tbuckley/cabot-search huggingface dataset:
Validation of Reported Predialysis Nephrology Care of Older Patients Initiating Dialysis
Authors: Jane Paik Kim, Manisha Desai, Glenn M. Chertow, Wolfgang C. Winkelmayer
Journal: Journal of the American Society of Nephrology (2012)

The Centers for Medicare and Medicaid Services (CMS) Medical Evidence Report (form CMS-2728) queries providers about the timing of the patient's first nephrologist consultation before initiation of dialysis. The monitoring of disease-specific goals in the Healthy People 2020 initiative will use information from this question, but the accuracy of the reported information is unknown. We defined a cohort of 80,509 patients aged ≥67 years who initiated dialysis between July 2005 and December 2008 with ≥2 years of uninterrupted Medicare coverage as their primary payer. The primary referent, determined from claims data, was the first observed outpatient nephrologist consultation; secondary analyses used the earliest nephrology consultation, whether inpatient or outpatient. We used linear regression models to assess the associations among the magnitude of discrepant reporting and patient characteristics and we tested for any temporal trends. When using the earliest recorded outpatient nephrology encounter, agreement between the two sources of ascertainment was 48.2%, and the κ statistic was 0.29 when we categorized the timing of the visit into four periods (never, <6, 6–12, and >12 months). When we dichotomized the timing of first predialysis nephrology care at >12 or ≤12 months, accuracy was 70% (κ=0.36), but it differed by patient characteristics and declined over time. In conclusion, we found substantial disagreement between information from the CMS Medical Evidence Report and Medicare physician claims on the timing of first predialysis nephrologist care. More-specific instructions may improve reporting and increase the utility of form CMS-2728 for research and public health surveillance.
Toward determining the lifetime occurrence of metastatic brain tumors estimated from 2007 United States cancer incidence data
Authors: Faith G. Davis, Therese A. Dolecek, Bridget J. McCarthy, John L. Villano
Journal: Neuro-Oncology (2012)

Few population estimates of brain metastasis in the United States are available, prompting this study. Our objective was to estimate the expected number of metastatic brain tumors that would subsequently develop among incident cancer cases for 1 diagnosis year in the United States. Incidence proportions for primary cancer sites known to develop brain metastasis were applied to United States cancer incidence data for 2007 that were retrieved from accessible data sets through Centers for Disease Control and Prevention (CDC Wonder) and Surveillance, Epidemiology, and End Results (SEER) Program Web sites. Incidence proportions were identified for cancer sites, reflecting 80% of all cancers. It was conservatively estimated that almost 70 000 new brain metastases would occur over the remaining lifetime of individuals who received a diagnosis in 2007 of primary invasive cancer in the United States. That is, 6% of newly diagnosed cases of cancer during 2007 would be expected to develop brain metastasis as a progression of their original cancer diagnosis; the most frequent sites for metastases being lung and bronchus and breast cancers. The estimated numbers of brain metastasis will be expected to be higher among white individuals, female individuals, and older age groups. Changing patterns in the occurrence of primary cancers, trends in populations at risk, effectiveness of treatments on survival, and access to those treatments will influence the extent of brain tumor metastasis at the population level. These findings provide insight on the patterns of brain tumor metastasis and the future burden of this condition in the United States.
Identification of Podocalyxin-like Protein as a High Endothelial Venule Ligand for L-selectin: Parallels to CD34
Authors: Christopher Sassetti, Kirsten Tangemann, Mark S. Singer, David B. Kershaw, Steven D. Rosen
Journal: The Journal of Experimental Medicine (1998)

The leukocyte adhesion molecule, L-selectin, mediates the recruitment of lymphocytes to secondary lymphoid organs via interactions with specific ligands presented on high endothelial venules (HEV). Although the HEV-derived ligands for L-selectin are still incompletely defined, they share a common sialomucin-like structure which is thought to present clustered oligosaccharides to the lectin domain of L-selectin. Podocalyxin-like protein (PCLP) is a transmembrane sialomucin that is similar in structure to the well-characterized L-selectin ligand CD34. PCLP has been shown previously to be expressed on the foot processes of podocytes in the kidney glomerulus as well as on vascular endothelium at some sites. We have determined that PCLP is present on HEV, where it binds to both recombinant L-selectin and the HEV-specific monoclonal antibody MECA-79. Furthermore, purified HEV-derived PCLP is able to support the tethering and rolling of lymphocytes under physiological flow conditions in vitro. These results suggest a novel function for PCLP as an adhesion molecule and allow the definition of conserved structural features in PCLP and CD34, which may be important for L-selectin ligand function.
Influenza- and respiratory syncytial virus-associated mortality and hospitalisations
Authors: A. G. S. C. Jansen, E. A. M. Sanders, A. W. Hoes, A. M. van Loon, E. Hak
Journal: European Respiratory Journal (2007)

