tbuckley/cabot-search huggingface dataset:
Oral Ganciclovir prophylaxis reduces cytomegalovirus disease during the first year after heart transplantation
Authors: G.M. Mullen, M.A. Silver, C.E. Lawless, J. Mendez, P.C. Barath, K. Malinowska, B.A. Pisani, P.J. O'Keefe, J.A. Robinson, V. Yeldandi
Journal: Journal of the American College of Cardiology (1998)
Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial
Authors: Matthew T Seymour, Lindsay C Thompson, Harpreet S Wasan, Gary Middleton, Alison E Brewster, Stephen F Shepherd, M Sinead O'Mahony, Timothy S Maughan, Mahesh Parmar, Ruth E Langley
Journal: The Lancet (2011)
The Relation Between Hospital Experience and In-Hospital Mortality for Patients With AIDS-Related PCP
Authors: Charles L. Bennett
Journal: JAMA (1989)

There is marked debate by physicians and policymakers regarding the creation of regionalized acquired immunodeficiency syndrome (AIDS) centers. A central issue is whether outcomes of care, particularly mortality, differ as a function of hospital experience with patients with AIDS. We evaluated the experience of 257 patients with AIDS and<i>Pneumocystis carinii</i>pneumonia treated at 15 California hospitals between October 1986 and October 1987. An overall 15.2% in-hospital mortality rate was observed. However, a markedly lower in-hospital mortality rate was observed in the group of patients treated at hospitals that had a high level of experience with patients with AIDS (≥30 human immunodeficiency virus-related discharges per 10 000 hospital discharges) relative to the group treated at hospitals with less experience (&lt;30 human immunodeficiency virus-related discharges per 10 000 hospital discharges): 12% vs 33%. Other factors significantly associated with in-hospital mortality included intensive care unit use, admission from an emergency department or through an interhospital transfer, and a history of hospitalizations. A logistic regression model indicated that, after controlling for severity indicators, AIDS experience remained significantly related to mortality. Our findings suggest that policymakers should consider three options: creating regional AIDS centers, implementing policies that promote a rapid but carefully monitored increase in experience of low-volume hospitals with human immunodeficiency virus-infected individuals, or providing highly focused educational efforts at low—AIDS-experience facilities. Without such policy initiatives, differences in mortality rates like those we have found might persist as cases of AIDS begin to occur in every area of the country. (<i>JAMA</i>1989;261:2975-2979)
Prospective Study of Bevacizumab Plus Temozolomide in Patients With Advanced Neuroendocrine Tumors
Authors: Jennifer A. Chan, Keith Stuart, Craig C. Earle, Jeffrey W. Clark, Pankaj Bhargava, Rebecca Miksad, Lawrence Blaszkowsky, Peter C. Enzinger, Jeffrey A. Meyerhardt, Hui Zheng, Charles S. Fuchs, Matthew H. Kulke
Journal: Journal of Clinical Oncology (2012)

Both tyrosine kinase inhibitors targeting the vascular endothelial growth factor (VEGF) receptor and bevacizumab, a monoclonal antibody targeting VEGF, have antitumor activity in neuroendocrine tumors (NETs). Temozolomide, an oral analog of dacarbazine, also has activity against NETs when administered alone or in combination with other agents. We performed a phase II study to evaluate the efficacy of temozolomide in combination with bevacizumab in patients with locally advanced or metastatic NETs.Thirty-four patients (56% with carcinoid, 44% with pancreatic NETs) were treated with temozolomide 150 mg/m(2) orally per day on days 1 through 7 and days 15 through 21, together with bevacizumab at a dose of 5 mg/kg per day intravenously on days 1 and 15 of each 28-day cycle. All patients received prophylaxis against Pneumocystis carinii and varicella zoster. Patients were followed for toxicity, biochemical and radiologic response, and survival.The combination of temozolomide and bevacizumab was associated with anticipated grade 3 to 4 toxicities, including lymphopenia (53%) and thrombocytopenia (18%). Although the overall radiographic response rate was 15% (five of 34), response rates differed between patients with pancreatic NETs (33%; five of 15) and those with carcinoid tumors (zero of 19). The median progression-free survival was 11.0 months (14.3 months for pancreatic NETs v 7.3 months for carcinoid tumors). The median overall survival was 33.3 months (41.7 months for pancreatic NETs v 18.8 months for carcinoid tumors).Temozolomide and bevacizumab can be safely administered together in patients with advanced NETs, and the combination regimen appears promising for patients with pancreatic NETs. Studies evaluating the relative contributions of these two agents to the observed antitumor activity are warranted.
Antitumor Activity of the Investigational Proteasome Inhibitor MLN9708 in Mouse Models of B-cell and Plasma Cell Malignancies
Authors: Edmund C. Lee, Michael Fitzgerald, Bret Bannerman, Jill Donelan, Kristen Bano, Jennifer Terkelsen, Daniel P. Bradley, Ozlem Subakan, Matthew D. Silva, Ray Liu, Michael Pickard, Zhi Li, Olga Tayber, Ping Li, Paul Hales, Mary Carsillo, Vishala T. Neppalli, Allison J. Berger, Erik Kupperman, Mark Manfredi, Joseph B. Bolen, Brian Van Ness, Siegfried Janz
Journal: Clinical Cancer Research (2011)

