tbuckley/cabot-search huggingface dataset:
Re-irradiation with concurrent chemotherapy for recurrent head and neck cancer
Authors: E. Roman, L. Raez, M. Biagioli, M. Harvey, M. Blaya, K. Tolba, R. Bathia, A. Markoe
Journal: Journal of Clinical Oncology (2006)

5559 Background: Despite aggressive therapy, over 70% of locally advanced squamous cell carcinomas of the head and neck (SCCHN) fail primary treatment. Salvage therapy with surgery, chemotherapy or brachytherapy alone or in combination has a 30–40% response rate, but few long-term survivors. Re-irradiation with concurrent chemotherapy for SCCHN has recently become a well established approach after two consecutive cooperative group studies were reported. Intensity Modulated Radiation Therapy (IMRT) is a new and safer way to deliver radiation therapy. This retrospective review evaluated the potential benefit and toxicity using every other week IMRT with concurrent chemotherapy. Design: Thirty-seven patients with locally recurrent SCCHN were evaluated. All patients received re-irradiation with IRMT every other week with concurrent weekly carboplatin (median AUC= 2) or cisplatin (60–100 mg/m 2 ) ± 5-FU (800–1000 mg/m 2 ) or paclitaxel 175mg/m 2 every three weeks. Patients received 6000 cGy at 200 cGy per fraction. Results: The median follow-up time was 12 months. The overall response rate was 75.7% with a complete response (CR) and partial response (PR) of 56.8% and 18.9%, respectively. Among complete responders, 33% recurred locally in a median time of 5 months. The Kaplan-Meier estimate of disease-free survival, progression-free survival, and overall survival at 48 months is 58%, 45%, and 28%, respectively. At the time of last follow-up, 51.4% of patients were still alive and 27.8% of patients had no evidence of disease. Grade 3 or 4 acute toxicities occurred in 20% of patients of which 13.3% were hematologic requiring either growth factors or delay in chemotherapy. No deaths occurred during the course of treatment. Long-term complications consisted of one patient with an esophageal stricture requiring repeated dilations, 2 patients with chronic dysphagia, and 2 patients developing a pharyngeal-cutaneous fistula, one of which died from a carotid blowout occurring 6 months after treatment. Conclusions: IMRT delivered every other week with concurrent platinum based chemotherapy produces good responses with only moderate toxicity in patients previously treated with radiation therapy for recurrent head and neck cancer. No significant financial relationships to disclose.
Retrospective analysis of HHV-8 viremia and cellular viral load in HIV-seropositive patients receiving interleukin 2 in combination with antiretroviral therapy
Authors: Mauro Malnati, Francesco Broccolo, Silvia Nozza, Loredana Sarmati, Silvia Ghezzi, Giuseppe Locatelli, Fanny Delfanti, Brunella Capiluppi, Anna Careddu, Massimo Andreoni, Paolo Monini, Guido Poli, Adriano Lazzarin, Paolo Lusso, Giuseppe Tambussi
Journal: Blood (2002)
In Vivo Expression of B7-1 and B7-2 By Follicular Lymphoma Cells Can Prevent Induction of T-Cell Anergy But Is Insufficient to Induce Significant T-Cell Proliferation
Authors: David M. Dorfman, Joachim L. Schultze, Aliakbar Shahsafaei, Sabine Michalak, John G. Gribben, Gordon J. Freeman, Geraldine S. Pinkus, Lee M. Nadler
Journal: Blood (1997)
Cytoplasmic myosin-exposed apoptotic cells appear with caspase-3 activation and enhance CLL cell viability
Authors: X Cui, L Zhang, A R Magli, R Catera, X-J Yan, D O Griffin, T L Rothstein, J Barrientos, J E Kolitz, S L Allen, K R Rai, N Chiorazzi, C C Chu
Journal: Leukemia (2015)
Diagnostic value of reversibility of chronic airway obstruction to separate asthma from chronic bronchitis: a statistical approach
Authors: N Meslier, JL Racineux, P Six, A Lockhart
Journal: European Respiratory Journal (1989)