The aim of the current study was to estimate influenza- and respiratory syncytial virus (RSV)-associated mortality and hospitalisations, especially the influenza-associated burden among low-risk individuals < or =65 yrs old, not yet recommended for influenza vaccination in many European countries. Retrospectively during 1997-2003, Dutch national all-cause mortality and hospital discharge figures and virus surveillance data were used to estimate annual average influenza- and RSV-associated excess mortality and hospitalisation using rate difference methods. Influenza virus active periods were significantly associated with excess mortality among 50-64-yr-olds and the elderly, but not in younger age categories. Influenza-associated hospitalisation was highest and about equal for 0-1-yr-olds and the elderly, and also significant for low-risk adults. Hospitalisation among children was mostly due to respiratory conditions, and among adults cardiovascular complications were frequent. RSV-active periods were associated with excess mortality and hospitalisation among the elderly. The highest RSV-related excess hospitalisation was found in 0-1-yr-olds. Influenza-associated mortality was demonstrated in 50-64-yr-olds. Among low-risk individuals < or =65 yrs of age, influenza-associated hospitalisation rates were highest for 0-4-yr-olds, but also significant for 5-64-yr-olds. These data may further support extension of recommendations for influenza vaccination to include younger low-risk persons. The respiratory syncytial virus-associated burden was highest for young children but also substantial for the elderly.
Long-Term Safety, Tolerability, and Weight Loss Associated With Metformin in the Diabetes Prevention Program Outcomes Study
Authors: George A. Bray, Sharon L. Edelstein, Jill P. Crandall, Vanita R. Aroda, Paul W. Franks, Wilfred Fujimoto, Edward Horton, Susan Jeffries, Maria G Montez, Sunder Mudaliar, F. Xavier Pi-Sunyer, Neil H. White, William C. Knowler
Journal: Diabetes Care (2012)

Metformin produced weight loss and delayed or prevented diabetes in the Diabetes Prevention Program (DPP). We examined its long-term safety and tolerability along with weight loss, and change in waist circumference during the DPP and its long-term follow-up.The randomized double-blind clinical trial of metformin or placebo followed by a 7-8-year open-label extension and analysis of adverse events, tolerability, and the effect of adherence on change in weight and waist circumference.No significant safety issues were identified. Gastrointestinal symptoms were more common in metformin than placebo participants and declined over time. During the DPP, average hemoglobin and hematocrit levels were slightly lower in the metformin group than in the placebo group. Decreases in hemoglobin and hematocrit in the metformin group occurred during the first year following randomization, with no further changes observed over time. During the DPP, metformin participants had reduced body weight and waist circumference compared with placebo (weight by 2.06 ± 5.65% vs. 0.02 ± 5.52%, P < 0.001, and waist circumference by 2.13 ± 7.06 cm vs. 0.79 ± 6.54 cm, P < 0.001 in metformin vs. placebo, respectively). The magnitude of weight loss during the 2-year double-blind period was directly related to adherence (P < 0.001). Throughout the unblinded follow-up, weight loss remained significantly greater in the metformin group than in the placebo group (2.0 vs. 0.2%, P < 0.001), and this was related to the degree of continuing metformin adherence (P < 0.001).Metformin used for diabetes prevention is safe and well tolerated. Weight loss is related to adherence to metformin and is durable for at least 10 years of treatment.
Pharmacogenomic and Pharmacokinetic Determinants of Erlotinib Toxicity
Authors: Charles M. Rudin, Wanqing Liu, Apurva Desai, Theodore Karrison, Xuemin Jiang, Linda Janisch, Soma Das, Jacqueline Ramirez, Balasubramanian Poonkuzhali, Erin Schuetz, Donna Lee Fackenthal, Peixian Chen, Deborah K. Armstrong, Julie R. Brahmer, Gini F. Fleming, Everett E. Vokes, Michael A. Carducci, Mark J. Ratain
Journal: Journal of Clinical Oncology (2008)

