tbuckley/cabot-search huggingface dataset:
Hemodialysis Infection Prevention with Polysporin Ointment
Authors: Charmaine E. Lok, Kenneth E. Stanley, Janet E. Hux, Robert Richardson, Sheldon W. Tobe, John Conly
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Hemodialysis patients in whom permanent vascular access cannot be achieved are dependent on a central venous catheter. In such patients, catheter-related infections are a common and serious complication. This study was a randomized clinical trial to determine if topical Polysporin Triple antibiotic ointment applied to the central venous catheter insertion site could reduce the incidence of catheter-related infections. A total of 169 patients receiving hemodialysis through a central venous catheter were randomized to receive Polysporin Triple or placebo using a double-blind study design. In the 6-mo study period, infections were observed in more patients in the placebo group than in the Polysporin Triple group (34 versus 12%; relative risk, 0.35; 95% CI, 0.18 to 0.68; P = 0.0013). The number of infections per 1000 catheter days (4.10 versus 1.02; P < 0.0001) and the number of bacteremias per 1000 catheter days (2.48 versus 0.63; P = 0.0004) were also greater in the placebo group. Within the 6-mo study period, there were 13 deaths in the placebo group as compared with 3 deaths in the Polysporin Triple group (P = 0.0041). When all available follow-up information was included, the difference in survival remained significant (19 versus 9 deaths; P = 0.0027). Within the first 6 mo, infections were observed in 7 of the 13 placebo subjects who died (54%) as compared with no infections in the three Polysporin Triple subjects who died. The prophylactic application of topical Polysporin Triple antibiotic ointment to the central venous catheter insertion site reduced the rate of infections and was associated with improved survival in hemodialysis patients. E-mail: [email protected]
AKAP150 signaling complex promotes suppression of the M-current by muscarinic agonists
Authors: Naoto Hoshi, Jia-Sheng Zhang, Miho Omaki, Takahiro Takeuchi, Shigeru Yokoyama, Nicolas Wanaverbecq, Lorene K Langeberg, Yukio Yoneda, John D Scott, David A Brown, Haruhiro Higashida
Journal: Nature Neuroscience (2003)
Systematic evaluation of connectivity map for disease indications
Authors: Jie Cheng, Lun Yang, Vinod Kumar, Pankaj Agarwal
Journal: Genome Medicine (2014)

Abstract Background Connectivity map data and associated methodologies have become a valuable tool in understanding drug mechanism of action (MOA) and discovering new indications for drugs. One of the key ideas of connectivity map (CMAP) is to measure the connectivity between disease gene expression signatures and compound-induced gene expression profiles. Despite multiple impressive anecdotal validations, only a few systematic evaluations have assessed the accuracy of this aspect of CMAP, and most of these utilize drug-to-drug matching to transfer indications across the two drugs. Methods To assess CMAP methodologies in a more direct setting, namely the power of classifying known drug-disease relationships, we evaluated three CMAP-based methods on their prediction performance against a curated dataset of 890 true drug-indication pairs. The disease signatures were generated using Gene Logic BioExpress™ system and the compound profiles were derived from the Connectivity Map database (CMAP, build 02, http://www.broadinstitute.org/CMAP/ ). Results The similarity scoring algorithm called eXtreme Sum (XSum) performs better than the standard Kolmogorov-Smirnov (KS) statistic in terms of the area under curve and can achieve a four-fold enrichment at 0.01 false positive rate level, with AUC = 2.2E-4, P value = 0.0035. Conclusion Connectivity map can significantly enrich true positive drug-indication pairs given an effective matching algorithm.
Phase II trial of PTK787/ZK 222584 (vatalanib) administered orally once-daily or in two divided daily doses as second-line monotherapy in relapsed or progressing patients with stage IIIB/IV non-small-cell lung cancer (NSCLC)
Authors: T.C. Gauler, B. Besse, A. Mauguen, J.B. Meric, V. Gounant, B. Fischer, T.R. Overbeck, H. Krissel, D. Laurent, M. Tiainen, F. Commo, J.C. Soria, W.E.E. Eberhardt
Journal: Annals of Oncology (2011)
Factor V Leiden mutation does not affect coagulopathy or outcome in lethal H1N1 influenza
Authors: M. Schouten, K.F. van der Sluijs, J.J.T.H. Roelofs, M. Levi, C. van't Veer, T. van der Poll
Journal: European Respiratory Journal (2010)