Our aim was to assess the usefulness of tests of reversibility of airways obstruction (AO) in the differential diagnosis of asthma (A) and chronic bronchitis (CB). We selected on strict clinical criteria 20 CB and 32 A patients with stable AO and measured maximal forced expiratory flows before and after increasing doses of inhaled salbutamol. The highest sensitivity (Se), specificity (Sp) and likelihood ratio (L) were obtained when the improvement in forced expiratory volume in one second (FEV1) was expressed as a percentage of predicted FEV1. Se, Sp and L were 0.97, 0.95 and 19.3 (highest possible L: 20) for an increase of 10% of predicted FEV1 on 0.2 mg of salbutamol, and 1.0, 1.0 and 20, respectively, for an increase of 15% on 1 mg of salbutamol. Conversely, L was only 2.8 when the widely used increase in FEV1 of 20% over baseline was tested. In a second group of 42 unselected patients, who were referred to the laboratory for routine lung function testing with a presenting diagnosis of A or CB, L was only 5.5 when the 10% increase in predicted FEV1 was used and even lower for the classical 20% increase over baseline FEV1. We submit that routine tests of reversibility of AO have little diagnostic usefulness in unselected patients with AO and that the commonly used criteria of 15 or 20% increase in FEV1 over baseline are of no value in separating A from CB.
Interleukin-10 polymorphisms influence the neonatal immune response and may be a risk factor for childhood allergic disease and wheeze
Authors: Diana Raedler, Sabina Illi, Isolde Schleich, Elisabeth Klucker, Elif Turan, Erika von Mutius, Bianca Schaub
Journal: European Respiratory Journal (2011)

Background:  The interleukin-10 gene ( IL10 ) encodes the anti-inflammatory cytokine IL-10, which is crucial for the development of immune tolerance and T cell regulation.  IL-10  polymorphisms were proposed to influence the asthma phenotype including pulmonary function. We studied the influence of  IL-10  single nucleotide polymorphisms (SNPs) early in life on Th1/Th2 lineage fate, T regulatory cells and pro-inflammatory cytokines. Furthermore, the effect of the SNPs on allergic diseases and wheeze was examined at 3 years of age.   Methods:  Cord blood of 200 healthy neonates was genotyped for 8 SNPs and one deletion in  IL-10.  CBMCs were cultured unstimulated or following stimulation [Lipid A, peptidoglycan, phytohemagglutinin, house dust mite (Derp1), Derp1+Lipid A]. Treg-marker mRNA expression (FOXP3, GITR, LAG3), Th1/Th2-cytokines, TNF-α and GM-CSF were assessed. A follow-up regarding allergic diseases and wheeze was performed (3ys).   Results:  The majority of  IL-10  SNP carriers showed a similar pattern of cytokine secretion and Treg-marker expression with increased IFN-γ secretion (Th1), reduced IL-5 (Th2), pro-inflammatory TNF-α and GM-CSF and reduced Treg-marker expression. The effects were primarily observed after innate and allergic stimulation. Carriers of five  IL-10  SNPs and the  IL-10  deletion showed increased risk for wheeze or atopic symptoms.   Conclusions:  Polymorphisms in  IL-10  influence primarily Th1/Th2 cytokine secretion and Treg-marker expression after innate and allergic stimulation early in life. This may be relevant for immune maturation and potentially for childhood atopy and wheeze.
Patterns of Invasive Growth In Vitro. Human Decidua Graviditatis Confronted With Established Human Cell Lines and Primary Human Explants2
Authors: A.B. Schleich, M. Frick, A. Mayer
Journal: JNCI Journal of the National Cancer Institute (1976)

