tbuckley/cabot-search huggingface dataset:
Quantitative Fluoroestradiol Positron Emission Tomography Imaging Predicts Response to Endocrine Treatment in Breast Cancer
Authors: Hannah M. Linden, Svetlana A. Stekhova, Jeanne M. Link, Julie R. Gralow, Robert B. Livingston, Georgiana K. Ellis, Philip H. Petra, Lanell M. Peterson, Erin K. Schubert, Lisa K. Dunnwald, Kenneth A. Krohn, David A. Mankoff
Journal: Journal of Clinical Oncology (2006)

In breast cancer, [(18)F]fluoroestradiol (FES) positron emission tomography (PET) correlates with estrogen receptors (ER) expression and predicts response to tamoxifen. We tested the ability of FES-PET imaging to predict response to salvage hormonal treatment in heavily pretreated metastatic breast cancer patients, predominantly treated with aromatase inhibitors.Initial FES uptake measurements in 47 patients with ER-positive tumors were correlated with subsequent tumor response to 6 months of hormonal treatment. Most patients had bone dominant disease and prior tamoxifen exposure. Response was compared to initial FES-PET uptake, measured qualitatively and quantitatively using standardized uptake value (SUV) and estradiol-binding flux.Eleven of 47 patients (23%) had an objective response. While no patients with absent FES uptake had a response to treatment, the association between qualitative FES-PET results and response was not significant (P = .14). However, quantitative FES uptake and response were significantly associated; zero of 15 patients with initial SUV less than 1.5 responded to hormonal therapy, compared with 11 of 32 patients (34%) with SUV higher than 1.5 (P < .01). In the subset of patients whose tumors did not overexpress HER2/neu, 11 of 24 patients (46%) with SUV higher than 1.5 responded.Quantitative FES-PET can predict response to hormonal therapy and may help guide treatment selection. Treatment selection using quantitative FES-PET in our patient series would have increased the rate of response from 23% to 34% overall, and from 29% to 46% in the subset of patients lacking HER2/neu overexpression. A multi-institutional collaborative trial would permit definitive assessment of the value of FES-PET for therapeutic decision making.
Changes in the FEV1/FVC ratio during childhood and adolescence: an intercontinental study
Authors: P.H. Quanjer, S. Stanojevic, J. Stocks, G.L. Hall, K.V.V. Prasad, T.J. Cole, M. Rosenthal, R. Perez-Padilla, J.L. Hankinson, E. Falaschetti, M. Golshan, B. Brunekreef, O. Al-Rawas, J. Kühr, Y. Trabelsi, M.S.M. Ip
Journal: European Respiratory Journal (2010)

In children, the ratio of forced expiratory volume in 1 s (FEV 1 ) to forced vital capacity (FVC) is reportedly constant or falls linearly with age, whereas the ratio of residual volume (RV) to total lung capacity (TLC) remains constant. This seems counter-intuitive given the changes in airway properties, body proportions, thoracic shape and respiratory muscle function that occur during growth. The age dependence of lung volumes, FEV 1 /FVC and RV/TLC were studied in children worldwide. Spirometric data were available for 22,412 healthy youths (51.4% male) aged 4–20 yrs from 15 centres, and RV and TLC data for 2,253 youths (56.7% male) from four centres; three sets included sitting height (SH). Data were fitted as a function of age, height and SH. In childhood, FVC outgrows TLC and FEV 1 , leading to falls in FEV 1 /FVC and RV/TLC; these trends are reversed in adolescence. Taking into account SH materially reduces differences in pulmonary function within and between ethnic groups. The highest FEV 1 /FVC ratios occur in those shortest for their age. When interpreting lung function test results, the changing pattern in FEV 1 /FVC and RV/TLC should be considered. Prediction equations for children and adolescents should take into account sex, height, age, ethnic group, and, ideally, also SH.
Response to Letter Regarding Article, “Effect of Chronotropy and Inotropy on Stitch Tension in the Edge-to-Edge Mitral Repair”
Authors: Tomasz A. Timek, David T. Lai, David Liang, D. Craig Miller, Sten L. Nielsen, George T. Daughters, Neil B. Ingels
Journal: Circulation (2008)

