tbuckley/cabot-search huggingface dataset:
Are Breast Density and Bone Mineral Density Independent Risk Factors for Breast Cancer?
Authors: K. Kerlikowske, J. Shepherd, J. Creasman, J. A. Tice, E. Ziv, S. R. Cummings
Journal: JNCI Journal of the National Cancer Institute (2005)

Background: Mammographic breast density and bone mineral density (BMD) are markers of cumulative exposure to estrogen. Previous studies have suggested that women with high mammographic breast density or high BMD are at increased risk of breast cancer. We determined whether mammographic breast density and BMD of the hip and spine are correlated and independently associated with breast cancer risk. Methods: We conducted a cross-sectional study (N = 15 254) and a nested case–control study (of 208 women with breast cancer and 436 control subjects) among women aged 28 years or older who had a screening mammography examination and hip BMD measurement within 2 years. Breast density for 3105 of the women was classified using the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) categories, and percentage mammographic breast density among the case patients and control subjects was quantified with a computer-based threshold method. Spearman rank partial correlation coefficient and Pearson's correlation coefficient were used to examine correlations between BI-RADS breast density and BMD and between percentage mammographic breast density and BMD, respectively, in women without breast cancer. Logistic regression was used to examine the association of breast cancer with percentage mammographic breast density and BMD. All statistical tests were two-sided. Results: Neither BI-RADS breast density nor percentage breast density was correlated with hip or spine BMD (correlation coefficient = −.02 and −.01 for BI-RADS, respectively, and −.06 and .01 for percentage breast density, respectively). Neither hip BMD nor spine BMD had a statistically significant relationship with breast cancer risk. Women with breast density in the highest sextile had an approximately threefold increased risk of breast cancer compared with women in the lowest sextile (odds ratio = 2.7, 95% confidence interval = 1.4 to 5.4); adjusting for hip or spine BMD did not change the association between breast density and breast cancer risk. Conclusion: Breast density is strongly associated with increased risk of breast cancer, even after taking into account reproductive and hormonal risk factors, whereas BMD, although a possible marker of lifetime exposure to estrogen, is not. Thus, a component of breast density that is independent of estrogen-mediated effects may contribute to breast cancer risk.
Pharmacokinetics, metabolism and tumour disposition of 8-chloroadenosine 3',5'-monophosphate in breast cancer patients and xenograft bearing mice
Authors: J. Cummings, S.P. Langdon, A.A. Ritchie, D.J. Bums, J. Mackay, P. Stockman, R.C.F. Leonard, W.R. Miller
Journal: Annals of Oncology (1996)

8-Chloroadenosine 3',5'-monophosphate (8-Cl-cAMP) is undergoing phase I clinical trials as an anticancer drug. However, there is debate as to whether it is a prodrug for its 8-Cl-adenosine metabolite.Pharmacokinetics, metabolism and tumour disposition studies have been performed in 7 breast cancer patients receiving continuous infusion (28 day) 8-Cl-cAMP (0.54 or 1.08 mg/kg/day) and tumour biopsies were obtained before and on the last day of infusion. Parallel studies were performed in nude mice bearing the HT29 human colon cancer xenograft after continuous infusion (7 day) of active drug doses (50 or 100 mg/kg/day).Steady state plasma levels (Css) of 8-Cl-cAMP in patients ranged from 0.15-0.72 microM but 8-Cl-adenosine was not detected in plasma. In contrast, 8-Cl-cAMP was not detectable in 3 tumour biopsies but 8-Cl-adenosine was present in 2 samples at high concentrations (1.33 and 2.02 microM). In mice, Css of 8-Cl-cAMP ranged from 3.2-4.6 microM and 8-Cl adenosine was present in plasma only at the higher dose (100 mg/kg/day, peak concentration of 2.3 microM). In the HT29 xenograft, 8-Cl-cAMP levels were considerably lower than in plasma (0.37-1.22 microM) while 8-Cl-adenosine was present at 5.3-21.0 microM and 8-Cl-AMP was found at 11.3-35.7 microM.The fate of 8-Cl-cAMP in human tumours is characterised by extensive metabolism to products which are not generally observed in plasma. These data raise the possibility that 8-Cl-cAMP is a prodrug for a product of its metabolism in human tumours.
Interleukin 10 (IL-10) regulation of tumour necrosis factor alpha (TNF-alpha) from human alveolar macrophages and peripheral blood monocytes.
Authors: L. Armstrong, N. Jordan, A. Millar
Journal: Thorax (1996)

