tbuckley/cabot-search huggingface dataset:
Lamivudine for the Prevention of Hepatitis B Virus Reactivation in Hepatitis B s-Antigen Seropositive Cancer Patients Undergoing Cytotoxic Chemotherapy
Authors: Winnie Yeo, Paul K.S. Chan, Wing M. Ho, Benny Zee, Kwok C. Lam, Kenny I.K. Lei, Anthony T.C. Chan, Tony S.K. Mok, Jam J. Lee, Thomas W.T. Leung, Sheng Zhong, Philip J. Johnson
Journal: Journal of Clinical Oncology (2004)

Purpose For cancer patients receiving cytotoxic chemotherapy, hepatitis B virus (HBV) reactivation is a well described complication resulting in varying degrees of liver damage. The objectives of this study were to assess the efficacy of the antiviral agent lamivudine in reducing the incidence of HBV reactivation and diminishing morbidity and mortality of cancer patients with chronic HBV infection during chemotherapy. Patients and Methods Two groups were compared in this nonrandomized study. The prophylactic lamivudine group consisted of 65 patients in a phase II study who were treated with lamivudine before and until 8 weeks after discontinuing chemotherapy. The historical controls consisted of 193 consecutive patients who underwent chemotherapy without prophylactic lamivudine. Significant prognosticators for the development of HBV reactivation were determined based on data from the controls. Potential confounding factors were identified between the two groups. The outcomes were compared. Results In the controls, lymphoma and anthracycline usage were factors identified to be associated with reactivation. The two groups were comparable in most baseline characteristics, although in the prophylactic lamivudine group, there were significantly more patients with lymphoma and receiving anthracyclines. In the prophylactic lamivudine group, there was significantly less HBV reactivation (4.6% v 24.4% in the controls; P &lt; .001), fewer incidences of hepatitis (17.5% v 44.6%; P &lt; .0001) that were less severe (4.8% v 18.7%; P = .0005), and less disruption of chemotherapy (15.4% v 34.6%; P = .0029). The reduction in overall mortality was not statistically different. Conclusion Prophylactic lamivudine significantly reduced the incidence of HBV reactivation and the overall morbidity of cancer patients undergoing chemotherapy.
Projected Effect of Dietary Salt Reductions on Future Cardiovascular Disease
Authors: Kirsten Bibbins-Domingo, Glenn M. Chertow, Pamela G. Coxson, Andrew Moran, James M. Lightwood, Mark J. Pletcher, Lee Goldman
Journal: New England Journal of Medicine (2010)

The U.S. diet is high in salt, with the majority coming from processed foods. Reducing dietary salt is a potentially important target for the improvement of public health.
Outcomes in Elderly Intensive Care Unit Patients, Pulmonary Hypertension in Sickle Cell Disease, and Total Liquid Ventilation for Therapeutic Hypothermia after Cardiac Arrest in Rabbits
Authors: Nathan E. Brummel, Meredith E. Pugh, Joshua P. Fessel
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

The incidence of critical illness increases with age (2). Aging of the baby-boomer generation will soon lead to a larger number of elderly Americans, with those over age 85 expected to increase nearly fourfold by 2040, to nearly 15 million people. Thus, outcomes including mortality, disability, and quality of life (QOL) for critically ill elderly patients are of increasing importance. Roch and colleagues (1) evaluated mortality and QOL in a retrospective observational cohort of 299 medical intensive care unit (ICU) patients greater than 80 years old at a tertiary care university hospital in France. ICU mortality was 46% and hospital mortality was 55%. Furthermore, 1and 2-year mortality was 72 and 79%, respectively. Among hospital survivors, mortality was 53% at 2 years with a standardized mortality ratio of 2.56 (95% confidence interval, 2.08–3.12) compared with the general French population. Adjusted analysis found that severity of illness at admission and presence of a disease expected to be fatal in the next 1 or 5 years were associated with 2-year mortality, whereas preexisting functional status and admission diagnosis were not. QOL scores at a median of 63 months after discharge were significantly lower than population norms in physical health domains, whereas mental health domain scores were not reduced. Mortality rates in this single-center study were higher than those observed in similar advanced age cohorts (3), perhaps relating to local ICU practices, patient triage decisions, and end-oflife planning. Thus, these findings may lack generalizability. This study used univariate analysis to determine cofactors in the multivariable model (i.e., including factors deemed statistically significant, which may be “noise” because of the large number of risk factors analyzed), which increases the risk of overfitting of the model and may distort study conclusions. Nevertheless, this study suggests a substantial mortality risk in critically ill patients over age 80. QOL may be an insensitive instrument to detect disability after critical illness, as a large cohort study of similarly aged Medicare patients found marked cognitive and functional impairment after severe sepsis (4). Future prospective studies are needed into predictors of mortality and morbidity in this growing population of the oldest-old.
Absence of the Endothelial Oxidase AOC3 Leads to Abnormal Leukocyte Traffic In Vivo
Authors: Craig M. Stolen, Fumiko Marttila-Ichihara, Kaisa Koskinen, Gennady G. Yegutkin, Raisa Turja, Petri Bono, Mikael Skurnik, Arno Hänninen, Sirpa Jalkanen, Marko Salmi
Journal: Immunity (2005)
Systemic manifestations and comorbidities of COPD
Authors: P. J. Barnes, B. R. Celli
Journal: European Respiratory Journal (2009)

