tbuckley/cabot-search huggingface dataset:
Easy bruising as a side-effect of inhaled corticosteroids
Authors: VH Mak, R Melchor, SG Spiro
Journal: European Respiratory Journal (1992)

We wished to determine the prevalence of easy bruising in patients taking inhaled corticosteroids (ICS) compared with those who do not. Differences in age, dosage and duration of use of ICS between patients who bruised and those who did not were also investigated. Confidential questionnaire surveys were conducted over a 6 month study period amongst patients attending a respiratory out-patient clinic and taking regular ICS, and a control group of patients attending non-respiratory clinics and not taking any form of corticosteroids. Patients with bleeding disorders or taking oral steroids, non-steroidal anti-inflammatory drugs or anticoagulants were excluded from the study. Questionnaires from 202 respiratory patients using ICS (group A) were compared with 204 non-ICS patients (Group B) of similar age and sex distribution. Significantly more patients in Group A reported easy bruising than in group B (47 vs 22%, relative risk 2.18, 95% confidence interval (95% CI) 1.62-2.94), and it was the commonest reported symptom. In Group A, the patients that reported easy bruising tended to be older (61 vs 52 yrs), on higher daily dosages (1,388 vs 1,067 micrograms) and had been taking inhaled corticosteroids for longer (55 vs 43 months) than non-bruisers. Overall, females reported easy bruising more frequently than males in both groups. However, comparing Group A with Group B, males taking ICS had a higher relative risk for bruising than females (males, relative risk 5.80, 95% CI 2.38-14.13; females, relative risk 1.80, 95% CI 1.32-2.44).(ABSTRACT TRUNCATED AT 250 WORDS)
Stereoselective pharmacokinetics of S-salbutamol after administration of the racemate in healthy volunteers
Authors: B Schmekel, I Rydberg, B Norlander, K.n Sjöswärd, J Ahlner, R.G.g Andersson
Journal: European Respiratory Journal (1999)

Racemic R,S-salbutamol is taken to relieve bronchial constriction. Only the R-enantiomer has bronchodilating properties. The S-enantiomer has been proposed to cause in vitro bronchial hyperreactivity in guinea-pigs. Stereoselective elimination of salbutamol has been shown, with S-salbutamol being eliminated at a slower rate than R-salbutamol. This study questioned whether rates of stereoselective elimination were similar after oral or lung delivery, and whether the S:R ratio would increase after repeated inhalations in a situation resembling a common clinical use. Eighteen healthy volunteers received single-dose racemic salbutamol as a solution instilled in the trachea during anaesthesia, as inhaled micronized powder and/or as ingested tablets. Five volunteers inhaled repeated doses of racemic salbutamol. Concentrations in plasma and urine were measured using a technique which allowed chiral separation of samples with concentrations as low as 0.1 ng x mL(-1). The bioavailability of S-salbutamol was significantly higher than that of R-salbutamol after the different modes of administration. Stereoselective elimination was more pronounced after oral administration than after inhalation. Repeated inhalations resulted in successive increases in the S:R ratio as steady state was approached. In conclusion, the clinical consequences of increasing plasma concentrations of S-salbutamol need to be further assessed.
Surveillance After Initial Surgery for Pediatric and Adolescent Girls With Stage I Ovarian Germ Cell Tumors: Report From the Children's Oncology Group
Authors: Deborah F. Billmire, John W. Cullen, Frederick J. Rescorla, Mary Davis, Marc G. Schlatter, Thomas A. Olson, Marcio H. Malogolowkin, Farzana Pashankar, Doojduen Villaluna, Mark Krailo, Rachel A. Egler, Carlos Rodriguez-Galindo, A. Lindsay Frazier
Journal: Journal of Clinical Oncology (2014)