BACKGROUND: Regulation of the inflammatory response within the human lung is essential to prevent this important part of the normal host defence response becoming a pathological process. Tumour necrosis factor alpha (TNF-alpha) is a cytokine involved in the pathogenesis of shock and in granuloma formation, tissue necrosis, and fibrosis in many organ systems including the lung. Interleukin 10 (IL-10) has been proposed as having an inhibitory effect on the production of several inflammatory cytokines including TNF-alpha. METHODS: The effect of IL-10 administration on TNF-alpha production was explored in human alveolar macrophages and peripheral blood monocytes from matched individuals. The effects of IL-10 on TNF-alpha protein production were determined by sandwich enzyme linked immunosorbant assay (ELISA), whereas the TNF-alpha mRNA response was established by Northeren blotting using a TNF-alpha specific oligonucleotide probe. The protein synthesis inhibitors actinomycin D and cyclohexamide were utilised to monitor IL-10 effects on mRNA degradation and de novo protein synthesis, respectively. RESULTS: The lipopolysaccharide-mediated TNF-alpha production in alveolar macrophages was reduced from 3.508 (0.629) to 2.035 (0.385) ng/ml by 100 U/ml IL-10. Lipopolysaccharide-induced TNF-alpha production in peripheral blood monocytes was reduced from 2.035 (0.284) to 0.698 (0.167) ng/ml. TNF-alpha gene expression was also inhibited in both alveolar macrophages and peripheral blood monocytes; lipopolysaccharide-induced TNF-alpha mRNA was reduced by 47.8 (15.2)% and 83.1 (4.2)%, respectively, by IL-10. The IL-10 mediated suppression of TNF-alpha mRNA was unaffected by addition of cyclohexamide, suggesting that de novo protein synthesis was not required for TNF-alpha inhibition. mRNA stability experiments indicated no acceleration in lipopolysaccharide-induced TNF-alpha mRNA degradation in response to IL-10. CONCLUSIONS: These findings suggest that IL-10 is a potent inhibitor of TNF-alpha expression and release from alveolar macrophages and peripheral blood monocytes, and thus it may have an important role in the cytokine network of the pulmonary immune response.
A Simple and Innovative Device to Measure Arm Volume at Home for Patients With Lymphedema After Breast Cancer
Authors: Jean Lette
Journal: Journal of Clinical Oncology (2006)

We designed an arm volumeter specifically for home use based on the water displacement method. The objective of this study was to determine its accuracy and precision, and compare it with a standard volumeter used in lymphedema clinics worldwide.Using a standard model hospital volumeter and our own device, we took three consecutive measurements of 11 specially cast cylinders, which had known volumes ranging from 10 mL to 4 L, and measurements of both arms of 15 volunteers.Measurements with both volumeters were highly accurate (R2 = 0.9999) when compared with the known volumes of the cast cylinders, and were strongly correlated (R2 = 0.9974) when each arm volume was compared between volumeters. Measurements with our volumeter were more precise both with the cylinders (average standard deviation [SD], 3.2 v 8 mL; P = .0553) and with the arms (average SD, 11.1 v 19 mL; P = .0034). Whereas the standard volumeter is expensive, fragile (acrylic), and prone to leaks, our volumeter is inexpensive, virtually indestructible, leak proof, and suitable for home use.Arm volumes can be measured quickly and accurately at home using a simple, inexpensive, and robust device based on water displacement. Readily accessible arm volumetry at home may have widespread influence on the management of lymphedema after breast cancer.
Respiratory viruses are not associated with acute graft rejection during the acute phase of infection
Authors: M. Elftise
Journal: Thorax (2010)

Although several studies support the association between respiratory viruses and chronic lung rejection, the relationship between viral infection and acute rejection has not been established.

In this prospective cohort study, bronchioalveolar lavage (BAL) fluid and biopsy specimens from 343 bronchoscopic procedures performed in 77 patients were analysed over …
PNEUMONIC LESIONS MADE BY INTRABRONCHIAL INSUFFLATION OF NON-VIRULENT PNEUMOCOCCI
Authors: Martha Wollstein, S. J. Meltzer
Journal: The Journal of Experimental Medicine (1913)