Increasing evidence indicates that chronic obstructive pulmonary disease (COPD) is a complex disease involving more than airflow obstruction. Airflow obstruction has profound effects on cardiac function and gas exchange with systemic consequences. In addition, as COPD results from inflammation and/or alterations in repair mechanisms, the “spill-over” of inflammatory mediators into the circulation may result in important systemic manifestations of the disease, such as skeletal muscle wasting and cachexia. Systemic inflammation may also initiate or worsen comorbid diseases, such as ischaemic heart disease, heart failure, osteoporosis, normocytic anaemia, lung cancer, depression and diabetes. Comorbid diseases potentiate the morbidity of COPD, leading to increased hospitalisations, mortality and healthcare costs. Comorbidities complicate the management of COPD and need to be evaluated carefully. Current therapies for comorbid diseases, such as statins and peroxisome proliferator-activated receptor-agonists, may provide unexpected benefits for COPD patients. Treatment of COPD inflammation may concomitantly treat systemic inflammation and associated comorbidities. However, new broad-spectrum anti-inflammatory treatments, such as phosphodiesterase 4 inhibitors, have significant side-effects so it may be necessary to develop inhaled drugs in the future. Another approach is the reversal of corticosteroid resistance, for example with effective antioxidants. More research is needed on COPD comorbidities and their treatment.
Dissociation between skin (SSNA) and muscle (MSNA) sympathetic nerve activity in liver cirrhosis
Authors: M. Pozzi, G. Grassi, R. Dell'Oro, E. Redaelli, G. Foglia, A. Redaelli, L. Ratti, L. Pasulo, G. Poli, A. Villa, G. Mancia
Journal: Journal of Hepatology (2001)
Drug treatments in upper gastrointestinal bleeding: value of endoscopic findings as surrogate end points
Authors: G M Hawkey, A T Cole, A S McIntyre, R G Long, C J Hawkey
Journal: Gut (2001)

<h3>INTRODUCTION</h3> Pharmacotherapy for upper gastrointestinal bleeding has been difficult to evaluate because clinical end points are infrequent and affected by other factors. <h3>AIMS</h3> To evaluate whether blood in the stomach at endoscopy reflected severity of bleeding, predicted clinical outcomes, and could be altered by therapeutic agents. <h3>METHODS</h3> We studied 414 consecutive admissions with suspected upper gastrointestinal bleeding. Patients were randomised to receive lansoprazole 60 mg followed by 30 mg four times daily, tranexamic acid 2 g followed by 1 g four times daily, both drugs, or placebo for four days, until discharge or a clinical end point occurred. Logistic regression analysis was used to determine predictors of endoscopic changes and clinical outcomes, and to investigate the effects of drug treatments on blood in the stomach. <h3>RESULTS</h3> Of 414 patients with suspected upper gastrointestinal bleeding, 379 were endoscoped. Upper gastrointestinal bleeding was confirmed in 316. Sixteen required surgery within 30 days and 16 died on the index admission. Trial treatments were evaluable on a per protocol basis in 228 patients. The amount of blood in the stomach was found to reflect initial risk, with significant associations with high risk categorisation (odds ratio 3.7 (95% confidence interval 1.5–9.4) for more than a trace <i>v</i> none/trace), age (1.5 (1.1–1.9) per decade), and initial pulse (1.02 (1.00–1.04) per beat), and to predict rebleeding (9.2 (4.6–18.7)) and surgery (8.2 (2.9–22.9)). Other stigmata were less significant in these respects. The amount of blood in the stomach at endoscopy was reduced significantly by both lansoprazole (0.22 (0.07–0.63)) and tranexamic acid (0.27 (0.09–0.81)), although there was no evidence of synergy. <h3>CONCLUSIONS</h3> Blood in the stomach reflects clinical features in patients with acute upper gastrointestinal bleeding and is reduced by treatment with lansoprazole and tranexamic acid.
Hypermobility and injuries in a professional ballet company.
Authors: P. Klemp, I. D. Learmonth
Journal: British Journal of Sports Medicine (1984)