Purpose To determine whether overall survival (OS) can be preserved for patients with stage I pediatric malignant ovarian germ cell tumor (MOGCT) with an initial strategy of surveillance after surgical resection. Patients and Methods Between November 2003 and July 2011, girls age 0 to 16 years with stage I MOGCT were enrolled onto Children's Oncology Group study AGCT0132. Required histology included yolk sac, embryonal carcinoma, or choriocarcinoma. Surveillance included measurement of serum tumor markers and radiologic imaging at defined intervals. In those with residual or recurrent disease, chemotherapy with compressed PEB (cisplatin, etoposide, and bleomycin) was initiated every 3 weeks for three cycles (cisplatin 33 mg/m 2 on days 1 to 3, etoposide 167 mg/m 2 on days 1 to 3, bleomycin 15 U/m 2 on day 1). Survivor functions for event-free survival (EFS) and OS were estimated using the Kaplan-Meier method. Results Twenty-five girls (median age, 12 years) with stage I MOGCT were enrolled onto AGCT0132. Twenty-three patients had elevated alpha-fetoprotein (AFP) at diagnosis. Predominant histology was yolk sac. After a median follow-up of 42 months, 12 patients had evidence of persistent or recurrent disease (4-year EFS, 52%; 95% CI, 31% to 69%). Median time to recurrence was 2 months. All patients had elevated AFP at recurrence; six had localized disease, two had metastatic disease, and four had tumor marker elevation only. Eleven of 12 patients experiencing relapse received successful salvage chemotherapy (4-year OS, 96%; 95% CI, 74% to 99%). Conclusion Fifty percent of patients with stage I pediatric MOGCT can be spared chemotherapy; treatment for those who experience recurrence preserves OS. Further study is needed to identify the factors that predict recurrence and whether this strategy can be extended successfully to older adolescents and young adults.
Colonisation of lung allografts with Pseudomonas aeruginosa in heart-lung transplant recipients with cystic fibrosis.
Authors: V Tsang, T L Pitt, M E Kaufmann, H Gaya, M E Hodson, M Yacoub
Journal: Thorax (1994)

Six patients (four with cystic fibrosis, two with bronchiectasis) harboured Pseudomonas aeruginosa in the lung before heart-lung transplantation. Three of the patients with cystic fibrosis were colonised by strains of different genotype postoperatively, and the colonisation tended to be short lived.
Impact of Subsequent Therapies on Outcome of the FIRE-3/AIO KRK0306 Trial: First-Line Therapy With FOLFIRI Plus Cetuximab or Bevacizumab in Patients With <i>KRAS</i> Wild-Type Tumors in Metastatic Colorectal Cancer
Authors: Dominik P. Modest, Sebastian Stintzing, Ludwig Fischer von Weikersthal, Thomas Decker, Alexander Kiani, Ursula Vehling-Kaiser, Salah-Eddin Al-Batran, Tobias Heintges, Christian Lerchenmüller, Christoph Kahl, Gernot Seipelt, Frank Kullmann, Martina Stauch, Werner Scheithauer, Svantje Held, Markus Möhler, Andreas Jung, Thomas Kirchner, Volker Heinemann
Journal: Journal of Clinical Oncology (2015)

Purpose We investigated choice and efficacy of subsequent treatment, with special focus on second-line therapy, in the FIRE-3 trial (FOLFIRI plus cetuximab [arm A] or bevacizumab [arm B]) for patients with KRAS wild-type metastatic colorectal cancer. Patients and Methods Start of subsequent-line (second or third) therapy was defined as use of an antitumor drug that was not part of the previous regimen. We evaluated choice, duration, and efficacy of subsequent therapy and determined the impact of subsequent-line treatment on outcome of patients in FIRE-3. Results Of 592 patients in the intent-to-treat population, 414 (69.9%) received second-line and 256 (43.2%) received third-line therapy. In subsequent treatment lines, 47.1% of patients originally assigned to arm A received bevacizumab, and 52.2% originally assigned to arm B received either cetuximab or panitumumab. Oxaliplatin was subsequently used in 55.9% (arm A) and 53.2% (arm B) of patients. Second-line therapy was administered for a median duration of 5.0 versus 3.2 months (P &lt; .001) in study arm A versus B. Progression-free (6.5 v 4.7 months; hazard ratio, 0.68; 95% CI, 0.54 to 0.85; P &lt; .001) and overall survival (16.3 v 13.2 months; hazard ratio, 0.70; 95% CI, 0.55 to 0.88; P = .0021) from start of second-line therapy were longer in patients in arm A compared with arm B. Conclusion Our data suggest that the sequence of drug application might be more important than exposure to single agents. In patients with RAS wild-type tumors, first-line application of anti–epidermal growth factor receptor–directed therapy may represent a favorable condition for promoting effective subsequent therapy including antiangiogenic agents.
Increased Splenic Transplantable Colony-Forming Units Related to Increased Radioresistance After Rauscher Leukemia Virus Infection of the SJL/J Mouse2
Authors: Arnold M. Markoe, James P. OKunewick, Penny Erhard, Eleanore Phillips
Journal: JNCI Journal of the National Cancer Institute (1973)

