tbuckley/cabot-search huggingface dataset:
Pre- and Post-Transplantation Risk Factors for Delirium Onset and Severity in Patients Undergoing Hematopoietic Stem-Cell Transplantation
Authors: Jesse R. Fann, Rebecca A. Hubbard, Catherine M. Alfano, Sari Roth-Roemer, Wayne J. Katon, Karen L. Syrjala
Journal: Journal of Clinical Oncology (2011)

To determine pre- and post-transplantation risk factors for delirium onset and severity during the acute phase of myeloablative hematopoietic stem-cell transplantation (HSCT).Ninety adult patients with malignancies admitted to the Fred Hutchinson Cancer Research Center for their first HSCT were assessed prospectively from 1 week before transplantation to 30 days after transplantation. Delirium was assessed three times per week using the Delirium Rating Scale and the Memorial Delirium Assessment Scale. Potential risk factors were assessed by patient self-report, charts, and computerized records. Multivariable analysis of time to onset of a delirium episode was undertaken using Cox proportional hazards regression with time-varying covariates. Analysis for delirium severity was carried out using a linear mixed effects model. Validation and sensitivity analyses were performed on the final models.Forty-five patients (50%) experienced a delirium episode. Pretransplantation risk factors for onset and higher severity of delirium were higher mean alkaline phosphatase and blood urea nitrogen (BUN) levels. Poorer pretransplantation executive functioning was also associated with higher delirium severity. Higher doses of opioid medications were the only post-transplantation risk factor for delirium onset (hazard ratio, 1.05; 95% CI, 1.02 to 1.08). Higher opioid doses, current and prior pain, and higher BUN levels were post-transplantation risk factors for greater delirium severity (all P < .01).Pre- and post-transplantation factors can assist in identifying patients who are at risk for delirium during myeloablative HSCT and may enable clinical interventions to prevent delirium onset or decrease delirium symptoms.
Maldistribution of heterogeneous coronary blood flow during canine endotoxin shock
Authors: A B J. Groeneveld, A. A v. Lambalgen, G. C v. d. Bos, W. Bronsveld, J. J P Nauta, L. G Thijs
Journal: Cardiovascular Research (1991)

Journal Article Maldistribution of heterogeneous coronary blood flow during canine endotoxin shock Get access A B Johan Groeneveld, A B Johan Groeneveld Search for other works by this author on: Oxford Academic PubMed Google Scholar Antonie A van Lambalgen, Antonie A van Lambalgen Search for other works by this author on: Oxford Academic PubMed Google Scholar Gerard C van den Bos, Gerard C van den Bos Search for other works by this author on: Oxford Academic PubMed Google Scholar Willem Bronsveld, Willem Bronsveld Search for other works by this author on: Oxford Academic PubMed Google Scholar Jos J P Nauta, Jos J P Nauta Search for other works by this author on: Oxford Academic PubMed Google Scholar Lambertus G Thijs Lambertus G Thijs Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 25, Issue 1, January 1991, Pages 80–88, https://doi.org/10.1093/cvr/25.1.80 Published: 01 January 1991 Article history Received: 08 May 1990 Accepted: 06 August 1990 Published: 01 January 1991
The Genomic Landscape of Pediatric Ewing Sarcoma
Authors: Brian D. Crompton, Chip Stewart, Amaro Taylor-Weiner, Gabriela Alexe, Kyle C. Kurek, Monica L. Calicchio, Adam Kiezun, Scott L. Carter, Sachet A. Shukla, Swapnil S. Mehta, Aaron R. Thorner, Carmen de Torres, Cinzia Lavarino, Mariona Suñol, Aaron McKenna, Andrey Sivachenko, Kristian Cibulskis, Michael S. Lawrence, Petar Stojanov, Mara Rosenberg, Lauren Ambrogio, Daniel Auclair, Sara Seepo, Brendan Blumenstiel, Matthew DeFelice, Ivan Imaz-Rosshandler, Angela Schwarz-Cruz y Celis, Miguel N. Rivera, Carlos Rodriguez-Galindo, Mark D. Fleming, Todd R. Golub, Gad Getz, Jaume Mora, Kimberly Stegmaier
Journal: Cancer Discovery (2014)

