tbuckley/cabot-search huggingface dataset:
Long-Term Use of Acetaminophen, Aspirin, and Other Nonsteroidal Anti-Inflammatory Drugs and Risk of Hematologic Malignancies: Results From the Prospective Vitamins and Lifestyle (VITAL) Study
Authors: Roland B. Walter, Filippo Milano, Theodore M. Brasky, Emily White
Journal: Journal of Clinical Oncology (2011)

Among previous studies examining the associations of over-the-counter analgesics or nonsteroidal anti-inflammatory drugs (NSAIDs) and incident hematologic malignancies, results were inconsistent for NSAIDs but suggested an increased risk with acetaminophen (paracetamol). Herein, we used a large prospective cohort study to examine these associations.In total, 64,839 men and women age 50 to 76 years were recruited from 2000 to 2002 to the Vitamins and Lifestyle (VITAL) study. Incident hematologic malignancies (n = 577) were identified through December 2008 by linkage to the Surveillance, Epidemiology and End Results cancer registry. Hazard ratios (HRs) associated with use of analgesics for total incident hematologic malignancies and cancer subcategories were estimated by Cox proportional hazards models. Models were adjusted for age, sex, race/ethnicity, education, smoking, self-rated health, arthritis, chronic musculoskeletal pain, migraines, headaches, fatigue, and family history of leukemia/lymphoma.After adjustment, there was an increased risk of incident hematologic malignancies associated with high use (≥ 4 days/week for ≥ 4 years) of acetaminophen (HR, 1.84; 95% CI, 1.35 to 2.50 for high use; P trend = .004). This association was seen for myeloid neoplasms (HR, 2.26; 95% CI, 1.24 to 4.12), non-Hodgkin's lymphomas (HR, 1.81; 95% CI, 1.12 to 2.93), and plasma cell disorders (HR, 2.42; 95% CI, 1.08 to 5.41), but not chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; HR, 0.84; 95% CI, 0.31 to 2.28). By comparison, there was no association with risk of incident hematologic malignancies for increasing use of aspirin, nonaspirin NSAIDs, or ibuprofen.High use of acetaminophen was associated with an almost two-fold increased risk of incident hematologic malignancies other than CLL/SLL. Neither aspirin nor nonaspirin NSAIDs are likely useful for prevention of hematologic malignancies.
Associations of the C2-CFB-RDBP-SKIV2L Locus with Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy
Authors: Ke Liu, Li Jia Chen, Pancy O.S. Tam, Yi Shi, Timothy Y.Y. Lai, David T.L. Liu, Sylvia W.Y. Chiang, Mingming Yang, Zhenglin Yang, Chi Pui Pang
Journal: Ophthalmology (2012)
Fibrinolytic therapy in subacute bacterial endocarditis: an experimental study
Authors: C. E JOHNSON, H. A DEWAR, W. A AHERNE
Journal: Cardiovascular Research (1980)

The effect of adding fibrinolytic to penicillin therapy in experimentally induced streptococcal bacterial endocarditis has been studied in the rabbit. In 9 day old infected lesions, the vegetations could be substantially reduced in size after a 3 day course of intravenous streptokinase. Quantitative microbiological techniques demonstrated that the addition of streptokinase to standard intravenous penicillin treatment led to more rapid sterilisation of the vegetations. Embolism to lungs and kidneys was assessed in treated and untreated rabbits. Penicillin reduced the rate of embolism but the addition of streptokinase reversed this effect and gave values similar to those recorded in untreated animals.
Intraoperative High-Dose Dexamethasone and Severe AKI after Cardiac Surgery
Authors: Kirolos A. Jacob, David E. Leaf, Jan M. Dieleman, Diederik van Dijk, Arno P. Nierich, Peter M. Rosseel, Joost M. van der Maaten, Jan Hofland, Jan C. Diephuis, Fellery de Lange, Christine Boer, Jolanda Kluin, Sushrut S. Waikar
Journal: Journal of the American Society of Nephrology (2015)

