tbuckley/cabot-search huggingface dataset:
Durable hematologic complete response and suppression of HTLV-1 viral load following alemtuzumab in zidovudine/IFN-α–refractory adult T-cell leukemia
Authors: Andrew Mone, Shannon Puhalla, Susan Whitman, Robert A. Baiocchi, Julio Cruz, Tamara Vukosavljevic, Amy Banks, Charles F. Eisenbeis, John C. Byrd, Michael A. Caligiuri, Pierluigi Porcu
Journal: Blood (2005)
Spirometric definition of COPD: exercise in futility or factual debate?
Authors: Vito Brusasco
Journal: Thorax (2012)

The current international guidelines for the diagnosis and management of COPD recognise spirometry as a major criterion to confirm a clinical diagnosis of COPD.1–3 The specific role of spirometry for the diagnosis of COPD is to identify the presence if airflow obstruction, which is the essential requirement for the definition of the disease. Although a reduction of the ratio of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) has been consistently adopted as an unquestionable sign of airflow obstruction, no consensus has been achieved regarding the cut-off to separate healthy from obstructed subjects.

In 1986 the American Thoracic Society (ATS) suggested an obstructive abnormality be present when FEV1/FVC is <0.75 independent of age and sex.4 By contrast, the European Respiratory Society (ERS) recommended the use of the ratio of FEV1 to slow vital capacity (VC) with cut-off values as percentage of predicted for age and sex (88% for males and 89% for females).5 These values, which roughly correspond to the lower 5th percentiles of a healthy population, take into account the physiological age-related decrease of lung elastic recoil. In line with this statistics-based approach, the recent joint document ATS/ERS on standardisation if lung function testing6 indicated an FEV1/VC or FEV1/FVC below the lower 5th percentile as the lower limit of normality (LLN) to define airflow obstruction. At variance with this recommendation, the Global Initiative for Chronic Obstructive Lung …
Cardiotoxic and Cardioprotective Features of Chronic β-Adrenergic Signaling
Authors: Xiaoying Zhang, Christopher Szeto, Erhe Gao, Mingxin Tang, Jianguo Jin, Qin Fu, Catherine Makarewich, Xiaojie Ai, Ying Li, Allen Tang, Jenny Wang, Hui Gao, Fang Wang, Xinyi Joy Ge, Satya P. Kunapuli, Lin Zhou, Chunyu Zeng, Kevin Yang Xiang, Xiongwen Chen
Journal: Circulation Research (2012)

In the failing heart, persistent β-adrenergic receptor activation is thought to induce myocyte death by protein kinase A (PKA)-dependent and PKA-independent activation of calcium/calmodulin-dependent kinase II. β-adrenergic signaling pathways also are capable of activating cardioprotective mechanisms.This study used a novel PKA inhibitor peptide to inhibit PKA activity to test the hypothesis that β-adrenergic receptor signaling causes cell death through PKA-dependent pathways and cardioprotection through PKA-independent pathways.In PKA inhibitor peptide transgenic mice, chronic isoproterenol failed to induce cardiac hypertrophy, fibrosis, and myocyte apoptosis, and decreased cardiac function. In cultured adult feline ventricular myocytes, PKA inhibition protected myocytes from death induced by β1-adrenergic receptor agonists by preventing cytosolic and sarcoplasmic reticulum Ca(2+) overload and calcium/calmodulin-dependent kinase II activation. PKA inhibition revealed a cardioprotective role of β-adrenergic signaling via cAMP/exchange protein directly activated by cAMP/Rap1/Rac/extracellular signal-regulated kinase pathway. Selective PKA inhibition causes protection in the heart after myocardial infarction that was superior to β-blocker therapy.These results suggest that selective block of PKA could be a novel heart failure therapy.
T and B lymphocytes in leukemia therapy
Authors: Elaine Esber, William Dinicola, Nasser Movassaghi, Sanford Leikin
Journal: American Journal of Hematology (1976)

Abstract In order to evaluate the effect of radio‐ and chemotherapy on immunity, T and B lymphocyte surface receptors were studied sequentially in the blood from 28 previously untreated leukemic children. Following the initiation of chemotherapy an increase in the percent T and B cells was noted in the peripheral blood. In association with sanctuary therapy and chemotherapy there was a decrease in the total number of circulating T and B cells and a relative increase in lymphocytes lacking markers. Based on total numbers at remission the reduction in B cells was greater than in T cells, and the most marked changes occurred during sanctuary therapy. A reduction in the mean serum immunoglobulin was associated with decreasing B cell numbers.
Randomized Phase III Placebo-Controlled Trial of Carboplatin and Paclitaxel With or Without the Vascular Disrupting Agent Vadimezan (ASA404) in Advanced Non–Small-Cell Lung Cancer
Authors: Primo N. Lara, Jean-Yves Douillard, Kazuhiko Nakagawa, Joachim von Pawel, Mark J. McKeage, Istvan Albert, György Losonczy, Martin Reck, Dae-Seog Heo, Xiaolin Fan, Abderrahim Fandi, Giorgio Scagliotti
Journal: Journal of Clinical Oncology (2011)

