tbuckley/cabot-search huggingface dataset:
Zoledronic Acid as a New Adjuvant Therapeutic Strategy for Ewing's Sarcoma Patients
Authors: Guillaume A. Odri, Sophie Dumoucel, Gaëlle Picarda, Séverine Battaglia, François Lamoureux, Nadège Corradini, Julie Rousseau, Franck Tirode, Karine Laud, Olivier Delattre, François Gouin, Dominique Heymann, Françoise Redini
Journal: Cancer Research (2010)

Ewing's sarcoma (ES) is the second most frequent pediatric bone tumor also arising in soft tissues (15% of cases). The prognosis of patients with clinically detectable metastases at diagnosis, not responding to therapy or with disease relapse, is still very poor. Among new therapeutic approaches, bisphosphonates represent promising adjuvant molecules to chemotherapy to limit the osteolytic component of bone tumors and to protect from bone metastases. The combined effects of zoledronic acid and mafosfamide were investigated on cell proliferation, viability, apoptosis, and cell cycle distribution of human ES cell lines differing in their p53 and p16/ink4 status. ES models were developed to reproduce both soft tissue and intraosseous tumor development. Mice were treated with 100 μg/kg zoledronic acid (two or four times per week) and/or ifosfamide (30 mg/kg, one to three cycles of three injections). ES cell lines showed different sensitivities to zoledronic acid and mafosfamide at the cell proliferation level, with no correlation with their molecular status. Both drugs induced cell cycle arrest, but in the S or G(2)M phase, respectively. In vivo, zoledronic acid had no effect on soft tissue tumor progression, although it dramatically inhibited ES development in bone. When combined with ifosfamide, zoledronic acid exerted synergistic effects in the soft tissue model: Its combination with one cycle of ifosfamide resulted in an inhibitory effect similar to three cycles of ifosfamide alone. This very promising result could allow clinicians to diminish the doses of chemotherapy.
Should ustekinumab really be used as first-line biological therapy in pityriasis rubra pilaris? Reply from authors
Authors: J. Wohlrab, B. Kreft
Journal: British Journal of Dermatology (2010)

Madam, We thank our Italian colleagues1 for their constructive comments on our letter entitled ‘Treatment of pityriasis rubra pilaris with ustekinumab’.2 As stated in our letter, the aetiology of pityriasis rubra pilaris (PRP) is still unclear and indeed it has not been proven yet if interleukin (IL)‐12, IL‐23 or even tumour necrosis factor (TNF)‐α is significantly involved. Therapy of patients with PRP is known to be difficult and, unfortunately, there is no approved preparation explicitly for this indication. Nevertheless, the use of retinoids with or without psoralen plus ultraviolet A therapy can be considered the therapeutic option which has the highest level of evidence. As validated in single clinical trials with small sample sizes, a response rate of 60–95% can be expected.3, 4 Therefore, all previously published therapy options (e.g. methotrexate, stanozolol, fumaric acid esters, phototherapy procedures, ciclosporin or biologics) have to be regarded as off‐label use and individual attempts to cure. The resulting conditions for a sound therapeutic decision require without doubt a case‐related benefit–risk ratio and, furthermore, individual aspects of comorbidity, quality of life and adherence have to be considered. At the same time, the relevant range of adverse reactions to the favoured therapy must be taken into account and should be discussed with the patient. Through immunosuppressive effects, infection and carcinogenicity risks are of particular importance. The latter is described or cannot be ruled out for methotrexate,5 ultraviolet therapy,5 ciclosporin,5 infliximab,5, 6 adalimumab5, 7 and ustekinumab.5, 8 Additionally, it is still not known if PRP, as such, with its characteristics of a chronic inflammatory disease, is loaded with an increased tumour risk, and it can appear as a paraneoplastic symptom.9
Esophageal Ulceration in Human Immunodeficiency Virus Infection: Causes, Response to Therapy, and Long-Term Outcome
Authors: C. Mel Wilcox
Journal: Annals of Internal Medicine (1995)

