tbuckley/cabot-search huggingface dataset:
Eltrombopag before Procedures in Patients with Cirrhosis and Thrombocytopenia
Authors: Nezam H. Afdhal, Edoardo G. Giannini, Ghias Tayyab, Aftab Mohsin, Jin-Woo Lee, Angelo Andriulli, Lennox Jeffers, John McHutchison, Pei-Jer Chen, Kwang-Hyub Han, Fiona Campbell, Denise Hyde, Andres Brainsky, Dickens Theodore
Journal: New England Journal of Medicine (2012)

Eltrombopag is an oral thrombopoietin-receptor agonist. This study evaluated the efficacy of eltrombopag for increasing platelet counts and reducing the need for platelet transfusions in patients with thrombocytopenia and chronic liver disease who are undergoing an elective invasive procedure.
P19 Vitamin D in the Prevention of Acute Respiratory Infection: A Systematic Review of Clinical Studies
Authors: DA Jolliffe, AR Martineau, CJ Griffiths
Journal: Thorax (2012)

<h3>Introduction and Objectives</h3> Acute respiratory infections (ARI) cause significant morbidity and mortality: in the UK, during 2004, 33,957 deaths occurred due to pneumonia alone. Vitamin D metabolites enhance immunity to a wide range of respiratory pathogens <i>in vitro</i>, and numerous clinical studies have investigated whether vitamin D deficiency is a risk factor for ARI, or whether vitamin D supplementation prevents ARI. Systematic reviews of this literature are lacking, however. Our objective was to conduct a systematic review of clinical studies investigating the relationship between vitamin D status or the effect of vitamin D supplementation on risk of ARI. <h3>Methods</h3> The PubMed database was searched on 7th June 2012 using the terms 'vitamin D' and' respiratory infection'. Cross-sectional studies, case-control studies, cohort studies or clinical trials in human subjects investigating the relationship between serum concentration of vitamin D metabolites or the effect of vitamin D supplementation on risk of ARI were included; ARI was defined as any infection of the respiratory tract with symptom duration of 30days or less. Studies relating exclusively to tuberculosis were excluded, as this is classically regarded as a chronic respiratory tract infection, with symptom duration usually exceeding 30 days. <h3>Results</h3> Thirty-one studies reporting data from a total of 43,272 participants were included in our review. Of these, 19 were observational studies (3 cross-sectional, 8 case-control and 8 cohort)and 12 were randomised controlled trials. Sixteen of the 19 observational studies reviewed reported statistically significant associations between vitamin D deficiency and susceptibility to ARI, and 3 reported no such association. Six of the 12 clinical trials reviewed reported protective effects of vitamin D against ARI, while five reported null effects, and one reported an adverse effect on pneumonia recurrence. <h3>Conclusions</h3> Observational studies report consistent associations between vitamin D deficiency and susceptibility to ARI in a wide range of age-groups in diverse clinical settings. By contrast, randomised controlled trials of vitamin D supplementation for the prevention of ARI report conflicting results, possibly reflecting varying prevalence of vitamin D deficiency in study populations and/or heterogeneity in vitamin D supplementation regimens investigated.
John Trevillian Wright
Authors: E. M. M. B. W. C. C. W. R. Cowan
Journal: BMJ (2015)

John Trevillian Wright spent much of his childhood in South America, where his father was a manager for an oil company. He attended Shrewsbury School and spent the holidays in South America and in the English countryside. These times, when he was often unaccompanied, fostered his independent spirit and sense of adventure from an early age: on one occasion, he jumped from the deck of one transatlantic liner to another. In addition to showing academic prowess, he was an excellent cross country runner and was taught to row by his father, with family trips in a camping skiff on the Thames.

He went up to Worcester College, Oxford, in 1940, crediting his place, characteristically modestly, to the correct identification at interview of a hornbeam tree in the quad. He won a Price university scholarship in anatomy and physiology, and after being admitted to the London Hospital Medical College in 1942, won prizes there in surgery, pathology, and chemical pathology. He undertook war service in and around London, and graduated in December 1944. On 20 January 1945 he married Kate Elliott, who was to be his wife for 56 years.