A study was conducted on members of the Cape Performing Arts Board (CAPAB) professional ballet company to determine the prevalence of hypermobility and to document the injuries sustained over a ten year period. If forward flexion, which is acquired through training, is excluded as a parameter the difference in hypermobility between dancers and controls is not statistically significant. Considering the stresses imposed on the musculoskeletal system, the number of injuries was surprisingly low. Ligamentous injuries about the ankle and knee were both common and accounted for the major morbidity. There were minor differences in the nature and severity of injuries in the male and female dancers. Back injuries, fractures and osteoarthrosis were uncommon and shin splints was not recorded in any of the dancers.
Columbia Classification Algorithm of Suicide Assessment (C-CASA): Classification of Suicidal Events in the FDA’s Pediatric Suicidal Risk Analysis of Antidepressants
Authors: Kelly Posner
Journal: American Journal of Psychiatry (2007)

Objective: To evaluate the link between antidepressants and suicidal behavior and ideation (suicidality) in youth, adverse events from pediatric clinical trials were classified in order to identify suicidal events. The authors describe the Columbia Classification Algorithm for Suicide Assessment (C-CASA), a standardized suicidal rating system that provided data for the pediatric suicidal risk analysis of antidepressants conducted by the Food and Drug Administration (FDA). Method: Adverse events (N=427) from 25 pediatric antidepressant clinical trials were systematically identified by pharmaceutical companies. Randomly assigned adverse events were evaluated by three of nine independent expert suicidologists using the Columbia classification algorithm. Reliability of the C-CASA ratings and agreement with pharmaceutical company classification were estimated. Results: Twenty-six new, possibly suicidal events (behavior and ideation) that were not originally identified by pharmaceutical companies were identified in the C-CASA, and 12 events originally labeled as suicidal by pharmaceutical companies were eliminated, which resulted in a total of 38 discrepant ratings. For the specific label of "suicide attempt," a relatively low level of agreement was observed between the C-CASA and pharmaceutical company ratings, with the C-CASA reporting a 50% reduction in ratings. Thus, although the C-CASA resulted in the identification of more suicidal events overall, fewer events were classified as suicide attempts. Additionally, the C-CASA ratings were highly reliable (intraclass correlation coefficient [ICC]=0.89). Conclusions: Utilizing a methodical, anchored approach to categorizing suicidality provides an accurate and comprehensive identification of suicidal events. The FDA's audit of the C-CASA demonstrated excellent transportability of this approach. The Columbia algorithm was used to classify suicidal adverse events in the recent FDA adult antidepressant safety analyses and has also been mandated to be applied to all anticonvulsant trials and other centrally acting agents and nonpsychotropic drugs.
Cloning, expression, and type II collagenolytic activity of matrix metalloproteinase-13 from human osteoarthritic cartilage.
Authors: P G Mitchell, H A Magna, L M Reeves, L L Lopresti-Morrow, S A Yocum, P J Rosner, K F Geoghegan, J E Hambor
Journal: Journal of Clinical Investigation (1996)