Purpose This phase III trial was conducted to test whether the novel vascular disrupting agent ASA404 (vadimezan), when combined with first-line platinum-based chemotherapy, improves survival in patients with advanced non–small-cell lung cancer (NSCLC) versus chemotherapy alone. Patients and Methods Patients with advanced stage IIIB or IV NSCLC, stratified by sex and tumor histology, were randomly assigned 1:1 to paclitaxel (200 mg/m 2 ) and carboplatin (area under the curve, 6.0) with or without ASA404 (1,800 mg m 2 ), given intravenously once every 3 weeks for six cycles followed by maintenance ASA404 or placebo. Primary end point was overall survival (OS); secondary end points included overall response rate (ORR) and progression-free survival (PFS). Results One thousand two hundred ninety-nine patients were randomly assigned. The trial was stopped for futility at interim analysis. At final analysis, there was no difference in OS seen between ASA404 (n = 649) and placebo (n = 650) arms: median OS was 13.4 and 12.7 months respectively (hazard ratio [HR], 1.01; 95% CI, 0.85 to 1.19; P = .535). Similarly, no OS difference was seen in the histologic (squamous or nonsquamous) and sex (male or female) strata. Median PFS was 5.5 months in both arms (HR, 1.04; P = .727), while ORR was 25% in both arms (P = 1.0). Overall rate of adverse events (AEs) was comparable between the ASA404 and placebo arms. Grade 4 neutropenia (27% v 19%) and infusion site pain (10% v 0.5%) were reported more frequently in the ASA404 arm. Conclusion The addition of ASA404 to carboplatin and paclitaxel, although generally well tolerated, failed to improve frontline efficacy in advanced NSCLC.
Remarks on the Treatment of Quinsy, Especially in Infants
Authors: W. E. Green
Journal: BMJ (1887)

any disposition of that part, even when no structural change is appa- rent in it, to occupy the room provide(d.The sock may easily cause sufficient pressure to prevent this, and the best plan is to cut a hole in it, in that way setting perfectly free the great toe, which may be clothed with a few turnis of bandage tied around.In time, socks may be substituted having a straight inner line, or, better still, a separate stall for the great toe.The invitation to occupy the space provided in the boot must also be kept open ; the leather must not be allowed to fall in, but be frequently pressed upwards, and may, when the boot is not in use, be supported by wool stuffed within.Better still, of course, is the use of a well-made boot-tree.MIore generally the loss of the power of voluntary action of the flexor muscles is the explanation why the great toe shows no disposition to return to its proper place, and it is with difficulty that this power can be restored.The best way to practise the movement is with bare feet ; the assist- ance of the eye in the attempt to do it is very great.In time the habit of walking with firm pressure of the great toe against the ground in every step becomes even automatic.Given sufficient patience and determination, and it is surprising how bad a condition may be removed, and perfect recovery of outline and of function at- tained by these means alone.Of course, all this holds good in less degree in proportion to the amount of structural change in the joints.It is important, I should add, that, in walking, the feet should be directed forwards, not everted when, as already stated, the action of the flexors is impeded.The connection of the deformity described by Mr. Davies-Colley with flit-foot arose at the Clinical Society's meeting.I recognise with him that generally or frequently they are not found together.It is rather in cases where the longf flexor muscle consents, so to speak, to entirely suspendI its functions that the additional deformity occurs.In such cases the bowstring or tie-rod effect (as I have called it) of the long flexor is lost, and the arch sinks for want of the persistent bracing which vigorous action of that muscle affords.
A phase II study in advanced gastro-esophageal cancer using epirubicin and cisplatin in combination with continuous infusion 5-fluorouracil (ECF)
Authors: M. Findlay, D. Cunningham, A. Norman, J. Mansi, M. Nicolson, T. Hickish, V. Nicolson, A. Nash, N. Sacks, H. Ford, R. Carter, A. Hill
Journal: Annals of Oncology (1994)

