tbuckley/cabot-search huggingface dataset:
Prevalence of atrial fibrillation in patients with sarcoidosis
Authors: Vasilios Kouranos, Aggeliki Rapti, Efrosini Manali, Kostantina Aggeli, Lemonia Velentza, Elias Peros, Theodore Papaioannou, Anastasios Kalianos, George Kaltsakas, Kostas Vlachos, Charalampos Kostopoulos, Spiros Papiris, Nikos Koulouris, Elias Gialafos
Journal: European Respiratory Journal (2013)

Introduction: Sarcoidosis is a multisystemic disease associated with arrhythmias, however the development of atrial fibrillation (AF) has not been described. Aim of this study was the estimation of AF in sarcoidosis.  Methods: 198 biopsy proven sarcoid patients underwent 24-hour- ECG, cardiac echo, cardiac MRI including viability (c-MRI) and pulmonary function tests including total lung capacity(TLC) and diffusion capacity (DLCO). B-natriuretic peptide (BNP) was measured.  Results: Group A consisted of 49 patients having paroxysmal AF (24. 7%) while the rest formed group B. Group A had higher age (56.2±13.1 vs 46.3±11.5 yo, p=0.0001), larger left ventricular end diastolic diameter (48.1±4.4 vs 49.55±4.23 mm, p=0.021), increased interventricular septum (10.3±1.1 vs 9. 6±1.2mm,p=0.001), lower ejection fraction(59.8±2 vs 58.5±4.5%,p=0.032),lower forced vital capacity (96.5±17.9 vs 88.5±21.2% of the predicted, p=0.012), lower TLC (85.23±14.4vs 80.24±14.05% of the predicted, p=0.041) and higher BNP level (21.05±23.44vs35.3±38.9 pg/dl, p=0.004). Higher percentage of gadolinium enhancement in MRI, cardiac involvement and cortisone were in group A (p=0.009, p=0.002 and p=0.011 respectively). Staging of the disease, DLCO and disease duration were not different among the two groups. Binary logistic regression showed that BNP (95%CI:1.003-1.043; p=0.018), c-MRI(95%CI:0.092-0.99;p=0.041), IVS (95%CI:1.312-4.290;p=0.001) and ejection fraction(95%CI:0.445-0.91;p=0.001) were inependently linked to the AF.  Discussion: BNP, gadolinium enhancement assessed by c-MRI, ejection fraction and interventricular septum are linked to the pathomechanism of atrial fibrillation in patients with sarcoidosis independent of cardiac involvement.
Platelet count is a marker of outcome in community-acquired pneumonia
Authors: D. Martínez, F. Sanz, E. Fernández, A. Cervera, M.L. Briones, M.C. Aguar, E. Chiner, J.N. Sancho, C. Senent, L. Gil, L. Novella, S. Herrera, C. Miralles, J. Berraondo, J. Blanquer
Journal: European Respiratory Journal (2013)

Background: Abnormal platelet count (PC) has been associated with most often complications and increased mortality in hospitalized patients with community-acquired pneumonia (CAP).  Aim: We investigated the association of PC at time of hospitalization, thrombocytosis (platelet count ≥ 400000/mm3) compared with thrombocytopenia (platelet count   Methods: A 12 months prospective multicenter and longitudinal study was performed in 10 hospitals of a Spanish mediterranean area. We included hospitalized adult patients with CAP. We excluded patients with immunosuppression, active tuberculosis or hematological disease. χ2, T student an logistic regression were used to compare groups.  Results: We analyzed 1314 patients. Forty-three patients (3%) presented thrombocytopenia, 107 (8%) thrombocytosis and 1164 (89%) had normal platelet count. The average of PC was 248923 ± SD 142952. Lower platelet counts were associated with an increase of severity of disease by PSI or CURB65 (p=0,014, p=0,004 respectively). Patients with thrombocytopenia presented more often severe sepsis (p  Conclusions: Abnormal platelet count is associated with severity of disease and more frequently complications in patients with CAP.
Rapidly responsive adaptations in malignant astrocytomas under hypoxic conditions, as targets for novel brain tumor treatments, includes the PI3K/Akt/GSK-3 pathway
Authors: Marie E. Beckner, Fatima Burovic, Roger Abounader, Daniel R. Premkumar, John Laterra, Ian F. Pollack
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