His house officer posts were at the London Hospital and his national service in the Royal Army Medical Corps between 1946 and 1948. He was senior registrar at St George’s Hospital in …
EFFECT OF HYALURONIDASE ON URINE AND ITS POSSIBLE SIGNIFICANCE IN RENAL LITHIASIS
Authors: Arthur J. Butt
Journal: JAMA (1952)

In 1950, one of us (A. J. B.) observed that subcutaneous injections of hyaluronidase (wydase®), mixed with isotonic sodium chloride solution, resulted in clearing of urine in patients who previously had turbid urine with much sedimentation. The effect of hyaluronidase was manifest within 30 minutes after injection and persisted for 24 to 72 hours.<sup>1</sup>In attempting to establish a mechanism by which hyaluronidase produces this effect, we examined urines under a microscope equipped with a standard dark-field condenser to ascertain whether hyaluronidase caused a change in the colloid chemical condition of the urine under investigation. Preliminary observations appeared to establish a correlation between the injection of hyaluronidase and the number of colloidal particles discernible in the urine sample. Certain colloidal phenomena (e. g., adhesion) made the statistical validity of this method questionable. In addition, considerable dispute as to the significance of such examination is already apparent. Since that time,
A Needle in a Haystack of Genes
Authors: Robert S. Schwartz
Journal: New England Journal of Medicine (2002)

The holy grail of cancer screening is a sensitive, specific, and noninvasive test for the detection of malignant cells. Cytologic analysis of urine or sputum has not lived up to its early promise because it lacks sensitivity. Far more sensitive is the polymerase chain reaction (PCR), which replicates minuscule quantities of DNA to generate amounts that allow exact identification of tumor-specific mutations. Its success in detecting such mutations in exfoliated cells in the urine, sputum, pancreatic juice, and stools has been mixed, however, and the utility of the method in screening for cancer-specific mutations remains unproved.Two genes, K-ras . . .
Gene Polymorphisms in Cyclophosphamide Metabolism Pathway,Treatment-Related Toxicity, and Disease-Free Survival in SWOG 8897 Clinical Trial for Breast Cancer
Authors: Song Yao, William E. Barlow, Kathy S. Albain, Ji-Yeob Choi, Hua Zhao, Robert B. Livingston, Warren Davis, James M. Rae, I-Tien Yeh, Laura F. Hutchins, Peter M. Ravdin, Silvana Martino, Alan P. Lyss, C. Kent Osborne, Martin Abeloff, Gabriel N. Hortobagyi, Daniel F. Hayes, Christine B. Ambrosone
Journal: Clinical Cancer Research (2010)

Abstract Purpose: There are no established genetic markers for prediction of outcomes after cyclophosphamide (CP)-containing adjuvant therapy for breast cancer. In an ancillary study to a SWOG (Southwest Oncology Group) trial (S8897), we investigated functional polymorphisms in 4 genes in CP pharmacokinetic pathways in relation to hematologic toxicity and disease-free survival (DFS). Experimental Design: Germline DNA was available from 458 women who were at high risk of relapse and was randomized to CAF (CP, intravenous doxorubicin, and 5-fluorouracil) versus CMF (CP, intravenous methotrexate, and 5-fluorouracil) ± tamoxifen, and from 874 women who had a presumed favorable prognosis and did not receive adjuvant therapy. Odds ratios for grade 3 and 4 hematologic toxicity in the treated group and hazard ratios for DFS associated with selected functional polymorphisms in CYP2B6CYP3A4GSTA1and GSTP1were estimated by logistic regression and Cox proportional hazard regression. Results: Compared with women with AA genotypes, those with at least 1 GSTP1 variant G allele had reduced risk of grade 3 and 4 neutropenia [odds ratios (OR) = 0.63, 95% CI = 0.41–0.97] and leucopenia (OR = 0.59, 95% CI = 0.39–0.89). No other associations between single nucleotide polymorphisms and toxicity or survival were found in the treated or untreated group. Conclusion: Known genetic variants in genes involved in CP pharmacokinetics may not have major effects on DFS in breast cancer patients. The lower risk of developing high-grade hematologic toxicity among women with variant GSTP1alleles suggests that genetic markers in combination with clinical factors may be useful in defining a subgroup of women who are less susceptible to adverse hematologic toxicities with CP-containing therapies.
The PedsQL™ in Type 1 and Type 2 Diabetes
Authors: James W. Varni, Tasha M. Burwinkle, Jenifer R. Jacobs, Michael Gottschalk, Francine Kaufman, Kenneth L. Jones
Journal: Diabetes Care (2003)