A phase II study was performed in patients with unresectable or metastatic gastric cancer evaluating the efficacy of a new chemotherapy schedule combining epirubicin and cisplatin with a continuous ambulatory infusion of 5-fluorouracil (ECF).One hundred thirty-nine consecutive, previously untreated patients were given ECF. Of these, 128 had measurable disease. Epirubicin (50 mg/m2 i.v.) and cisplatin (60 mg/m2 i.v.) were administered every three weeks for 8 cycles during a 21 week continuous i.v. infusion of 5-fluorouracil (200 mg/m2/day). In total 773 cycles of chemotherapy were given.Objective tumour responses was seen in 91 (71%) of the 128 patients with measurable disease, of which 15 (12%) had a complete response. Twenty patients with locally advanced disease responding to ECF had attempted resection of the primary--11 (55%) were completely removed, 4 of these had no residual tumour in the resected specimen. The overall median survival was 8.2 months with 1 and 2 year survivals of 30% and 10% respectively. Grade 3 or 4 emesis occurred in 13%, stomatitis in 7%, diarrhoea in 4%, infection in 6%, leucopenia in 21% and thrombocytopenia in 8% of patients. Myelosuppression delayed treatment in 39 (5%) of the 773 cycles. Six of the 139 patients (4.3%) had treatment related deaths. There was no measurable reduction in quality of life during chemotherapy, while 67% of the 66 patients with dysphagia had complete resolution of this symptom.The ECF regimen displays high anti-tumour activity with moderate toxicity in patients with gastric cancer and in some cases enabled resection of previously inoperable tumours.
Assessment of Neonatal Diaphragm Function Using Magnetic Stimulation of the Phrenic Nerves
Authors: GERRARD F. RAFFERTY, ANNE GREENOUGH, GABRIEL DIMITRIOU, VALIA KAVADIA, BERNARD LAUBSCHER, MICHAEL I. POLKEY, M. LOU HARRIS, JOHN MOXHAM
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

A nonvolitional test to assess diaphragm strength in neonates has not been previously described. Our aim was to assess the feasibility of cervical (CMS) and anterior (AMS) magnetic stimulation of the phrenic nerves in neonates. Double circular stimulating coils (90-mm) were used. For CMS, one coil was placed over the cervical spine to bilaterally stimulate the phrenic nerve roots, whereas for AMS the coils were placed on the anterolateral aspect of the neck to allow unilateral and bilateral stimulation. Diaphragm contractility was assessed as transdiaphragmatic pressure (Pdi) measured with balloon catheters positioned in the midesophagus and stomach. Stimulus supramaximality was assessed by examining diaphragm twitch Pdi (TwPdi) across a range of stimulator outputs; 85, 90, 95, and 100% of maximum. Pressure signals were measured by differential pressure transducer and displayed in real time on a computer. Patients were studied supine during sleep. CMS was performed on seven neonates (mean gestational age [GA] 38 wk, range 33 to 40 wk) and AMS on 18 neonates (mean GA 37 wk, range 32 to 41 wk). The mean (SD) TwPdi with CMS was 2.5 (0.8) cm H(2)O. CMS was not supramaximal; reducing the stimulator output below 100% caused marked reductions in TwPdi, also the shape of the pressure waveforms suggested that CMS may not have activated the diaphragm alone. Mean (SD) TwPdi with AMS was 4.5 (1.3) cm H(2)O on the left, 4.1 (0.9) cm H(2)O on the right, and 8.7 (3.9) cm H(2)O for bilateral stimulation. The shape of the pressure waveforms suggested that AMS was more specific and a plateau in TwPdi at higher stimulator outputs indicated supramaximality. We conclude that AMS may provide a useful technique to assess diaphragm function in the neonate.
Comprehensive array CGH of normal karyotype myelodysplastic syndromes reveals hidden recurrent and individual genomic copy number alterations with prognostic relevance
Authors: A Thiel, M Beier, D Ingenhag, K Servan, M Hein, V Moeller, B Betz, B Hildebrandt, C Evers, U Germing, B Royer-Pokora
Journal: Leukemia (2011)
Expression of vascular remodelling markers in relation to bradykinin receptors in asthma and COPD
Authors: Fabio L M Ricciardolo, Federica Sabatini, Valentina Sorbello, Sabrina Benedetto, Ilaria Defilippi, Loredana Petecchia, Cesare Usai, Isabella Gnemmi, Bruno Balbi, Virginia De Rose, Nick H T ten Hacken, Dirkje S Postma, Wim Timens, Antonino Di Stefano
Journal: Thorax (2013)