Human decidua graviditatis was used as a receptor tissue to demonstrate invasive properties of human cells in vitro. In the confrontation between decidua and established cell lines of tumors and of normal origin as well as primary explanted cells, we noted differences in the cells' interactions with decidual tissue. The two original tumor cell lines, HeLa (carcinoma) and AFi (sarcoma), and a spontaneously transformed lymphoblastoid cell line showed aggressiveness, i.e., invasion, rapid proliferation, injury, and destruction of the decidual tissue. Strain HeLa S3 and two established cell lines, FL (amnion) and Girardi Heart, which are regarded as transformed cells because of their increased mitotic rate and polyploidy, exhibited various degrees of aggressiveness but did not invade. Freshly explanted fetal lung and endometrium caused no injury to the receptor tissue and were included in the decidual tissue.
The brain as a dream state generator: an activation-synthesis hypothesis of the dream process
Authors: J A Hobson, R W McCarley
Journal: American Journal of Psychiatry (1977)

Recent research in the neurobiology of dreaming sleep provides new evidence for possible structural and functional substrates of formal aspects of the dream process. The data suggest that dreaming sleep is physiologically determined and shaped by a brain stem neuronal mechanism that can be modeled physiologically and mathematically. Formal features of the generator processes with strong implications for dream theory include periodicity and automaticity of forebrain activation, suggesting a preprogrammed neural basis for dream mentation in sleep; intense and sporadic activation of brain stem sensorimotor circuits including reticular, oculomotor, and vestibular neurons, possibly determining spatiotemporal aspects of dream imagery; and shifts in transmitter ratios, possibly accounting for dream amnesia. The authors suggest that the automatically activated forebrain synthesizes the dream by comparing information generated in specific brain stem circuits with information stored in memory.
Transient gastric ischemia as a complication of cystotomy in endoscopic pancreatic pseudocyst drainage
Authors: João Santos-Antunes, Pedro Moutinho-Ribeiro, Guilherme Macedo
Journal: Endoscopy (2015)

A 70-year-old man was referred to our department for endoscopic drainage of a pancreatic pseudocyst. He had acute pancreatitis as a result of choledocolithiasis, which developed following a cholecystectomy 2 years previously. Computed tomography (CT) revealed a 7-cm cystic lesion in the head of the pancreas, which was compatible with a pseudocyst.
NHS needs transformation fund to develop new models of care, say Health Foundation and King’s Fund
Authors: Nigel Hawkes
Journal: BMJ (2015)

The NHS needs yearly investment of £1.5bn to £2.1bn (€2.1bn to €3bn; $2.3bn to $3.3bn), on top of the increases already announced, to lubricate the process of change outlined in the Five Year Forward View , two influential think tanks believe.

The Health Foundation and the King’s Fund1 have called for a transformation fund with dedicated funding from now …
The role of two stage tuberculin skin test in screening of household contacts
Authors: Rashid Rifat, Claire Peplow, Khan Sadiqullah, Heinke Kunst
Journal: European Respiratory Journal (2011)

