tbuckley/cabot-search huggingface dataset:
Genetic Deletion of Toll-Like Receptor 4 on Platelets Attenuates Experimental Pulmonary Hypertension
Authors: Eileen M. Bauer, R. Savanh Chanthaphavong, Chhinder P. Sodhi, David J. Hackam, Timothy R. Billiar, Philip M. Bauer
Journal: Circulation Research (2014)

Recent studies demonstrate a role for toll-like receptor 4 (TLR4) in the pathogenesis of pulmonary hypertension (PH); however, the cell types involved in mediating the effects of TLR4 remain unknown.The objective of this study was to determine the contribution of TLR4 expressed on nonparenchymal cells to the pathogenesis of PH.TLR4 bone marrow chimeric mice revealed an equal contribution of TLR4 on nonparenchymal and parenchymal cells in the pathogenesis of PH as determined by measuring right ventricular (RV) systolic pressure and RV hypertrophy. However, the deletion of TLR4 from myeloid lineage cells had no effect on the development of PH because we found no difference in RV systolic pressure or RV hypertrophy in wild-type versus LysM-TLR4(-/-) mice. To explore the potential role of platelet TLR4 in the pathogenesis of PH, platelet-specific TLR4(-/-) mice were generated (PF4-TLR4(-/-) mice). TLR4(-/-) platelets from either global TLR4(-/-) or PF4-TLR4(-/-) mice were functional but failed to respond to lipopolysaccharide, demonstrating a lack of TLR4. PF4-TLR4(-/-) mice demonstrated significant protection from hypoxia-induced PH, including attenuated increases in RV systolic pressure and RV hypertrophy, decreased platelet activation, and less pulmonary vascular remodeling. The deletion of TLR4 from platelets attenuated serotonin release after chronic hypoxia, and lipopolysaccharide-stimulated platelets released serotonin and promoted pulmonary artery smooth muscle cell proliferation in a serotonin-dependent manner.Our data demonstrate that TLR4 on platelets contributes to the pathogenesis of PH and further highlights the role of platelets in PH.
A dose response study of oxitropium bromide in chronic bronchitis.
Authors: E T Peel, G Anderson
Journal: Thorax (1984)

In a dose response study 12 patients with chronic bronchitis and airflow obstruction received inhaled placebo and incremental doses of oxitropium bromide. Significant improvements in peak expiratory flow rate, forced expiratory volume in one second, and forced vital capacity were recorded at all times up to 10 hours after all doses of oxitropium bromide. Oxitropium bromide is an effective bronchodilator in chronic bronchitis with an optimal dose of 400-600 micrograms.
A Specific Reaction in Acute Rheumatism and Rheumatoid Arthritis
Authors: A. J. Mester
Journal: Annals of the Rheumatic Diseases (1941)

THE need for an objective sign or test for the existence or non- existence of rheumatic infection of joints is of great importance.Researches to this end have been carried out during a period of several years in the First Medical Clinic, Jagellons University, Cracow, Poland.Injection of many different substances-his- tamine, pilocarpine, atropine, adrenaline, milk, etc.-intra- cutaneously, subcutaneously and intravenously, were tested by many methods but no specific reaction was identified.Search was made for " H " substances released by strictly regulated skin trauma, but no obvious specific reaction could be detected.Blood was taken from rheumatic and non-rheumatic patients be- fore and after fixed skin trauma.At the height of Lewis's triple response blood was taken from the vein and both injected intra- muscularly on the next day-Si, without H substance and Sii containing H substance.All the patients were in bed and fasting, and examinations were made for general, local, and blood reactions.It was found that rheumatic patients had a greater production of H substances than the control patients, but thyro-toxic and neurotic patients revealed also an increased production of H substances.After prolonged investigations a reaction, however, was found which proved to have a high specificity for rheumatism.This reaction depends on the special sensitivity of rheumatic patients to salicylic acid.The patients are kept in bed preferably, but ambulatory patients may be examined in the sitting position; in either case they must be fasting.A count is made of the white blood corpuscles, and after this count 1 cubic centimetre of a 0-1 per cent.aqueous solution of salicylic acid is injected intradermally, forming five blebs each of 0-2 c.cm. on the flexor aspect of the forearm, and after thirty minutes another white count is made.During this time the patient is forbidden to eat, drink, or make any effort.Nearly all rheumatic patients, acute, subacute or chronic, show after the injection a drop in the number of white cells after thirty minutes; in a further group a second count was made after sixty minutes, but only a small number of rheumatic patients 266 copyright.
Using a Self-Report Depression Scale to Identify Remission in Depressed Outpatients
Authors: Mark Zimmerman, Michael A Posternak, Iwona Chelminski
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Some have suggested that standardized rating scales be used in clinical practice to monitor the course of treatment; however, the time demands of clinical practice make it difficult to use such measures. This study derived a cutoff on a self-report depression questionnaire corresponding to the most widely used definition of remission (a score ≤7 on the 17-item Hamilton Depression Rating Scale). METHOD: Two hundred sixty-seven depressed outpatients were rated on the Hamilton depression scale and completed the Clinically Useful Depression Outcome Scale (CUDOS). The authors used receiver operating curve analysis to examine the ability of the CUDOS to identify remission on the Hamilton depression scale. RESULTS: A high level of agreement was found between the self-report and Hamilton depression scale assessments of remission. CONCLUSIONS: Self-report questionnaires represent a practical option for thoroughly and objectively evaluating the course of treatment and determining remission in depressed patients.
Two Essentially Distinct Conditions of Kidney Giving Rise to what is Called Bright's Disease
Authors: W. H. Dickinson
Journal: BMJ (1859)

