tbuckley/cabot-search huggingface dataset:
Estimates of the Need for Palliative Care Consultation across United States Intensive Care Units Using a Trigger-based Model
Authors: May S. Hua, Guohua Li, Craig D. Blinderman, Hannah Wunsch
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Use of triggers for palliative care consultation has been advocated in intensive care units (ICUs) to ensure appropriate specialist involvement for patients at high risk of unmet palliative care needs. The volume of patients meeting these triggers, and thus the potential workload for providers, is unknown.
Reactivation of latent leishmaniasis by inhibition of inducible nitric oxide synthase.
Authors: S Stenger, N Donhauser, H Thüring, M Röllinghoff, C Bogdan
Journal: The Journal of Experimental Medicine (1996)

Nitric oxide (NO) synthase (iNOS) is required for the resolution of acute cutaneous leishmaniasis in resistant C57BL/6 mice. As is the case in several other infections, the clinically cured host organism still harbors small amounts of live Leishmania major parasites. Here, we demonstrate lifelong expression of iNOS at the site of the original skin lesion and in the draining lymph node of long-term-infected C57BL/6 mice. iNOS activity in the lymph node was dependent on CD4+, but not on the CD8+ T cells. By double labeling techniques, iNOS and L. major were each found in macrophages (F4/80+, BM-8+, and/or MOMA-2+) and dendritic cells (NLDC-145+), but not in granulocytes or endothelial cells. In situ triple labeling of lymph node sections revealed that approximately 30-40% of the L. major foci were associated with iNOS-positive macrophages or dendritic cells. The majority of the L. major foci (60-70%), however, was located in areas that were negative for both iNOS and the macrophage and dendritic cell markers. In L. major-infected C57BL/6 mice, which had cured their cutaneous lesions, administration of L-N6-iminoethyl-lysine (L-NIL), a potent inhibitor of iNOS, led to a 10(4)-10(5)-fold increase of the parasite burden in the cutaneous and lymphoid tissue and caused clinical recrudescence of the disease. Persistent expression of iNOS and resumption of parasite replication after application of L-NIL was also observed in resistant C3H/HeN and CBA/J mice. We conclude that iNOS activity is crucial for the control of Leishmania persisting in immunocompetent hosts after resolution of the primary infection. Failure to maintain iNOS activity might be the mechanism underlying endogenous reactivation of latent infections with NO-sensitive microbes during phases of immunosuppression.
ACUTE ALCOHOLISM TREATED WITH INSULIN
Authors: SIDNEY J. TILLIM
Journal: American Journal of Psychiatry (1944)

Insulin therapy has proven superior to other available methods for the treatment of acute alcoholism. It shortens the period of disability and is highly acceptable to patients. In war time, a saving in man-hours and avoidance of replacements are important considerations, especially as the incidence of acute alcoholism is bound to be reflected in life. The method of treatment was described and the results indicated by the reported cases.
Intensive follow-up strategies improve outcomes in nonmetastatic colorectal cancer patients after curative surgery: a systematic review and meta-analysis
Authors: S. Pita-Fernández, M. Alhayek-Aí, C. González-Martín, B. López-Calviño, T. Seoane-Pillado, S. Pértega-Díaz
Journal: Annals of Oncology (2014)

