tbuckley/cabot-search huggingface dataset:
Many fixed dose drug combinations for sale in India are not approved
Authors: I. Torjesen
Journal: BMJ (2015)

Patients with obstructive sleep apnoea–hypopnoea syndrome (OSAHS) have elevated circulating levels of tumour necrosis factor (TNF)-α. The hypothesis in this study was that OSAHS might be associated with the TNF-α (−308A) gene polymorphism, which results in increased TNF-α production. This hypothesis was examined in OSAHS patients, their siblings and population controls. A total of 206 subjects were recruited. All underwent sleep studies and clinical review, and were subsequently classified as having OSAHS or not depending on apnoea–hypopnoea frequency, sex, age and symptoms. All subjects had blood collected and genotyping was performed on DNA extracted from peripheral leukocytes. Some 192 random UK blood donors were used as population controls. The results demonstrated a significant association for TNF-α (−308A) allele carriage with OSAHS (OR = 1.8; 95% Confidence interval: 1.18–2.75) when compared with population controls. Siblings with OSAHS were significantly more likely to carry the TNF-α (−308A) allele. In addition, 21 pairs of male siblings discordant for carriage of the −308A allele showed a significant level of discordance for the OSAHS phenotype. In conclusion, this study demonstrates an association of tumour necrosis factor-α (−308A) carriage with obstructive sleep apnoea–hypopnoea syndrome, suggesting that inflammation may be implicated in the pathogenesis of this condition.
NHS England drops 16 medicines from Cancer Drugs Fund
Authors: Nigel Hawkes
Journal: BMJ (2015)

NHS England has stemmed rising costs in the Cancer Drugs Fund by eliminating a further 16 medicines, used in 23 treatments, from the list it is prepared to pay for. At the beginning of 2015, 84 therapies were paid for by the fund, but, after a cull in May and this new review, the number has more than halved.

Among high profile casualties was Kadcyla (trastuzumab emtansine), a medicine from Roche for advanced breast cancer that can extend life by six months but costs £90 000 (€123 000; $137 000) a year for each patient. Avastin (bevacizumab), another Roche product, was also deleted for three indications in colorectal, breast, and cervical cancer.1 Existing patients on any of the excluded drugs will be able to continue their treatments.

Roche and cancer charities reacted strongly to the changes, Breast Cancer Now calling it “a dreadful day.” Daniel Thurley, medical director of Roche Products, condemned a “stop and start” approach to cancer medicines and disclosed …
Abstract 1845: Sensitivity of PC9 cells to erlotinib is affected by extracellular matrix
Authors: Halina M. Onishko, Jie Zhao, Katherine L. Jameson, Peter L. Frick, Darren R. Tyson, Vito Quaranta, Thomas E. Yankeelov, Erin C. Rericha
Journal: Cancer Research (2014)

Abstract Tyrosine kinase inhibitors of epidermal growth factor receptor, such as erlotinib and gefinitib, have been effective in the initial treatment of non-small cell lung cancer. With time, however, initially responsive tumors almost invariably rebound and proliferate under therapy. Of general interest is the impact of tumor cell heterogeneity on rebound time. Previously, we isolated 89 single-cell derived discrete sublines (DS) from the commonly studied PC9 cell line by monitoring the distribution of cell fates (division, quiescence, and cell death) and the drug-induced proliferation (DIP) rate under erlotinib treatment. In this work we examine the role of the extracellular matrix (ECM) in determining proliferation behavior and the distribution of cell fates. Cells suspended in 3D matrices show increased sensitivity to erlotinb with the rate of cell death depending on the ECM composition. DS sublines that were highly resilient in 2D culture (i.e., positive DIP rate and &amp;lt;10% cell death under treatment) asymptote to about 40% cell death in Matrigel after ten days in 1 µM erlotinb. Both the rate of cell death and the total percentage of the cell population that dies increased in collagen I and in collagen I coated hydrogel. At asymptotic levels, the cell population contained both dividing and quiescent cells. In contrast, DS sublines with negative DIP rates in 2D culture reached 90-99% cell death in each ECM considered. We conclude that the pathways conferring resilience in these cells are sensitive to ECM conditions. Intriguingly, we find that resilient DS sublines tend to have diversity in cluster morphologies in the matrices, suggesting a possible correlation between ECM engagement and/or adhesion and resilience. Molecular studies should clarify mechanistic relationships between ECM and sensitivity to targeted therapy, and whether such relationship may extend to clinical tumors. Citation Format: Halina M. Onishko, Jie Zhao, Katherine L. Jameson, Peter L. Frick, Darren R. Tyson, Vito Quaranta, Thomas E. Yankeelov, Erin C. Rericha. Sensitivity of PC9 cells to erlotinib is affected by extracellular matrix. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1845. doi:10.1158/1538-7445.AM2014-1845
A case of unilateral dermatomal cavernous haemangiomatosis
Authors: H. Watabe, M. Kashima, T. Baba, M. Mizoguchi
Journal: British Journal of Dermatology (2000)