which it is an attendant do not prove fatal, will gradually sub- side spontaneously; and the veins usually become clear again.Considering the nature and cause of the maladv, we should be unwillin, to resort to the use of leeches.Nevertheless, I have knoWn decided relief follow their application when the pain and 1. Near the capsule an effusion is often seen, obviously between the tubules.
Remission of asthma: a prospective longitudinal study from northern Europe (RHINE study)
Authors: M. Holm, E. Omenaas, T. Gíslason, C. Svanes, R. Jögi, E. Norrman, C. Janson, K. Torén
Journal: European Respiratory Journal (2007)

The aim of the present study was to investigate the remission rate of adult asthma in a general population sample in relation to age, sex, asthma symptoms, allergic rhinitis and smoking. A follow-up of the random population samples from the European Community Respiratory Health Survey in Northern Europe was conducted from 1999–2001 on 1,153 individuals (aged 26–53 yrs) with reported asthma. Remission was defined as no asthmatic symptoms in two consecutive years and no current use of asthma medication. Remission rates per 1,000 person-yrs were calculated and Cox regression models, adjusting for confounders, were used to estimate hazard ratios (HR) with 95% confidence intervals (CI). An average remission rate of 20.2 per 1,000 person-yrs was found. There was no significant difference according to sex; the remission rates were 21.7 and 17.8 per 1,000 person-yrs in females and males, respectively. An increased remission rate was observed among subjects who quit smoking during the observation period. Subjects not reporting any asthma symptom at baseline had an increased remission rate. In the Cox regression model, ex-smoking (HR 1.65, 95% CI 1.01–2.71) was associated with increased remission rate, and reporting any asthma symptom at baseline was associated with decreased remission rate (HR 0.7, 95% CI 0.40–0.90). In conclusion, the present prospective longitudinal study showed that quitting smoking and the presence of mild disease appeared to favour remission.
Nonlinear dynamics of rate-dependent activation in models of single cardiac cells.
Authors: A Vinet, D R Chialvo, D C Michaels, J Jalife
Journal: Circulation Research (1990)

Recent studies in isolated cardiac tissue preparations have demonstrated the applicability of a one-dimensional difference equation model describing the global behavior of a driven nonpacemaker cell to the understanding of rate-dependent cardiac excitation. As a first approximation to providing an ionic basis to complex excitation patterns in cardiac cells, we have compared the predictions of the one-dimensional model with those of numerical simulations using a modified high-dimensional ionic model of the space-clamped myocyte. Stimulus-response ratios were recorded at various stimulus magnitudes, durations, and frequencies. Iteration of the difference equation model reproduced all important features of the ionic model results, including a wide spectrum of stimulus-response locking patterns, period doubling, and irregular (chaotic) dynamics. In addition, in the parameter plane, both models predict that the bifurcation structure of the cardiac cell must change as a function of stimulus duration, because stimulus duration modifies the type of supernormal excitability present at short diastolic interval. We conclude that, to a large extent, the bifurcation structure of the ionic model under repetitive stimulation can be understood by two functions: excitability and action potential duration. The characteristics of these functions depend on the stimulus duration.
The Ingleby Lecture ON PUERPERAL INFECTION, WITH SPECIAL REFERENCE TO VACCINE TREATMENT
Authors: J. F. Jordan
Journal: BMJ (1912)