A wide variety of follow-up strategies are used for patients with colorectal cancer (CRC) after curative surgery. The aim of this study is to review the evidence of the impact of different follow-up strategies in patients with nonmetastatic CRC after curative surgery, in relation to overall survival and other outcomes.A systematic search of PubMed, EMBASE, SCOPUS and ISI Web of Knowledge up to June 2014 was carried out. Eligible studies were all randomized clinical trials comparing the effectiveness of different follow-up strategies after curative resection in nonmetastatic CRC.Eleven studies with n = 4055 participants were included in a meta-analysis. A significant improvement in overall survival was observed in patients with more intensive follow-up strategies [hazard ratio = 0.75; 95% confidence interval (CI) 0.66-0.86]. A higher probability of detection of asymptomatic recurrences [relative risk (RR) = 2.59; 95% CI 1.66-4.06], curative surgery attempted at recurrences (RR = 1.98; 95% CI 1.51-2.60), survival after recurrences (RR = 2.13; 95% CI 1.24-3.69), and a shorter time in detecting recurrences (mean difference = -5.23 months; 95% CI -9.58 to -0.88) was observed in the intervention group. There were no significant differences in the total tumor recurrences, nor in the mortality related to disease.Intensive follow-up strategies improve overall survival, increase the detection of asymptomatic recurrences and curative surgery attempted at recurrence, and are associated with a shorter time in detecting recurrences. This more intensive follow-up could not be associated with an improvement in cancer-specific survival nor with an increased detection of total tumor recurrences. Follow-up with serum carcinoembryonic antigen and colonoscopies are related to an increase in overall survival.
The Structural Basis for Serotype-Specific Neutralization of Dengue Virus by a Human Antibody
Authors: Ee Ping Teoh, Petra Kukkaro, En Wei Teo, Angeline P. C. Lim, Tze Tong Tan, Andy Yip, Wouter Schul, Myint Aung, Victor A. Kostyuchenko, Yee Sin Leo, Soh Ha Chan, Kenneth G. C. Smith, Annie Hoi Yi Chan, Gang Zou, Eng Eong Ooi, D. Michael Kemeny, Grace K. Tan, Jowin K. W. Ng, Mah Lee Ng, Sylvie Alonso, Dale Fisher, Pei-Yong Shi, Brendon J. Hanson, Shee-Mei Lok, Paul A. MacAry
Journal: Science Translational Medicine (2012)

The mechanism of action of a serotype-specific natural human antibody against dengue virus has been identified.
Vitamin D deficiency alters airway structure and function in a chronic house dust mite exposure model
Authors: Rachel Foong, Luke Berry, Prue Hart, Shelley Gorman, Graeme Zosky
Journal: European Respiratory Journal (2013)

Introduction Reduced levels of vitamin D are associated with airway hyperresponsiveness (AHR), airway remodelling and poor asthma control, however the causal link between these is yet to be established. We aimed to determine whether vitamin D deficiency would increase AHR and airway remodelling in a mouse model of chronic allergic asthma.

Methods A physiologically relevant mouse model of vitamin D deficiency was developed by raising BALB/c mice on vitamin D-deficient or -replete diets. Offspring from -deficient and -replete mice of both sexes at 8 weeks of age were intranasally inoculated with house dust mite (HDM) extract (25 μg of protein in 50 μL of saline) or saline as a control 5 days a week for 5 weeks. AHR was assessed by measuring lung function responses to increasing doses of inhaled methacholine (MCh) 72 hours after the last HDM exposure. Lungs were fixed in formalin, embedded in paraffin and cut into 5 μm thick sections. Sections were stained with Masson’s Trichrome for airway smooth muscle (ASM) measurement.

Results Both HDM and vitamin D deficiency on their own caused an increase in both ASM (p   0.05).

Conclusions Both vitamin D deficiency and HDM on their own increased ASM and airway resistance in mice but, paradoxically, when both were combined the responses were dampened.
Localization and Density of Immune Cells in the Invasive Margin of Human Colorectal Cancer Liver Metastases Are Prognostic for Response to Chemotherapy
Authors: Niels Halama, Sara Michel, Matthias Kloor, Inka Zoernig, Axel Benner, Anna Spille, Thora Pommerencke, Doeberitz Magnus von Knebel, Gunnar Folprecht, Birgit Luber, Nadine Feyen, Uwe M. Martens, Philipp Beckhove, Sacha Gnjatic, Peter Schirmacher, Esther Herpel, Juergen Weitz, Niels Grabe, Dirk Jaeger
Journal: Cancer Research (2011)