Purpose To assess the pharmacogenomic and pharmacokinetic determinants of skin rash and diarrhea, the two primary dose-limiting toxicities of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib. Patients and Methods A prospective clinical study of 80 patients with non–small-cell lung cancer, head and neck cancer, and ovarian cancer was performed. Detailed pharmacokinetics and toxicity of erlotinib were assessed. Polymorphic loci in EGFR, ABCG2, CYP3A4, and CYP3A5 were genotyped, and their effects on pharmacokinetics and toxicities were evaluated. Results A novel diplotype of two polymorphic loci in the ABCG2 promoter involving −15622C/T and 1143C/T was identified, with alleles conferring lower ABCG2 levels associated with higher erlotinib pharmacokinetic parameters, including area under the curve (P = .019) and maximum concentration (P = .006). Variability in skin rash was best explained by a multivariate logistic regression model incorporating the trough erlotinib plasma concentration (P = .034) and the EGFR intron 1 polymorphism (P = .044). Variability in diarrhea was associated with the two linked polymorphisms in the EGFR promoter (P &lt; .01), but not with erlotinib concentration. Conclusion Although exploratory in nature, this combined pharmacogenomic and pharmacokinetic model helps to define and differentiate the primary determinants of skin and gastrointestinal toxicity of erlotinib. The findings may be of use both in designing trials targeting a particular severity of rash and in considering dose and schedule modifications in patients experiencing dose-limiting toxicities of erlotinib or similarly targeted agents. Further studies of the relationship between germline polymorphisms in EGFR and the toxicity and efficacy of EGFR inhibitors are warranted.
Net Clinical Benefit Analysis of Radiation Therapy Oncology Group 0525: A Phase III Trial Comparing Conventional Adjuvant Temozolomide With Dose-Intensive Temozolomide in Patients With Newly Diagnosed Glioblastoma
Authors: Terri S. Armstrong, Jeffrey S. Wefel, Meihua Wang, Mark R. Gilbert, Minhee Won, Andrew Bottomley, Tito R. Mendoza, Corneel Coens, Maria Werner-Wasik, David G. Brachman, Ali K. Choucair, Minesh Mehta
Journal: Journal of Clinical Oncology (2013)

Radiation Therapy Oncology Group trial 0525 tested whether dose-intensifying temozolomide versus standard chemoradiotherapy improves overall survival (OS) or progression-free survival (PFS) in newly diagnosed glioblastoma. Tests of neurocognitive function (NCF) and symptoms (using the MD Anderson Symptom Inventory-Brain Tumor module; MDASI-BT) and of quality of life (European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ] -C30/BN20) examined the net clinical benefit (NCB) of therapy.NCF tests (Hopkins Verbal Learning Test-Revised, Trail Making Test, and Controlled Oral Word Association), MDASI-BT, and EORTC QLQ-C30/BN20 were completed in a subset of patients. Multivariate Cox proportional hazard regression modeling determined the prognostic value of baseline and early change from baseline to cycle 1 for OS and PFS. Two-sample proportional test statistic was used to evaluate differences between treatments (dose-dense v standard-dose) on NCB measures from baseline to cycle 4 in stable patients.Overall, 182 patients participated in the study. Baseline NCF tests and the physical functioning quality of life scale were associated with OS and PFS. Baseline to cycle 1 in all NCB components were associated with OS and PFS. There was greater deterioration in the dose-dense arm from baseline to cycle 4 in the Global Health and Motor Function subscales (EORTC QLQ-C30/BN20) as well as in overall symptom burden, overall symptom interference, and activity-related symptom interference subscales (MDASI-BT). There were no between-arm differences in NCF.Longitudinal collection of NCB measures is feasible in cooperative group studies and provides an added dimension to standard outcome measures. Greater adverse symptom burden and functional interference, as well as decreased global health and motor function were observed in patients randomly assigned to the dose-dense arm. Baseline and early change in NCB measures were associated with decreased rates of survival.
The CIBERES Pulmonary Biobank Consortium: an opportunity for cooperative international respiratory research
Authors: C. Villena, F. Pozo, J.A. Barberà, P. Vaquer, A. Agusti
Journal: European Respiratory Journal (2010)

To the Editors:

Research into the pathogenesis of diseases often requires access to appropriate tissue specimens 1. The lung is not an easily accessible organ. Hence, respiratory research is often hampered by the lack of a large number of adequately preserved lung samples harvested from patients whose phenotype had been carefully and consistently characterised 2.