PUERPERAL INFECTION.LJULY 6, I912.be iniclined to give a hopeftul prognosis.In reality the prognosis is very grave: the pulse gets weaker and weaker, the tongtue becomiies furred, and dry sordes appear on the lips and gums; tlle nourisliment takeni becomes less anld less, rigors may or may not occur, prostration becomiies niore nmarked, tlhe distension of the abdcomen increases, constipation gives way to septic diarrhoea with involuntary evacuation, and the patient rapidly sinks from acute toxin poisoning.The rapidly fatal cases at Sparkhill were all in the latest stages of acute infection on admission, alnd it was impossible to render them immuine to the infection; but that these cases are not neces- sarilv fatal, a,nd that they are not naturally bound to follow the distressing course I hrave briefly outlined, is kinown to all and is well illustrated by tlhree cases I -have seeln recently outside the -hospitaL.Th6 hlistory of these cases is as follows: CASE I.Mrs. F., patient of D;.Middleton.
Subtype and Prognostic Classification of Rhabdomyosarcoma by Immunohistochemistry
Authors: Marco Wachtel, Tina Runge, Ivo Leuschner, Sabine Stegmaier, Ewa Koscielniak, Jörn Treuner, Bernhard Odermatt, Silvia Behnke, Felix K. Niggli, Beat W. Schäfer
Journal: Journal of Clinical Oncology (2006)

Rhabdomyosarcoma (RMS) is classified into two main subgroups: the embryonal (ERMS) and the alveolar (ARMS) form. The majority of the ARMSs are associated with specific chromosomal translocations (pARMS). Because ARMS is much more aggressive than ERMS, RMS subclassification has clinical relevance. However, diagnosis of RMS subgroups on the basis of histology or molecular biology can be difficult, and supplementing diagnostic methods would be desirable. The aim of this study was to establish a panel of markers for RMS subgroup classification by immunohistochemistry.Gene expression data were used for selection of subgroup-specific markers. Single sections of RMS with available expression data were used for establishment of the immunohistochemistry. Evaluation of the sensitivity and specificity of the markers was carried out using a tissue array representing 252 RMSs. Kaplan-Meier survival curves were calculated for determination of differences in overall survival of the different staining subgroups.AP2beta and P-cadherin were selected as markers for pARMS, and epidermal growth factor receptor (EGFR) and fibrillin-2 as markers for ERMS. EGFR + fibrillin-2 detected ERMS with a specificity of 90% and with a sensitivity of 60%. AP2beta + P-cadherin detected pARMS with a specificity of 98% and a sensitivity of 64%, and allowed the detection of several misclassified tumors. The EGFR + fibrillin-2-positive group is associated with a favorable outcome, and the AP2beta + P-cadherin-positive group is associated with an unfavorable outcome.The presented set of marker proteins detects RMS subgroups with high specificity and may be useful in routine subtype classification of RMS.
Fertility and borderline ovarian tumor: a systematic review of conservative management, risk of recurrence and alternative options
Authors: Emile Daraï, Raffaèle Fauvet, Catherine Uzan, Sébastien Gouy, Pierre Duvillard, Philippe Morice
Journal: Human Reproduction Update (2012)

The aim of this systematic review was to evaluate the fertility outcome after borderline ovarian tumor (BOT) management and the results of conservative management, risk of recurrence and alternative options.The search strategy was based on relevant terms concerning BOT using Medline and the Central Cochrane Library. Both early and advanced stages of serous and mucinous BOT were included, but not rare entities such as endometrioid, Brenner or clear-cell BOT because of their low incidence. We considered all articles-case reports, original studies, meta-analyses and reviews-in English and French.Overall, 230 articles were screened of which 120 were retained for review. Most pregnancies were spontaneous but some data were obtained from studies analyzing the contribution of assisted reproductive technology (ART). However, not all studies differentiated spontaneous pregnancy from those obtained after fertility treatment including ovulation induction, intrauterine insemination and IVF. Conservative management of early stage BOT resulted in a pooled estimate for spontaneous pregnancy rate of 54% with a low risk of lethal recurrence (pooled estimate: 0.5%). In patients with advanced stage BOT, the spontaneous pregnancy rates was lower (34% in the single series reporting pregnancy rate in this context) and the risk of lethal recurrence increased (pooled estimate: 2%).This systematic review underlines that fertility subsequent to treatment of BOT depends mainly on histology and initial staging to distinguish early from advanced stages. In patients with advanced stage BOT, several alternative options to conservative management are available to allow patients to conceive without compromising their prognosis.
Defining the atherogenicity of large and small lipoproteins containing apolipoprotein B100
Authors: Murielle M. Véniant, Meghan A. Sullivan, Sun K. Kim, Patricia Ambroziak, Alice Chu, Martha D. Wilson, Marc K. Hellerstein, Lawrence L. Rudel, Rosemary L. Walzem, Stephen G. Young
Journal: Journal of Clinical Investigation (2000)