To determine the causes of esophageal ulceration, the response rate to currently available therapies, and the long-term outcome in patients with human immunodeficiency virus (HIV) infection.Prospective cohort study.An urban county hospital.Consecutive patients with HIV infection and endoscopically detected esophageal ulceration during a 4-year period.Causes of ulcers were determined from clinical, endoscopic, and pathologic findings. Standard medical therapies for the identified causes were instituted, and ulcer healing was endoscopically confirmed when possible.Symptomatic and endoscopic response to therapy and long-term outcome, including survival.100 patients with esophageal ulcer were identified. Ulcers caused by cytomegalovirus alone were the most common (n = 45); idiopathic ulcers were almost as frequent (n = 40). Herpes simplex virus esophagitis alone was identified as a cause in only 5 patients. Several potential causes of ulcer were found in 5 patients, including Candida esophagitis in 27 patients. Ten patients developed more than one cause of ulceration during long-term follow-up. Eighty-five patients had specific medical therapy for their identified disorders and had an overall response rate of 98%. Median survival from time of diagnosis was 8.9 months (range, 2 days to > 42 months). A difference in median survival was found between patients with cytomegalovirus esophagitis and those with idiopathic esophageal ulcer (7.6 months compared with 13.1 months; P = 0.03).Given 1) the broad spectrum of causes of esophageal ulceration, 2) that each of these causes requires specific therapy, and 3) the apparent high response rate, it is important to do endoscopic evaluation with mucosal biopsy in patients with HIV infection so that a diagnosis can be established and appropriate therapy instituted. Despite effective therapy, long-term survival is poor; however, long-term remission and survival may occur in some patients.
Summary of Views Expressed at the Discussion on Serum Diagnosis at the Meeting of the American Medcal Association at Philadelphia.
Authors: W. H. Welch
Journal: JAMA (1897)

The committee appointed by the Chairman of the Section on Practice of Medicine make the following report: In selecting the material used in making the test the choice between: a, serum, b, dried blood, c, fluid blood, and d, blister fluid, will depend largely upon whether the object be scientific research, clinical diagnosis in hospital or private practice, or public laboratory diagnosis where the samples have to be sent some distance. In spite of considerable variation in technique, there has been a remarkable uniformity in the results obtained by those taking part in the discussion, and their average of about 95 per cent. of successes agrees with the general average of the cases, nearly four thousand, thus far recorded in medical literature. Each of several methods of technique advocated may thus give good results in the hands of those thoroughly familiar with the details found necessary in each case and the
A quasi-universal medium to break the aerobic/anaerobic bacterial culture dichotomy in clinical microbiology
Authors: N. Dione, S. Khelaifia, B. La Scola, J.C. Lagier, D. Raoult
Journal: Clinical Microbiology and Infection (2015)

In the mid-19th century, the dichotomy between aerobic and anaerobic bacteria was introduced. Nevertheless, the aerobic growth of strictly anaerobic bacterial species such as Ruminococcus gnavus and Fusobacterium necrophorum, in a culture medium containing antioxidants, was recently demonstrated. We tested aerobically the culture of 623 bacterial strains from 276 bacterial species including 82 strictly anaerobic, 154 facultative anaerobic, 31 aerobic and nine microaerophilic bacterial species as well as ten fungi. The basic culture medium was based on Schaedler agar supplemented with 1 g/L ascorbic acid and 0.1 g/L glutathione (R-medium). We successively optimized this media, adding 0.4 g/L uric acid, using separate autoclaving of the component, or adding haemin 0.1 g/L or α-ketoglutarate 2 g/L. In the basic medium, 237 bacterial species and ten fungal species grew but with no growth of 36 bacterial species, including 22 strict anaerobes. Adding uric acid allowed the growth of 14 further species including eight strict anaerobes, while separate autoclaving allowed the growth of all tested bacterial strains. To extend its potential use for fastidious bacteria, we added haemin for Haemophilus influenzae, Haemophilus parainfluenzae and Eikenella corrodens and α-ketoglutarate for Legionella pneumophila. This medium allowed the growth of all tested strains with the exception of Mycobacterium tuberculosis and Mycobacterium bovis. Testing primoculture and more fastidious species will constitute the main work to be done, but R-medium coupled with a rapid identification method (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry) will facilitate the anaerobic culture in clinical microbiology laboratories.
Evidence that thrombocytopenia observed in humans treated with orally bioavailable glycoprotein IIb/IIIa antagonists is immune mediated
Authors: Jeffrey T. Billheimer, Ira B. Dicker, Richard Wynn, Jodi D. Bradley, Debra A. Cromley, Helen E. Godonis, Lisa C. Grimminger, Bokang He, Cathy J. Kieras, Donna L. Pedicord, Susan M. Spitz, Beth E. Thomas, Nina I. Zolotarjova, Mary A. Gorko, Gregory F. Hollis, Robert N. Daly, Andrew M. Stern, Dietmar Seiffert
Journal: Blood (2002)
Leucoderma in chronic graft-versus-host disease: excellent repigmentation with noncultured cellular grafting
Authors: A.W. Tan, L.P. Koh, B.K. Goh
Journal: British Journal of Dermatology (2011)