The clinical success of the first-in-class proteasome inhibitor bortezomib (VELCADE) has validated the proteasome as a therapeutic target for treating human cancers. MLN9708 is an investigational proteasome inhibitor that, compared with bortezomib, has improved pharmacokinetics, pharmacodynamics, and antitumor activity in preclinical studies. Here, we focused on evaluating the in vivo activity of MLN2238 (the biologically active form of MLN9708) in a variety of mouse models of hematologic malignancies, including tumor xenograft models derived from a human lymphoma cell line and primary human lymphoma tissue, and genetically engineered mouse (GEM) models of plasma cell malignancies (PCM).Both cell line-derived OCI-Ly10 and primary human lymphoma-derived PHTX22L xenograft models of diffuse large B-cell lymphoma were used to evaluate the pharmacodynamics and antitumor effects of MLN2238 and bortezomib. The iMyc(Cα)/Bcl-X(L) GEM model was used to assess their effects on de novo PCM and overall survival. The newly developed DP54-Luc-disseminated model of iMyc(Cα)/Bcl-X(L) was used to determine antitumor activity and effects on osteolytic bone disease.MLN2238 has an improved pharmacodynamic profile and antitumor activity compared with bortezomib in both OCI-Ly10 and PHTX22L models. Although both MLN2238 and bortezomib prolonged overall survival, reduced splenomegaly, and attenuated IgG2a levels in the iMyc(Cα)/Bcl-X(L) GEM model, only MLN2238 alleviated osteolytic bone disease in the DP54-Luc model.Our results clearly showed the antitumor activity of MLN2238 in a variety of mouse models of B-cell lymphoma and PCM, supporting its clinical development. MLN9708 is being evaluated in multiple phase I and I/II trials.
CKD and the Risk of Incident Cancer
Authors: William T. Lowrance, Juan Ordoñez, Natalia Udaltsova, Paul Russo, Alan S. Go
Journal: Journal of the American Society of Nephrology (2014)