Rationale:  The role of two stage tuberculin skin test (TST) of persons who have had close contact with a case of smear-or culture positive pulmonary tuberculosis TB (PTB) is unclear. A booster phenomenon with TST may occur and therefore screening with TST in a two stage approach may not be ideal [1].   Methods:  We conducted a prospective study including consecutive household contacts of patients with active PTB between Jan 2010 and Jan 2011. All contacts below the age of 35 years of age were interviewed and screened by TST. If the TST was below 6mm, contacts were asked to return for a second TST six weeks later. TST conversion was defined as a TST of greater than 6mm or a 5mm increase of the initial TST. Interferon Gamma Recptor Assay (IGRA), (T-spot test) was performed on those that had TST conversion to evaluate the booster phenomenon.   Results:  Out of 589 adult and peadiatric contacts screened who had an initial TST of less than 6 mm, 189 contacts did not attend for a second TST. A total of 406 had TST performed. 344 contacts attended and did not show TST conversion and were therefore discharged. 68 contacts underwent TST conversion of whom 43 had an IGRA. Out of 43 contacts, 6 had a positive IGRA, 7 out of 43 were indeterminate and 30 were negative. Indeterminate and negative IGRA results were more common in children than in adults.   Conclusion:  A two stage approach of TST may cause a booster effect and therefore should be confirmed by IGRA.   Reference:   1Menzies D. Interpretation of repeated tuberculin tests. Boosting, conversion, and reversion.  Am.J.Respir.Crit Care Med.  1999;159:15-21.
RhoA and Rho Kinase Activation in Human Pulmonary Hypertension
Authors: Christophe Guilluy, Saadia Eddahibi, Christian Agard, Christophe Guignabert, Mohamed Izikki, Ly Tu, Laurent Savale, Marc Humbert, Elie Fadel, Serge Adnot, Gervaise Loirand, Pierre Pacaud
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: The complex and multifactorial pathogenesis of pulmonary hypertension (PH) involves constriction, remodeling, and in situ thrombosis of pulmonary vessels. Both serotonin (5-HT) and Rho kinase signaling may contribute to these alterations.Objectives: To investigate possible links between the 5-HT transporter (5-HTT) and RhoA/Rho kinase pathways, as well as their involvement in the progression of human and experimental PH.Methods: Biochemical and functional analyses of lungs, platelets, and pulmonary artery smooth muscle cells (PA-SMCs) from patients with idiopathic PH (iPH) and 5-HTT overexpressing mice.Measurements and Main Results: Lungs, platelets, and PA-SMCs from patients with iPH were characterized by marked elevation in RhoA and Rho kinase activities and a strong increase in 5-HT binding to RhoA indicating RhoA serotonylation. The 5-HTT inhibitor fluoxetine and the type 2 transglutaminase inhibitor monodansylcadaverin prevented 5-HT–induced RhoA serotonylation and RhoA/Rho kinase activation, as well as 5-HT–induced proliferation of PA-SMCs from iPH patients that was also inhibited by the Rho kinase inhibitor fasudil. Increased Rho kinase activity, RhoA activation, and RhoA serotonylation were also observed in lungs from SM22–5-HTT+mice, which overexpress 5-HTT in smooth muscle and spontaneously develop PH. Treatment of SM22–5-HTT+ mice with either fasudil or fluoxetine limited PH progression and RhoA/Rho kinase activation.Conclusions: RhoA and Rho kinase activities are increased in iPH, in association with enhanced RhoA serotonylation. Direct involvement of the 5-HTT/RhoA/Rho kinase signaling pathway in 5-HT–mediated PA-SMC proliferation and platelet activation during PH progression identify RhoA/Rho kinase signaling as a promising target for new treatments against PH.
Increased rituximab (R) doses and effect on risk of elderly male patients with aggressive CD20+ B-cell lymphomas: Results from the SEXIE-R-CHOP-14 trial of the DSHNHL.
Authors: Michael Pfreundschuh, Gerhard Held, Samira Zeynalova, Carsten Zwick, Mathias Haenel, Lorenz Truemper, Martin H. Dreyling, Judith Dierlamm, Markus Loeffler, Norbert Schmitz, Niels Murawski
Journal: Journal of Clinical Oncology (2014)