Journal Article Leucoderma in chronic graft‐versus‐host disease: excellent repigmentation with noncultured cellular grafting Get access A.W. Tan, A.W. Tan National Skin Centre, 1 Mandalay Road, Singapore 308205 Search for other works by this author on: Oxford Academic Google Scholar L.P. Koh, L.P. Koh Department of Haematology‐Oncology, National University Cancer Institute, National University Health System, Singapore Search for other works by this author on: Oxford Academic Google Scholar B.K. Goh B.K. Goh National Skin Centre, 1 Mandalay Road, Singapore 308205 Boon‐Kee Goh. E‐mail: bkgoh@nsc.gov.sg Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 165, Issue 2, 1 August 2011, Pages 435–437, https://doi.org/10.1111/j.1365-2133.2011.10341.x Published: 01 August 2011
The Biochemical Basis of Life History Adaptation: Molecular and Enzymological Causes of NADP+-Isocitrate Dehydrogenase Activity Differences Between Morphs of Gryllus firmus That Differ in Lipid Biosynthesis and Life History
Authors: Rudolf J. Schilder, Anthony J. Zera, Christine Black, Mallary Hoidal, Cody Wehrkamp
Journal: Molecular Biology and Evolution (2011)

Although whole-organism aspects of life-history physiology are well studied and molecular information (e.g., transcript abundance) on life-history variation is accumulating rapidly, much less information is available on the biochemical (enzymological) basis of life-history adaptation. The present study investigated the biochemical and molecular causes of specific activity differences of the lipogenic enzyme, NADP+-isocitrate dehydrogenase, between genetic lines of the wing-polymorphic cricket, Gryllus firmus, which differ in lipid biosynthesis and life history. With one exception, variation among 21 Nadp+-Idh genomic sequences, which spanned the entire coding sequence of the gene, was restricted to a few synonymous substitutions within and among replicate flight-capable or flightless lines. No NADP+-IDH electromorph variation was observed among individuals within or among lines as determined by polyacrylamide gel electrophoresis. Nor did any NADP+-IDH kinetic or stability parameter, such as KM for substrate or cofactor, kcat, or thermal denaturation, differ between flight-capable and flightless lines. By contrast, line differences in NADP+-IDH–specific activity strongly covaried with transcript abundance and enzyme protein concentration. These results demonstrate that NADP+-IDH–specific activity differences between artificially selected lines of G. firmus are due primarily, if not exclusively, to genetic variation in regulators of NADP+-IDH gene expression, with no observed contribution from altered catalytic efficiency of the enzyme due to changes in amino acid sequence or posttranslational modification. Kinetic analyses indicate that in vitro differences in enzyme-specific activity between flight-capable and flightless lines likely occur in vivo. This study constitutes the most comprehensive analysis to date of the biochemical and molecular causes of naturally occurring genetic variation in enzyme activity that covaries strongly with life history.
Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma
Authors: Dirk Schadendorf, F. Stephen Hodi, Caroline Robert, Jeffrey S. Weber, Kim Margolin, Omid Hamid, Debra Patt, Tai-Tsang Chen, David M. Berman, Jedd D. Wolchok
Journal: Journal of Clinical Oncology (2015)

To provide a more precise estimate of long-term survival observed for ipilimumab-treated patients with advanced melanoma, we performed a pooled analysis of overall survival (OS) data from multiple studies.
Use of mortality within 30 days of a COPD hospitalisation as a measure of COPD care in UK hospitals
Authors: P P Walker, E Thompson, H Crone, G Flatt, K Holton, S L Hill, M G Pearson
Journal: Thorax (2013)