Since 2006, the Spanish government has funded a national network for respiratory research (CIBERES), which is currently formed of 34 research groups working cooperatively on the investigation of basic, clinical and epidemiological aspects of the main respiratory diseases (www.ciberes.org) 3. To facilitate translational respiratory research, CIBERES has taken advantage of its multicentric nature and has designed, organised and established a nonprofit CIBERES Pulmonary Biobank Consortium (CPBC) that follows the recommendations of the International Society for Biological and Environmental Repositories 4 and Organisation for Economic Co-operation and Development 5. The CPBC initiative is fully funded by public, competitive research funds, and is similar to the Lung Tissue Research Consortium …
Comparison of transcriptomes of mesenchymal stem cell lines derived from amniotic fluid, amniotic membrane, cord blood, and bone marrow
Authors: Tzu-Hao H. Wang, Shiaw-Min M. Hwang, Kuan-Den D. Chen, Yun-Shien S. Lee, Hsin-Shih S. Wang
Journal: Clinical Cancer Research (2006)

A73  Multipotent mesenchymal stem cells (MSCs) are the promising resource of cells for cell-based therapeutics, because of their ability to self-renew and differentiate into functional cell types. MSCs have been used to delivery of interferon beta to tumors and suppress the growth of pulmonary metastases, suggesting that MSC may be an effective platform for the targeted delivery of therapeutic proteins to cancer sites.High-throughput, genome-wide analyses of transcriptome have been recently used to identify the characteristics of human umbilical cord blood-derived MSC, murine MSC, mouse embryonic stem cells and adult stem cells, and human cord blood-derived CD133+ cells. It is interesting to determine both the core transcriptome in all MSCs and the individual signature gene expression profile in each group of MSC cell lines derived from different origins. Using high-density oligonucleotide microarrays in this study, we have compared gene expression profiles of 4 groups of human MSC cells that were isolated from amniotic fluid, amniotic membrane, fetal umbilical cord blood, and adult bone marrow. Furthermore, we contrasted the gene expression profiles of all MSC lines to those in six human fetal organs (brain, heart, lung, liver, kidney, muscle). We have identified (i) a stable gene expression profile in individual human MSC line during in vitro culture between passages 6 to 10, (ii) that each group of MSC lines derived from 4 origins exhibited their signature expression profile, and (iii) that all human MSC lines expressed a core MSC profile distinct from that of various fetal organs. Results of this study provide essential expression profiles about MSCs in general and derived from various sources, respectively. The information may become instrumental for us during the development of effective strategies of cell-based cancer therapeutics.
Patterns of failure, prognostic factors and survival in locoregionally advanced head and neck cancer treated with concomitant chemoradiotherapy: a 9-year, 337-patient, multi-institutional experience
Authors: B. Brockstein, D.J. Haraf, A.W. Rademaker, M.S. Kies, K.M. Stenson, F. Rosen, B.B. Mittal, H. Pelzer, B.B. Fung, M.-E. Witt, B. Wenig, L. Portugal, R.W. Weichselbaum, E.E. Vokes
Journal: Annals of Oncology (2004)
Pioglitazone-Induced Acute Rhabdomyolysis
Authors: Raoudha Slim, Chaker Ben Salem, Michele Zamy, Michel Biour
Journal: Diabetes Care (2009)

ioglitazone, a peroxisome proliferator-activated receptor ␥ agonist, is a relatively new oral antidiabetes agent.It has been shown to decrease insulin resistance in patients with type 2 diabetes, resulting in lowered blood glucose concentrations and A1C values.It can be used alone or in combination with metformin or a sulfonylurea.The adverse effects of pioglitazone include weight gain, headache, and edema.We report here a case of a patient who developed severe acute rhabdomyolysis after receiving pioglitazone.A 52-yearold man had a 2-year history of type 2 diabetes that was treated with gliclazide (60 mg/day).Six weeks after addition for pioglitazone (15 mg/day), the patient was admitted to hospital for 4 days for myalgia and severe muscle weakness.He had no recent viral illness or other complaints.He denied any change from his normal level of activity.No alcohol ingestion, illicit drugs, unprescribed medication use, or trauma was present.A physical examination revealed severe proximal muscle weakness and tenderness affecting all four limbs.Laboratory tests showed marked increases in the serum creatinine phosphokinase (9,851 IU/l [normal limit 150 IU/l]), serum myoglobin, and aspartate aminotransferase (98 IU/l) levels.His creatinine serum level was normal at 60 mol/l.There were no signs of severe hyperglycemia, diabetic ketoacidosis, hypokalemia, or hypophosphatemia.Autoantibody screening and viral serologies were negative.Thyroid function was normal.
Protective role of metallothionein in acute lung injury induced by bacterial endotoxin
Authors: H Takano
Journal: Thorax (2004)