The intrabronchial insufflation of a non-virulent pneumococcus causes, like the insufflation of a virulent pneumococcus, the development of an exudate in the lungs which, in general, leaves the framework unaffected, and the lesion presents the gross appearance of a lobar pneumonia. It differs, however, materially from the pneumonia produced by virulent pneumococci in the important points that the consolidation tends to a more rapid resolution, the disease is non-fatal, the blood is not invaded by the organism, and the exudate is strikingly poor in fibrin. As to the question which was the starting point for the foregoing investigation, namely, whether the pneumonic lesion produced by the streptococcus is merely a form of pneumonia caused by a less virulent organism, it may be answered for the dog, it seems, in the negative. The leucocytic infiltration of the framework of the lungs which occurs invariably in streptococcus pneumonia, and which is practically absent in the lesions caused by the virulent as well as by the non-virulent pneumococcus, is a strong enough feature to form a dividing line between the two forms of experimental pneumonia previously described.
Phase I Trial of the Novel Mammalian Target of Rapamycin Inhibitor Deforolimus (AP23573; MK-8669) Administered Intravenously Daily for 5 Days Every 2 Weeks to Patients With Advanced Malignancies
Authors: Monica M. Mita, Alain C. Mita, Quincy S. Chu, Eric K. Rowinsky, Gerald J. Fetterly, Michelle Goldston, Amita Patnaik, Lesley Mathews, Alejandro D. Ricart, Theresa Mays, Heather Knowles, Victor M. Rivera, Jeff Kreisberg, Camille L. Bedrosian, Anthony W. Tolcher
Journal: Journal of Clinical Oncology (2008)

This phase I trial was conducted to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of deforolimus (previously known as AP23573; MK-8669), a nonprodrug rapamycin analog, in patients with advanced solid malignancies.Patients were treated using an accelerated titration design with sequential escalating flat doses of deforolimus administered as a 30-minute intravenous infusion once daily for 5 consecutive days every 2 weeks (QDx5) in a 28-day cycle. Safety, pharmacokinetic, pharmacodynamic, and tumor response assessments were performed.Thirty-two patients received at least one dose of deforolimus (3 to 28 mg/d). Three dose-limiting toxicity events of grade 3 mouth sores were reported. The maximum-tolerated dose (MTD) was 18.75 mg/d. Common treatment-related adverse events included reversible mouth sores and rash. Whole-blood clearance increased with dose. Pharmacodynamic analyses demonstrated mammalian target of rapamycin inhibition at all dose levels. Four patients (one each with non-small-cell lung cancer, mixed müllerian tumor [carcinosarcoma], renal cell carcinoma, and Ewing sarcoma) experienced confirmed partial responses, and three additional patients had minor tumor regressions.The MTD of this phase I trial using an accelerated titration design was determined to be 18.75 mg/d. Deforolimus was well tolerated and showed encouraging antitumor activity across a broad range of malignancies when administered intravenously on the QDx5 schedule. On the basis of these overall results, a dose of 12.5 mg/d is being evaluated in phase II trials.
Role of interleukin 10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus.
Authors: L Llorente, W Zou, Y Levy, Y Richaud-Patin, J Wijdenes, J Alcocer-Varela, B Morel-Fourrier, J C Brouet, D Alarcon-Segovia, P Galanaud, D Emilie
Journal: The Journal of Experimental Medicine (1995)

Interleukin-10 (IL-10) is produced at a high level by B lymphocytes and monocytes of patients with systemic lupus erythematosus (SLE). In the present work, we analyzed whether this increased production of IL-10 contributed to the abnormal production of immunoglobulins (Ig) and of autoantibodies in SLE. The role of IL-10 was compared with that of IL-6, another cytokine suspected to play a role in these abnormalities. The spontaneous in vitro production of IgM, IgG, and IgA by peripheral blood mononuclear cells from SLE patients was weakly increased by recombinant IL (rIL)-6, but strongly by rIL-10. This production was not significantly affected by an anti-IL-6 mAb but was decreased by an anti-IL-10 mAb. We then tested the in vivo effect of these antibodies in severe combined immunodeficiency mice injected with PBMC from SLE patients. The anti-IL-6 mAb did not significantly affect the serum concentration of total human IgG and of anti-double-stranded DNA IgG in the mice. In contrast, the anti-IL-10 mAb strongly inhibited the production of autoantibodies, and, to a lesser extent, that of total human IgG. These results indicate that the Ig production by SLE B lymphocytes is largely IL-10 dependent, and that the increased production of IL-10 by SLE B lymphocytes and monocytes may represent a critical mechanism in the emergence of the autoimmune manifestations of the disease.
MEMORIAL TO THE LATE PROFESSOR TOM JONES,
Authors: Henry Ashby, Joseph Collier, Alfred Hopkinson, A. Mclaren, JohnD. Milne, W.P. Montgomery, D. Lloyd Roberts, Edward Roberts, Alfred Simpson, F.A. Southam, W. Thorburn, Walter Whitehead, A.H. Young, G.A. Wright, J.E. Platt, F.J.H. Coutts
Journal: The Lancet (1901)
Cd4+ T Cell Subsets during Virus Infection
Authors: Kevin J. Maloy, Christoph Burkhart, Tobias M. Junt, Bernhard Odermatt, Annette Oxenius, Luca Piali, Rolf M. Zinkernagel, Hans Hengartner
Journal: The Journal of Experimental Medicine (2000)