Apo-E–deficient apo-B100–only mice (Apoe–/–Apob100/100) and LDL receptor–deficient apo-B100–only mice (Ldlr–/–Apob100/100) have similar total plasma cholesterol levels, but nearly all of the plasma cholesterol in the former animals is packaged in VLDL particles, whereas, in the latter, plasma cholesterol is found in smaller LDL particles. We compared the apo-B100–containing lipoprotein populations in these mice to determine their relation to susceptibility to atherosclerosis. The median size of the apo-B100–containing lipoprotein particles in Apoe–/–Apob100/100 plasma was 53.4 nm versus only 22.1 nm in Ldlr–/–Apob100/100 plasma. The plasma levels of apo-B100 were three- to fourfold higher in Ldlr–/–Apob100/100 mice than in Apoe–/–Apob100/100 mice. After 40 weeks on a chow diet, the Ldlr–/–Apob100/100 mice had more extensive atherosclerotic lesions than Apoe–/–Apob100/100 mice. The aortic DNA synthesis rate and the aortic free and esterified cholesterol contents were also higher in the Ldlr–/–Apob100/100 mice. These findings challenge the notion that all non-HDL lipoproteins are equally atherogenic and suggest that at a given cholesterol level, large numbers of small apo-B100–containing lipoproteins are more atherogenic than lower numbers of large apo-B100–containing lipoproteins.
New Approaches to Supporting the Failing Liver
Authors: Sean Cao, Carlos O. Esquivel, Emmet B. Keeffe
Journal: Annual Review of Medicine (1998)

With the continued, growing disparity between the numbers of organ donations and patients waiting for liver transplantation, various efforts have been made to optimize the allocation of organs, as well as to devise means to support the failing liver. Over the years, the development of bioartificial liver-assist devices has aimed at replacing the three main functions of hepatocytes, which are synthetic, metabolic, and excretory. The application of porcine hepatocytes in humans to carry out biotransformation, as well as other metabolic functions and refinement of the membrane separator, have yielded some promising results in supporting patients with acute liver failure. Further advances will need to be made before these bioartificial devices can be considered for routine application in clinical settings.
Phase II and pharmacogenomics study of enzastaurin plus temozolomide during and following radiation therapy in patients with newly diagnosed glioblastoma multiforme and gliosarcoma
Authors: N. Butowski, S. M. Chang, K. R. Lamborn, M.-Y. Polley, R. Pieper, J. F. Costello, S. Vandenberg, R. Parvataneni, A. Nicole, P. K. Sneed, J. Clarke, E. Hsieh, B. M. Costa, R. M. Reis, M. Hristova-Kazmierski, S. J. Nicol, D. E. Thornton, M. D. Prados
Journal: Neuro-Oncology (2011)