We report a 39‐year‐old man with unilateral dermatomal cavernous haemangiomatosis (UDCH). Clinically, three haemangiomas were unilaterally distributed in the C6 dermatome. Histologically, these haemangiomas were distinct from routine cavernous haemangioma in that hyperplasia of smooth muscle cells on the vascular wall was observed, and electron microscopy showed that smooth muscle cells contained myofilaments and a crystal‐like structure in the endothelial cells. This is distinct from Weibel–Palade bodies, which are rod‐shaped cytoplasmic organelles measuring approximately 0·1 µm in diameter with a parallel linear structure. In UDCH, the haemangiomas occur only in the skin. They are clinically and histologically similar to those of blue rubber bleb naevus syndrome (BRBNS), but in BRBNS there are multiple haemangiomas in the digestive tract and other organs. UDCH is distinct from Maffucci syndrome in that enchondromata and malignant tumours are absent. To our knowledge, this is the second case of UDCH reported in the literature.
Association Between Immunoparesis and a Skewed Free Light Chain (FLC) Ratio: A New Prognostic Factor Of Progression from MGUS To Multiple Myeloma?
Authors: Michele Pizzuti, Alberto Santagostino, Giuseppina Smaldore, Ida Chitarrelli, Domenico Vertone, Sara Pasquina Pascale, Angela Matturro, Immacolata Attolico, Angela Amendola, Michele Cimminiello, Nunzio Filardi, Antonella Girardi, Romina Penitente, Roberta Nuccorini, Sabrina Coluzzi, Enza Scavone
Journal: Blood (2013)
Nitric oxide metabolites and erythrocyte deformability in a group of subjects with obstructive sleep apnea syndrome
Authors: Baldassare Canino, Eugenia Hopps, Vincenzo Calandrino, Rosalia Lo Presti, Maria Montana, Gregorio Caimi
Journal: European Respiratory Journal (2014)

Our aim was to evaluate nitric oxide metabolites (nitrite and nitrate), expressed as NOx, and erythrocyte deformability, expressed as elongation index, in a group of subjects with obstructive sleep apnea syndrome (OSAS). We enrolled 48 subjects (36 men and 12 women; mean age 50.3±14.68 yrs) with OSAS diagnosed after a 1-night cardiorespiratory sleep study. OSAS severity was assessed evaluating the apnea/hypopnea index (AHI) and subjects were subdivided in two subgroups: Low (L= AHI 30). NOx was examined converting nitrate into nitrite with a nitrate reductase and then assessing nitrite with spectrophotometry after the addition of Griess reagent. The elongation index was obtained using the diffractometer Rheodyn SSD of Myrenne at shear stresses of 30 and 60 Pa and it was expressed as elongation index (EI). We found no difference in NOx among the entire group of OSAS subjects and normal controls, while we observed a NOx decrease in the H subgroup in comparison with L subgroup, but not in comparison with normal controls. We noted a significant decrease in EI at each shear stress in the entire group and also in the two subgroups in comparison with controls. The decrease in NO bioavailability and in erythrocyte deformability might contribute to explain the increased cardiovascular risk in OSAS subjects.
British Medical Bulletin: A Series of Expert Reviews--Asthma
Journal: Thorax (1992)

Letters to the Editor sequestration (not true "margination") in the pulmonary microvasculature.We would, however, suggest that such a rapid retention and subsequent release is much more likely to be due to changes in cell deformability, which is now generally believed to be the initiating factor in leucocyte sequestration before an increase in adherence.The importance of cell deformability as a determinant of neutrophil sequestration within human lungs has been demonstrated.'We2 and others' have shown that the effect of this tripeptide in vitro is to increase neutrophil rigidity within seconds by assembly of F-actin.Such a change is much more rapid than any up regulation of either leucocyte or endothelial adhesion ligands, which require minutes to hours.It is attractive to speculate that the inhala- tion of FMLP, either by a direct effect across the alveolar capillary cellular barrier or by indirect action via mediators released from macrophages or mesenchymal cells, impairs the deformability and hence transit ofneutro- phils through the pulmonary vascular bed.
A comparison between the diagnostic value of bronchodilator response in spirometry and questionnaire in determining asthma
Authors: Mahdi Yadollahzadeh, Fariba Ghorbani, Katayoun Najafizadeh
Journal: European Respiratory Journal (2012)