Metallothionein (MT) is a protein that can be induced by inflammatory mediators and participate in cytoprotection. However, its role in inflammation remains to be established. A study was undertaken to determine whether intrinsic MT protects against acute inflammatory lung injury induced by bacterial endotoxin in MT-I/II knock out (-/-) and wild type (WT) mice.MT (-/-) and WT mice were given vehicle or lipopolysaccharide (LPS, 125 microg/kg) intratracheally and the cellular profile of the bronchoalveolar lavage (BAL) fluid, pulmonary oedema, lung histology, expression of proinflammatory molecules, and nuclear localisation of nuclear factor-kappaB (NF-kappaB) in the lung were evaluated.MT (-/-) mice were more susceptible than WT mice to lung inflammation, especially to lung oedema induced by intratracheal challenge with LPS. After LPS challenge, MT deficiency enhanced vacuolar degeneration of pulmonary endothelial cells and type I alveolar epithelial cells and caused focal loss of the basement membrane. LPS treatment caused no significant differences in the enhanced expression of proinflammatory cytokines and chemokines nor in the activation of the NF-kappaB pathway in the lung between the two genotypes. Lipid peroxide levels in the lungs were significantly higher in LPS treated MT (-/-) mice than in LPS treated WT mice.Endogenous MT protects against acute lung injury related to LPS. The effects are possibly mediated by the enhancement of pulmonary endothelial and epithelial integrity, not by the inhibition of the NF-kappaB pathway.
CLINICAL AND TOXICOLOGICAL RELEVANCE OF CYP2C9: Drug-Drug Interactions and Pharmacogenetics
Authors: Allan E. Rettie, Jeffrey P. Jones
Journal: The Annual Review of Pharmacology and Toxicology (2005)

CYP2C9 is a major cytochrome P450 enzyme that is involved in the metabolic clearance of a wide variety of therapeutic agents, including nonsteroidal antiinflammatories, oral anticoagulants, and oral hypoglycemics. Disruption of CYP2C9 activity by metabolic inhibition or pharmacogenetic variability underlies many of the adverse drug reactions that are associated with the enzyme. CYP2C9 is also the first human P450 to be crystallized, and the structural basis for its substrate and inhibitor selectivity is becoming increasingly clear. New, ultrapotent inhibitors of CYP2C9 have been synthesised that aid in the development of quantitative structure-activity relationship (QSAR) models to facilitate drug redesign, and extensive resequencing of the gene and studies of its regulation will undoubtedly help us understand interindividual variability in drug response and toxicity controlled by this enzyme.
Evolutionary and Structural Analyses of GDAP1, Involved in Charcot-Marie-Tooth Disease, Characterize a Novel Class of Glutathione Transferase-Related Genes
Authors: A. Marco
Journal: Molecular Biology and Evolution (2003)

Mutations in the Ganglioside-induced differentiation-associated protein-1 (GDAP1) gene cause autosomal recessive Charcot-Marie-Tooth disease type 4A. The protein encoded by GDAP1 shows clear similarity to glutathione transferases (also known as glutathione S-transferases or GSTs). The human genome contains a paralog of GDAP1 called GDAP1L1. Using comparative genomics, we show that orthologs of GDAP1 and GDAP1L1 are found in mammals, birds, amphibians, and fishes. Likely orthologs of those genes in invertebrates and a low but consistent similarity with some plant and eubacterial genes have also been found. We demonstrate that GDAP1 and GDAP1L1 do not belong to any of the known classes of GST genes. In addition to having distinctive sequences, GDAP1 and its relatives are also characterized by an extended region in GST domain II, absent in most other GSTs, and by a C-terminal end predicted to contain transmembrane domains. Mutations affecting any of those characteristic domains are known to cause Charcot-Marie-Tooth disease. These features define the GDAP1 class of GST-like proteins.