<h3>Background</h3> Vascular remodelling plays a central role in asthma and chronic obstructive pulmonary disease (COPD). Bradykinin (BK) is a vasoactive proinflammatory peptide mediating acute responses in asthma. We investigated the role of angiogenic factors in relation to BK receptors in asthma and COPD. <h3>Methods</h3> Bronchial biopsies from 33 patients with COPD, 24 old (≥50 years) patients with (≥50 years) asthma, 18 old control smokers, 11 old control non-smokers, 15 young (≤40yrs) patients with (≤40 years) asthma and 10 young control non-smokers were immunostained for CD31, vascular endothelial growth factor-A (VEGF-A), angiogenin and BK receptors (B2R and B1R). Fibroblast and endothelial co-localisation of relevant molecules were performed by immunofluorescence. BK-induced VEGF-A and angiogenin release was studied (ELISA) in bronchial fibroblasts from subjects with asthma and COPD. <h3>Results</h3> In bronchial lamina propria of old patients with asthma, CD31 and VEGF-A<sup>+</sup> cell numbers were higher than old control non-smokers (p&lt;0.05). Angiogenin<sup>+</sup>, B2R<sup>+</sup> and B1R<sup>+</sup> cell numbers in old patients with asthma were higher than in old control non-smokers, control smokers and patients with COPD (p&lt;0.01). Angiogenin<sup>+</sup> cell numbers were higher in patients with COPD than both old control groups (p&lt;0.05). In all patients with asthma the number of B2R<sup>+</sup> cells was positively related to the numbers of B1R<sup>+</sup> (r<sub>s</sub>=0.43), angiogenin<sup>+</sup> (r<sub>s</sub>=0.42) and CD31 cells (r<sub>s</sub>=0.46) (p&lt;0.01). Angiogenin<sup>+</sup> cell numbers were negatively related to forced expiratory volume in 1 s (r<sub>s</sub>=−0.415, p=0.008). Double immunofluorescence revealed that CD31 cells of capillary vessels coexpressed B2R and that fibroblasts coexpressed B2R, VEGF-A and angiogenin. BK (10<sup>−6</sup>M) induced significant angiogenin release in fibroblasts from asthma and to a lesser extent in COPD. <h3>Conclusions</h3> Unlike COPD, this study suggests the involvement of BK receptors in bronchial vascular remodelling in asthma.
Pilot Randomized Clinical Trial of Prehospital Induction of Mild Hypothermia in Out-of-Hospital Cardiac Arrest Patients With a Rapid Infusion of 4°C Normal Saline
Authors: Francis Kim, Michele Olsufka, W.T. Longstreth, Charles Maynard, David Carlbom, Steven Deem, Peter Kudenchuk, Michael K. Copass, Leonard A. Cobb
Journal: Circulation (2007)

Although delayed hospital cooling has been demonstrated to improve outcome after cardiac arrest, in-field cooling started immediately after the return of spontaneous circulation may be more beneficial. The aims of the present pilot study were to assess the feasibility, safety, and effectiveness of in-field cooling.We determined the effect on esophageal temperature, before hospital arrival, of infusing up to 2 L of 4 degrees C normal saline as soon as possible after resuscitation from out-of-hospital cardiac arrest. A total of 125 such patients were randomized to receive standard care with or without intravenous cooling. Of the 63 patients randomized to cooling, 49 (78%) received an infusion of 500 to 2000 mL of 4 degrees C normal saline before hospital arrival. These 63 patients experienced a mean temperature decrease of 1.24+/-1 degrees C with a hospital arrival temperature of 34.7 degrees C, whereas the 62 patients not randomized to cooling experienced a mean temperature increase of 0.10+/-0.94 degrees C (P<0.0001) with a hospital arrival temperature of 35.7 degrees C. In-field cooling was not associated with adverse consequences in terms of blood pressure, heart rate, arterial oxygenation, evidence for pulmonary edema on initial chest x-ray, or rearrest. Secondary end points of awakening and discharged alive from hospital trended toward improvement in ventricular fibrillation patients randomized to in-field cooling.These pilot data suggest that infusion of up to 2 L of 4 degrees C normal saline in the field is feasible, safe, and effective in lowering temperature. We propose that the effect of this cooling method on neurological outcome after cardiac arrest be studied in larger numbers of patients, especially those whose initial rhythm is ventricular fibrillation.
Writers join experts to campaign to save NHS from privatisation
Authors: Sophie Arie
Journal: BMJ (2005)

Some of Britain's leading writers have joined a growing campaign to stop government plans to extend the privatisation of the NHS in certain areas.