Proteolysis of triple-helical collagen is an important step in the progression toward irreversible tissue damage in osteoarthritis. Earlier work on the expression of enzymes in cartilage suggested that collagenase-1 (MMP-1) contributes to the process. Degenerate reverse transcription polymerase chain reaction experiments, Northern blot analysis, and direct immunodetection have now provided evidence that collagenase-3 (MMP-13), an enzyme recently cloned from human breast carcinoma, is expressed by chondrocytes in human osteoarthritic cartilage. Variable levels of MMP-13 and MMP-1 in cartilage was significantly induced at both the message and protein levels by interleukin-1 alpha. Recombinant MMP-13 cleaved type II collagen to give characteristic 3/4 and 1/4 fragments; however, MMP-13 turned over type II collagen at least 10 times faster than MMP-1. Experiments with intact type II collagen as well as a synthetic peptide suggested that MMP-13 cleaved type II collagen at the same bond as MMP-1, but this was then followed by a secondary cleavage that removed three amino acids from the 1/4 fragment amino terminus. The expression of MMP-13 in osteoarthritic cartilage and its activity against type II collagen suggest that the enzyme plays a significant role in cartilage collagen degradation, and must consequently form part of a complex target for proposed therapeutic interventions based on collagenase inhibition.
The CXCL12–CXCR4 Chemokine Pathway: A Novel Axis Regulates Lymphangiogenesis
Authors: Wei Zhuo, Lin Jia, Nan Song, Xin-an Lu, Yanping Ding, Xiaofeng Wang, Xiaomin Song, Yan Fu, Yongzhang Luo
Journal: Clinical Cancer Research (2012)

Lymphangiogenesis, the growth of lymphatic vessels, contributes to lymphatic metastasis. However, the precise mechanism underlying lymphangiogenesis remains poorly understood. This study aimed to examine chemokine/chemokine receptors that directly contribute to chemoattraction of activated lymphatic endothelial cells (LEC) and tumor lymphangiogenesis.We used quantitative RT-PCR to analyze specifically expressed chemokine receptors in activated LECs upon stimulation of vascular endothelial growth factor-C (VEGF-C). Subsequently, we established in vitro and in vivo models to show lymphangiogenic functions of the chemokine axis. Effects of targeting the chemokine axis on tumor lymphangiogenesis and lymphatic metastasis were determined in an orthotopic breast cancer model.VEGF-C specifically upregulates CXCR4 expression on lymphangiogenic endothelial cells. Moreover, hypoxia-inducible factor-1α (HIF-1α) mediates the CXCR4 expression induced by VEGF-C. Subsequent analyses identify the ligand CXCL12 as a chemoattractant for LECs. CXCL12 induces migration, tubule formation of LECs in vitro, and lymphangiogenesis in vivo. CXCL12 also stimulates the phosphorylation of intracellular signaling Akt and Erk, and their specific antagonists impede CXCL12-induced chemotaxis. In addition, its level is correlated with lymphatic vessel density in multiple cancer tissues microarray. Furthermore, the CXCL12-CXCR4 axis is independent of the VEGFR-3 pathway in promoting lymphangiogenesis. Intriguingly, combined treatment with anti-CXCL12 and anti-VEGF-C antibodies results in additive inhibiting effects on tumor lymphangiogenesis and lymphatic metastasis.These results show the role of the CXCL12-CXCR4 axis as a novel chemoattractant for LECs in promoting lymphangiogenesis, and support the potential application of combined targeting of both chemokines and lymphangiogenic factors in inhibiting lymphatic metastasis.
Human appendix B cells naturally express receptors for and respond to interleukin 6 with selective IgA1 and IgA2 synthesis.
Authors: K Fujihashi, J R McGhee, C Lue, K W Beagley, T Taga, T Hirano, T Kishimoto, J Mestecky, H Kiyono
Journal: Journal of Clinical Investigation (1991)