Influenza A is a major cause of mortality. Knowledge on coagulation activation in influenza infection is limited. The factor V Leiden (FVL) mutation is possibly subject to positive selection pressure. It is unknown whether this mutation impacts on the outcome of severe influenza. In the present study, the effect of lethal influenza on pulmonary and systemic coagulation activation and whether or not FVL mutation alters coagulation activation in and the course of lethal influenza, was determined. Wild-type mice, and mice heterozygous or homozygous for FVL were infected intranasally with a lethal dose of H1N1 (haemagglutinin 1 and neuraminidase 1) influenza A. Mice were sacrificed after 48 or 96 h for determination of coagulation activation, histopathology, pulmonary inflammatory parameters and viral load, or were observed in a survival study. Extensive local and systemic coagulation activation during lethal influenza was demonstrated by increased lung and plasma levels of thrombin–antithrombin complexes and fibrin degradation products, and by pulmonary fibrin deposition. FVL mutation did not influence the procoagulant response, lung histopathology or survival. FVL mice demonstrated elevated viral loads 48 h after infection. In conclusion, coagulation is activated locally and systemically during lethal murine influenza A infection. The FVL mutation does not influence coagulation activation, lung inflammation or survival in lethal influenza A.
American Society of Clinical Oncology 2003 Update on the Role of Bisphosphonates and Bone Health Issues in Women With Breast Cancer
Authors: Bruce E. Hillner, James N. Ingle, Rowan T. Chlebowski, Julie Gralow, Gary C. Yee, Nora A. Janjan, Jane A. Cauley, Brent A. Blumenstein, Kathy S. Albain, Allan Lipton, Susan Brown
Journal: Journal of Clinical Oncology (2003)

Purpose: To update the 2000 ASCO guidelines on the role of bisphosphonates in women with breast cancer and address the subject of bone health in these women. Results: For patients with plain radiographic evidence of bone destruction, intravenous pamidronate 90 mg delivered over 2 hours or zoledronic acid 4 mg over 15 minutes every 3 to 4 weeks is recommended. There is insufficient evidence supporting the efficacy of one bisphosphonate over the other. Starting bisphosphonates in women who demonstrate bone destruction through imaging but who have normal plain radiographs is considered reasonable treatment. Starting bisphosphonates in women with only an abnormal bone scan but without evidence of bone destruction is not recommended. The presence or absence of bone pain should not be a factor in initiating bisphosphonates. In patients with a serum creatinine less than 3.0 mg/dL (265 μmol/L), no change in dosage, infusion time, or interval is required. Infusion times less than 2 hours with pamidronate or less than 15 minutes with zoledronic acid should be avoided. Creatinine should be monitored before each dose of either agent in accordance with US Food and Drug Administration (FDA) labeling. Oncology professionals, especially medical oncologists, need to take an expanded role in the routine and regular assessment of the osteoporosis risk in women with breast cancer. The panel recommends an algorithm for patient management to maintain bone health. Conclusion: Bisphosphonates provide a supportive, albeit expensive and non–life-prolonging, benefit to many patients with bone metastases. Current research is focusing on bisphosphonates as adjuvant therapy. Although new data addressing when to stop therapy, alternative doses or schedules for administration, and how to best coordinate bisphosphonates with other palliative therapies are needed, they are not currently being investigated.
Runx2 transcriptome of prostate cancer cells: insights into invasiveness and bone metastasis
Authors: Sanjeev K Baniwal, Omar Khalid, Yankel Gabet, Ruchir R Shah, Daniel J Purcell, Deepak Mav, Alice E Kohn-Gabet, Yunfan Shi, Gerhard A Coetzee, Baruch Frenkel
Journal: Molecular Cancer (2010)