Administration of prophylactic glucocorticoids has been suggested as a strategy to reduce postoperative AKI and other adverse events after cardiac surgery requiring cardiopulmonary bypass. In this post hoc analysis of a large placebo-controlled randomized trial of dexamethasone in 4465 adult patients undergoing cardiac surgery, we examined severe AKI, defined as use of RRT, as a primary outcome. Secondary outcomes were doubling of serum creatinine level or AKI-RRT, as well as AKI-RRT or in-hospital mortality (RRT/death). The primary outcome occurred in ten patients (0.4%) in the dexamethasone group and in 23 patients (1.0%) in the placebo group (relative risk, 0.44; 95% confidence interval, 0.19 to 0.96). In stratified analyses, the strongest signal for potential benefit of dexamethasone was in patients with an eGFR<15 ml/min per 1.73 m(2). In conclusion, compared with placebo, intraoperative dexamethasone appeared to reduce the incidence of severe AKI after cardiac surgery in those with advanced CKD.
Evaluation of Biologic End Points and Pharmacokinetics in Patients With Metastatic Breast Cancer After Treatment With Erlotinib, an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor
Authors: Antoinette R. Tan, Xiaowei Yang, Stephen M. Hewitt, Arlene Berman, Erin R. Lepper, Alex Sparreboom, Allyson L. Parr, William D. Figg, Catherine Chow, Seth M. Steinberg, Stephen L. Bacharach, Millie Whatley, Jorge A. Carrasquillo, Jaime S. Brahim, Seth A. Ettenberg, Stan Lipkowitz, Sandra M. Swain
Journal: Journal of Clinical Oncology (2004)

To evaluate changes in epidermal growth factor receptor (EGFR) phosphorylation and its downstream signaling in tumor and surrogate tissue biopsies in patients with metastatic breast cancer treated with erlotinib, an EGFR tyrosine kinase inhibitor, and to assess relationships between biomarkers in tumor and normal tissues and between biomarkers and pharmacokinetics.Eighteen patients were treated orally with 150 mg/d of erlotinib. Ki67, EGFR, phosphorylated EGFR (pEGFR), phosphorylated mitogen-activated protein kinase (pMAPK), and phosphorylated AKT (pAKT) in 15 paired tumor, skin, and buccal mucosa biopsies (at baseline and after 1 month of therapy) were examined by immunohistochemistry and analyzed quantitatively. Pharmacokinetic sampling was also obtained.The stratum corneum layer and Ki67 in keratinocytes of the epidermis in 15 paired skin biopsies significantly decreased after treatment (P = .0005 and P = .0003, respectively). No significant change in Ki67 was detected in 15 tumors, and no responses were observed. One was EGFR-positive and displayed heterogeneous expression of the receptor, and 14 were EGFR-negative. In the EGFR-positive tumor, pEGFR, pMAPK, and pAKT were reduced after treatment. Paradoxically, pEGFR was increased in EGFR-negative tumors post-treatment (P = .001). Although markers were reduced in surrogate and tumor tissues in the patient with EGFR-positive tumor, no apparent associations were observed in patients with EGFR-negative tumor.Erlotinib has inhibitory biologic effects on normal surrogate tissues and on an EGFR-positive tumor. The lack of reduced tumor proliferation may be attributed to the heterogeneous expression of receptor in the EGFR-positive patient and absence of target in this cohort of heavily pretreated patients.
Seroepidemiology of <i>Helicobacter pylori </i>infection and hepatitis A in a rural area: evidence against a common mode of transmission
Authors: F Luzza, M Imeneo, M Maletta, G Paluccio, A Giancotti, F Perticone, A Focà, F Pallone
Journal: Gut (1997)