Analysis of tumor-infiltrating lymphocytes (TIL) in primary human colorectal cancer (CRC) by in situ immunohistochemical staining supports the hypothesis that the adaptive immune response influences the course of human CRC. Specifically, high densities of TILs in the primary tumor are associated with good prognosis independent of other prognostic markers. However, the prognostic role of TILs in metastatic CRC lesions is unknown, as is their role in response or resistance to conventional chemotherapy. We analyzed the association of TIL densities at the invasive margin of CRC liver metastases with response to chemotherapy and progression-free survival in a set of 101 large section samples. High-resolution automated microscopy on complete tissue sections was used to objectively generate cell densities for CD3, CD8, granzyme B, or FOXP3 positive immune cells. A predictive scoring system using TIL densities was developed in a training set and tested successfully in an independent validation set. TIL densities at the invasive margin of liver metastases allowed the prediction of response to chemotherapy with a sensitivity of 79% and specificity of 100%. The association of high density values with longer progression-free survival under chemotherapy was statistically significant. Overall, these findings extend the impact of the local immune response on the clinical course from the primary tumor also to metastatic lesions. Because detailed quantification of TILs in metastatic lesions revealed a strong association with chemotherapy efficacy and prognosis, we suggest that the developed scoring system may be used as a predictive tool for response to chemotherapy in metastatic CRC.
T Cell Accumulation in B Cell Follicles Is Regulated by Dendritic Cells and Is Independent of B Cell Activation
Authors: Simon Fillatreau, David Gray
Journal: The Journal of Experimental Medicine (2003)

We investigated the mechanism of CD4 T cell accumulation in B cell follicles after immunization. Follicular T cell numbers were correlated with the number of B cells, indicating B cell control of the niche that T cells occupy. Despite this, we found no role for B cells in the follicular migration of T cells. Instead, T cells are induced to migrate into B cell follicles entirely as a result of interaction with dendritic cells (DCs). Migration relies on CD40-dependent maturation of DCs, as it did not occur in CD40-deficient mice but was reconstituted with CD40+ DCs. Restoration was not achieved by the activation of DCs with bacterial activators (e.g., lipopolysaccharide, CpG), but was by the injection of OX40L–huIgG1 fusion protein. Crucially, the up-regulation of OX40L (on antigen-presenting cells) and CXCR-5 (on T cells) are CD40-dependent events and we show that T cells do not migrate to follicles in immunized OX40-deficient mice.
Haemoglobin and ferritin concentrations in men and women: cross sectional study
Authors: J. Waalen
Journal: BMJ (2002)

Rushton et al found that of all the primates, only in humans do females have lower blood haemoglobin concentrations than males. 1 The usual explanation, of the effect of androgens on erythropoiesis, does not explain the difference between species. 2 The explanation of Rushton et al of iron deficiency among females, does not withstand scrutiny.
Phase Ib dose-escalation study of MetMAb, a monovalent antagonist antibody to the receptor MET, in combination with bevacizumab in patients with locally advanced or metastatic solid tumors.
Authors: R. A. Moss, J. G. Bothos, E. Filvaroff, M. Merchant, S. Eppler, W. Yu, K. Harris, P. Scott, J. M. Mehnert, P. H. Patel
Journal: Journal of Clinical Oncology (2010)