Prostate cancer (PCa) cells preferentially metastasize to bone at least in part by acquiring osteomimetic properties. Runx2, an osteoblast master transcription factor, is aberrantly expressed in PCa cells, and promotes their metastatic phenotype. The transcriptional programs regulated by Runx2 have been extensively studied during osteoblastogenesis, where it activates or represses target genes in a context-dependent manner. However, little is known about the gene regulatory networks influenced by Runx2 in PCa cells. We therefore investigated genome wide mRNA expression changes in PCa cells in response to Runx2.We engineered a C4-2B PCa sub-line called C4-2B/Rx2 dox, in which Doxycycline (Dox) treatment stimulates Runx2 expression from very low to levels observed in other PCa cells. Transcriptome profiling using whole genome expression array followed by in silico analysis indicated that Runx2 upregulated a multitude of genes with prominent cancer associated functions. They included secreted factors (CSF2, SDF-1), proteolytic enzymes (MMP9, CST7), cytoskeleton modulators (SDC2, Twinfilin, SH3PXD2A), intracellular signaling molecules (DUSP1, SPHK1, RASD1) and transcription factors (Sox9, SNAI2, SMAD3) functioning in epithelium to mesenchyme transition (EMT), tissue invasion, as well as homing and attachment to bone. Consistent with the gene expression data, induction of Runx2 in C4-2B cells enhanced their invasiveness. It also promoted cellular quiescence by blocking the G1/S phase transition during cell cycle progression. Furthermore, the cell cycle block was reversed as Runx2 levels declined after Dox withdrawal.The effects of Runx2 in C4-2B/Rx2 dox cells, as well as similar observations made by employing LNCaP, 22RV1 and PC3 cells, highlight multiple mechanisms by which Runx2 promotes the metastatic phenotype of PCa cells, including tissue invasion, homing to bone and induction of high bone turnover. Runx2 is therefore an attractive target for the development of novel diagnostic, prognostic and therapeutic approaches to PCa management. Targeting Runx2 may prove more effective than focusing on its individual downstream genes and pathways.
Excess mortality rates in a cohort of patients infected with the hepatitis C virus: a prospective study
Authors: K. R Neal
Journal: Gut (2007)

We analysed the Trent Hepatitis C cohort to determine standardised mortality ratios in patients infected with hepatitis C virus (HCV), and to identify risk factors and associations with all-cause and liver-related mortality.Cohort study.Patients with HCV infection attending secondary care within the Trent region of England.2285 patients with hepatitis C, followed for 1 year or more.The death rate in the cohort was compared to that seen in an age- and sex-matched English population. We performed Cox regression analyses to identify factors predictive of all-cause mortality and deaths from liver disease.Standardised mortality ratios in the cohort were three times higher than those expected in the general population of England. The excess deaths were due to liver-related causes and those associated with a drug-using lifestyle. Significant independent predictors of all-cause mortality were age, sex, treatment (protective) and liver biopsy fibrosis. Age, treatment, liver biopsy fibrosis and mean alcohol consumption were predictors of liver-related mortality. HCV was mentioned on 23% of death certificates overall, and on 52% of those of patients dying from a liver-related cause.Our findings demonstrate that the death rate in patients infected with hepatitis C is three times higher than expected. Severity of disease is associated with a worse prognosis, whilst treatment improves outcome, particularly in those who respond. Use of death certificate data on HCV infection for planning purposes will result in considerable under-estimation of the HCV-related disease burden.
Accelerated Approval of Oncology Products: The Food and Drug Administration Experience
Authors: John R. Johnson, Yang-Min Ning, Ann Farrell, Robert Justice, Patricia Keegan, Richard Pazdur
Journal: JNCI Journal of the National Cancer Institute (2011)

We reviewed the regulatory history of the accelerated approval process and the US Food and Drug Administration (FDA) experience with accelerated approval of oncology products from its initiation in December 11, 1992, to July 1, 2010. The accelerated approval regulations allowed accelerated approval of products to treat serious or life-threatening diseases based on surrogate endpoints that are reasonably likely to predict clinical benefit. Failure to complete postapproval trials to confirm clinical benefit with due diligence could result in removal of the accelerated approval indication from the market. From December 11, 1992, to July 1, 2010, the FDA granted accelerated approval to 35 oncology products for 47 new indications. Clinical benefit was confirmed in postapproval trials for 26 of the 47 new indications, resulting in conversion to regular approval. The median time between accelerated approval and regular approval of oncology products was 3.9 years (range = 0.8–12.6 years) and the mean time was 4.7 years, representing a substantial time savings in terms of earlier availability of drugs to cancer patients. Three new indications did not show clinical benefit when confirmatory postapproval trials were completed and were subsequently removed from the market or had restricted distribution plans implemented. Confirmatory trials were not completed for 14 new indications. The five longest intervals from receipt of accelerated approval to July 1, 2010, without completion of trials to confirm clinical benefit were 10.5, 6.4, 5.5, 5.5, and 4.7 years. The five longest intervals between accelerated approval and successful conversion to regular approval were 12.6, 9.7, 8.1, 7.5, and 7.4 years. Trials to confirm clinical benefit should be part of the drug development plan and should be in progress at the time of an application seeking accelerated approval to prevent an ineffective drug from remaining on the market for an unacceptable time.
Loss of Heterozygosity 1p36 and 19q13 Is a Prognostic Factor for Overall Survival in Patients With Diffuse WHO Grade 2 Gliomas Treated Without Chemotherapy
Authors: Luigi Mariani, Gianluca Deiana, Erik Vassella, Ali-Reza Fathi, Christine Murtin, Marlène Arnold, Istvan Vajtai, Joachim Weis, Peter Siegenthaler, Martina Schobesberger, Michael M. Reinert
Journal: Journal of Clinical Oncology (2006)