Response to Letter Regarding Article, "Effect of Chronotropy and Inotropy on Stitch Tension in the Edge-to-Edge Mitral Repair"We welcome the salient comments by Dasi and colleagues pertaining to our work on the effect of chronotropy and inotropy on leaflet stitch tension in the Alfieri mitral valve repair. 1 The authors make sound scientific arguments, and we agree that knowing instantaneous flow rate would enhance our understanding of the true determinants of stitch tension.For this reason, we are setting out to analyze the influence of instantaneous flow (derived as a differential function of left ventricular volume as a function of time) on leaflet tension during the hemodynamic interventions of the current and prior 2 experimental protocols.We believe these in vivo data will supplement the elegant in vitro experiments and computational models of Dr Yoganathan's Georgia Tech Group. 3s to the study at hand, we have amended our original article with revised versions of Figures 2 and3 to include standard deviation bars so as to address the potential inconsistencies pointed out by Dasi and colleagues.Neither mitral annular area nor stitch tension decreased during diastole as shown in the revised Figure 2 and confirmed by frame-to-frame statistical analysis throughout diastole.Similarly, revised Figure 3 shows that during calcium infusion no significant increase in stitch tension occurred, which again was confirmed by frame-to-frame statistical analysis throughout diastole.The standard deviation error bars were originally omitted for the sake of clarity; we apologize that their omission could lead to alternative interpretations of the data.We hope that these figures and our statistical calculations address these concerns.We hope to present the instantaneous flow data in the future and thank Dasi and colleagues for their insightful commentary that furthers the scientific process.
Prospective evaluation of computed tomography and mediastinoscopy in mediastinal lymph node staging
Authors: A Gdeedo, P Van Schil, B Corthouts, F Van Mieghem, J Van Meerbeeck, E Van Marck
Journal: European Respiratory Journal (1997)

Precise mediastinal lymph node (LN) staging is imperative in otherwise operable non-small cell lung cancer (NSCLC), as it determines subsequent treatment and possible inclusion in a neoadjuvant trial. The roles of mediastinoscopy and computed tomography (CT) remain controversial. To determine the accuracy of current CT scanners, a prospective study was performed. From April 1993 until September 1995, 100 consecutive patients with NSCLC without distant metastases underwent staging by CT and cervical mediastinoscopy. Naruke's map was used for classification, and LNs larger than 1 cm were considered CT positive. There were 91 males and 9 females, with a mean age of 64 (range 45-82) yrs. Fifty nine tumours were central and 41 peripheral, 64 right-sided and 36 left-sided. Thoracotomy with mediastinal LN sampling was performed in 74 patients, nonoperated patients having multilevel stage IIIA or stage IIIB disease. Twenty five (25%) mediastinoscopies were positive and three were false-negative (3%). There were 29 false-positive CT scans and 12 false-negative. Overall sensitivity and specificity of CT were 63 and 57%, respectively, and of mediastinoscopy 89 and 100%, respectively. Positive and negative predictive values of CT were 41 and 77%, respectively, and of mediastinoscopy 100 and 96%, respectively. Accuracy of CT was 59% and of mediastinoscopy 97%. Accuracy of CT was lowest for left-sided and centrally located tumours, and for LN station 7. Even with current computed tomography scanners, sensitivity and specificity remain low. Although overall cost may increase, routine cervical mediastinoscopy is necessary for precise staging of non-small cell lung cancer, and subcarinal lymph nodes should be routinely sampled.
High-Density Lipoprotein Regulates Calcification of Vascular Cells
Authors: Farhad Parhami, Benjamin Basseri, Jason Hwang, Yin Tintut, Linda L. Demer
Journal: Circulation Research (2002)