8501 Background: Elderly male patients have significantly lower R serum levels, shorter exposure times and a worse outcome in RICOVER-60, RICOVER-noRTh, and Pegfilgrastim trials (Blood 2012, 119:3276; Blood 2014, 123:640-646). Methods: To test increasing R doses, male patients received 500 instead of 375 mg/m2 in the SEXIE-R-CHOP-14 trial which also compared six cycles of CHOP-14 in combination with eight 2-week applications with eight upfront dose-dense applications of R (days -1, 0, 3, 7, 14, 21, 28, 42) in a randomized phase-II trial. 271 patients (61-80 years) were randomized, 268 patients are evaluable. 148 patients males received 500 mg/m2, 120 females 375 mg/m2R. Results: Protocol adherence was excellent with median relative doses of R and myelosuppressive drugs >98%. During the treatment period, the increased R dose in males resulted in slightly higher trough serum levels than in females; however, R levels dropped faster in males resulting in nearly identical serum levels thereafter and a very similar overall R exposure time. The increased R dose in males was not associated with increased toxicities. 3-year PFS was 74% in males and 68% in females (p=0.396), 3-year OS was 80% in males and 72% in females (p=0.111). In a multivariable analysis adjusting for IPI factors, male hazard was 0.9 (p=0.817) for PFS, and 0.8 for OS (p=0.317). In a historical comparison by multivariable analysis adjusting IPI risk factors and age >70 years, of 148 elderly males who received 500 mg/m2 in SEXIE-R-CHOP-14 and 250 males who received 375 mg/m2 in RICOVER-60, the increased dose of R was associated with a reduced risk for an event in PFS (HR=0.7; p=0.128) and 0.7 in OS (p=0.223). Conclusions: Increasing R dose by one third from 375 mg/m2 to 500 mg/m2 eliminated the increased risk of elderly males. That the increased R dose significantly improves outcome not only of elderly male patients, but also in young male and female patients who have a R pharmacokinetics similar to elderly males should be confirmed in a larger randomized study of these subpopulations with aggressive CD20+ B-cell lymphomas. Supported by Roche and Deutsche Krebshilfe. Clinical trial information: NCT00290667.
Abstract 16472: Robotic Totally Endoscopic Coronary Artery Bypass Grafting - Approaching 500 Cases
Authors: Nikolaos Bonaros, Thomas Schachner, Eric Lehr, Felix Weidinger, Benedikt Hofauer, Andreas De Biasi, Brody Weheman, David Zimrin, Guy Friedrich, Johannes Bonatti
Journal: Circulation (2011)

Objective: Robotic technology has enabled performance of closed chest, port-only, and totally endoscopic coronary artery bypass grafting (TECAB). Graft harvesting and anastomotic suturing are carri...
Internet server with targeted access would cure information deficiency in developing countries
Authors: R. E LaPorte
Journal: BMJ (1997)

Editor–The internet is reaching developing nations, and all major health journals and other journals are moving on to the internet. Soon full text articles will be available through the internet–at a price. The price is too high for developing countries. Moreover, journals are afraid that if their works are freely accessible their paid subscription base will dry up.

There is a solution: an internet server with targeted access. Thus the BMJ could be made available exclusively to Uganda, Bolivia, and Peru. An agricultural, psychology, or chemistry …
Possible cut-off values for stable or instable COPD as measured by the clinical COPD questionnaire (CCQ)
Authors: Maarten Prinsen, Ellen Van Heijst, Siebrig Schokker, Corina de Jong, Roland Riemersma, Jan Willem Kocks, Thys van der Molen
Journal: European Respiratory Journal (2011)

Background: Based on GINA the cut-off values for the Asthma Control Questionnaire (ACQ) have been established for “well-controlled” and “not well-controlled” asthma. Cut-off values for health status questionnaires like the Clinical COPD Questionnaire (CCQ) for use in COPD, however, are lacking.

Objective: To give insight into possible cut-off values of the CCQ by comparing it with the ACQ.

Method: In 7599 patients with respiratory disease, referred by the general practitioner to a diagnostic center, data on both the ACQ and CCQ were collected. Scores on both questionnaires were compared and possible cut-off values for the CCQ were determined by using the ACQ as gold standard.

Results: After consultation with the diagnostic center, a diagnosis of COPD, asthma or a asthma/COPD was established in respectively 16,8%, 46,3% and 7,4% of the patients. The correlation between the ACQ and CCQ was 0.81. The mean ACQ and CCQ scores in these patients according to the level of control are presented in table 1.