Purpose This study was conducted to elucidate the impact of loss of heterozygosity (LOH) for chromosomes 1p36 and 19q13 on the overall survival of patients with diffusely infiltrating WHO grade 2 gliomas treated without chemotherapy. Patients and Methods We assessed the LOH status of tumors from patients harboring WHO grade 2 gliomas diagnosed between 1991 and 2000. Patients were either followed after initial biopsy or treated by surgery and/or radiation therapy (RT). Overall survival, time to malignant transformation, and progression-free survival were last updated as of March 2005. Results Of a total of 79 patients, LOH 1p36 and LOH 19q13 could be assessed in 67 and 66 patients, respectively. The median follow-up after diagnosis was 6 years. Loss of either 1p or 19q, in particular codeletion(s) at both loci, was found to positively impact on both overall survival (log-rank P &lt; .01), progression-free survival, and survival without malignant transformation (P &lt; .05). Tumor volume (P &lt; .0001), neurologic deficits at diagnosis (P &lt; .01), involvement of more than one lobe (P &lt; .01), and absence of an oligodendroglial component (P &lt; .05) were also predictors of shorter overall survival. The extent of surgery was similar in patients with or without LOH 1p and/or 19q; RT was more frequently resorted to for patients without than for patients with LOH 1p/19q (30% v 60%). Conclusion The presence of LOH on either 1p36 or 19q13, and in particular codeletion of both loci is a strong, nontreatment-related, prognostic factor for overall survival in patients with diffusely infiltrating WHO grade 2 gliomas.
Type 2 Diabetes and Subsequent Incidence of Breast Cancer in the Nurses’ Health Study
Authors: Karin B. Michels, Caren G. Solomon, Frank B. Hu, Bernard A. Rosner, Susan E. Hankinson, Graham A. Colditz, JoAnn E. Manson
Journal: Diabetes Care (2003)

OBJECTIVE—Hyperinsulinemia may promote mammary carcinogenesis. Insulin resistance has been linked to an increased risk of breast cancer and is also characteristic of type 2 diabetes. We prospectively evaluated the association between type 2 diabetes and invasive breast cancer incidence in the Nurses’ Health Study. RESEARCH DESIGN AND METHODS—A total of 116,488 female nurses who were 30–55 years old and free of cancer in 1976 were followed through 1996 for the occurrence of type 2 diabetes and through 1998 for incident invasive breast cancer, verified by medical records and pathology reports. RESULTS—During 2.3 million person-years of follow-up, we identified 6,220 women with type 2 diabetes and 5,189 incident cases of invasive breast cancer. Women with type 2 diabetes had a modestly elevated incidence of breast cancer (hazard ratio [HR] = 1.17; 95% CI 1.01–1.35) compared with women without diabetes, independent of age, obesity, family history of breast cancer, history of benign breast disease, reproductive factors, physical activity, and alcohol consumption. This association was apparent among postmenopausal women (1.16; 0.98–1.62) but not premenopausal women (0.83; 0.48–1.42). The association was predominant among women with estrogen receptor-positive breast cancer (1.22; 1.01–1.47). CONCLUSIONS—Women with type 2 diabetes may have a slightly increased risk of breast cancer.
<i>The CRP</i> and <i>GDNF</i> Genes Do Not Contribute to Apnea–Hypopnea Index or Risk of Obstructive Sleep Apnea
Authors: Thorarinn Gislason, Allan I. Pack, Hafdis T. Helgadottir, Kari Stefansson, Sören Besenbacher, Ingileif Jonsdottir
Journal: American Journal of Respiratory and Critical Care Medicine (2011)
4 ONCE DAILY ALISPORIVIR (DEB025) PLUS PEGIFNALFA2A/RIBAVIRIN RESULTS IN SUPERIOR SUSTAINED VIROLOGIC RESPONSE (SVR24) IN CHRONIC HEPATITIS C GENOTYPE 1 TREATMENT NAIVE PATIENTS
Authors: R. Flisiak, J.-M. Pawlotsky, R. Crabbé, P.I. Calistru, W. Kryczka, D. Haüssinger, G. Mazzella, M. Romero-Gomez, D. Purcea, G. Vuagniaux, W. Bao, C. Avila, S. Zeuzem
Journal: Journal of Hepatology (2011)
Lentigo-maligna melanoma: an ultrastructural study
Authors: S.S. Bleehen, Lisa Hartley, Jennifer Senior
Journal: British Journal of Dermatology (2006)