e13050 Background: Crosstalk between the Met and vascular endothelial growth factor (VEGF) pathways may be important during tumorigenesis. Aberrant activation of the HGF/Met pathway may promote angiogenesis via tumor cell secretion of angiogenic factors or directly activating endothelial cells. The combination of Met and VEGF inhibition resulted in enhanced antitumor activity in multiple preclinical models than either treatment alone. MetMAb is a recombinant, humanized, monovalent (one-armed) monoclonal antibody antagonist of HGF-induced Met signaling. In phase Ia, MetMAb was generally well tolerated up to 30 mg/kg IV Q3W. Herein, we describe results from a phase Ib study in which we tested MetMAb in combination with bevacizumab. Methods: The phase Ib trial tested the combination of MetMAb with bevacizumab in two cohorts: 3 patients in cohort 1 received MetMAb, 10 mg/kg, and bevacizumab, 15 mg/kg, IV Q3W; and 6 patients in cohort 2 received MetMAb,15 mg/kg, and bevacizumab,15 mg/kg IV Q3W. Pre- and post-dose sera were collected for evaluation of pharmacodynamic (PD) biomarkers that could be affected by inhibition of Met and/or VEGF signaling. Results: The combination of MetMAb with bevacizumab was generally well tolerated at all doses tested. No Gr3-5 drug- related toxicities were observed. One DLT of Gr1 hemoptysis in cohort 2 was observed in a patient who had central-necrosis of pulmonary metastases. Gr2 drug-related toxicities included peripheral edema and hypoalbuminemia. The most frequently observed toxicities (>30 %) included fatigue and increased weight. The best response was stable disease, with 3 patients receiving ≥ 6 cycles. PD biomarker data will be discussed. MetMAb PK was similar to that from phase Ia and no apparent interaction with bevacizumab was observed. Conclusions: This phase Ib trial demonstrated that the combination of MetMAb and bevacizumab is generally safe and well tolerated at the recommended dose of 15mg/kg Q3W for each agent. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech
Prognostic Relevance of Gene Amplifications and Coamplifications in Breast Cancer
Authors: Khawla Al-Kuraya, Peter Schraml, Joachim Torhorst, Coya Tapia, Boriana Zaharieva, Hedvika Novotny, Hanspeter Spichtin, Robert Maurer, Martina Mirlacher, Ossi Köchli, Markus Zuber, Holger Dieterich, Friedrich Mross, Kim Wilber, Ronald Simon, Guido Sauter
Journal: Cancer Research (2004)

Abstract Multiple different oncogenes have been described previously to be amplified in breast cancer including HER2, EGFR, MYC, CCND1, and MDM2. Gene amplification results in oncogene overexpression but may also serve as an indicator of genomic instability. As such, presence of one or several gene amplifications may have prognostic significance. To assess the prognostic importance of amplifications and coamplifications of HER2, EGFR, MYC, CCND1, and MDM2 in breast cancer, we analyzed a breast cancer tissue microarray containing samples from 2197 cancers with follow-up information. Fluorescence in situ hybridizations revealed amplifications of CCND1 in 20.1%, HER2 in 17.3%, MDM2 in 5.7%, MYC in 5.3%, and EGFR in 0.8% of the tumors. All gene amplifications were significantly associated with high grade. HER2 (P &amp;lt; 0.001) and MYC amplification (P &amp;lt; 0.001) were also linked to shortened survival. In case of HER2, this was independent of grade, pT, and pN categories. MYC amplification was almost 3 times more frequent in medullary cancer (15.9%), than in the histologic subtype with the second highest frequency (ductal; 5.6%; P = 0.0046). HER2 and MYC amplification were associated with estrogen receptor/progesterone receptor negativity (P &amp;lt; 0.001) whereas CCND1 amplification was linked to estrogen receptor/progesterone receptor positivity (P &amp;lt; 0.001). Coamplifications were more prevalent than expected based on the individual frequencies. Coamplifications of one or several other oncogenes occurred in 29.6% of CCND1, 43% of HER2, 55.7% of MDM2, 65% of MYC, and 72.8% of EGFR-amplified cancers. HER2/MYC-coamplified cancers had a worse prognosis than tumors with only one of these amplifications. Furthermore, a gradual decrease of survival was observed with increasing number of amplifications. In conclusion, these data support a major prognostic impact of genomic instability as determined by a broad gene amplification survey in breast cancer.
Endothelin A Receptor Blockade Reduces Diabetic Renal Injury via an Anti-Inflammatory Mechanism
Authors: Jennifer M Sasser, Jennifer C Sullivan, Janet L Hobbs, Tatsuo Yamamoto, David M Pollock, Pamela K Carmines, Jennifer S Pollock
Journal: Journal of the American Society of Nephrology (2006)