Accumulating evidence has suggested the protective role of HDL in cardiovascular disease processes. Calcification is a common feature of atherosclerotic lesions and contributes to cardiovascular complications due to the loss of aortic resilience and function. Recent studies have suggested that vascular calcification shares several features with skeletal bone formation at the cellular and molecular levels. These include the presence of osteoblast-like calcifying vascular cells in the artery wall that undergo osteoblastic differentiation and calcification in vitro. We hypothesized that HDL may also protect against vascular calcification by regulating the osteogenic activity of these calcifying vascular cells. When treated with HDL, alkaline phosphatase activity, a marker of osteogenic differentiation of osteoblastic cells, was significantly reduced in those cells. Prolonged treatment with HDL also inhibited calcification of these cells, further supporting the antiosteogenic differentiation property of HDL when applied to vascular cells. Furthermore, HDL inhibited the osteogenic activity that was induced by inflammatory cytokines interleukin (IL)-1beta and IL-6 as well as by minimally oxidized LDL. HDL also partially inhibited the IL-6-induced activation of signal transducer and activator of transcription 3 in calcifying vascular cells, suggesting that HDL may inhibit cytokine-induced signal transduction pathways. The inhibitory effects of HDL were mimicked by lipids extracted from HDL but not by HDL-associated apolipoproteins or reconstituted HDL. Furthermore, oxidation of HDL rendered it pro-osteogenic. Taken together, these results suggest that HDL regulates the osteoblastic differentiation and calcification of vascular cells and that vascular calcification may be another target of HDL action in the artery wall.
Use of Antidepressants and Risk of Cancer in Individuals Infected With HIV
Authors: Justin Stebbing, Tom Powles, Sundhiya Mandalia, Mark Nelson, Brian Gazzard, Mark Bower
Journal: Journal of Clinical Oncology (2008)

Purpose Preclinical and cohort studies suggest that certain antidepressants are associated with a predisposition to cancer whereas others decrease the risk. We aimed to assess whether different classes of antidepressants were associated with changes in cancer incidence in a population of HIV-1 infected individuals, based on duration of exposure. Methods Antidepressant exposure was measured from date of first prescription of the antidepressant until the date of last follow-up or cancer diagnosis. Univariate and multivariate analyses were performed to establish the risk of AIDS-related cancers and non–AIDS-related cancers according to whether patients were receiving selective serotonin reuptake inhibitors, tricyclic antidepressants, or other medicines for depression. We analyzed data for time exposed to antidepressants, before and during the era of highly active antiretroviral therapy (HAART). Results From a cohort of 10,997 patients representing 52,656 years of follow-up attending a large HIV center during the pre-HAART and HAART eras, a total of 2,004 (18%) were prescribed antidepressants representing 15,850 years exposed. A total of 1,607 (15%) individuals were diagnosed with cancer. There were no significant associations between any class of antidepressant and any type of cancer (P = .19), in either the pre-HAART or HAART era (P = .23), and use of serotonin reuptake inhibitors did not alter the risk of Burkitt lymphoma. Conclusion Antidepressants, irrespective of their class, do not affect cancer risk in HIV-infected individuals.
Focal pulmonary oedema: an unusual presentation of acute mitral regurgitation
Authors: Paul D Morris, David R Warriner, Kevin S Channer
Journal: Thorax (2012)

A 46-year-old man presented with dyspnoea, haemoptysis, orthopnoea and a pan-systolic murmur. His chest radiograph (see figure 1) demonstrated asymmetric pulmonary infiltrates, predominantly affecting the right-upper lobe. He was diagnosed with lobar-pneumonia but failed to improve with antibiotic therapy. Echocardiography subsequently demonstrated severe mitral regurgitation (MR), directed towards …
Relationships Between Hyperglycemia and Cognitive Performance Among Adults With Type 1 and Type 2 Diabetes
Authors: Daniel J. Cox, Boris P. Kovatchev, Linda A. Gonder-Frederick, Kent H. Summers, Anthony McCall, Kevin J. Grimm, William L. Clarke
Journal: Diabetes Care (2005)