Previous studies report a higher risk of cancer in patients with ESRD, but the impact of less severe CKD on risk of cancer is uncertain. Our objective was to evaluate the association between level of kidney function and subsequent cancer risk. We performed a retrospective cohort study of 1,190,538 adults who were receiving care within a health care delivery system, had a measurement of kidney function obtained between 2000 and 2008, and had no prior cancer. We examined the association between level of eGFR and the risk of incident cancer; the primary outcome was renal cancer, and secondary outcomes were any cancer and specific cancers (urothelial, prostate, breast, lung, and colorectal). During 6,000,420 person-years of follow-up, we identified 76,809 incident cancers in 72,875 subjects. After adjustment for time-updated confounders, lower eGFR (in milliliters per minute per 1.73 m2) was associated with an increased risk of renal cancer (adjusted hazard ratio [HR], 1.39; 95% confidence interval [95% CI], 1.22 to 1.58 for eGFR=45–59; HR, 1.81; 95% CI, 1.51 to 2.17 for eGFR=30–44; HR, 2.28; 95% CI, 1.78 to 2.92 for eGFR<30). We also observed an increased risk of urothelial cancer at eGFR<30 but no significant associations between eGFR and prostate, breast, lung, colorectal, or any cancer overall. In conclusion, reduced eGFR is associated with an independently higher risk of renal and urothelial cancer but not other cancer types.
Splenic Gas As a Result of a Non-Hodgkin's Lymphoma in a Patient With Common Variable Immunodeficiency
Authors: Frederik N. Croles, Konnie M. Hebeda, Gürsah Kats-Ugurlu, John J. Hermans, Han J. Bonenkamp, Walter J.F.M. van der Velden
Journal: Journal of Clinical Oncology (2011)
Clinical and <i>In vitro</i> Studies of Imatinib in Advanced Carcinoid Tumors
Authors: James C. Yao, Jun X. Zhang, Asif Rashid, Sai-Ching J. Yeung, Janio Szklaruk, Kenneth Hess, Keping Xie, Lee Ellis, James L. Abbruzzese, Jaffer A. Ajani
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Effective systemic therapy options for carcinoid tumors are lacking. We conducted in vitro studies and a phase II clinical trial to explore the activity of imatinib in carcinoid tumors. Experimental Design: Cells of the human bronchial carcinoid cell line NCI-H727 and the human pancreatic carcinoid cell line BON-1 were treated with increasing concentrations of imatinib using standard procedures to assess in vitro growth-inhibitory activity. A clinical trial using a two-stage phase II design to assess the response rate and safety profile of imatinib at a dose of 400 mg given twice daily in patients with advanced carcinoid tumors was completed. Results: In both cell lines, there was a dose- and time-dependent cytotoxic effect. The clinical trial enrolled 27 evaluable patients. Median duration on trial was 16 weeks. One patient had a partial response, 17 had stable disease, and 9 had progressive disease by the Response Evaluation Criteria in Solid Tumors criteria. Median progression-free survival time was 24 weeks. Median overall survival is 36 months. Seven patients who achieved a biochemical response had a superior progression-free survival time compared with patients without biochemical response (115 weeks compared with 24 weeks; P = 0.003). An increase in plasma basic fibroblast growth factor was associated with a shorter progression-free survival duration (P = 0.02). Conclusions: Our data suggest that imatinib is active in vitro and has a modest clinical activity in carcinoid patients. Changes in tumor markers may help select patients who are likely to benefit from therapy.
Correlation of immunoglobulin and C reactive protein levels in ankylosing spondylitis and rheumatoid arthritis.
Authors: K.M Sanders, A Hertzman, M.R Escobar, B.H Littman
Journal: Annals of the Rheumatic Diseases (1987)

Serum C reactive protein (CRP), IgG, and IgA levels were measured in 22 patients with ankylosing spondylitis (AS) and in 20 patients with rheumatoid arthritis (RA) to study the regulation of these proteins in inflammatory disease states. In both RA and AS the mean CRP, IgG, and IgA levels were raised above normal values. Although IgA and CRP levels showed a significant positive correlation in RA (r = 0.53, p = 0.02), there was no correlation between these values in AS (r = 0.24, p = 0.29). The difference in correlation coefficients between the AS and RA groups was significant at a p = 0.05 level. In RA the raised IgA levels may be another manifestation of the acute phase response, as shown by the good correlation between IgA and CRP in that disease. In AS, however, the IgA levels, although raised, do not correlate with CRP levels, suggesting that the mechanism of increase of IgA in the two diseases is different. Gut mediated immune stimulation has been proposed as a cause of raised IgA levels in AS.
Facilitating Informed Decisions Regarding Microsatellite Instability Testing Among High-Risk Individuals Diagnosed With Colorectal Cancer
Authors: Sharon L. Manne, Neal J. Meropol, David S. Weinberg, Hetal Vig, Zohra Ali-Khan Catts, Cheri Manning, Eric Ross, Kristen Shannon, Daniel C. Chung
Journal: Journal of Clinical Oncology (2010)

To evaluate the impact of a CD-ROM intervention in the education of patients with suspected Lynch syndrome (LS) about microsatellite instability (MSI) and immunohisochemistry (IHC) testing.Two hundred thirteen patients meeting Bethesda criteria were randomly assigned to receive either a brief educational session with a health educator (n = 105) or a brief educational session plus a CD-ROM (n = 108). Assessments were administered at baseline and 2 weeks post-treatment. Primary outcomes included MSI and IHC knowledge and level of satisfaction with and completeness of the preparation to make the decision for MSI testing. Secondary outcomes included decisional conflict, difficulty making the decision, cancer-specific and global anxiety, and level of discussion about MSI testing with family and friends.Participants in the education plus CD-ROM condition reported significant increases in knowledge about the MSI and IHC tests, greater satisfaction with the preparation to make a decision for testing, lower decisional conflict, and greater decisional self-efficacy. The effects of the education plus CD-ROM on most outcomes were not moderated by preintervention levels of exposure to MSI testing, family support for MSI testing, or the family history of cancer.Incorporation of new media education strategies for individuals at risk for LS may be a valuable component of the informed consent process. As clinical criteria for MSI and IHC testing continue to expand, the need for alternative educational approaches to meet this increased demand could be met by the self-administered computer-based strategy that we described.
Multidrug Resistance-Associated Proteins: Expression and Function in the Central Nervous System
Authors: Shannon Dallas, David S. Miller, Reina Bendayan
Journal: Pharmacological Reviews (2006)