Pediatric Ewing sarcoma is characterized by the expression of chimeric fusions of EWS and ETS family transcription factors, representing a paradigm for studying cancers driven by transcription factor rearrangements. In this study, we describe the somatic landscape of pediatric Ewing sarcoma. These tumors are among the most genetically normal cancers characterized to date, with only EWS-ETS rearrangements identified in the majority of tumors. STAG2 loss, however, is present in more than 15% of Ewing sarcoma tumors; occurs by point mutation, rearrangement, and likely nongenetic mechanisms; and is associated with disease dissemination. Perhaps the most striking finding is the paucity of mutations in immediately targetable signal transduction pathways, highlighting the need for new therapeutic approaches to target EWS-ETS fusions in this disease.We performed next-generation sequencing of Ewing sarcoma, a pediatric cancer involving bone, characterized by expression of EWS-ETS fusions. We found remarkably few mutations. However, we discovered that loss of STAG2 expression occurs in 15% of tumors and is associated with metastatic disease, suggesting a potential genetic vulnerability in Ewing sarcoma.
Patients own marrow cells improve heart function
Authors: J. Hopkins Tanne
Journal: BMJ (2003)

Patients with end stage ischaemic heart failure who were not eligible for coronary bypass surgery or angioplasty benefited when their own bone marrow cells were injected into sites of myocardial ischaemia. This is the first time the technique, which may promote growth of new blood vessels, has been used in patients with chronic heart failure.

Myocardial perfusion and contractility improved in the patients, says the report by Dr Emerson Perin, director of new cardiovascular interventional techniques at the Texas Heart Institute, Houston, and colleagues at the Hospital Procardiaco in Rio de Janeiro, …
Switching children previously exposed to nevirapine to nevirapine-based treatment after initial suppression with a protease-inhibitor-based regimen: long-term follow-up of a randomised, open-label trial
Authors: Louise Kuhn, Ashraf Coovadia, Renate Strehlau, Leigh Martens, Chih-Chi Hu, Tammy Meyers, Gayle Sherman, Gillian Hunt, Deborah Persaud, Lynn Morris, Wei-Yann Tsai, Elaine J Abrams
Journal: The Lancet Infectious Diseases (2012)
A noninvasive electromyographic study on threshold and intensity of cough in humans
Authors: GA Fontana, T Pantaleo, F Lavorini, V Boddi, P Panuccio
Journal: European Respiratory Journal (1997)

The assessment of cough threshold and intensity is important in respiratory medicine. We have developed a method for objectively and noninvasively assessing cough threshold and intensity of expiratory muscle efforts in response to inhalation of ultrasonically nebulized distilled water (UNDW). Thirty (83%) out of 36 volunteers studied coughed in response to UNDW inhalation. Cough threshold was taken as the lowest nebulizer output (mL x min(-1)) that induced cough in two challenges performed at a 30 min interval. At threshold level, repeatability of peak and slope of the integrated electromyographic (IEMG) activity of abdominal muscles was evaluated. Short- and long-term repeatability of cough threshold were evaluated in 15 subjects following a 3 h and a 6-9 month interval, respectively. Dose-response relationships between nebulizer outputs and IEMG-related variables were also investigated, as were the correlations between the latter and expiratory flow during voluntary coughing. The median (1st and 3rd quartile) cough threshold value was 0.89 (0.40 and 1.54) mL x min(-1). At threshold level, peak and slope of IEMG activity were highly reproducible. Cough threshold displayed a high degree of short- and long-term repeatability. Peak and slope of IEMG activity displayed a clear trend to increase (p&lt;0.01) following inhalation of progressively higher UNDW outputs. Maximum flow during voluntary coughs of varying intensity correlated with the peak (p&lt;0.05) and, more closely, with the slope (p&lt;0.01) of abdominal IEMG activity. The assessment of cough threshold as well as the evaluation of the intensity of cough efforts by abdominal integrated electromyographic recordings may represent useful and reliable tools for cough research in humans.
A8.32 Regulatory B-cell supress T-cell proliferation through a TGFβ/IDO axis and are deficient in chronic humoral rejection
Authors: A Nouel, I Segalen, C Jamin, J -O Pers, Y Le Meur, S Hillion
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> In kidney transplantation, B cell is increasingly identified as an important determinant for graft outcome. Chronic antibody mediated rejection (cABMR) represent today the major complication in clinic. Patients with cABMR display a unique B cell phenotype characterised by a disturbance in B cell distribution. Here, the aim of our study was to research if cABMR B cells present also impaired regulatories functions. Experiments are realised in 12 stable patients (ST) (delay from graft &gt;12 months, no rejection, proteinuria &lt;0.5g/24h, PRA &lt;10%, no DSA and a one year biopsy without allograft glomerulopathy or rejection), 14 patients with cABMR (positive DSA, allograft glomerulopathy and/or C4d staining) and 17 controls (blood donors). B-cell functions were analysed using coculture with B and T cells. Proliferation and Th1 cytokine secretion of isolated CFSE labelled T cells in presence of autologous B cells was compared between the 3 groups. T cells were stimulated with anti CD3 and anti CD28, and co-cultured with CpG-activated B cells. Suppressive cytokines like TGFβ and IL-10 and the regulatory enzyme indoleamine 2,3-dioxygenase (IDO) were evaluated during the course of the culture. First, we have demonstrated that compared with situation of stable graft function and healthy volunteers, B cells from cABMR patients display an impaired regulatory function on T cell proliferation and Th1 production. Furthermore, B cells induce more T regulatory cells (Tregs) in coculture after 4 days in HV and ST groups compared to cABMR group (p&lt;10<sup>-3</sup>). We also evidenced that TGFβ and IDO expressed by B cells are involved in inhibition of T cell proliferation and Treg cells generation in HV and ST patients. We additionally shown that B cells from cABMR patients present a failure of TGFβ and IL-10 secretion in co-culture associated with a significantly decrease of IDO production leading to a defect in the capacity of activated-B cells to induce Treg cells and control T cell responses. Finally, B cells from cABMR patients display functional abnormalities as evidenced by the loss of B cell suppressive activity. This work represents interesting perspectives with the discovered of new cellular targets who can be might guide therapy in transplantation in the future.
Prospective Study of Talc Use and Ovarian Cancer
Authors: Dorota M. Gertig, David J. Hunter, Daniel W. Cramer, Graham A. Colditz, Frank E. Speizer, Walter C. Willett, Susan E. Hankinson
Journal: JNCI Journal of the National Cancer Institute (2000)