Background and Aim:  Because of unknown physiopathology of asthma the diagnosis of this common respiratory disorder is a challenging issue. In this study we compared the usefulness of a short questionnaire and response to bronchodilator in spirometry for differentiating asthma from other causes of chronic dyspnea.  Method:  208 patients suffering from chronic dyspnea (>6 months) and had definite clinical diagnosis of asthma, chronic obstructive pulmonary disease, pulmonary fibrosis or bronchiectasis were enrolled. A questionnaire was designed by using the questions showed the best sensitivity and specificity in previous researches for diagnosing asthma. 9 of 43 questions were selected for final questionnaire by regression analysis. All of the patients were interviewed to complete questionnaire and spirometric response to bronchodilator was assessed. SPSS 18 and EPI 6 software were used for statistical analysis.  Results:  53.8% of cases had asthma. In determining asthma, bronchodilator test had 48.2% sensitivity, 78.1% specificity, 72% and 56.4% positive and negative predictive values, 2.2 and 0.66 positive and negative likelihood ratios, 21.9% and 51.8% false positive and negative error rates and 62.01% accuracy. 9-question questionnaire showed 97.3% sensitivity, 77.1% specificity, 83.2% and 96.1% positive and negative predictive values, 4.24 and 0.03 positive and negative likelihood ratios, 22.9% and 2.7% false positive and negative error rates and 87.98% accuracy.  Conclusion:  According to our findings, this 9-question questionnaire has better diagnostic values than response to bronchodilator in spirometry for defining asthma between patients with chronic dyspnea.
Acute Respiratory Distress Syndrome
Authors: Ards Definition Task Force, V Marco Ranieri, Gordon D Rubenfeld, B Taylor Thompson, Niall D Ferguson, Ellen Caldwell, Eddy Fan, Luigi Camporota, Arthur S Slutsky
Journal: JAMA (2012)

The acute respiratory distress syndrome (ARDS) was defined in 1994 by the American-European Consensus Conference (AECC); since then, issues regarding the reliability and validity of this definition have emerged. Using a consensus process, a panel of experts convened in 2011 (an initiative of the European Society of Intensive Care Medicine endorsed by the American Thoracic Society and the Society of Critical Care Medicine) developed the Berlin Definition, focusing on feasibility, reliability, validity, and objective evaluation of its performance. A draft definition proposed 3 mutually exclusive categories of ARDS based on degree of hypoxemia: mild (200 mm Hg &lt; PaO<sub>2</sub>/FIO<sub>2</sub> ≤ 300 mm Hg), moderate (100 mm Hg &lt; PaO<sub>2</sub>/FIO<sub>2</sub> ≤ 200 mm Hg), and severe (PaO<sub>2</sub>/FIO<sub>2</sub> ≤ 100 mm Hg) and 4 ancillary variables for severe ARDS: radiographic severity, respiratory system compliance (≤40 mL/cm H<sub>2</sub>O), positive end-expiratory pressure (≥10 cm H<sub>2</sub>O), and corrected expired volume per minute (≥10 L/min). The draft Berlin Definition was empirically evaluated using patient-level meta-analysis of 4188 patients with ARDS from 4 multicenter clinical data sets and 269 patients with ARDS from 3 single-center data sets containing physiologic information. The 4 ancillary variables did not contribute to the predictive validity of severe ARDS for mortality and were removed from the definition. Using the Berlin Definition, stages of mild, moderate, and severe ARDS were associated with increased mortality (27%; 95% CI, 24%-30%; 32%; 95% CI, 29%-34%; and 45%; 95% CI, 42%-48%, respectively; P &lt; .001) and increased median duration of mechanical ventilation in survivors (5 days; interquartile [IQR], 2-11; 7 days; IQR, 4-14; and 9 days; IQR, 5-17, respectively; P &lt; .001). Compared with the AECC definition, the final Berlin Definition had better predictive validity for mortality, with an area under the receiver operating curve of 0.577 (95% CI, 0.561-0.593) vs 0.536 (95% CI, 0.520-0.553; P &lt; .001). This updated and revised Berlin Definition for ARDS addresses a number of the limitations of the AECC definition. The approach of combining consensus discussions with empirical evaluation may serve as a model to create more accurate, evidence-based, critical illness syndrome definitions and to better inform clinical care, research, and health services planning.
Seasonal H1N1 2007 influenza virus infection is associated with elevated pre‐exposure antibody titers to the 2009 pandemic influenza A (H1N1) virus
Authors: M. Lemaitre, M. Leruez‐Ville, X.N. De Lamballerie, N. Salez, P. Garrone, A.‐C. Fluckiger, D. Klatzmann, F. Carrat
Journal: Clinical Microbiology and Infection (2010)
Late-breaking abstract: Comparative analysis of cardiopulmonary and clinical responses to six minute walking test and maximal exercising test in obese women
Authors: Luciana Di Thommazo-Luporini, Soraia Pilon Jürgensen, Viviane Castello, Camila Negrão Dias, Rafael Luís Luporini, José Carlos Bonjorno-Júnior, Claudio Ricardo de Oliveira, Aparecida Maria Catai, Audrey Borghi-Silva
Journal: European Respiratory Journal (2011)