Recent studies have shown that the age-specific seroprevalence of H pylori infection parallels hepatitis A (HAV), suggesting similar modes of transmission. The aim of this study was to investigate the seroepidemiology of H pylori and HAV in the same setting.A sample of 705 resident subjects (273 men, age range 1-87 years, median 50) who attended the outpatient medical centre of the rural town of Cirò, Southern Italy (11,000 inhabitants) for blood testing were recruited.All subjects completed a structured questionnaire. A serum sample was drawn from each subject and assayed for H pylori IgG by a validated in house enzyme linked immunosorbent assay. Antibodies to HAV were determined in 466 subjects (163 men, age range 1-87 years, median 49). A measure of agreement between H pylori and HAV seropositivity, the kappa statistic, was used.Overall, 446 (63%) subjects were seropositive for H pylori. Of the 466 subjects screened for both H pylori and HAV, 291 (62%) were seropositive for H pylori and 407 (87%) for HAV. Cross-tabulation of these data showed that 275 (59%) were seropositive and 43 (9%) seronegative for both H pylori and HAV, 16 (3%) were seropositive for H pylori, and 132 (28%) were seropositive for HAV (OR = 5.6, CI 3 to 10). There was a parallel, weakly correlated (r = 0.287) rise in the seroprevalence of the two infections with increasing age. However, the agreement between H pylori and HAV seropositivity was little better than chance (kappa = 0.21) and in those aged less than 20 years it was worse than chance (kappa = -0.064). Furthermore, multiple logistic regression analysis did not show any risk factor shared by both infections.The correlation between H pylori and HAV reflects the age-specific seroprevalence of both infections rather than a true association. This study provides evidence against a common mode of transmission of H pylori and HAV.
Electron Microscopy of Human Plasma Lipoprotein Separated by Ultracentrifugation
Authors: D. E. BEISCHER
Journal: Circulation Research (1954)

The particle size distribution of the S f 30 "class" of serum lipoprotein was determined by the electron microscope. Most of the lipoprotein molecules are not spherical but have the shape of ellipsoids of rotation with an axis ratio of 1.5. The molecules of a homogeneous flotation "class" show differences in the reactivity of their lipid moiety demonstrated by their staining properties with osmium tetroxide.
Effect of Exogenous Surfactant (Calfactant) in Pediatric Acute Lung Injury&lt;SUBTITLE&gt;A Randomized Controlled Trial&lt;/SUBTITLE&gt;
Authors: Douglas F. Willson
Journal: JAMA (2005)

CUTE RESPIRATORY DISTRESS syndrome (ARDS) was originally termed the adult respiratory distress syndrome because it resembled the clinical picture of infant respiratory distress syndrome (IRDS), and both exhibited hyaline membranes at autopsy. 1,2 Avery and Mead 3 first reported that lung surfactant quantity and activity were abnormal in infants with IRDS and surfactant replacement has subsequently become standard therapy for premature infants at risk for or having IRDS.Petty and Ashbaugh 2 described qualitative and quantitative surfactant deficiencies in their initial description of ARDS and the subsequent scientific literature (recently reviewed by Notter 4 ) has supported the role of surfactant dysfunction in both ARDS and less severe acute lung injury (ALI). 5Surfactant replacement in ARDS and ALI has been
Relationship between Quantitative <i>GRB7</i> RNA Expression and Recurrence after Adjuvant Anthracycline Chemotherapy in Triple-Negative Breast Cancer
Authors: Joseph A. Sparano, Lori J. Goldstein, Barrett H. Childs, Steven Shak, Diana Brassard, Sunil Badve, Frederick L. Baehner, Roberto Bugarini, Steve Rowley, Edith A. Perez, Lawrence N. Shulman, Silvana Martino, Nancy E. Davidson, Paraic A. Kenny, George W. Sledge, Robert Gray
Journal: Clinical Cancer Research (2011)

To conduct an exploratory analysis of the relationship between gene expression and recurrence in patients with operable triple-negative breast cancer (TNBC) treated with adjuvant doxorubicin-containing chemotherapy.
Impact of pretransplantation GB virus C infection on the outcome of renal transplantation.
Authors: B V Murthy, A S Muerhoff, S M Desai, J Yamaguchi, I K Mushahwar, C H Schmid, A S Levey, B J Pereira
Journal: Journal of the American Society of Nephrology (1997)