OBJECTIVE—The Pediatric Quality of Life Inventory (PedsQL) is a modular instrument designed to measure health-related quality of life (HRQOL) in children and adolescents aged 2–18 years. The PedsQL 4.0 Generic Core Scales are child self-report and parent proxy-report scales developed as the generic core measure to be integrated with the PedsQL disease-specific modules. The PedsQL 3.0 Type 1 Diabetes Module was designed to measure diabetes-specific HRQOL. RESEARCH DESIGN AND METHODS—The PedsQL Generic Core Scales and Diabetes Module were administered to 300 pediatric patients with type 1 or type 2 diabetes and 308 parents. RESULTS—Internal consistency reliability for the PedsQL Generic Core Total Scale score (α = 0.88 child, 0.89 parent-report) and most Diabetes Module scales (average α = 0.71 child, 0.77 parent-report) was acceptable for group comparisons. The PedsQL 4.0 distinguished between healthy children and children with diabetes. The Diabetes Module demonstrated intercorrelations with dimensions of generic and diabetes-specific HRQOL. CONCLUSIONS—The results demonstrate the reliability and validity of the PedsQL in diabetes. The PedsQL may be used as an outcome measure for diabetes clinical trials and research.
Are there opportunities for chemotherapy in the treatment of hepatocellular cancer?
Authors: Uzma Asghar, Tim Meyer
Journal: Journal of Hepatology (2011)

Hepatocellular cancer is a significant global health problem yet the prognosis for the majority of patients has not changed significantly over the past few decades. For patients with advanced disease, sorafenib is currently the standard of care providing a survival advantage of 2-3 months in selected patients. Cytotoxic chemotherapy has been used for over 30 years but definite evidence that it prolongs survival has been lacking. Resistance remains a significant barrier for both targeted and cytotoxic agents and an understanding of the underlying mechanisms is critical if outcomes are to be improved. Here, we summarise the past and current data that constitute the evidence base for chemotherapy in HCC, review the causes of chemoresistance and suggest strategies to overcome these barriers.
Carcinogen-Specific Gene Expression Profiles in Short-term Treated Eker and Wild-type Rats Indicative of Pathways Involved in Renal Tumorigenesis
Authors: Kerstin Stemmer, Heidrun Ellinger-Ziegelbauer, Hans-Juergen Ahr, Daniel R. Dietrich
Journal: Cancer Research (2007)

Abstract Eker rats heterozygous for a dominant germline mutation in the tuberous sclerosis 2 (Tsc2) tumor suppressor gene were used as a model to study renal carcinogenesis. Eker and corresponding wild-type rats were exposed to genotoxic aristolochic acid (AA) or non-genotoxic ochratoxin A (OTA) to elucidate early carcinogen-specific gene expression changes and to test whether Eker rats are more sensitive to carcinogen-induced changes in gene expression. Male Eker and wild-type rats were gavaged daily with AA (10 mg/kg body weight) or OTA (210 μg/kg body weight). After 1, 3, 7, and 14 days of exposure, renal histopathology, tubular cell proliferation, and Affymetrix gene expression profiles from renal cortex/outer medulla were analyzed. AA-treated Eker and wild-type rats were qualitatively comparable in all variables assessed, suggesting a Tsc2-independent mechanism of action. OTA treatment resulted in slightly increased cortical pathology and significantly elevated cell proliferation in both strains, although Eker rats were more sensitive. Deregulated genes involved in the phosphatidylinositol 3-kinase-AKT-Tsc2-mammalian target of rapamycin signaling, among other important genes prominent in tumorigenesis, in conjunction with the enhanced cell proliferation and presence of preneoplastic lesions suggested involvement of Tsc2 in OTA-mediated toxicity and carcinogenicity, especially as deregulation of genes involved in this pathway was more prominent in the Tsc2 mutant Eker rat. [Cancer Res 2007;67(9):4052–68]
Metformin Sensitizes EGFR-TKI–Resistant Human Lung Cancer Cells <i>In Vitro</i> and <i>In Vivo</i> through Inhibition of IL-6 Signaling and EMT Reversal
Authors: Li Li, Rui Han, Hualiang Xiao, Caiyu Lin, Yubo Wang, Hao Liu, Kunlin Li, Hengyi Chen, Fenfen Sun, Zhenzhou Yang, Jianxin Jiang, Yong He
Journal: Clinical Cancer Research (2014)