Background:  The six minute walking test on the treadmill (tread6MWT) can be an efficient method to evaluate the functional capacity in obese population comparable to cardiopulmonary exercising test (CPET).   Aims:  To compare the cardiopulmonary and subjective responses to tread6MWT and CPET in obese and eutrophic women.   Methods:  Fourteen obese women were recruited to obese group (OG) and 15 women to eutrophic group (EG). Both groups performed a CPET and a tread6MWT. Cardiopulmonary variables and dyspnea level were registered. Absolute limits of agreement between cardiopulmonary and subjective responses to CPET and tread6MWT were assessed by Bland–Altman analysis.   Results:  OG presented higher oxygen uptake (V9O2), minute ventilation (V9E), and systolic blood pressure (SBP) than EG (p   Conclusions:  The tread6MWT was able to promote metabolic and cardiopulmonary responses in agreement to the CPET. The tread6MWT seems to be an appropriate method to evaluate the functional limitation in obese women without submitting them to such a significative dyspnea as the CPET does.  Financial support: FAPESP (09/01842-0) and CAPES.
Vinorelbine and low dose cyclophosphamide in pediatric sarcoma. A pilot study for the future European rhabdomyosarcoma protocol
Authors: M. Casanova, A. Ferrari, G. Bisogno, J. H. Merks, G. L. De Salvo, K. Tettoni, M. Provenzi, F. Fossati Bellani, M. Carli
Journal: Journal of Clinical Oncology (2004)

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The Singapore 5-Fluorouracil Trabeculectomy Study
Authors: Tina T. Wong, Peng T. Khaw, Tin Aung, Paul J. Foster, Hla Myint Htoon, Francis T.S. Oen, Gus Gazzard, Rahat Husain, Joe G. Devereux, Darwin Minassian, Say-Beng Tan, Paul T.K. Chew, Steve K.L. Seah
Journal: Ophthalmology (2009)
Short-term isotretinoin treatment decreases insulin-like growth factor-1 and insulin-like growth factor binding protein-3 levels: does isotretinoin affect growth hormone physiology?
Authors: A.S. Karadag, D.T. Ertugrul, E. Tutal, K.O. Akin
Journal: British Journal of Dermatology (2010)

Isotretinoin is an effective treatment for acne vulgaris. However, it has numerous side-effects. It was previously reported that serum growth hormone (GH) levels decreased with isotretinoin treatment.To analyse whether isotretinoin has any effects on insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP3) and GH levels.Forty-seven patients aged 21.5 +/- 5.1 years (mean +/- SD) with acne vulgaris were included in this study. Isotretinoin therapy was initiated at a dose of 0.5-0.75 mg kg(-1) daily and then adjusted to 0.88 mg kg(-1) daily as maintenance dosage after 1 month. Screening for biochemical and hormonal parameters was performed just before initiation and after 3 months of isotretinoin treatment.IGF-1 and IGFBP3 levels decreased significantly after treatment (P < 0.01), while GH levels did not change. Post-treatment, significant increases were seen in aspartate aminotransferase, total cholesterol, low-density lipoprotein cholesterol, triglycerides and low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (P < 0.0001) while high-density lipoprotein cholesterol levels were significantly decreased (P < 0.0001).Isotretinoin therapy may have an effect on GH physiology, and further studies are needed to understand this association.
Abstract 406: A potential new mechanism for PTEN to maintain genome stability
Authors: Lili Gong, Shiaw-Yih Lin
Journal: Cancer Research (2014)