Using the exogenous colony-forming unit (CFU) assay of Till and McCulloch, we studied changes in splenic CFU content as a function of time after Rauscher leukemia virus (RLV) infection of the SJL/J mouse, and we related splenic CFU content to previously reported changes in radiosensitivity after infection. Total splenic CFU content [colony-forming potential (CFP)/spleen] first increased after the 6th day of infection, correlating with the appearance of splenomegaly and of radioresistance. CFP/spleen continued to increase until day 22 after infection, reaching 16 times normal levels. This increase was positively correlated with greater radioresistance. Beyond the 22d day of infection, CFP/spleen fell somewhat but was never <9 times normal values. However, calculations based on existing information regarding spleen cell radiation survival and turnover indicated that this level of splenic CFU was sufficient to provide radioprotection at the level of X-ray exposure used. We conclude, from these studies, that RLV infection increased the number of splenic hematopoietic stem cells of the SJL/J mouse and this increase resulted in the greater radio-resistance.
LETTER FROM JAMAICA
Authors: R. D. SWEET
Journal: British Journal of Dermatology (1965)

Journal Article LETTER FROM JAMAICA Get access R. D. SWEET R. D. SWEET Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 77, Issue 1, 1 January 1965, Pages 55–57, https://doi.org/10.1111/j.1365-2133.1965.tb14566.x Published: 01 January 1965
GPs accept government’s offer on extended hours as lesser of two evils
Authors: Adrian O’Dowd
Journal: BMJ (2008)

A large majority of GPs have voted for the first of two government options on how they will provide extended opening hours in surgeries.

The BMA, however, says that GPs will effectively see their pay cut when they start working under the new system from April, as part of changes to the GP contract being imposed after negotiations broke down between the two sides.

More than nine out of 10 (92%) of the GPs who took part in a BMA opinion poll voted for the first of two government options, …
Influence of sleep onset on upper-airway muscle activity in apnea patients versus normal controls.
Authors: W S Mezzanotte, D J Tangel, D P White
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Current evidence suggests that patients with obstructive sleep apnea (OSA) may have augmented pharyngeal dilator muscle activity during wakefulness, to compensate for deficient anatomy. However, the isolated effect of sleep on the activity of these muscles (comparing OSA patients with controls) has not been studied. We therefore determined waking levels of genioglossus (GG) and tensor palatini (TP) muscle activity (% of maximum electromyographic [EMG] activity) in 10 OSA patients and eight controls, and then assessed the impact of the first two breaths of sleep (theta electroencephalographic [EEG] activity) following a period of stable wakefulness. Apnea patients demonstrated greater genioglossal (27.4 +/- 4.0 versus 10.7 +/- 2.1%) and tensor palatini (31.9 +/- 6.5 versus 10.6 +/- 1.9%) EMG activity than did controls during wakefulness. This augmented muscle activity in apnea patients could be reduced to near control levels during wakefulness with the application of continuous positive airway pressure (CPAP) to the upper airway. At sleep onset, control subjects demonstrated small but consistent decrements in the activity of both the TP and GG muscles. On the other hand, apnea patients demonstrated large, significantly greater decrements in TP EMG at sleep onset than did the control subjects. The effect of sleep on GG EMG in apnea patients was inconsistent, with most (n = 7) demonstrating large (significantly larger than controls) decrements in genioglossal activity. However, three OSA patients demonstrated small increments in GG EMG at sleep onset despite falling TP EMG and obstructive apnea or hypopnea. We conclude that sleep onset is associated with significantly larger decrements in TP muscle EMG activity in OSA patients than in controls, which may represent a loss of neuromuscular compensation that is present during wakefulness. However, our results for the GG muscle were more variable, and did not always support this hypothesis.
Surface maturation scoring for oesophageal squamous intraepithelial neoplasia: a novel diagnostic approach inspired by first endomicroscopic 3-dimensional reconstruction
Authors: Ming Li, Xiu-Li Zuo, Tao Yu, Xiao-Meng Gu, Cheng-Jun Zhou, Zhen Li, Hong Liu, Rui Ji, Yan-Yan Dong, Chang-Qing Li, Yan-Qing Li
Journal: Gut (2012)