Mortality rate has been proposed as a metric of hospital chronic obstructive pulmonary disease (COPD) care in light of variation seen in national COPD audits. Using Hospital Episode Statistics (hospital 'coding') we examined 30-day mortality after COPD hospitalisation in 150 UK hospitals during 2006-2007 and 2007-2008. Mean and median 30-day mortalities were similar each year but the coefficient of variation was >20% and hospitals could change from a low or high quartile to the median by chance. We could not detect any reasons for hospitals being at the extremes. 30-day mortality after COPD hospitalisation is a complex variable and unlikely to be useful as a primary annual COPD metric.
Effect of inhaled ozone on exhaled nitric oxide, pulmonary function, and induced sputum in normal and asthmatic subjects
Authors: J. A Nightingale, D. F Rogers, P. J Barnes
Journal: Thorax (1999)

Nitric oxide (NO) may have a role in the pathophysiology of tissue injury in response to inhaled ozone in animals.A double blind, randomised, placebo controlled, crossover study was undertaken to investigate the effects of inhaled ozone in 10 normal and 10 atopic asthmatic volunteers. Subjects were exposed to 200 ppb ozone or clean air for four hours with intermittent exercise, followed by hourly measurement of spirometric parameters and exhaled NO for four hours. Nasal NO and methacholine reactivity were measured and exhaled breath condensate and induced sputum samples were collected four and 24 hours after exposure.Exposure to ozone caused a fall in forced expiratory volume in one second (FEV(1)) of 7% in normal subjects (p<0.05) and 9% in asthmatic subjects (p<0.005). There was a 39% increase in sputum neutrophils at four hours in normal subjects (p<0.05) and a 35% increase at four hours in asthmatic subjects, remaining high at 24 hours (p<0.005 and p<0.05, respectively). There were no differences between normal and asthmatic subjects. There were no changes in methacholine reactivity, exhaled or nasal NO, nitrite levels in exhaled breath condensate, or sputum supernatant concentrations of interleukin 8, tumour necrosis factor alpha, or granulocyte-macrophage colony stimulating factor in either group.Exposure to 200 ppb ozone leads to a neutrophil inflammatory response in normal and asthmatic subjects but no changes in exhaled NO or nitrite levels.
Importance of Treadmill Exercise Time as an Initial Prognostic Screening Tool in Patients With Systolic Left Ventricular Dysfunction
Authors: Eileen Hsich, Eiran Z. Gorodeski, Randall C. Starling, Eugene H. Blackstone, Hemant Ishwaran, Michael S. Lauer
Journal: Circulation (2009)

Background— We sought to determine whether treadmill exercise time may be of value as an initial prognostic screening tool in ambulatory patients with impaired systolic function who are referred for cardiopulmonary exercise testing. Methods and Results— We studied 2231 adult systolic heart failure patients (27% of whom were women) who underwent cardiopulmonary stress testing using a modified Naughton protocol. We assessed the value of treadmill exercise time for prediction of all-cause death and a composite of death or United Network for Organ Sharing status 1 heart transplantation. During a mean follow-up of 5 years, 742 patients (33%) died. There were 249 United Network for Organ Sharing status 1 heart transplants (11%). Treadmill exercise time was predictive of death and the composite outcome in both women and men, even after accounting for peak oxygen consumption and other clinical covariates (adjusted hazard ratio of lowest versus high sex-specific quartile for prediction of death 1.70, 95% confidence interval 1.05 to 2.75, P =0.03; for prediction of the composite outcome, 1.75, 95% confidence interval 1.15 to 2.66, P =0.009). For a 1-minute change in exercise time, there was a 7% increased hazard of death (eg, comparing 480 to 540 seconds, hazard ratio =1.07, 95% confidence interval 1.02 to 1.12, P =0.004). Conclusions— Because cardiopulmonary stress testing is not available in every hospital, treadmill exercise time with a modified Naughton protocol may be of value as an initial prognostic screening tool.
Progress in cancer genetics: Lessons from pancreatic cancer
Authors: M. Goggins, S.E. Kern, J.A. Offerhaus, R.H. Hruban
Journal: Annals of Oncology (1999)