OBJECTIVE—Hyperglycemia is a common event among patients with type 1 and type 2 diabetes. While the cognitive-motor slowing associated with hypoglycemia is well documented, the acute effects of hyperglycemia have not been studied extensively, despite patients’ reports of negative effects. This study prospectively and objectively assessed the effects of hyperglycemia on cognitive-motor functioning in subjects’ natural environment. RESEARCH DESIGN AND METHODS—Study 1 investigated 105 adults with type 1 diabetes (mean age 37 years and mean duration of diabetes 20 years), study 2 investigated 36 adults with type 2 diabetes (mean age 50 years and mean duration of diabetes 10 years), and study 3 investigated 91 adults with type 1 diabetes (mean age 39 years and mean duration of diabetes 20 years). Subjects used a hand-held computer for 70 trials over 4 weeks, which required them to complete various cognitive-motor tasks and then measure and enter their current blood glucose reading. RESULTS—Hyperglycemia (blood glucose &amp;gt;15 mmol/l) was associated with slowing of all cognitive performance tests (P &amp;lt; 0.02) and an increased number of mental subtraction errors for both type 1 and type 2 diabetic subjects. The effects of hyperglycemia were highly individualized, impacting ∼50% of the subjects. CONCLUSIONS—Acute hyperglycemia is not a benign event for many individuals with diabetes, but it is associated with mild cognitive dysfunction.
Visual Fields and Driving
Authors: W. B. Brownlie
Journal: BMJ (1966)

<b>SUMMARY:</b> CT perfusion (CTP) is a functional imaging technique that provides important information about capillary-level hemodynamics of the brain parenchyma and is a natural complement to the strengths of unenhanced CT and CT angiography in the evaluation of acute stroke, vasospasm, and other neurovascular disorders. CTP is critical in determining the extent of irreversibly infarcted brain tissue (infarct “core”) and the severely ischemic but potentially salvageable tissue (“penumbra”). This is achieved by generating parametric maps of cerebral blood flow, cerebral blood volume, and mean transit time.
PTEN Loss Accelerates <i>Kras</i> <i>G12D</i>-Induced Pancreatic Cancer Development
Authors: Reginald Hill, Joseph Hargan Calvopina, Christine Kim, Ying Wang, David W. Dawson, Timothy R. Donahue, Sarah Dry, Hong Wu
Journal: Cancer Research (2010)