This open-label, single-arm, phase II study combined enzastaurin with temozolomide plus radiation therapy (RT) to treat glioblastoma multiforme (GBM) and gliosarcoma. Adults with newly diagnosed disease and Karnofsky performance status (KPS) ≥ 60 were enrolled. Treatment was started within 5 weeks after surgical diagnosis. RT consisted of 60 Gy over 6 weeks. Temozolomide was given at 75 mg/m(2) daily during RT and then adjuvantly at 200 mg/m(2) daily for 5 days, followed by a 23-day break. Enzastaurin was given once daily during RT and in the adjuvant period at 250 mg/day. Cycles were 28 days. The primary end point was overall survival (OS). Progression-free survival (PFS), toxicity, and correlations between efficacy and molecular markers analyzed from tumor tissue samples were also evaluated. A prospectively planned analysis compared OS and PFS of the current trial with outcomes from 3 historical phase II trials that combined novel agents with temozolomide plus RT in patients with GBM or gliosarcoma. Sixty-six patients were enrolled. The treatment regimen was well tolerated. OS (median, 74 weeks) and PFS (median, 36 weeks) results from the current trial were comparable to those from a prior phase II study using erlotinib and were significantly better than those from 2 other previous studies that used thalidomide or cis-retinoic acid, all in combination with temozolomide plus RT. A positive correlation between O-6-methylguanine-DNA methyltransferase promoter methylation and OS was observed. Adjusting for age and KPS, no other biomarker was associated with survival outcome. Correlation of relevant biomarkers with OS may be useful in future trials.
The use of match day imaging in professional sport
Authors: John W Orchard
Journal: British Journal of Sports Medicine (2010)

In the era of evidence-based medicine, case series are becoming less frequent in BJSM , but such papers can provide the first reports of true innovations in a specialty. The use of ultrasound on the sidelines in the professional sports team setting is likely to become widespread now that portable high-quality machines are available in the £20 000–30 000 price range. James, Barbour and Stone ( see page 1149 ), suggest there will be some, albeit limited, ability of sideline ultrasound to …
Development of a Validated Immunofluorescence Assay for γH2AX as a Pharmacodynamic Marker of Topoisomerase I Inhibitor Activity
Authors: Robert J. Kinders, Melinda Hollingshead, Scott Lawrence, Jiuping Ji, Brian Tabb, William M. Bonner, Yves Pommier, Larry Rubinstein, Yvonne A. Evrard, Ralph E. Parchment, Joseph Tomaszewski, James H. Doroshow
Journal: Clinical Cancer Research (2010)

Phosphorylated histone H2AX (γH2AX) serves as a biomarker for formation of DNA double-strand break repair complexes. A quantitative pharmacodynamic immunofluorescence assay for γH2AX was developed, validated, and tested in human tumor xenograft models with the use of clinically relevant procedures.The γH2AX immunofluorescence assay uses a novel data quantitation and image processing algorithm to determine the extent of nuclear-specific γH2AX staining in tumor needle biopsies and hair follicles collected from mice bearing topotecan-responsive A375 xenografts. After method validation with the topoisomerase I (Top1) inhibitor topotecan, the assay was used to compare pharmacodynamic properties of three structurally related indenoisoquinoline Top1 inhibitors.γH2AX response to topotecan was quantified over a 60-fold dose range (0.016-1.0 times the murine single-dose maximum tolerated dose), and significant pharmacodynamic response was measured at the mouse equivalent of the 1.5 mg/m(2) clinical dose as well as the lowest dose tested. Responses were within a time window amenable for biopsy collection in clinical trials. These studies enabled characterization of dose and time responses for three indenoisoquinolines, resulting in selection of two for clinical evaluation. γH2AX response to Top1 inhibitors in hair follicles was also observable above a minimal dose threshold.Our γH2AX assay is sufficiently accurate and sensitive to quantify γH2AX in tumor samples and will be used in correlative studies of two indenoisoquinolines in a phase I clinical trial at the National Cancer Institute. Data suggest that hair follicles may potentially serve as a surrogate tissue to evaluate tumor γH2AX response to Top1 inhibitors.
Hamiltonian Systems and Optimal Control in Computational Anatomy: 100 Years Since D'Arcy Thompson
Authors: Michael I. Miller, Alain Trouvé, Laurent Younes
Journal: Annual Review of Biomedical Engineering (2015)

The Computational Anatomy project is the morphome-scale study of shape and form, which we model as an orbit under diffeomorphic group action. Metric comparison calculates the geodesic length of the diffeomorphic flow connecting one form to another. Geodesic connection provides a positioning system for coordinatizing the forms and positioning their associated functional information. This article reviews progress since the Euler-Lagrange characterization of the geodesics a decade ago. Geodesic positioning is posed as a series of problems in Hamiltonian control, which emphasize the key reduction from the Eulerian momentum with dimension of the flow of the group, to the parametric coordinates appropriate to the dimension of the submanifolds being positioned. The Hamiltonian viewpoint provides important extensions of the core setting to new, object-informed positioning systems. Several submanifold mapping problems are discussed as they apply to metamorphosis, multiple shape spaces, and longitudinal time series studies of growth and atrophy via shape splines.