The EGF receptor tyrosine kinase inhibitors (EGFR-TKI) have become a standard therapy in patients with EGFR-activating mutations. Unfortunately, acquired resistance eventually limits the clinical effects and application of EGFR-TKIs. Studies have shown that suppression of epithelial-mesenchymal transition (EMT) and the interleukin (IL)-6/STAT3 pathway may abrogate this acquired mechanism of drug resistance of TKIs. This study aims to investigate the effect of metformin on sensitizing EGFR-TKI-resistant human lung cancer cells in vitro and in vivo through inhibition of IL-6 signaling and EMT reversal.The effect of metformin on reversing TKI resistance was examined in vitro and in vivo using MTT, BrdUrd incorporation assay, invasion assay, flow cytometry analysis, immunostaining, Western blot analysis, and xenograft implantation.In this study, metformin, a widely used antidiabetic agent, effectively increased the sensitivity of TKI-resistant lung cancer cells to erlotinib or gefitinib. Metformin reversed EMT and decreased IL-6 signaling activation in TKI-resistant cells, while adding IL-6 to those cells bypassed the anti-TKI-resistance effect of metformin. Furthermore, overexpression or addition of IL-6 to TKI-sensitive cells induced TKI resistance, which could be overcome by metformin. Finally, metformin-based combinatorial therapy effectively blocked tumor growth in xenografts with TKI-resistant cancer cells, which was associated with decreased IL-6 secretion and expression, EMT reversal, and decreased IL-6-signaling activation in vivo.Metformin, generally considered nontoxic and remarkably inexpensive, might be used in combination with TKIs in patients with non-small cell lung cancer, harboring EGFR mutations to overcome TKI resistance and prolong survival.
Management of primary ciliary dyskinesia in European children: recommendations and clinical practice
Authors: Marie-Pierre F. Strippoli, Thomas Frischer, Angelo Barbato, Deborah Snijders, Elisabeth Maurer, Jane S.A. Lucas, Ernst Eber, Bulent Karadag, Petr Pohunek, Zorica Zivkovic, Amparo Escribano, Chris O’Callaghan, Andrew Bush, Claudia E. Kuehni
Journal: European Respiratory Journal (2012)

The European Respiratory Society Task Force on primary ciliary dyskinesia (PCD) in children recently published recommendations for diagnosis and management. This paper compares these recommendations with current clinical practice in Europe. Questionnaires were returned by 194 paediatric respiratory centres caring for PCD patients in 26 countries. In most countries, PCD care was not centralised, with a median (interquartile range) of 4 (2-9) patients treated per centre. Overall, 90% of centres had access to nasal or bronchial mucosal biopsy. Samples were analysed by electron microscopy (77%) and ciliary function tests (57%). Nasal nitric oxide was used for screening in 46% of centres and saccharine tests in 36%. Treatment approaches varied widely, both within and between countries. European region, size of centre and the country's general government expenditure on health partly defined availability of advanced diagnostic tests and choice of treatments. In conclusion, we found substantial heterogeneity in management of PCD within and between countries, and poor concordance with current recommendations. This demonstrates how essential it is to standardise management and decrease inequality between countries. Our results also demonstrate the urgent need for research: to simplify PCD diagnosis, to understand the natural history and to test the effectiveness of interventions.
AID from bony fish catalyzes class switch recombination
Authors: Vasco M. Barreto, Qiang Pan-Hammarstrom, Yaofeng Zhao, Lennart Hammarstrom, Ziva Misulovin, Michel C. Nussenzweig
Journal: The Journal of Experimental Medicine (2005)

Class switch recombination was the last of the lymphocyte-specific DNA modification reactions to appear in the evolution of the adaptive immune system. It is absent in cartilaginous and bony fish, and it is common to all tetrapods. Class switching is initiated by activation-induced cytidine deaminase (AID), an enzyme expressed in cartilaginous and bony fish that is also required for somatic hypermutation. Fish AID differs from orthologs found in tetrapods in several respects, including its catalytic domain and carboxy-terminal region, both of which are essential for the switching reaction. To determine whether evolution of class switch recombination required alterations in AID, we assayed AID from Japanese puffer and zebra fish for class-switching activity in mouse B cells. We find that fish AID catalyzes class switch recombination in mammalian B cells. Thus, AID had the potential to catalyze this reaction before the teleost and tetrapod lineages diverged, suggesting that the later appearance of a class-switching reaction was dependent on the evolution of switch regions and multiple constant regions in the IgH locus.
High-Cost Imaging in Elderly Patients with Stage IV Cancer
Authors: Yue-Yung Hu, Alvin C. Kwok, Wei Jiang, Nathan Taback, Elizabeth T. Loggers, Gladys V. Ting, Stuart R. Lipsitz, Jane C. Weeks, Caprice C. Greenberg
Journal: JNCI Journal of the National Cancer Institute (2012)