<h3>Objective</h3> Loss of surface maturation and cytonuclear atypia have been regarded as the pathological 'gold standard' for the diagnosis of oesophageal squamous cell intraepithelial neoplasia. However, there has been no satisfactory endomicroscopic method similar to this pathological approach to detect surface maturation and screen for oesophageal squamous cell intraepithelial neoplasia. The aim of this study was to apply a 3-dimensional (3D) confocal endomicroscopic imaging technique to investigate the surface maturation of the oesophageal epithelium and develop new 2-dimensional confocal endomicroscopic criteria based on surface maturation. <h3>Design</h3> In the 3D reconstruction phase, intrapapillary capillary loops were reconstructed to demonstrate the stereo configuration of the oesophageal epithelium, and a novel surface maturation scoring (SMS) method for plane confocal images was developed based on the interpretation of the 3D microstructure. In the SMS diagnostic phase, 1214 patients were screened and confocal images from 64 non-invasive oesophageal lesions were independently evaluated using SMS and previous methods. <h3>Results</h3> We successfully obtained and interpreted 3D confocal images of the human oesophageal epithelium for the first time. The sensitivity (81.0%, 95% CI 58.1% to 94.6%) and specificity (90.7%, 95% CI 77.9% to 97.4%) of the newly established SMS were superior to previous confocal approaches in distinguishing squamous intraepithelial neoplasia from other non-invasive lesions. <h3>Conclusions</h3> 3D confocal endomicroscopic imaging provides valuable insight into the stereo configuration of the human oesophageal epithelium. SMS is a novel and promising diagnostic method to distinguish neoplasia during ongoing endoscopy.
Phenotypic modulation of chondrocytes as a potential therapeutic target in osteoarthritis: a hypothesis
Authors: T Aigner, J Dudhia
Journal: Annals of the Rheumatic Diseases (1997)

One central hallmark of osteoarthritic cartilage degeneration is the loss of matrix molecules, in particular proteoglycans. However, chondrocytes of osteoarthritic cartilage are generally thought to be anabolically hyperactive. Thus, in osteoarthritic cartilage degeneration, the ongoing net loss of the cartilage matrix components is attributed not to a lack of synthesis of cartilage matrix molecules by the cartilage cells, but to an increase in matrix catabolism by most authors.1-3 In contrast, our in situ analysis on the single cell level showed a suppression of aggrecan and collagen type II expression in the chondrocytes in the upper cartilage zone, which is critical for the progression of the cartilage destruction. Phenotyping of the osteoarthritic chondrocytes in this zone furthermore shows that the decrease in anabolic activity was presumably not simply because of cell deactivation, but may entail a specific cell differentiation pathway taken by the osteoarthritic chondrocytes. Based on our in situ analyses, we suggest a three step process of cellular events as one central pathway during osteoarthritic cartilage destruction. We conclude that stimulation of matrix anabolism via redifferentiation of osteoarthritic chondrocytes may be a relevant goal in future therapeutic approaches to osteoarthritic cartilage destruction.

The functioning of articular cartilage is dependent on its extracellular matrix, which is synthesised and maintained by the cartilage cells, the chondrocytes. The functional properties of cartilage matrix are mainly provided by a network of type II collagen fibres4 and the entrapped aggregates of the proteoglycan aggrecan.5 The hallmarks of osteoarthritic cartilage degeneration are depletion of the matrix proteoglycans, damage to the collagen network, and finally, progressing matrix erosion.3 6-8 Based on our own work and that of others, we present a hypothesis for the basis of progressive cartilage destruction, focusing on the selective changes that occur in the different cartilage zones.

Generally, osteoarthritic …
B cells lacking RelB are defective in proliferative responses, but undergo normal B cell maturation to Ig secretion and Ig class switching.
Authors: C M Snapper, F R Rosas, P Zelazowski, M A Moorman, M R Kehry, R Bravo, F Weih
Journal: The Journal of Experimental Medicine (1996)