Journal Article Lentigo‐maligna melanoma: an ultrastructural study Get access S.S. Bleehen, S.S. Bleehen Department of Dermatology, Hallamshire Hospital and University of Sheffield Search for other works by this author on: Oxford Academic Google Scholar Lisa Hartley, Lisa Hartley Department of Dermatology, Hallamshire Hospital and University of Sheffield Search for other works by this author on: Oxford Academic Google Scholar Jennifer Senior Jennifer Senior Department of Dermatology, Hallamshire Hospital and University of Sheffield Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 95, Issue s14, 1 December 1976, Pages 14–15, https://doi.org/10.1111/j.1365-2133.1976.tb07884.x Published: 01 December 1976
Impact of Ethnicity on Primary Treatment Choice and Mortality in Men With Prostate Cancer: Data From CaPSURE
Authors: Kelvin A. Moses, Alan T. Paciorek, David F. Penson, Peter R. Carroll, Viraj A. Master
Journal: Journal of Clinical Oncology (2010)

PURPOSE Men diagnosed with prostate cancer have multiple options available for treatment. Previous reports have indicated a trend of differing modalities of treatment chosen by African American and white men. We investigated the role of ethnicity in primary treatment choice and how this affected overall and cancer-specific mortality. METHODS By utilizing data abstracted from Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), patients were compared by ethnicity, primary treatment, number of comorbidities, risk level according to modified D'Amico criteria, age, highest educational level attained, type of insurance, treatment facility, and perception of general health. Multinomial logistic regression analysis was performed to determine the effect of the tested variables on primary treatment and mortality. Results African American men were more likely to receive nonsurgical therapy than white men with equivalent disease characteristics. Whites were 48% less likely than African Americans to receive androgen deprivation therapy (ADT) compared with surgery (P = .02) and were 25% less likely than African Americans to receive radiation therapy compared with surgery (P = .08). Whites with low-risk disease were 71% less likely to receive ADT than African American men with similar disease (P = .01). Adjusted overall and prostate cancer-specific mortality were not significantly different between whites and African Americans (hazard ratios, 0.73 and 0.37, respectively). Risk level, type of treatment, and type of insurance had the strongest effects on risk of mortality. CONCLUSION There is a statistically significant difference in primary treatment for prostate cancer between African American and white men with similar risk profiles. Additional research on the influence of patient/physician education and perception and the role that socioeconomic factors play in mortality from prostate cancer may be areas of focus for public health initiatives.
Novel aspects of the pathogenesis of aneurysms of the abdominal aorta in humans
Authors: J.-B. Michel, J.-L. Martin-Ventura, J. Egido, N. Sakalihasan, V. Treska, J. Lindholt, E. Allaire, U. Thorsteinsdottir, G. Cockerill, J. Swedenborg
Journal: Cardiovascular Research (2010)

Aneurysm of the abdominal aorta (AAA) is a particular, specifically localized form of atherothrombosis, providing a unique human model of this disease. The pathogenesis of AAA is characterized by a breakdown of the extracellular matrix due to an excessive proteolytic activity, leading to potential arterial wall rupture. The roles of matrix metalloproteinases and plasmin generation in progression of AAA have been demonstrated both in animal models and in clinical studies. In the present review, we highlight recent studies addressing the role of the haemoglobin-rich, intraluminal thrombus and the adventitial response in the development of human AAA. The intraluminal thrombus exerts its pathogenic effect through platelet activation, fibrin formation, binding of plasminogen and its activators, and trapping of erythrocytes and neutrophils, leading to oxidative and proteolytic injury of the arterial wall. These events occur mainly at the intraluminal thrombus-circulating blood interface, and pathological mediators are conveyed outwards, where they promote matrix degradation of the arterial wall. In response, neo-angiogenesis, phagocytosis by mononuclear cells, and a shift from innate to adaptive immunity in the adventitia are observed. Abdominal aortic aneurysm thus represents an accessible spatiotemporal model of human atherothrombotic progression towards clinical events, the study of which should allow further understanding of its pathogenesis and the translation of pathogenic biological activities into diagnostic and therapeutic applications.