Drug delivery to the brain is highly restricted, since compounds must cross a series of structural and metabolic barriers to reach their final destination, often a cellular compartment such as neurons, microglia, or astrocytes. The primary barriers to the central nervous system are the blood-brain and blood-cerebrospinal fluid barriers. Through structural modifications, including the presence of tight junctions that greatly limit paracellular transport, the cells that make up these barriers restrict diffusion of many pharmaceutically active compounds. In addition, the cells that comprise the blood-brain and blood-cerebrospinal fluid barriers express multiple ATP-dependent, membrane-bound, efflux transporters, such as members of the multidrug resistance-associated protein (MRP) family, which contribute to lowered drug accumulation. A relatively new concept in brain drug distribution just beginning to be explored is the possibility that cellular components of the brain parenchyma could act as a "second" barrier to brain permeation of pharmacological agents via expression of many of the same transporters. Indeed, efflux transporters expressed in brain parenchyma may facilitate the overall export of xenobiotics from the central nervous system, essentially handing themoff to the barrier tissues. We propose that these primary and secondary barriers work in tandem to limit overall accumulation and distribution of xenobiotics in the central nervous system. The present review summarizes recent knowledge in this area and emphasizes the clinical significance of MRP transporter expression in a variety of neurological disorders.
DNA Damage Primes the Type I Interferon System via the Cytosolic DNA Sensor STING to Promote Anti-Microbial Innate Immunity
Authors: Anetta Härtlova, Saskia F. Erttmann, Faizal AM. Raffi, Anja M. Schmalz, Ulrike Resch, Sharath Anugula, Stefan Lienenklaus, Lisa M. Nilsson, Andrea Kröger, Jonas A. Nilsson, Torben Ek, Siegfried Weiss, Nelson O. Gekara
Journal: Immunity (2015)
Identification of a heparin-binding hemagglutinin present in mycobacteria.
Authors: F D Menozzi, J H Rouse, M Alavi, M Laude-Sharp, J Muller, R Bischoff, M J Brennan, C Locht
Journal: The Journal of Experimental Medicine (1996)

Adherence to mammalian host tissues is an important virulence trait in microbial pathogenesis, yet little is known about the adherence mechanisms of mycobacteria. Here, we show that binding of mycobacteria to epithelial cells but not to macrophages can be specifically inhibited by sulfated carbohydrates. Using heparin-Sepharose chromatography, a 28-kD heparin-binding protein was purified from culture supernatants and cell extracts of Mycobacterium bovis and Mycobacterium tuberculosis. This protein, designated heparin-binding hemagglutinin (HBHA), promotes the agglutination of rabbit erythrocytes, which is specifically inhibited by sulfated carbohydrates. HBHA also induce mycobacterial aggregation, suggesting that it can mediate bacteria-bacteria interactions as well. Hemagglutination, mycobacterial aggregation, as well as attachment to epithelial cells are specifically inhibited in the presence of anti-HBHA antibodies. Immunoelectron microscopy using anti-HBHA monoclonal antibodies revealed that the protein is surface exposed, consistent with a role in adherence. Immunoblot analyses using antigen-specific antibodies indicated that HBHA is different from the fibronectin-binding proteins of the antigen 85 complex and p55, and comparison of the NH2-terminal amino acid sequence of purified HBHA with the protein sequence data bases did not reveal any significant similarity with other known proteins. Sera from tuberculosis patients but not from healthy individuals were found to recognize HBHA, indicating its immunogenicity in humans during mycobacterial infections. Identification of putative mycobacterial adhesins, such as the one described in this report, may provide the basis for the development of new therapeutic and prophylactic strategies against mycobacterial diseases.
Extended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda: an analysis of three randomised controlled trials
Authors: Six Week Extended-Dose Nevirapine (Swen) Study Team, Abubaker Bedri, Berhanu Gudetta, Abdulhamid Isehak, Solomon Kumbi, Sileshi Lulseged, Yohannes Mengistu, Arvind V Bhore, Ramesh Bhosale, Venkat Varadhrajan, Nikhil Gupte, Jayagowri Sastry, Nishi Suryavanshi, Srikanth Tripathy, Francis Mmiro, Michael Mubiru, Carolyne Onyango, Adrian Taylor, Philippa Musoke, Clemensia Nakabiito, Aida Abashawl, Rahel Adamu, Gretchen Antelman, Robert C Bollinger, Patricia Bright, Mohammad A Chaudhary, Jacqueline Coberly, Laura Guay, Mary Glenn Fowler, Amita Gupta, Elham Hassen, J Brooks Jackson, Lawrence H Moulton, Uma Nayak, Saad B Omer, Lidia Propper, Malathi Ram, Vivian Rexroad, Andrea J Ruff, Anita Shankar, Sheryl Zwerski
Journal: The Lancet (2008)
Does a Mailed Continuing Education Program Improve Physician Performance?
Authors: C. Edward Evans
Journal: JAMA (1986)