Perineal talc use has been associated with an increased risk of ovarian cancer in a number of case-control studies; however, this association remains controversial because of limited supporting biologic evidence and the potential for recall bias or selection bias in case-control studies. In this study, we conducted a prospective analysis of perineal talc use and the risk of ovarian cancer.The Nurses' Health Study is a prospective study of 121 700 female registered nurses in the United States who were aged 30-55 years at enrollment in 1976. Talc use was ascertained in 1982 by use of a self-administered questionnaire: after exclusions, 78 630 women formed the cohort for analysis. Three hundred seven epithelial ovarian cancers subsequently diagnosed in this cohort through June 1, 1996, were confirmed by medical record review and met inclusion criteria. Proportional hazards models by use of pooled logistic regression were used to derive relative risks (RRs) and 95% confidence intervals (CIs).In 1982, 40.4% (n = 31 789) of the cohort reported ever using talc, and 14.5% (n = 11 411) reported ever using talc daily. We observed no overall association with ever talc use and epithelial ovarian cancer (multivariate RR = 1.09; 95% CI = 0.86-1.37) and no increase in risk of ovarian cancer with increasing frequency of use. There was a modest elevation in risk for ever talc use and invasive serous ovarian cancer (multivariate RR = 1.40; 95% CI = 1.02-1.91). The risk of epithelial ovarian cancer for talc users was not greater among women who had never had a tubal ligation (multivariate RR = 0.97; 95% CI = 0.71-1.32).Our results provide little support for any substantial association between perineal talc use and ovarian cancer risk overall; however, perineal talc use may modestly increase the risk of invasive serous ovarian cancer.
Factor I is required for the development of membranoproliferative glomerulonephritis in factor H–deficient mice
Authors: Kirsten L. Rose, Danielle Paixao-Cavalcante, Jennifer Fish, Anthony P. Manderson, Talat H. Malik, Anne E. Bygrave, Tao Lin, Steven H. Sacks, Mark J. Walport, H. Terence Cook, Marina Botto, Matthew C. Pickering
Journal: Journal of Clinical Investigation (2008)