3002 

Objective: Malignant astrocytomas are deadly, treatment-resistant brain tumors. Our goal is to identify new treatment targets in malignant astrocytomas. Previous therapies, developed using normoxic conditions, have not worked well. Astrocytic potential for gluconeogenic removal of lactate may help to counteract metabolic stress during treatment. We propose that astrocytic metabolism requires brain tumor therapy to target cellular adaptations to hypoxia, as well as normoxic functions. Phosphorylations and dephosphorylations of key proteins, including phosphatidylinositol-3-kinase (PI3K)/Akt/glycogen synthase kinase-3 (GSK-3) pathway components, are proposed to trigger rapid, critical responses to hypoxia. Mutated phosphatase and tensin homolog, PTEN , commonly seen in malignant astrocytomas, allows anomalous activation of the PI3K/Akt/GSK-3 pathway, leading to activated glycogen synthase, thus providing additional removal of lactate as glycogen in poorly-perfused, invading tumor cells. Methods: Quantifying cellular adjustments to hypoxia, within 5 hrs of exposure, provided detection of the rapid adaptations that bypass the need for transcription factor-mediated alterations of protein levels. Quantifying 5 hr migration assays of U87 astrocytoma cells (mutated PTEN ) under hypoxic conditions, following restoration of PTEN- wild type (WT) with transient adenoviral transfections, revealed PTEN’s contribution to control of hypoxic cell migration via its negative regulation of the pathway. Peptide competition studies of GSK-3alpha’s phosphorylation by Akt indicated whether inhibitory drugs can be developed to shut down downstream signaling leading to glycogen synthesis in PTEN -mutated astrocytomas. Results: Previously, wortmannin (3.0 –30.0 nM), a specific PI3K inhibitor, suppressed hypoxic U87 migration with a dose response. Restoration of PTEN -WT in U87 cells, followed by functional assays showed significantly decreased, 50.4% (95% CI = 35.0 to 65.8%), migration in hypoxia compared to normoxia, when control vector hypoxic migration was maintained at levels comparable to normoxic migration (p=0.3, two-tailed, paired samples, 4 assays). Previously, whole cell and pseudopodal lysates showed that GSK-3alpha was phosphorylated at peak levels in the pseudopodal leading edge. Preliminary competition studies showed that a peptide containing an 11 residue sequence of the GSK-3alpha phosphorylation site inhibited phosphorylation by cell derived Akt with a dose response at 250 to 1000-fold greater amounts than substrate. Conclusion: Anomalous PI3K/Akt/GSK-3alpha pathway activity in PTEN -mutated astrocytoma cells offers novel targets for future drug therapies to suppress hypoxic migration required for invasion. We thank The Nick Eric Wichman Foundation for encouragement and financial support.
Organic psychosis without anemia or spinal cord symptoms in patients with vitamin B12 deficiency
Authors: D L Evans, G A Edelsohn, R N Golden
Journal: American Journal of Psychiatry (1983)

The authors describe two patients with organic psychosis who had vitamin B12 deficiency and no hematologic or spinal cord abnormalities. They review the literature that supports a causal relationship between B12 deficiency and cerebral dysfunction, as measured by the EEG, and consequent organic mental changes. The authors cite evidence that these EEG and organic mental changes are reversible with B12 replacement. They emphasize that psychiatric manifestations may be the first symptoms of vitamin B12 deficiency and thus antedate anemia and spinal cord disease. They recommend consideration of B12 deficiency and serum B12 determinations in all patients with organic mental symptoms.
Pharmacokinetics of tissue-type plasminogen activator during acute myocardial infarction in men. Effect of a prostacyclin analogue.
Authors: D M Kerins, L Roy, S Kunitada, A Adedoyin, G A FitzGerald, D J Fitzgerald
Journal: Circulation (1992)

BACKGROUND Coronary reocclusion complicates the thrombolytic therapy of acute myocardial infarction despite the routine use of aspirin. This is consistent with experimental studies demonstrating that multiple agonists, in addition to thromboxane A2, mediate the platelet activation underlying reocclusion. Consequently, a more potent antiplatelet therapy with a broader spectrum of activity than aspirin may be required in this setting. Prostacyclin and its more stable analogue, iloprost, inhibit platelet aggregation to all known agonists and exert an additional effect over aspirin alone. Experiments in animal models have demonstrated, however, that iloprost increases the clearance of tissue-type plasminogen activator (t-PA) and impairs thrombolysis in vivo. This study examines whether a similar interaction occurs in humans. METHODS AND RESULTS Twelve patients with acute myocardial infarction received t-PA intravenously, 60 mg in the first hour and a maintenance infusion of 13.3 mg/hr for 3 hours. Patients were assigned in a double-blind fashion to iloprost (2 ng/kg/min) or placebo following the initial 90 minutes of the maintenance infusion of t-PA. Iloprost decreased mean arterial blood pressure (-10 +/- 2.9 mm Hg, p less than 0.05) but did not alter heart rate. Steady-state plasma iloprost concentration was 591 +/- 64 pmol/l. At this concentration, iloprost markedly inhibited platelet aggregation in vitro, particularly in the presence of aspirin. Steady-state clearance of t-PA was unchanged by iloprost (454 +/- 65 versus 443 +/- 136 ml/min in controls, p = NS). Furthermore, neither elimination kinetics nor plasma protein binding of t-PA was altered by iloprost. CONCLUSIONS At plasma levels that exert a potent antiplatelet effect, iloprost did not alter the pharmacokinetics of t-PA in men. Prostacyclin analogues may prove useful as an adjunct to plasminogen activators, particularly in patients at high risk for thrombotic reocclusion.
Activity of fludarabine in previously treated non-Hodgkin's low-grade lymphoma: results of an Eastern Cooperative Oncology Group study.
Authors: H S Hochster, K M Kim, M D Green, R B Mann, R S Neiman, M M Oken, P A Cassileth, P Stott, P Ritch, M J O'Connell
Journal: Journal of Clinical Oncology (1992)