Evidence is sparse concerning the value of the "educational" materials that physicians receive in the mail. We conducted a randomized trial of a mailed continuing education program on hypertension for primary care physicians. Although formal pretesting documented that the program led to significant improvements in physician knowledge over the short term, the current study showed no lasting effect on physician knowledge (mean scores on an end-of-study questionnaire were 50% and 52% for study and control physicians, respectively) and no influence on performance in lowering the blood pressures of patients referred from screening (mean blood pressure drop for study patients, 12.2/10.4 mm Hg vs 13.0/10.6 mm Hg for control patients). The chance that we missed a difference in diastolic blood pressure as great as 3 mm Hg is less than 5%. Resources spent on instructional materials mailed to physicians may be wasted. (<i>JAMA</i>1986;255:501-504)
Super-resolution imaging reveals that loss of the C-terminus of connexin43 limits microtubule plus-end capture and NaV1.5 localization at the intercalated disc
Authors: Esperanza Agullo-Pascual, Xianming Lin, Alejandra Leo-Macias, Mingliang Zhang, Feng-Xia Liang, Zhen Li, Anna Pfenniger, Indra Lübkemeier, Sarah Keegan, David Fenyö, Klaus Willecke, Eli Rothenberg, Mario Delmar
Journal: Cardiovascular Research (2014)

AimsIt is well known that connexin43 (Cx43) forms gap junctions. We recently showed that Cx43 is also part of a protein-interacting network that regulates excitability. Cardiac-specific truncation of Cx43 C-terminus (mutant 'Cx43D378stop') led to lethal arrhythmias. Cx43D378stop localized to the intercalated disc (ID); cell–cell coupling was normal, but there was significant sodium current (INa) loss. We proposed that the microtubule plus-end is at the crux of the Cx43–INa relation. Yet, specific localization of relevant molecular players was prevented due to the resolution limit of fluorescence microscopy. Here, we use nanoscale imaging to establish: (i) the morphology of clusters formed by the microtubule plus-end tracking protein 'end-binding 1' (EB1), (ii) their position, and that of sodium channel alpha-subunit NaV1.5, relative to N-cadherin-rich sites, and (iii) the role of Cx43 C-terminus on the above-mentioned parameters and on the location-specific function of INa.
The evolution and impact of science in tennis: eight advances for performance and health
Authors: Babette M Pluim
Journal: British Journal of Sports Medicine (2014)

The effect of conjugated and unconjugated bile acids on the binding of vitamin B12 to intrinsic factor was investigated. The dihydroxy bile acids (deoxycholic, glycodeoxycholic, taurodeoxycholic, glycochenodeoxycholic, and taurochenodeoxycholic) inhibit the binding of intrinsic factor to vitamin B12 at physiological concentrations. On the other hand, the trihydroxy bile acids (cholic, glycocholic, and taurocholic) are not effective in this respect. The inhibition is dependent both on concentration and time, and its pattern is similar to that previously reported for duodenal juice. On column chromatography, there is a close correlation between the degree in intrinsic factor inhibition and the total acid concentration in the duodenal juice. The binding of vitamin B12 by R protein in saliva is not affected by bile acids. The results show that bile acids at concentrations found in duodenal juice inhibit intrinsic factor vitamin B12 binding. It is suggested that this observation may have physiological significance for vitamin B12 absorption.