Past studies have shown that freshly isolated human B cells from peripheral blood and tonsils do not express IL-6 receptors (IL-6R); however, mitogen or antigen activation of these B cells induces IL-6R and responsiveness to IL-6. In this study, we have shown that a high proportion of B cells enzymatically dissociated from human appendix, a gut-associated lymphoreticular tissue (GALT), expresses the IL-6R, and that recombinant human IL-6 induces significant increases in the number of Ig-producing cells. The recombinant human IL-6-induced increase in Ig-producing cells is restricted to the IgA isotype. Further, IgA2 is the major subclass; however, significant numbers of IgA1 producing cells are also seen. In contrast, human tonsillar and peripheral blood B cells express low levels of IL-6R, and exogenous IL-6 does not increase numbers of Ig-producing cells. When PBMC or tonsillar cells are stimulated with PWM, the former display an equal distribution of IgA1 and IgA2 secreting cells, while tonsillar B cells are mainly of the IgA1 subclass. The distribution of surface Ig-positive (sIg+) B cells in the appendix B cell population is sIgA+ greater than sIgG+ greater than sIgM+, and the sIgA+ B cells express higher levels of IL-6R when compared with sIgG+ or sIgM+ B cells. These studies show that human appendix contains B cell subsets that constitutively express IL-6R, and that a high proportion of these cells are committed to the IgA isotype. Furthermore, higher numbers of IL-6 responsive IgA2 B cells are present in the human appendix as compared to tonsils or PBMC.
Second Lung Cancers in Patients After Treatment for an Initial Lung Cancer
Authors: Bruce E. Johnson
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: Prospectively and retrospectively identified patient cohorts that were successfully treated for primary lung cancer have been followed to document the rate of development of and the effectiveness of treatment of second lung cancers. This review was performed to assess rates of second lung cancer development, factors associated with the development of these cancers, and the success of their treatment. Methods: The MEDLINE database was searched to identify articles published in English concerning lung cancers, second primary cancers, treatment of these cancers, and patient survival. Results: The risk of developing a second lung cancer in patients who survived resection of a non-small-cell lung cancer is approximately 1%-2% per patient per year. Approximately one half of the patients who develop second non-small-cell lung cancers can have these tumors resected. The median survival from diagnosis of a second lung cancer in these patients is between 1 and 2 years, with a 5-year survival of approximately 20% (range, 4%-32%). The average risk of developing a second lung cancer in patients who survived small-cell lung cancer is approximately 6% per patient per year. For patients who survived small-cell cancer, the risk increases from approximately 2% to greater than 10% per patient per year 10 years after initial treatment. Only 7% (range, 6%-12%) of patients treated for small-cell lung cancer survive 2 years or more. Survivors who continue to smoke cigarettes have an increased risk of developing a second lung cancer. Conclusions: In patients surviving an initial lung cancer, the cumulative risk for the development of a second primary lung cancer makes this cancer a common cause of death. The high risk of developing a second lung cancer makes patients with these cancers an important population for study of surveillance strategies and chemoprevention agents. [J Natl Cancer Inst 1998;90:1335-45]
To What Extent Is the Familial Risk of Rheumatoid Arthritis Explained by Established Rheumatoid Arthritis Risk Factors?
Authors: Xia Jiang, Thomas Frisell, Johan Askling, Elizabeth W. Karlson, Lars Klareskog, Lars Alfredsson, Henrik Källberg
Journal: Arthritis & Rheumatology (2014)

Family history of rheumatoid arthritis (RA) is one of the strongest risk factors for developing RA, and information on family history is, therefore, routinely collected in clinical practice. However, as more genetic and environmental risk factors shared by relatives are identified, the importance of family history may diminish. The aim of this study was to determine how much of the familial risk of RA can be explained by established genetic and nongenetic risk factors.History of RA among first-degree relatives of individuals in the Epidemiological Investigation of Rheumatoid Arthritis case-control study was assessed through linkage to the Swedish Multigeneration Register and the Swedish Patient Register. We used logistic regression models to investigate the decrease in familial risk after successive adjustment for combinations of nongenetic risk factors (smoking, alcohol intake, parity, silica exposure, body mass index, fatty fish consumption, and education), and genetic risk factors (shared epitope [SE] and 76 single-nucleotide polymorphisms [SNPs]).Established nongenetic risk factors did not explain familial risk of either seropositive or seronegative RA to any significant degree. Genetic risk factors accounted for a limited proportion of the familial risk of seropositive RA (unadjusted odds ratio [OR] 4.10, SE-adjusted OR 3.72, SNP-adjusted OR 3.46, and SE and SNP-adjusted OR 3.35).Established risk factors only provided an explanation for familial risk of RA in minor part, suggesting that many (familial) risk factors remain to be identified, in particular for seronegative RA. Family history of RA therefore remains an important clinical risk factor for RA, the value of which has not yet been superseded by other information. There is thus a need for further etiologic studies of both seropositive and seronegative RA.
mTOR signaling in glioblastoma: lessons learned from bench to bedside
Authors: D. Akhavan, T. F. Cloughesy, P. S. Mischel
Journal: Neuro-Oncology (2010)

Phosphatidyl-inositol-3 kinases (PI3Ks) constitute a family of intracellular lipid kinases that are frequently hyperactivated in glioblastoma. The PI3K complex links growth factor signaling with cellular proliferation, differentiation, metabolism, and survival. Mammalian target of rapamycin (mTOR) acts both as a downstream effector and upstream regulator of PI3K, thus highlighting its importance in glioblastoma. This review highlights laboratory and clinical evidence of mTOR's role in glioblastoma. Mechanisms of escape from mTOR inhibition are also discussed, as well as future clinical strategies of mTOR inhibition.