View this table:

Mean ACQ and CCQ scores per diagnosis selected by ACQ cut-off values





Discussion: The average CCQ per ACQ-score has been calculated and using the ACQ as gold standard this study estimated the cut-off points for the CCQ to be  1.7 for COPD with instable or uncontrolled disease.
Investigation of selected cytokine genes suggests that <i>IL2RA</i> and the <i>TNF</i> / <i>LTA</i> locus are risk factors for severe alopecia areata
Authors: S. Redler, F. Albert, F.F. Brockschmidt, C. Herold, S. Hanneken, S. Eigelshoven, K.A. Giehl, R. Kruse, G. Lutz, H. Wolff, B. Blaumeiser, M. Böhm, T. Becker, M.M. Nöthen, R.C. Betz
Journal: British Journal of Dermatology (2012)

Alopecia areata (AA) is the second most common cause of hair loss in humans, and has a genetically complex inheritance. The hypothesis that AA is autoimmune in nature is supported by previous studies. These report an association with specific HLA alleles, as well as genetic variants of other genes implicated in autoimmunity, such as various cytokine genes. However, these cannot yet be considered proven susceptibility loci, as many of these association findings were derived from small patient samples.To investigate the association between AA and selected cytokine genes using a sample of 768 patients with AA and 658 controls of Central European origin.Eleven single-nucleotide polymorphisms (SNPs) from cytokine genes implicated in previous AA studies were genotyped. These genes were IL1B, IL1A, IL1RN, MIF, IFNG and the TNF/LTA gene region. We also genotyped 15 SNPs selected from cytokine genes that have shown significant association with other autoimmune diseases. These genes were IL10, IL36RN, IL12B, IL6, IL2, IL23, IL2RA and IL4R.Significant association was found for two variants within both IL2RA and TNF/LTA. In the overall sample, the most significant results were obtained for the IL2RA variant rs706778 (P = 0·00038) and the TNF/LTA locus variant rs1800629 (P = 0·0017). In subgroup analyses, according to severity, age at onset and family history these effects were stronger in the severely affected patients, with the lowest P-values being obtained for rs706778 (P = 3·8 × 10(-6) ).Our results point to the involvement of IL2RA and the TNF/LTA region in the aetiology of AA, in particular severe AA, and provide further support for the hypothesis that AA is autoimmune in nature.
Molecular study of genetic modifiers in patients with pulmonary arterial hypertension
Authors: Guillermo Pousada, Adolfo Baloira, Diana Valverde
Journal: European Respiratory Journal (2014)

Pulmonary arterial hypertension (PAH; OMIM 178600) is a disorder characterized by pulmonary vascular resistance increase, vascular remodelling and right heart failure. There is variable phenotypic expression of PAH, likely related to environmental and genetic modifiers. Studies have implicated the serotonin transporter, endothelin, nitric oxide sintase, angiotensine, and others as genetic modifiers. The aim of this work was to analyse several polymorphisms in SERT, EDN1, NOS2 and AGTR1 genes in patients with PAH.

We included 55 PAH patients and 52 controls. The analysis was performed by PCR and sequencing.

We found statistically differences between patients and controls for the following genes; EDN1 (p=0.009), the genotype GT appears in 62% of patients and in 40% of controls, NOS2 (p<0.001), patients have less repetitions than controls in CCTTT microsatellite, and AGTR1 (p<0.001), the genotype AC appears in 60% of patients and in 20% of controls. On the contrary, the SERT gene don´t show differences (p=0.956). For the genotype/phenotype correlation we don´t found differences for carriers of changes in EDN1 and NOS2 genes. The statistical analysis showed significant differences in age of diagnosis (p=0.043), for the SERT gene, and systolic pulmonary pressure (p=0.037), cardiac index (p=0.012) and PAH subtypes (IPAH vs APAH) (p=0.028), for the AGTR1 gene.

In conclusion, HAP is a heterogeneity disease and the genetic modifiers may predispose individuals to an increased risk of developing of PAH, producing a more severe phenotype in patients with PAH. Perhaps the combination of more than one modifier increases the risk of develop it and might be involved in the low penetrance of this disease.