In the near future advances in the molecular basis of cancer are expected to facilitate cancer diagnosis, to rationalize treatment, to facilitate screening, and to identify individuals requiring cancer prevention strategies.The literature was reviewed concerning the genetic alterations that contribute to pancreatic cancer development.Virtually all pancreatic cancers have inactivation of the p16 pathway, and the majority inactivate the TGF beta/DPC4 and p53 tumor-suppressive pathways. Pancreatic cancers with mismatch repair deficiency have a characteristic histology and may have an improved prognosis. The recently discovered tumor suppressor genes, ALK-5, MKK4, and STK11 (the gene responsible for Peutz-Jeghers syndrome) are all targeted for mutation in a small proportion of sporadic pancreatic cancers. Germline mutations of the BRCA2 gene are present in 5-10% of patients with pancreatic cancer. Typically such patients do not have a family history of pancreatic cancer and are mistaken as patients with sporadic disease. Five to 10% of patients with pancreatic cancer have first-degree relatives that will develop pancreatic cancer. Some such families also have a family history of melanoma and harbor germline p16 mutations. However, the gene(s) responsible for much of the inherited predisposition to pancreatic cancer remain to be identified.Further advances in pancreatic cancer molecular genetics are needed to facilitate the development of molecular screening tests, to identify additional familial susceptibility genes, and to identify targets for rational therapeutic targeting.
Ventilator-induced lung injury
Authors: J‐D. Ricard, D. Dreyfuss, G. Saumon
Journal: European Respiratory Journal (2003)

During mechanical ventilation, high end-inspiratory lung volume (whether it be because of large tidal volume ( V T ) and/or high levels of positive end-expiratory pressure) results in a permeability type pulmonary oedema, called ventilator-induced lung injury (VILI). Previous injury sensitises lung to mechanical ventilation. This experimental concept has recently received a resounding clinical illustration after a 22% reduction of mortality was observed in acute respiratory distress syndrome patients whose V T had been reduced. In addition, it has been suggested that repetitive opening and closing of distal units at low lung volume could induce lung injury but this notion has been challenged both conceptually and clinically after the negative results of the Acute Respiratory Distress Syndrome clinical Network Assessment of Low tidal Volume and Elevated end-expiratory volume to Obviate Lung Injury (ARDSNet ALVEOLI) study. Experimentally and clinically, involvement of inflammatory cytokines in VILI has not been unequivocally demonstrated. Cellular response to mechanical stretch has been increasingly investigated, both on the epithelial and the endothelial side. Lipid membrane trafficking has been thought to be a means by which cells respond to stress failure. Alterations in the respiratory system pressure/volume curve during ventilator-induced lung injury that include decrease in compliance and position of the upper inflection point are due to distal obstruction of airways that reduce aerated lung volume. Information from this curve could help avoid potentially harmful excessive tidal volume reduction.
Effects of stretching before and after exercising on muscle soreness and risk of injury: systematic review
Authors: R. D Herbert
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective</b>: To determine the effects of stretching before and after exercising on muscle soreness after exercise, risk of injury, and athletic performance. <b>Method</b>: Systematic review. <b>Data sources</b>: Randomised or quasi-randomised studies identified by searching Medline, Embase, CINAHL, SPORTDiscus, and PEDro, and by recursive checking of bibliographies. <b>Main outcome measures</b>: Muscle soreness, incidence of injury, athletic performance. <b>Results</b>: Five studies, all of moderate quality, reported sufficient data on the effects of stretching on muscle soreness to be included in the analysis. Outcomes seemed homogeneous. Stretching produced small and statistically non-significant reductions in muscle soreness. The pooled estimate of reduction in muscle soreness 24 hours after exercising was only 0.9 mm on a 100 mm scale (95% confidence interval −2.6 mm to 4.4 mm). Data from two studies on army recruits in military training show that muscle stretching before exercising does not produce useful reductions in injury risk (pooled hazard ratio 0.95, 0.78 to 1.16). <b>Conclusions</b>: Stretching before or after exercising does not confer protection from muscle soreness. Stretching before exercising does not seem to confer a practically useful reduction in the risk of injury, but the generality of this finding needs testing. Insufficient research has been done with which to determine the effects of stretching on sporting performance.