Endothelin (ET) receptor blockade delays the progression of diabetic nephropathy; however, the mechanism of this protection is unknown. Therefore, the aim of this study was to test the hypothesis that ET(A) receptor blockade attenuates superoxide production and inflammation in the kidney of diabetic rats. Diabetes was induced by streptozotocin (diabetic rats with partial insulin replacement to maintain modest hyperglycemia [HG]), and sham rats received vehicle treatments. Some rats also received the ETA antagonist ABT-627 (sham+ABT and HG+ABT; 5 mg/kg per d; n = 8 to 10/group). During the 10-wk study, urinary microalbumin was increased in HG rats, and this effect was prevented by ET(A) receptor blockade. Indices of oxidative stress, urinary excretion of thiobarbituric acid reactive substances, 8-hydroxy--deoxyguanosine, and H2O2 and plasma thiobarbituric acid reactive substances were significantly greater in HG rats than in sham rats. These effects were not prevented by ABT-627. In addition, renal cortical expression of 8-hydroxy--deoxyguanosine and NADPH oxidase subunits was not different between HG and HG+ABT rats. ETA receptor blockade attenuated increases in macrophage infiltration and urinary excretion of TGF-beta and prostaglandin E2 metabolites in HG rats. Although ABT-627 did not alleviate oxidative stress in HG rats, inflammation and production of inflammatory mediators were reduced in association with prevention of microalbuminuria. These observations indicate that ETA receptor activation mediates renal inflammation and TGF-beta production in diabetes and are consistent with the postulate that ETA blockade slows progression of diabetic nephropathy via an anti-inflammatory mechanism.
Predicting Posttraumatic Stress Symptoms From Pretraumatic Risk Factors: A 2-Year Prospective Follow-Up Study in Firefighters
Authors: Markus Heinrichs, Dieter Wagner, Walter Schoch, Leila M Soravia, Dirk H Hellhammer, Ulrike Ehlert
Journal: American Journal of Psychiatry (2005)

Most studies focusing on risk factors for posttraumatic stress disorder (PTSD) have used retrospective study designs. Only a small number of studies have prospectively examined risk factors in the immediate aftermath of trauma exposure in predicting PTSD symptoms. The purpose of this study was to identify predictive risk factors for posttraumatic stress symptoms and comorbid psychopathological symptoms present during the time before exposure to traumatic stress in a high-risk population.Forty-three professional firefighters were assessed immediately after basic training (baseline) and at 6, 9, 12, and 24 months after entry into firefighter service. Subjects were screened for psychopathological symptoms, including symptoms of PTSD, depression, and anxiety. Subjects were also characterized with regard to personality traits such as self-efficacy, hostility, and alexithymia. Neuroendocrine activity was assessed by examination of awakening and diurnal salivary cortisol profiles and 24-hour urinary catecholamine excretion. Multiple linear regression analysis was used to analyze posttraumatic stress symptoms at 24-month follow-up as a function of pretraumatic characteristics.A high level of hostility and a low level of self-efficacy at baseline accounted for 42% of the variance in posttraumatic stress symptoms after 2 years. Subjects who had both risk factors at baseline showed a significant increase in measures of PTSD symptoms, depression, anxiety, general psychological morbidity, global symptom severity, and alexithymia during the 2-year period. Biological characteristics were not predictive of the development of psychopathological symptoms.These results suggest that specific personality traits may constitute markers of vulnerability to the development of psychopathological symptoms after trauma exposure. Early identification of preexisting risk factors is needed to provide effective prevention and intervention for individuals who are at risk of developing trauma-related disorders.
Sleep quality evaluation, chronotype, sleepiness and anxiety of Paralympic Brazilian athletes: Beijing 2008 Paralympic Games
Authors: Andressa Silva, Sandra Souza Queiroz, Ciro Winckler, Roberto Vital, Ronnie Andrade Sousa, Vander Fagundes, Sergio Tufik, Marco Túlio de Mello
Journal: British Journal of Sports Medicine (2010)