Fludarabine (2-fluoro-arabanoside-monophosphate) is a new antimetabolite chemotherapeutic agent. We performed a multicenter, phase II study of this drug in previously treated patients with refractory or relapsed non-Hodgkin's lymphoma (NHL) to determine its response rate by histologic classification.Sixty-two assessable patients were given 18 mg/m2 by intravenous (IV) bolus injection daily for 5 days, every 28 days. Forty-eight percent had previously had one chemotherapy regimen, and the remainder had had two regimens; 42% had had radiation.Patients received 273 cycles of fludarabine chemotherapy, with a median of two cycles and ranging up to 25 cycles. Sixty patients were assessable for response, including nine complete responses (CRs; 15%) and nine partial responses (PRs; 15%). The response rate for patients with lower-grade histology was 52% (13 of 25); the greatest response rate was seen in those with follicular small cleaved-cell lymphoma, including seven of 11 treated. Five responders remain in unmaintained remission; the median survival of responders is greater than 30 months. Toxicity included mild neutropenia and a 10% incidence of grade 3 neurologic toxicity with occasional reversible visual and auditory changes.Fludarabine is active in patients with previously treated NHL (particularly low-grade histologies). Future studies will examine its activity in combination with other chemotherapeutic agents in previously untreated patients.
Abstract 912: Sulforaphane suppresses the growth of triple-negative breast cancer stem-like cells in vitro and in vivo
Authors: Nadia P. Castro, Cristina M. Rangel, David Salomon, Karen Saylor, Young S. Kim
Journal: Cancer Research (2015)

Abstract Approximately 10-20% of breast cancer consists of triple-negative tumors, which present the poorest prognosis among the different subtypes. The triple-negative breast cancer (TNBC) tumors are known to be enriched with stem-like cells that are resistant to standard targeted drugs. Thus, it is extremely important to develop new agents that are non-toxic and specifically efficacious against these cancer stem-like cells (CSCs) that are suggested to be responsible for the initiation and maintenance of tumors. Here, we show that sulforaphane (SFN), a dietary component abundant in broccoli and broccoli sprouts, inhibits cell proliferation and sphere formation of the CSC population in TNBC cells. TNBC stem-like cells were isolated from MDA-MB-231 Luci D3H1human triple negative breast cancer cells using fluorescently activated cell sorting (FACS) analysis. Six week old BalbC/nude mice were purchased from Jackson laboratory and fed with an AIN-96G-purified diet containing no SFN (Harlan Teklad Inc) until the end of experiments. The mice (n = 40) were treated with or without daily i.p. injection of 50mg SFN/kg b.w. for 2 weeks prior to the inoculation with MDA-MB-231 Luci D3H1 cells. The tumor cells were planted into both sides of the 4th inguinal mammary fat pads. The SFN treatment was continued for 3 additional weeks after the tumor cell xenografts. Our results revealed that the CSC population isolated with CD49f+, CD24-/CD44high showed the ability to form mammoshperes, which is a characteristic of stemness. When these cells were treated with natural dietary constituent SFN at the concentration of 7.5 μM, they lost the property of mammosphere formation in vitro. Furthermore, SFN pre-treated animals (n = 20) exhibited a thirty percent reduction in tumor volume compared with control (saline 0.9%) at day 30 after the tumor cell inoculation. These data indicate that SFN suppresses triple negative mammary tumor formation both in vitro (7.5uM) and in vivo (50mg/kg bw) by targeting a CSC population. Further analysis on gene expression and protein profiles are being performed to elucidate whether stem-related developmental signaling pathways are being modulated by SFN. Citation Format: Nadia P. Castro, Cristina M. Rangel, David Salomon, Karen Saylor, Young S. Kim. Sulforaphane suppresses the growth of triple-negative breast cancer stem-like cells in vitro and in vivo. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 912. doi:10.1158/1538-7445.AM2015-912
Abstract 13519: Signaling via PI3Kβ and PI3Kγ and Increased Glucose Oxidation Contribute to the Marked Protection Against Ischemia/Reperfusion Injury in PI3KαDN Hearts
Authors: Brent A McLean, Wang Wang, Petra C Kienesberger, Grant Masson, Jason Dyck, Gavin Y Oudit
Journal: Circulation (2012)