The inflammatory kidney disease membranoproliferative glomerulonephritis type II (MPGN2) is associated with dysregulation of the alternative pathway of complement activation. MPGN2 is characterized by the presence of complement C3 along the glomerular basement membrane (GBM). Spontaneous activation of C3 through the alternative pathway is regulated by 2 plasma proteins, factor H and factor I. Deficiency of either of these regulators results in uncontrolled C3 activation, although the breakdown of activated C3 is dependent on factor I. Deficiency of factor H, but not factor I, is associated with MPGN2 in humans, pigs, and mice. To explain this discordance, mice with single or combined deficiencies of these factors were studied. MPGN2 did not develop in mice with combined factor H and I deficiency or in mice deficient in factor I alone. However, administration of a source of factor I to mice with combined factor H and factor I deficiency triggered both activated C3 fragments in plasma and GBM C3 deposition. Mouse renal transplant studies demonstrated that C3 deposited along the GBM was derived from plasma. Together, these findings provide what we believe to be the first evidence that factor I-mediated generation of activated C3 fragments in the circulation is a critical determinant for the development of MPGN2 associated with factor H deficiency.
Analyses Adjusting for Selective Crossover Show Improved Overall Survival With Adjuvant Letrozole Compared With Tamoxifen in the BIG 1-98 Study
Authors: Marco Colleoni, Anita Giobbie-Hurder, Meredith M. Regan, Beat Thürlimann, Henning Mouridsen, Louis Mauriac, John F. Forbes, Robert Paridaens, István Láng, Ian Smith, Jacquie Chirgwin, Tadeusz Pienkowski, Andrew Wardley, Karen N. Price, Richard D. Gelber, Alan S. Coates, Aron Goldhirsch
Journal: Journal of Clinical Oncology (2011)

Among postmenopausal women with endocrine-responsive breast cancer, the aromatase inhibitor letrozole, when compared with tamoxifen, has been shown to significantly improve disease-free survival (DFS) and time to distant recurrence (TDR). We investigated whether letrozole monotherapy prolonged overall survival (OS) compared with tamoxifen monotherapy.Of 8,010 postmenopausal women with hormone receptor-positive, early breast cancer enrolled on the Breast International Group (BIG) 1-98 study, 4,922 were randomly assigned to 5 years of continuous adjuvant therapy with either letrozole or tamoxifen. Of 2,459 patients enrolled in the tamoxifen treatment arm, 619 (25.2%) selectively crossed over to either adjuvant or extended letrozole after initial trial results were presented in January 2005. To gain better estimates of relative treatment effects in the presence of selective crossover, we used inverse probability of censoring weighted (IPCW) modeling.Weighted Cox models, by using IPCW, estimated a statistically significant, 18% reduction in the hazard of an OS event with letrozole treatment (hazard ratio [HR], 0.82; 95% CI, 0.70 to 0.95). Estimates of 5-year OS on the basis of IPCW were 91.8% and 90.4% for letrozole and tamoxifen, respectively. The HRs of DFS and TDR events by using IPCW modeling were 0.83 (95% CI, 0.74 to 0.94) and 0.80 (95% CI, 0.67 to 0.94), respectively (P < .05 for DFS, OS, and TDR). Median follow-up was 74 months.Adjuvant treatment with letrozole, compared with tamoxifen, significantly reduces the risk of death, the risk of recurrent disease, and the risk of recurrence at distant sites in postmenopausal women with hormone receptor-positive breast cancer.
Conventional treatments for ankylosing spondylitis
Authors: M Dougados, B Dijkmans, M Khan, W Maksymowych, S. van der Linden, J Brandt
Journal: Annals of the Rheumatic Diseases (2002)

Management of ankylosing spondylitis (AS) is challenged by the progressive nature of the disease. To date, no intervention is available that alters the underlying mechanism of inflammation in AS. Currently available conventional treatments are palliative at best, and often fail to control symptoms in the long term. Current drug treatment may perhaps induce a spurious state of "disease remission," which is merely a low level of disease activity. Non-steroidal anti-inflammatory drugs are first line treatment, but over time, the disease often becomes refractory to these agents. Disease modifying antirheumatic drugs are second line treatment and may offer some clinical benefit. However, conclusive evidence of the efficacy of these drugs from large placebo controlled trials is lacking. Additionally, these drugs can cause treatment-limiting adverse effects. Intra-articular corticosteroid injection guided by arthrography, computed tomography, or magnetic resonance imaging is an effective means of reducing inflammatory back pain, but controlled studies are lacking. A controlled study has confirmed moderate but significant efficacy of intravenous bisphosphonate (pamidronate) treatment in patients with AS; further evaluation of bisphosphonate treatment is warranted. Physical therapy and exercise are necessary adjuncts to pharmacotherapy; however, the paucity of controlled data makes it difficult to identify the best way to administer these interventions. Surgical intervention may be required to support severe structural damage. Thus, for patients with AS, the future of successful treatment lies in the development of pharmacological agents capable of both altering the disease course through intervention at sites of disease pathogenesis, and controlling symptoms.
A Large Rubella Outbreak With Spread From the Workplace to the Community
Authors: M. Carolina Danovaro-Holliday
Journal: JAMA (2000)