To analyze the antiviral protective capacities of CD4+ T helper (Th) cell subsets, we used transgenic T cells expressing an I-Ab–restricted T cell receptor specific for an epitope of vesicular stomatitis virus glycoprotein (VSV-G). After polarization into Th1 or Th2 effectors and adoptive transfer into T cell–deficient recipients, protective capacities were assessed after infection with different types of viruses expressing the VSV-G. Both Th1 and Th2 CD4+ T cells could transfer protection against systemic VSV infection, by stimulating the production of neutralizing immunoglobulin G antibodies. However, only Th1 CD4+ T cells were able to mediate protection against infection with recombinant vaccinia virus expressing the VSV-G (Vacc-IND-G). Similarly, only Th1 CD4+ T cells were able to rapidly eradicate Vacc-IND-G from peripheral organs, to mediate delayed-type hypersensitivity responses against VSV-G and to protect against lethal intranasal infection with VSV. Protective capacity correlated with the ability of Th1 CD4+ T cells to rapidly migrate to peripheral inflammatory sites in vivo and to respond to inflammatory chemokines that were induced after virus infection of peripheral tissues. Therefore, the antiviral protective capacity of a given CD4+ T cell is governed by the effector cytokines it produces and by its migratory capability.
Frequency and peak stretch magnitude affect alveolar epithelial permeability
Authors: T S Cohen, K J Cavanaugh, S S Margulies
Journal: European Respiratory Journal (2008)

The present study measured stretch-induced changes in transepithelial permeability to uncharged tracers (1.5–5.5 Å) using cultured monolayers of alveolar epithelial type-I like cells. Cultured alveolar epithelial cells were subjected to uniform cyclic (0, 0.25 and 1.0 Hz) biaxial stretch from 0% to 12, 25 or 37% change in surface area (ΔSA) for 1 h. Significant changes in permeability of cell monolayers were observed when stretched from 0% to 37% ΔSA at all frequencies, and from 0% to 25% ΔSA only at high frequency (1 Hz), but not at all when stretched from 0% to 12% ΔSA compared with unstretched controls. At stretch oscillation amplitudes of 25 and 37% ΔSA, imposed at 1 Hz, tracer permeability increased compared with that at 0.25 Hz. Cells subjected to a single stretch cycle at 37% ΔSA (0.25 Hz), to simulate a deep sigh, were not distinguishable from unstretched controls. Reducing stretch oscillation amplitude while maintaining a peak stretch of 37% ΔSA (0.25 Hz) via the application of a simulated post-end-expiratory pressure did not protect barrier properties. In conclusion, peak stretch magnitude and stretch frequency were the primary determining factors for epithelial barrier dysfunction, as opposed to oscillation amplitude.
Psychosocial burden of caregivers is a hurdle for adherence to pulmonary rehabilitation program in a resource-scarce setting
Authors: Ruby Stella Robert, Vishal Bansal, Anjali Malik, Rajendra Prasad
Journal: European Respiratory Journal (2014)

Background:  Poor adherence rates pose a significant challenge to the success of pulmonary rehabilitation programs across the world and more so in the developing countries.  Aim:  To investigate the reasons and the impact of psychosocial burden of primary caregivers on drop-out from an outpatient pulmonary rehabilitation program in a resource-scarce setting where social security is non-existent.  Method:  62 consecutive symptomatic patients on optimal medical treatment with chronic respiratory diseases (COPD, ILD and post-TB sequelae) were enrolled in our 30 session out-patient rehabilitation program (thrice a week, 3 hours duration session which included breathing retraining, endurance and resistance training, stairs practice and self-management education) over last 18 months. Telephonic interview was conducted to document the reasons for drop-out using a structured check-list on the patient and the burden assessment schedule (BAS) on the primary caregiver. Unpaired t-test was used for statistical analysis.  Results:  23 out of the 25 patients (40.32%, 2 patients could not be interviewed) dropped out for the following reasons: financial and logistic constraints (72%), other physical illnesses (60%), exacerbation (52%), perception regarding illness as incurable (26.92%) and death (4%). Psychosocial burden of primary caregivers was significantly associated with drop-out (p=0.028); specifically, financial burden (p=0.015) and disruption of routine activities (p=0.025).  Conclusion:  Psychosocial burden of the care-givers needs to be addressed by service providers to improve success of pulmonary rehabilitation programs, particularly in the developing countries.
Urinary Tract Infections in Women: Diagnosis and Treatment
Authors: James R. Johnson
Journal: Annals of Internal Medicine (1989)