The poet laureate, Andrew Motion, and the authors Philip Pullman, Nick Hornby, and Clare Tomalin are among several unexpected public figures joining a campaign to “keep our NHS public.”

They joined over 30 experts on public health, including the former Labour health secretary Frank Dobson, former BMA chairman Sandy Macara, and former …
P06.16 * INTRACRANIAL MENINGIOMA: PROGNOSTIC FACTORS AND TREATMENT OUTCOME IN PATIENTS UNDERGOING RADIATION THERAPY
Authors: K. Anvari, S. Hosseini, S. Rahighi, M. S. Toussi, N. Roshani, M. Torabi-Nami
Journal: Neuro-Oncology (2014)

BACKGROUND: Meningioma constitutes 20% of the intracranial neoplasms. Followed by surgery as the primary treatment for most patients, radiotherapy becomes indicated in high-grade tumors with incomplete surgical removal. We evaluated the prognostic factors and overall outcome in meningioma patients who underwent radiotherapy. MATERIALS AND METHODS: In this retrospective analysis, data from all patients with documented diagnosis of meningioma who referred to Omid and Ghaem Oncology Centers (Mashhad, Iran) from 2001 to 2012 were included. We calculated the overall survival rates using the Kaplan-Meier method and compared the survival curves between groups by Log-Rank test. RESULTS: 83 patients with a median age of 50 years (ranging 16-84) were included. Grade I, II and III meningiomas were seen in 40 (48%), 31(37%) and 12(15%) patients, respectively. Radiation therapy were indicated due to tumor recurrence, incomplete excision or tumor grade in 32, 8 and 43 patients, respectively. Tumor grade had a significant effect on the overall survival with a 3-year overall survival of 76.7%, 43.5% and 13.3% in grade I, II and III, respectively (p< 0.001). Gender, age and tumor location were not correlated with the overall survival. Moreover, patients with grade II and III who underwent total resection had a significantly higher overall survival than those with subtotal resection or biopsy alone (5-year survival rates of 82% vs. 17.1%, respectively; p= 0.008). CONCLUSION: Tumor grade was the most important prognostic factors in meningioma patients undergoing radiation therapy. In patients with grade II and III tumors, the extent of surgical resection is significantly correlated with the overall survival.
Cell Cycle–Dependent Variation of a CD133 Epitope in Human Embryonic Stem Cell, Colon Cancer, and Melanoma Cell Lines
Authors: Marie Jaksch, Jorge Múnera, Ruchi Bajpai, Alexey Terskikh, Robert G. Oshima
Journal: Cancer Research (2008)

Abstract CD133 (Prominin1) is a pentaspan transmembrane glycoprotein expressed in several stem cell populations and cancers. Reactivity with an antibody (AC133) to a glycoslyated form of CD133 has been widely used for the enrichment of cells with tumor-initiating activity in xenograph transplantation assays. We have found by fluorescence-activated cell sorting that increased AC133 reactivity in human embryonic stem cells, colon cancer, and melanoma cells is correlated with increased DNA content and, reciprocally, that the least reactive cells are in the G1-G0 portion of the cell cycle. Continued cultivation of cells sorted on the basis of high and low AC133 reactivity results in a normalization of the cell reactivity profiles, indicating that cells with low AC133 reactivity can generate highly reactive cells as they resume proliferation. The association of AC133 with actively cycling cells may contribute to the basis for enrichment for tumor-initiating activity. [Cancer Res 2008;68(19):7882–6]
The latency-associated nuclear antigen of Kaposi sarcoma-associated herpesvirus induces B cell hyperplasia and lymphoma
Authors: F. D. Fakhari
Journal: Journal of Clinical Investigation (2006)

Kaposi sarcoma-associated herpesvirus (KSHV) is a human lymphotropic herpesvirus. It is implicated in B cell neoplasias such as primary effusion lymphoma and multicentric Castleman disease in AIDS patients. The KSHV latency-associated nuclear antigen (LANA) is consistently expressed in all KSHV-associated tumor cells and was shown to bind the tumor suppressor proteins p53 and pRb. To test LANA's contribution to lymphomagenesis in vivo we generated transgenic mice expressing LANA under the control of its own promoter, which is B cell specific. All of the transgenic mice developed splenic follicular hyperplasia due to an expansion of IgM+ IgD+ B cells and showed increased germinal center formation. We also observed lymphomas, implying that LANA can activate B cells and provide the first step toward lymphomagenesis.
Gonadal Steroid Induction of Structural Sex Differences in the Central Nervous System
Authors: Arthur P. Arnold, Roger A. Gorski
Journal: Annual Review of Neuroscience (1984)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More