a 29-year-old man residing in Douglas County, Nebraska, sought treatment in 3 health care facilities for what he thought was a sexually transmitted disease.At his third visit, he was noted to have a maculopapular rash, low-grade fever, and lymphadenopathy.Though no case of rubella had been reported in Douglas County in the previous 9 years, the patient had a positive rubella IgM test result.The patient worked in a meatpacking plant where a second rubella case was identified.Surveillance for rash illness was enhanced, resulting in the detection of more individuals in other meatpacking plants and in the community, almost all of whom were young adults born in Latin American countries, where rubella vaccination only recently has been implemented for children.Vaccination campaigns in 7 Douglas County meatpacking plants targeted 3000 workers.Physicians and clinics enhanced immunization efforts, and the health department provided other activities that included press, radio, and television coverage, and distribution of information through churches and community organizations.Despite these efforts, the outbreak continued for 4 months.Of the 125 cases reported from this outbreak, 83 occurred in Douglas County (Omaha), 12 in other Nebraska counties, and 30 in neighboring Iowa.Among the 83 cases in Douglas County, 14 were US-born children who attended 2 day care centers, and at least 7 pregnant women were infected.This outbreak ultimately became the largest US rubella outbreak in the past 5 years.
Activation-dependent contractility of rat hepatic lipocytes in culture and in vivo.
Authors: D C Rockey, C N Housset, S L Friedman
Journal: Journal of Clinical Investigation (1993)

Hepatic lipocytes are perisinusoidal cells that have been thought to be analogous to tissue pericytes, a cell type with purported vasoregulatory properties. However, we and others have recently demonstrated that lipocytes acquire markers of smooth muscle cells or myofibroblasts only after liver injury, via a process termed "activation." In this study, we document lipocyte contractility on collagen lattices and examine the importance of activation in this process. In culture, lipocytes became contractile only after spreading and activating, coincident with expression of smooth muscle alpha actin, a marker of activation (1990. Virchows Arch. B Cell Pathol. 59:349). After 5 d in culture, lipocytes induced rapid and sustained contraction of collagen lattices (to 43.7 +/- 2.3% of their original size 24 h after detachment). There was no contraction of lattices containing hepatocytes. Scanning electron microscopy demonstrated intimate associations of lipocyte cell membranes and collagen fibrils. Reduction in cell volume during contraction was also prominent. Lattice contraction by lipocytes was proportional to cell number. Serum was a potent stimulator of lipocyte contraction, as were endothelin types 1, 2, and 3; the effect of serum and endothelin 1 were additive. Neither thrombin, angiotensin-II, serotonin, nor the cytokines PDGF and TGF beta induced contraction. Cytochalasin B treatment resulted in concentration-dependent inhibition of contraction. As a test of the in vivo relevance of the culture findings, lipocytes were isolated from fibrotic animals and examined immediately after adherence. Whereas lipocytes from normal liver were initially compact, smooth muscle alpha actin negative and noncontractile, cells from animals with hepatic injury due to CCl4 displayed an activated appearance, expressed smooth muscle alpha actin, and were contractile immediately after adherence. Additionally, IFN-gamma, an agent which blocks lipocyte activation (1992. Hepatology. 16:776), inhibited lipocyte contraction. The data document that normal (i.e., quiescent) lipocytes are not contractile, but that activation is associated with the development of contractility. These findings suggest that a role for lipocytes in organ contraction or vasoregulation may be confined to injured, not normal liver.
ANGIOTENSIN II, NOREPINEPHRINE, AND RENAL TRANSPORT OF ELECTROLYTES AND WATER IN NORMAL MAN AND IN CIRRHOSIS WITH ASCITES*
Authors: John H. Laragh, Paul J. Cannon, Carl J. Bentzel, Alfred M. Sicinski, Jay I. Meltzer
Journal: Journal of Clinical Investigation (1963)

Effect of angiotensin and norepinephrine infusions on blood pressure, renal hemodynamics, and excretion of