A number of distinct functional abnormalities have been observed in B cells derived from p50/ NF-kappa B or c-rel knockout mice. RelB, another member of the NF-kappa B/Rel family of transcription factors, is expressed during the latter stages of B cell maturation and can bind to regulatory sites within the Ig heavy chain locus. Therefore, we tested the ability of B cells from relB knockout mice (relB-/-) to proliferate, undergo maturation to IgM secretion, and switch to the expression of downstream Ig isotypes in response to distinct activators including LPS, anti-CD40 mAb or CD40 ligand, and/or dextran anti-IgD antibodies in combination with various cytokines, including IL-4, IL-5, IFN-gamma, and TGF-beta. B cells lacking RelB showed up to 4-fold reductions in DNA synthesis in response to LPS, CD40, and membrane Ig-dependent activation relative to controls. However, relB-/- B cells were comparable to control B cells in their ability to undergo maturation to IgM secretion and switch to the expression of IgG3, IgG1, IgG2b, IgG2a, IgE, and/or IgA under all activation conditions tested. Thus, RelB, like c-Rel and p50/NF-kappa B, plays a role in B cell proliferation. However, in contrast to c-Rel and p50/ NF-kappa B, it is not critically involved in maturation to Ig secretion or expression of Ig isotypes.
Quantitative and Qualitative Analysis of Rhinovirus Infection in Bronchial Tissues
Authors: Anne G. Mosser, Rose Vrtis, Lacinda Burchell, Wai-Ming Lee, Claire R. Dick, Elizabeth Weisshaar, Diane Bock, Cheri A. Swenson, Richard D. Cornwell, Keith C. Meyer, Nizar N. Jarjour, William W. Busse, James E. Gern
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Although rhinovirus (RV) infections can cause asthma exacerbations and alter lower airway inflammation and physiology, it is unclear how important bronchial infection is to these processes. To study the kinetics, location, and frequency of RV appearance in lower airway tissues during an acute infection, immunohistochemistry and quantitative polymerase chain reaction analysis were used to analyze the presence of virus in cells from nasal lavage, sputum, bronchoalveolar lavage, bronchial brushings, and biopsy specimens from 19 subjects with an experimental RV serotype 16 (RV16) cold. RV was detected by polymerase chain reaction analysis on cells from nasal lavage and induced sputum samples from all subjects after RV16 inoculation, as well as in 5 of 19 bronchoalveolar lavage cell samples and in 5 of 18 bronchial biopsy specimens taken 4 days after virus inoculation. Immunohistochemistry detected RV16 in 39 and 36% of all biopsy and brushing samples taken 4 and 15 days, respectively, after inoculation. Infected cells were primarily distributed in discrete patches on the epithelium. These results confirm that infection of lower airway tissues is a frequent finding during a cold and further demonstrate a patchy distribution of infected cells, a pattern similar to that reported in upper airway tissues.
Cirrhosis Associated With Methotrexate Treatment of Psoriasis
Authors: R. Owen Coe
Journal: JAMA (1968)

Postnecrotic cirrhosis of the liver developed in three nonalcoholic patients with psoriasis who were maintained on a long-term (11 to 40 months) regimen of orally administered folic acid antagonists. Portal hypertension with esophageal varices developed in two. The signs of cirrhosis developed insidiously and were not accompanied by signs of acute gastrointestinal or hematologic toxic conditions. There is a need for caution in the use of methotrexate in benign disease. A prospective study should be carried out to determine the best method of monitoring the hepatotoxicity of this drug during long-term administration.
Targeting the GD3 acetylation pathway selectively induces apoptosis in glioblastoma
Authors: Suzanne M. Birks, John Owusu Danquah, Linda King, Reinhardt Vlasak, Dariusz C. Gorecki, Geoffrey J. Pilkington
Journal: Neuro-Oncology (2011)

The expression of ganglioside GD3, which plays crucial roles in normal brain development, decreases in adults but is upregulated in neoplastic cells, where it regulates tumor invasion and survival. Normally a buildup of GD3 induces apoptosis, but this does not occur in gliomas due to formation of 9-O-acetyl GD3 by the addition of an acetyl group to the terminal sialic acid of GD3; this renders GD3 unable to induce apoptosis. Using human biopsy-derived glioblastoma cell cultures, we have carried out a series of molecular manipulations targeting GD3 acetylation pathways. Using immunocytochemistry, flow cytometry, western blotting, and transwell assays, we have shown the existence of a critical ratio between GD3 and 9-O-acetyl GD3, which promotes tumor survival. Thus, we have demonstrated for the first time in primary glioblastoma that cleaving the acetyl group restores GD3, resulting in a reduction in tumor cell viability while normal astrocytes remain unaffected. Additionally, we have shown that glioblastoma viability is reduced due to the induction of mitochondrially mediated apoptosis and that this occurs after mitochondrial membrane depolarization. Three methods of cleaving the acetyl group using hemagglutinin esterase were investigated, and we have shown that the baculovirus vector transduces glioma cells as well as normal astroctyes with a relatively high efficacy. A recombinant baculovirus containing hemagglutinin esterase could be developed for the clinic as an adjuvant therapy for glioma.