Acute urinary tract infection is a major health problem among women, accounting for considerable morbidity and health care costs. We review recent developments in the diagnosis and treatment of these infections. In acute lower urinary tract infection, empiric short-course therapy (single-dose or 3-day therapy) with one of several antibiotics is recommended in the absence of complicating factors. When complicating factors are present, the antibiotic susceptibility profile of the infecting organism should be determined and therapy with an appropriate agent should be provided for 7 days. Ampicillin and related drugs are probably inferior to trimethoprim-sulfamethoxazole in the treatment of occult renal infection. In acute pyelonephritis, most patients require hospitalization and treatment with intravenous antibiotics until they can take oral medications. In uncomplicated cases, a single broad-spectrum intravenous agent can be used initially, followed by an oral agent selected on the basis of antibiotic-susceptibility testing results. Patients with uncomplicated acute pyelonephritis who are less ill can be managed with oral therapy as outpatients, again with reference to the results of antibiotic-susceptibility testing. Complicated acute pyelonephritis requires more aggressive diagnostic and therapeutic measures. Therapy for uncomplicated acute pyelonephritis should be given for 14 days. The role of post-therapy cultures in the management of urinary tract infection is not well defined, but cultures probably can be safely omitted in most cases of uncomplicated acute cystitis.
Development of a symptom specific health status measure for patients with chronic cough: Leicester Cough Questionnaire (LCQ)
Authors: S S Birring
Journal: Thorax (2003)

Chronic cough is a common condition which has a significant impact on quality of life. Assessment and management are hampered by the absence of well validated outcome measures. The development and validation of the Leicester Cough Questionnaire (LCQ), a self-completed health related quality of life measure of chronic cough, is presented.Patients with chronic cough were recruited from outpatient clinics. The development of the LCQ consisted of three phases: phase 1 (item generation); phase 2 (item reduction, allocation of items to domains and validation of questionnaire); phase 3 (repeatability and responsiveness testing of final version of questionnaire).Phase 1: Literature review, multidisciplinary team meeting and 15 structured interviews with chronic cough patients generated 44 items (LCQ1) with a 7 point Likert response scale. Phase 2: 104 chronic cough outpatients completed the LCQ1 along with an importance rating for each item. The clinical impact factor method was used for item reduction to 19 items (LCQ2: final version). These items were divided into three domains (physical, psychological and social) following expert opinion. Internal reliability, as assessed using Cronbach's alpha coefficients, varied between 0.79 and 0.89. Concurrent validity was high when the LCQ2 (n=56) was compared with a cough visual analogue score (r=-0.72). There was a moderate relationship with response to the St George's Respiratory Questionnaire (r=-0.54) and SF36 total score (r=0.46). Phase 3: Two week repeatability (n=24) was high with intraclass correlation coefficients for domains varying between 0.88 and 0.96. Responsiveness in nine patients whose cough was successfully treated varied within domains from an effect size of 0.84 to 1.75.The LCQ is a valid, repeatable 19 item self-completed quality of life measure of chronic cough which is responsive to change. It should be a useful tool in clinical trials and longitudinal studies.
An unusual complication of colonic interposition for oesophageal replacement.
Authors: J G Harvey, M G Kettlewell
Journal: Thorax (1979)

We report a case of delayed fibrosis of the interposed left colon in a 65-year-old man after an operation for peptic oesophageal stricture and suggest that short-term postoperative ventilation should be used in patients undergoing oesophageal replacement by means of colonic interposition.
Distinct brain transcriptome profiles in C9orf72-associated and sporadic ALS
Authors: Mercedes Prudencio, Veronique V Belzil, Ranjan Batra, Christian A Ross, Tania F Gendron, Luc J Pregent, Melissa E Murray, Karen K Overstreet, Amelia E Piazza-Johnston, Pamela Desaro, Kevin F Bieniek, Michael DeTure, Wing C Lee, Sherri M Biendarra, Mary D Davis, Matthew C Baker, Ralph B Perkerson, Marka van Blitterswijk, Caroline T Stetler, Rosa Rademakers, Christopher D Link, Dennis W Dickson, Kevin B Boylan, Hu Li, Leonard Petrucelli
Journal: Nature Neuroscience (2015)