Introduction:  The phosphatidylinositol 3-kinase (PI3K)γ isoform is an important mediator of signals from ligands such as adenosine, which cause protection against ischemia reperfusion (IR) injury. The class 1 PI3K isoforms primarily expressed in the heart are α, β and γ. Reduced PI3Kα signaling in the heart resulted in dramatic protection from IR injury. Here we test the hypothesis that the IR protection with reduced PI3Kα signaling is the result of increased PI3Kγ activation.   Methods:  PI3Kα dominant negative (DN) mice were crossed with PI3Kγ-/- to create a PI3K double mutant (DM). Also, PI3K DM and PI3Kα DN hearts were perfused with the PI3Kβ selective inhibitor TGX-221 (500 nM). Langendorff perfused hearts were treated with 30 minutes ischemia, and functional recovery was assessed upon 40 minutes of reperfusion. Signaling via Akt and GSK3β pathways was assessed by Western blot. To assess metabolic profile, PI3Kα DN hearts were perfused in the working heart mode with radio labeled substrates for glycolysis and glucose oxidation.   Results:  PI3K DM hearts showed improved recovery from IR compared to wildtype (wt) hearts: heart rate pressure product (RPP) recovery was 81.4±10.1% and 37.9±2.8%, and LV developed pressure (LVDP) recovery was 98.7±8.4% and 49.6±3.6 (n=6-9) respectively. IR recovery was reduced (RPP: 37.1±6.4%, LVDP: 47.5±7.9% recovery (n=8)) upon pharmacological inhibition of PI3Kβ in the PI3K DM hearts but was not effective against PI3KαDN hearts (RPP: 74.2±4.5%, LVDP: 85.1±8.7% (n=7). Induction of downstream targets correlated with functional recovery, but PI3K DM had reduced Akt and GSK3β phosphorylation under aerobic conditions. Interestingly, PI3Kα DN hearts displayed increased glucose oxidation (PI3Kα DN: 10.2±1.1 vs wt: 6.9±1.1 nmol/g/min; p   Conclusions:  Protection from IR injury observed in PI3Kα DN hearts is dependent on alternate PI3K signaling, and suggests a redundancy between PI3Kβ and PI3Kγ isoforms. Increased glucose oxidation in the PI3KαDN hearts may also serve as a protective mechanism against IR injury, and decreased AMPK phosphorylation is indicative of decreased metabolic stress.
Cells biomarkers of bronchial brush-biopsies at COPD exacerbation
Authors: Sofya Nesterovich, Ekaterina Bukreeva
Journal: European Respiratory Journal (2013)

To define bronchial brush-biopsies cytogramms peculiarities in dependence on infectional agent species associated with COPD exacerbation.  46 COPD exacerbation patients were examined. Cytological research of brush-biopsies were taken at bronchoscopy was made; the quantitative bacteriological sputum research, definition of diagnostic main IgG, IgM levels to Ch.pneumoniae, M.pneumoniae in serum by means immuno-assay method, definition of their genomes fragments in sputum by means of PCR method were made.  Infectional character of COPD exacerbation was confirmed at 36 patients. Typical ciliated epithelial cells count in H.influenzae, Ch.pneumoniae, M.pneumoniae infection was 14.6±2.2%, 15.1±2.5%, 15.5±3.1%, that was low (p  Infectional agent species influence on degree of bronchial mucosa damage. H.influenzae, Ch.pneumoniae have more injured effects and M.catarrhalis have least injured effects.
The influence of airway supporting maneuvers on glottis view in paediatric patients undergoing diagnostic flexible fiberoptic bronchoscopy
Authors: Tarik Umutoglu, Ahmet Hakan Gedik, Mefkur Bakan, Ufuk Topuz, Hayrettin Daskaya, Erdogan Ozturk, Erkan Cakir, Ziya Salihoglu
Journal: European Respiratory Journal (2014)