KRAS mutations are found in ∼90% of human pancreatic ductal adenocarcinomas (PDAC). However, mice genetically engineered to express Kras(G12D) from its endogenous locus develop PDACs only after a prolonged latency, indicating that other genetic events or pathway alterations are necessary for PDAC progression. The PTEN-controlled phosphatidylinositol 3-kinase (PI3K)/AKT signaling axis is dysregulated in later stages of PDAC. To better elucidate the role of PTEN/PI3K/AKT signaling in Kras(G12D)-induced PDAC development, we crossed Pten conditional knockout mice (Pten(lox/lox)) to mice with conditional activation of Kras(G12D). The resulting compound heterozygous mutant mice showed significantly accelerated development of acinar-to-ductal metaplasia (ADM), malignant pancreatic intraepithelial neoplasia (mPanIN), and PDAC within a year. Moreover, all mice with Kras(G12D) activation and Pten homozygous deletion succumbed to cancer by 3 weeks of age. Our data support a dosage-dependent role for PTEN, and the resulting dysregulation of the PI3K/AKT signaling axis, in both PDAC initiation and progression, and shed additional light on the signaling mechanisms that lead to the development of ADM and subsequent mPanIN and pancreatic cancer.
Assessment of Environmental Asbestos Exposure in Turkey by Bronchoalveolar Lavage
Authors: P. DUMORTIER, L. ÇOPLÜ, V. de MAERTELAER, S. EMRI, I. BARIS, P. DE VUYST
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Environmental or domestic exposure to asbestos fibers originating from local soil is responsible for a high incidence of diseases in large rural areas of Turkey. Bronchoalveolar lavage fluids (BALF) were obtained for 65 Turkish subjects originating from these areas and for 42 Turkish controls. Asbestos bodies (ABs) and uncovered fibers (UFs) were quantified by phase contrast light microscopy. Total fiber burden was determined by transmission electron microscopy. The main asbestos types disclosed were tremolite and to a lesser extent chrysotile. AB and fiber concentrations were higher in environmentally exposed subjects (geometric mean [geometric standard deviation]: 5.20 [6.22] AB/ml, 444 [11.6] tremolite fibers/ml) than in control subjects (0.22 [1.45] AB/ml, 12.0 [15.4] tremolite fibers/ml) (p < 0.001). In subjects environmentally exposed in Turkey, AB burdens on tremolite were in the same range as those on commercial amphiboles in subjects occupationally exposed in Belgium. In Turkish subjects, values above either 1 AB/ml, 3 uncovered fiber/ml in light microscopy, or 300 fibers/ml in electron microscopy indicated usually an abnormal alveolar retention reflecting a significant cumulative exposure from environmental or domestic origin. These observations are probably valid for other areas in the world where diseases associated with environmental exposure to soil- derived asbestos fibers occur and for immigrants originating from these areas.
Different alterations in the insulin-stimulated glucose uptake in the athlete's heart and skeletal muscle.
Authors: P Nuutila, M J Knuuti, O J Heinonen, U Ruotsalainen, M Teräs, J Bergman, O Solin, H Yki-Järvinen, L M Voipio-Pulkki, U Wegelius
Journal: Journal of Clinical Investigation (1994)

Physical training increases skeletal muscle insulin sensitivity. Since training also causes functional and structural changes in the myocardium, we compared glucose uptake rates in the heart and skeletal muscles of trained and untrained individuals. Seven male endurance athletes (VO2max 72 +/- 2 ml/kg/min) and seven sedentary subjects matched for characteristics other than VO2max (43 +/- 2 ml/kg/min) were studied. Whole body glucose uptake was determined with a 2-h euglycemic hyperinsulinemic clamp, and regional glucose uptake in femoral and arm muscles, and myocardium using 18F-fluoro-2-deoxy-D-glucose and positron emission tomography. Glucose uptake in the athletes was increased by 68% in whole body (P < 0.0001), by 99% in the femoral muscles (P < 0.01), and by 62% in arm muscles (P = 0.06), but it was decreased by 33% in the heart muscle (P < 0.05) as compared with the sedentary subjects. The total glucose uptake rate in the heart was similar in the athletes and control subjects. Left ventricular mass in the athletes was 79% greater (P < 0.001) and the meridional wall stress smaller (P < 0.001) as estimated by echocardiography. VO2max correlated directly with left ventricular mass (r = 0.87, P < 0.001) and inversely with left ventricular wall stress (r = -0.86, P < 0.001). Myocardial glucose uptake correlated directly with the rate-pressure product (r = 0.75, P < 0.02) and inversely with left ventricular mass (r = -0.60, P < 0.05) or with the whole body glucose disposal (r = -0.68, P < 0.01). Thus, in athletes, (a) insulin-stimulated glucose uptake is enhanced in the whole body and skeletal muscles, (b) whereas myocardial glucose uptake per muscle mass is reduced possibly due to decreased wall stress and energy requirements or the use of alternative fuels, or both.
Diffusional shunting in the canine myocardium.
Authors: A C Roth, E O Feigl
Journal: Circulation Research (1981)

