in the prevention of antibiotic-associated diarrhea: a randomized, double-blind, placebo-controlled trial. Can J Gastroenterol. 2007;21:732-6. 18026577
Genetic Screening: Programs, Principles, and Research
Authors: Marc Lappé
Journal: JAMA (1975)

In this ambitious book, a 16-member multidisciplinary committee surveys issues generated by the growing number of genetic screening programs in the United States. The group wished to demonstrate how and under what circumstances such programs can meaningfully become integrated into medical care. If nothing else, reading it will awaken the general practitioner to the need to take genetics seriously. The data show a lamentable degree of understanding of the proper place of genetics in medical practice. Only 29% of the family practitioners surveyed believe that a total cessation of treatment for genetic disorders would have an extremely serious impact on affected children and the families. Similarly, only 20% believe that screening for PKU has proved beneficial, while 15% are fully convinced that carrying the sickle cell trait "frequently causes medical problems"! Some of these statistics become credible in light of the report that only slightly more than half of all