Introduction and aim : The aim of this study is to investigate the influence of the airway supporting maneuvers on glottis view during pediatric flexible fiberoptic bronchoscopy(FOB).  Material and Method: In this randomised, controlled, crossover study; patients aged between 0-15 years who underwent FOB procedure having ASA I-II risk score were included. Patients having risk of difficult intubation, intubated or patients with tracheostomy, and patients with reduced neck mobility or having cautions for neck mobility were excluded from this study. After obtaining best glottic view at the neutral position, patients were positioned Jaw trust with open mouth (A), Jaw trust with teeth prottution (B) head tilt chin lift (C) and triple airway (D) manoeuvres and best glottic scores were recorded. Results: 57 girl total 121 pediatric patients were included in this study. Both A and B maneuvers improved the glottis view compared with neutral position (pl0,001), but we didn9t found any difference between A and B maneuvers (pg0.05). C and D maneuvers improved glottis view when compared both A and B maneuvers and neutral position (pl0,001), however we found no differences between C and D maneuvers (pg0.05). Conclusion:All airway supporting maneuvers improved glottic view during pediatric FOB, however head tilt chin lift and triple airway maneuvers were found to be the most effective maneuvers.
Clinicians who enter patients into randomised controlled trials should be acknowledged
Authors: S. Mason, S. Haining
Journal: BMJ (1996)

their residual risk of having a child with cystic fibrosis.Couples in which one partner has no identifiable mutation and the other partner is not tested have a risk of 1 in 16100 (1/25xl/161xl/ 4); they represent 96.6% of the couples.Couples in which one partner but not the other has an identifiable mutation have a risk of 1 in 644 (1/lxl/161xl/4); they represent 3.3% of the couples.Couples in which both partners are car- riers have a risk of 1 in 4; they represent 0. 1% of the population.
Systemic Vascular Load in Calcific Degenerative Aortic Valve Stenosis
Authors: Raquel Yotti, Javier Bermejo, Enrique Gutiérrez-Ibañes, Candelas Pérez del Villar, Teresa Mombiela, Jaime Elízaga, Yolanda Benito, Ana González-Mansilla, Alicia Barrio, Daniel Rodríguez-Pérez, Pablo Martínez-Legazpi, Francisco Fernández-Avilés
Journal: Journal of the American College of Cardiology (2015)

Systemic arterial load impacts the symptomatic status and outcome of patients with calcific degenerative aortic stenosis (AS). However, assessing vascular properties is challenging because the arterial tree's behavior could be influenced by the valvular obstruction.This study sought to characterize the interaction between valvular and vascular functions in patients with AS by using transcatheter aortic valve replacement (TAVR) as a clinical model of isolated intervention.Aortic pressure and flow were measured simultaneously using high-fidelity sensors in 23 patients (mean 79 ± 7 years of age) before and after TAVR. Blood pressure and clinical response were registered at 6-month follow-up.Systolic and pulse arterial pressures, as well as indices of vascular function (vascular resistance, aortic input impedance, compliance, and arterial elastance), were significantly modified by TAVR, exhibiting stiffer vascular behavior post-intervention (all, p < 0.05). Peak left ventricular pressure decreased after TAVR (186 ± 36 mm Hg vs. 162 ± 23 mm Hg, respectively; p = 0.003) but remained at >140 mm Hg in 70% of patients. Wave intensity analysis showed abnormally low forward and backward compression waves at baseline, increasing significantly after TAVR. Stroke volume decreased (-21 ± 19%; p < 0.001) and correlated with continuous and pulsatile indices of arterial load. In the 48 h following TAVR, a hypertensive response was observed in 12 patients (52%), and after 6-month follow-up, 5 patients required further intensification of discharge antihypertensive therapy.Vascular function in calcific degenerative AS is conditioned by the upstream valvular obstruction that dampens forward and backward compression waves in the arterial tree. An increase in vascular load after TAVR limits the procedure's acute afterload relief.
The Use of Acyclovir in Suspected Encephalitis
Authors: Jonathan Gleadle, Christine Dixon, Martin M Brown, Frederick Schon
Journal: Journal of the Royal Society of Medicine (1994)

The early use of intravenous acyclovir in herpes simplex encephalitis (HSE) is essential. However, rapid diagnostic tests are not freely available. Hence, all patients with suspected encephalitis may need to be commenced on acyclovir. In our study, of 34 patients with suspected encephalitis, only two eventually had HSE confirmed, 19 had encephalitis not due to herpes simplex and in 13 a non-encephalitis illness was finally diagnosed. Guidelines for the use of acyclovir in suspected encephalitis are given aimed at minimizing the drug cost whilst still protecting all cases of presumed HSE.