The objective of this study was to evaluate the sleep quality, sleepiness, chronotype and the anxiety level of Brazilian Paralympics athletes before the 2008 Beijing Paralympic Games.Cross-sectional study. Setting Exercise and Psychobiology Studies Center (CEPE) and Universidade Federal de São Paulo, an urban city in Brazil.A total of 27 Paralympics athletes of both genders (16 men and 11 women) with an average age of 28±6 years who practised athletics (track and field events) were evaluated.Sleep quality was evaluated using the Pittsburgh Scale and the Epworth Sleepiness Scale to evaluate sleepiness. Chronotype was determined by the Horne and Östberg questionnaire and anxiety through the State-Trait Anxiety Inventory. The evaluations were performed in Brazil 10 days before the competition.The study's results demonstrate that 83.3% of the athletes that presented excessive daytime sleepiness also had poor sleep quality. The authors noted that 71.4% were classified into the morning type and 72% of the athletes who presented a medium anxiety level also presented poor sleep quality. Athletes with poor sleep quality showed significantly lower sleep efficiency (p=0.0119) and greater sleep latency (p=0.0068) than athletes with good sleep quality. Athletes who presented excessive daytime sleepiness presented lower sleep efficiency compared to non-sleepy athletes (p=0.0241).The authors conclude that the majority of athletes presented poor sleep quality before the competition. This information should be taken into consideration whenever possible when scheduling rest, training and competition times.
Tumor Necrosis Factor-α Induces Endothelial Dysfunction in the Prediabetic Metabolic Syndrome
Authors: Andrea Picchi, Xue Gao, Souad Belmadani, Barry J. Potter, Marta Focardi, William M. Chilian, Cuihua Zhang
Journal: Circulation Research (2006)

Inflammation is a condition that underscores many cardiovascular pathologies including endothelial dysfunction, but no link is yet established between the vascular pathology of the metabolic syndrome with a particular inflammatory cytokine. We hypothesized that impairments in coronary endothelial function in the obese condition the prediabetic metabolic syndrome is caused by TNF-α overexpression. To test this, we measured endothelium-dependent (acetylcholine) and -independent vasodilation (sodium nitroprusside) of isolated, pressurized coronary small arteries from lean control and Zucker obese fatty (ZOF, a model of prediabetic metabolic syndrome) rats. In ZOF rats, dilation to ACh was blunted compared with lean rats, but sodium nitroprusside–induced dilation was comparable. Superoxide (O 2 · − ) generation was elevated in vessels from ZOF rats compared with lean rats, and administration of the O 2 · − scavenger TEMPOL, NAD(P)H oxidase inhibitor (apocynin), or anti–TNF-α restored endothelium-dependent dilation in the ZOF rats. Real-time PCR and Western blotting revealed that mRNA and protein of TNF-α were higher in ZOF rats than that in lean rats, whereas eNOS protein levels were reduced in the ZOF versus lean rats. Immunostaining showed that TNF-α in ZOF rat heart is localized in endothelial cells and vascular smooth muscle cells. Expression of NAD(P)H subunits p22 and p40-phox were elevated in ZOF compared with lean animals. Administration of TNF-α more than 3 days also induced expression of these NAD(P)H subunits and abrogated endothelium-dependent dilation. In conclusion, the results demonstrate the endothelial dysfunction occurring in the metabolic syndrome is the result of effects of the inflammatory cytokine TNF-α and subsequent production of O 2 · − .