Abstract Purpose: PTEN (phosphatase and tensin homolog) is among the most mutated or lost tumor suppressors. Recent studies revealed that nuclear PTEN represses tumorigenesis by stabilizing the centromere, a highly condensed heterochromatin domain featured with long array of DNA repeats (namely, satellite DNA), repressive histones, such as trimethylated Histone H3 at Lys9 residue (H3K9me3), and heterochromatin proteins. Our studies are aimed to explore the molecular mechanism that PTEN regulates this heterochromatin structure and thus maintaining genome stability. Methods and Results: Co-immunoprecipitation (Co-IP) assay showed that PTEN and the heterochromatin proteins directly interact. Chromatin immunoprecipitation (ChIP) assay showed that PTEN is enriched in satellite locus. Depletion of PTEN leads to abnormal heterochromatin structure, indicated by reduced H3K9m3 foci (detected by immunofluorescent staining) and occupancy to satellite locus (ChIP assay), decreased heterochromatin protein levels (Westernblot analysis), and overexpression of satellite transcripts (quantitative RT-PCR). Through a knockdown-and-mutant rescue strategy, we found that the C-terminal of PTEN is essential for its repressive function on satellite transcription. Furthermore, overexpression of the C-terminal truncated PTEN into PTEN-null BT549 cells, as compared to wild-type PTEN overexpression, lost its function to suppress cell growth (MTT assay), cell cycle progression (flow cytometry analysis) and protection from DNA damage (MTT and colony formation assays). Conclusions: Our finding showed that PTEN guards the genome stability through maintaining the normal structure of heterochromatin domain. Citation Format: Lili Gong, Shiaw-Yih Lin. A potential new mechanism for PTEN to maintain genome stability. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 406. doi:10.1158/1538-7445.AM2014-406
Impact of smoking on the severity of sleep apnea syndrome
Authors: Amira Sallami, Zied Moatemri, Samira Mhamedi, Salsabil Dabboussi, Rania Klai, Ghassen Soussi, Hassen Belhaj Hsan, Chiraz Aichaouia, Mohsen Khadraoui, Rezaiek Cheikh
Journal: European Respiratory Journal (2014)

Smoking is a public health problem. There is evidence that smoking is a risk factor for sleep apnea obstructive syndrome (SAS). The influence of smoking on the severity of SAS remains poorly documented.  We evaluate the influence of smoking on the severity of SAS. 100 patients were investigated for suspected SAS over a period of 2 years. Only 61 patients had a SAS confirmed by polygraphic recordings. Clinical data, spirometry and smoking status were collected from these 61 patients.  Among the 61 patients, 28 were non-smokers and 33 were smokers (32 male and one female). Sex distribution showed a male predominance, the thyroid dysfunction was noted in 54 % of cases with a female predominance (32versus1, p = 0.05), no difference in the Epworth score, no difference in terms of clinical signs, the body mass index was higher in the non smoker group with no significant difference, the apnoea-hypopnoea index is higher in the smoking group (43versus24, p = 0.03). The percentage of subjects with severe SAS was higher in the smokers (52% versus22 %, p = 0.04). ventilatory obstructive disorder was noted in 10 cases including 5 (50%) smokers , obstruction of the small airways was noticed in 45% of the patient all smokers.  Conclusion: Smoking is a risk factor for occurrence and severity of SAS. Tobacco cessation must be included in the therapy of the SAS.
Chronic Fatigue Syndrome: Sufferers' Evaluation of Medical Support
Authors: Susanne Ax, Vernon H Gregg, David Jones
Journal: Journal of the Royal Society of Medicine (1997)

In response to reports of negative cooperation between sufferers of chronic fatigue syndrome (CFS) and their doctors, semi-structured interviews were conducted with sufferers from two different patient samples. Satisfaction with support received and with medical professionals in general was low. Sufferers complained about insufficient informational as well as emotional support from their doctors, and as a consequence most opted for alternative or complementary forms of treatment. In addition, disagreements over illness aetiology and treatment precluded effective cooperation. If satisfaction and compliance are to improve, sufferers will need more information about CFS and more support.