A test for the existence of a diffusional shunt in the myocardium was performed in closed-chest, chloralose-anesthetized dogs. Coronary blood flow was varied from 0.21 to 1.17 ml/min per g with a roller pump via a stainless steel coronary perfusion cannula. Following intracoronary artery bolus indicator injection, the coronary sinus venous appearance times of hydrogen, plasma protein labeled with indocyanine green dye, and red blood cells labeled with 99mTc were measured. Venous appearance time was calculated, either as the time from injection until the indicator reached 5% of its peak venous concentration or the time from injection until 0.1% of the injected material arrived at the coronary sinus. At low coronary flow rates (0.4 sec dye appearance time) hydrogen appearance preceded by about 1 second the appearance of the intravascular 99mTc-labeled red blood cells and the dyed plasma, indicating that hydrogen traversed an extravascular shunt path from small arteries to veins. As flow was increased, this hydrogen precession was reduced, and at high flows detectable levels of hydrogen arrived in the coronary sinus after the intravascular indicators. The difference in appearance time between hydrogen and the intravascular indicators was related linearly to the dye appearance time (proportional to l/flow), as would be expected with diffusional shunting. These data indicate that there is arterial-venous shunting of hydrogen in the myocardium. Furthermore, diffusional shunting may be important in the delivery of oxygen to, or removal of carbon dioxide from, the heart.
Antibody-dependent cellular cytotoxicity by allosensitized human T cells.
Authors: R L Evans, L Chess, H Levine, S F Schlossman
Journal: The Journal of Experimental Medicine (1978)

Peripheral human T cells, isolated by sheep erythrocyte-rosette formation and density centrifugation, were highly cytotoxic to both Ab-coated autologous lymphocytes and antibody (Ab)-coated chicken erythrocytes when stimulated in mixed lymphocyte culture, but were not lytic when freshly purified, or when unstimulated in 6-day culture. Allosensitized T cells were shown to effect this activity by a specific effector-target cell interaction dependent on Ab, as indicated by: (a) induction of killing by Ab to target cells not lysed in the absence of Ab. (b) inhibition of Ab-dependent killing by aggregated Ig. The mechanism by which allosensitized T cells effect antibody-dependent cellular cytotoxicity is discussed.
Inactivation of the <b> <i>FHIT</i> </b> Gene Favors Bladder Cancer Development
Authors: Andrea Vecchione, Cinzia Sevignani, Enrico Giarnieri, Nicola Zanesi, Hideshi Ishii, Rossano Cesari, Louise Y. Y. Fong, Leonard G. Gomella, Carlo M. Croce, Raffaele Baffa
Journal: Clinical Cancer Research (2004)

Abstract The fragile histidine triad (FHIT) gene located on chromosome 3p14.2 is frequently deleted in human tumors. We have previously reported deletions at the FHIT locus in 50% of bladder carcinoma derived cell lines and reduced expression in 61% of primary transitional carcinomas of the urinary bladder. To additionally investigate the role of FHIT alterations in the development of bladder cancer, we used heterozygous and nullizygous Fhit-deficient mice in a chemically induced carcinogenesis model. Results showed that 8 of 28 (28%) and 6 of 13 (46%) of the Fhit −/− and +/−, respectively, versus 2 of 25 (8%) Fhit +/+ mice developed invasive carcinoma after treatment with N-butyl-N-(4-hydroxybutyl) nitrosamine. To explore the possibility of a FHIT-based gene therapy for bladder cancer, we studied the effects of restored Fhit protein expression on cell proliferation, cell kinetics, and tumorigenicity in BALB/c nude mice, with human SW780 Fhit-null transitional carcinoma derived cells. In vitro transduction of SW780 Fhit-negative cells with adenoviral-FHIT inhibited cell growth, increased apoptotic cell population, and suppressed s.c. tumor growth in nude mice. These findings suggest the important role of Fhit in bladder cancer development and support the effort to additionally investigate a FHIT-based gene therapy.