Medicare expenditures for high-cost diagnostic imaging have risen faster than those for total cancer care and have been targeted for potential cost reduction. We sought to determine recent and long-term patterns in high-cost diagnostic imaging use among elderly (aged ≥65 years) patients with stage IV cancer. We identified claims within the Surveillance, Epidemiology, and End Results (SEER)-Medicare database with computed tomography, magnetic resonance imaging, positron emission tomography, and nuclear medicine scans between January 1994 and December 2009 for patients diagnosed with stage IV breast, colorectal, lung, or prostate cancer between January 1995 and December 2006 (N = 100 594 patients). The proportion of these patients imaged and rate of imaging per-patient per-month of survival were calculated for each phase of care in patients diagnosed between January 2002 and December 2006 (N = 55 253 patients). Logistic regression was used to estimate trends in imaging use in stage IV patients diagnosed between January 1995 and December 2006, which were compared with trends in imaging use in early-stage (stages I and II) patients with the same tumor types during the same period (N = 192 429 patients). Among the stage IV patients diagnosed between January 2002 and December 2006, 95.9% underwent a high-cost diagnostic imaging procedure, with a mean number of 9.79 (SD = 9.77) scans per patient and 1.38 (SD = 1.24) scans per-patient per-month of survival. After the diagnostic phase, 75.3% were scanned again; 34.3% of patients were scanned in the last month of life. Between January 1995 and December 2006, the proportion of stage IV cancer patients imaged increased (relative increase = 4.6%, 95% confidence interval [CI] = 3.7% to 5.6%), and the proportion of early-stage cancer patients imaged decreased (relative decrease = −2.5%, 95% CI = −3.2% to −1.9%). Diagnostic imaging is used frequently in patients with stage IV disease, and its use increased more rapidly over the decade of study than that in patients with early-stage disease.
Comparison between cimetidine and Caved-S in the treatment of gastric ulceration, and subsequent maintenance therapy.
Authors: A G Morgan, W A McAdam, C Pacsoo, A Darnborough
Journal: Gut (1982)

One hundred patients with benign gastric ulceration were treated in a single-blind, endoscopically controlled trial to assess the relative efficacy of cimetidine (1 g daily) and Caved-S (six tablets daily). Ulcer healing was assessed after six weeks9 treatment, and, if incomplete, after a further six weeks. There was no significant difference between the two drug regimens (approximately 63% at six weeks and 91% at 12 weeks). If an ulcer remains unhealed after 10 weeks9 treatment the patient should undergo surgery. There was no difference in the relief of day pain between the two drug regimens but cimetidine was more effective over the first two weeks of treatment relieving night pain, than was Caved-S (p less than 0 . 02). After ulcer healing, drug dosage was reduced (cimetidine to 400 mg at night and Caved-S to two tablets twice daily). So far, 56 patients, 28 in each group, have completed the first year9s maintenance treatment, and there have been four ulcer recurrences in each group (14%).
Predictors of indoor exposure to mouse allergen in urban and suburban homes in Boston
Authors: W. Phipatanakul, D. R. Gold, M. Muilenberg, D. L. Sredl, S. T. Weiss, J. C. Celedón
Journal: Allergy (2005)

Background: Mouse allergen exposure is prevalent among urban children with asthma. Little is known about mouse allergen exposure in children at risk for the development of allergic diseases. Aims of the study: To assess indoor mouse allergen exposure in early life among children with parental history of asthma or allergies. Methods: Prospective birth cohort study of 498 children with a history of allergy or asthma in at least one parent living in metropolitan Boston. Results: Of the 498 participating children, 357 (71.7%) resided outside the city of Boston and 439 (90.7%) lived in households with incomes &gt;$30 000. Mouse allergen was detected in 42% of the homes of study participants. In a multivariate analysis adjusting for sex, income, and endotoxin, black race [odds ratio (OR) = 3.0; 95% confidence interval (CI) = 1.3–6.6, P = 0.009], signs of mice in the home at age 2–3 months (OR = 3.0; 95% CI = 1.6–5.6, P = 0.0006), and kitchen cockroach allergen levels ≥0.05 to &lt;2 U/g (OR = 1.8; 95% CI = 1.1–3.2, P = 0.02) were associated with detectable mouse allergen in the kitchen. In this model, living in a single detached house was inversely associated with detectable kitchen mouse allergen levels (OR = 0.4; 95% CI = 0.2–0.6, P = 0.0001). Conclusion: Infants with a parental history of asthma or allergies are commonly exposed to mouse allergen in their homes. Among infants at high risk for atopy, predictors of increased mouse allergen levels included black race, reported mice exposure, and moderate levels of cockroach allergen.
Focal Laser Ablation for Prostate Cancer Followed by Radical Prostatectomy: Validation of Focal Therapy and Imaging Accuracy
Authors: Uri Lindner, Nathan Lawrentschuk, Robert A. Weersink, Sean R.H. Davidson, Orit Raz, Eugen Hlasny, Deanna L. Langer, Mark R. Gertner, Theodorus Van der Kwast, Masoom A. Haider, John Trachtenberg
Journal: European Urology (2010)