Among renal transplant recipients with posttransplantation liver disease, the etiology remains unknown in 10 to 16% of patients. The discovery of yet another parenterally transmitted hepatitis virus, GB virus C (GBV-C), has opened avenues to study the prevalence and risk factors for GBV-C infection among patients undergoing renal transplantation and its impact on posttransplantation clinical outcomes. A cohort of 103 randomly selected recipients of kidneys were examined from anti-hepatitis C virus (HCV)-negative donors between 1986 and 1990. Pretransplantation sera were available in 99 of 103 (96%) recipients and were tested for anti-HCV, using a second-generation ELISA, and for GBV-C RNA by reverse transcription PCR. Pretransplantation GBV-C RNA was present in 18 of 99 (18%, 95% confidence interval [CI], 17.2 to 18.8%) recipients. GBV-C RNA was present in 5 of 22 (23%) anti-HCV-positive recipients compared with 13 of 77 (17%) anti-HCV-negative recipients (P = 0.53). The median number of pretransplantation blood transfusion among recipients with GBV-C RNA before transplantation was significantly higher than among recipients without GBV-C RNA (10 versus 7, P = 0.05). Posttransplantation liver disease and non-A, non-B hepatitis (NANBH) was observed in 35 and 18%, respectively, of GBV-C RNA-positive recipients compared with 28 and 10%, respectively, of GBV-C RNA-negative recipients. Using Cox regression analysis, the relative risk (RR) of posttransplantation liver disease among recipients with GBV-C RNA before transplantation was 1.37 (95% CI, 0.55 to 3.41), and posttransplantation NANBH was 2.09 (95% CI, 0.64 to 6.79). The RR of graft loss and death were not increased (0.88 and 0.92, respectively). When adjusted for pretransplantation anti-HCV, the RR of posttransplantation liver disease, NANBH, graft loss, and death did not change appreciably. In summary, although a higher risk of posttransplantation liver disease was observed among recipients with pretransplantation GBV-C infection, the analyses presented here do not allow for a precise estimate of this risk.
The molecular biology of WHO grade I astrocytomas
Authors: N. F. Marko, R. J. Weil
Journal: Neuro-Oncology (2012)

World Health Organization (WHO) grade I astrocytomas include pilocytic astrocytoma (PA) and subependymal giant cell astrocytoma (SEGA). As technologies in pharmacologic neo-adjuvant therapy continue to progress and as molecular characteristics are progressively recognized as potential markers of both clinically significant tumor subtypes and response to therapy, interest in the biology of these tumors has surged. An updated review of the current knowledge of the molecular biology of these tumors is needed. We conducted a Medline search to identify published literature discussing the molecular biology of grade I astrocytomas. We then summarized this literature and discuss it in a logical framework through which the complex biology of these tumors can be clearly understood. A comprehensive review of the molecular biology of WHO grade I astrocytomas is presented. The past several years have seen rapid progress in the level of understanding of PA in particular, but the molecular literature regarding both PA and SEGA remains nebulous, ambiguous, and occasionally contradictory. In this review we provide a comprehensive discussion of the current understanding of the chromosomal, genomic, and epigenomic features of both PA and SEGA and provide a logical framework in which these data can be more readily understood.
Acute effects of air pollution on respiratory health of 50-70 yr old adults
Authors: S.C. van der Zee, G. Hoek, M.H. Boezen, J.P. Schouten, J.h van Wijnen, B. Brunekreef
Journal: European Respiratory Journal (2000)

The aim of this study was to investigate the association between daily changes in respiratory health and air pollution in 489 adults, aged 50-70 yrs, with and without chronic respiratory symptoms, living in urban and nonurban areas in the Netherlands. Subjects were selected from the general population with a screening questionnaire. During three consecutive winters starting in 1992/1993, peak expiratory flow (PEF) and respiratory symptoms were registered in a daily diary. Daily measurements of particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10), black smoke (BS), sulphate, sulphur dioxide (SO2) and nitrogen dioxide (NO2) were conducted. The difference in PM10, BS and sulphate concentrations between urban and nonurban areas was small, but there was more contrast in the concentrations of SO2 and NO2. In symptomatic subjects from urban areas, PM10, BS, sulphate and SO2 concentrations were associated with the prevalence of large decrements in morning PEF (&gt;20% below the median). BS in particular was also associated with upper respiratory symptoms (URS). The magnitude of the effect estimates was in the order of an 80% increase in PEF decrements and a 20% increase in URS for a 40 microg x m-3 increase of the same day BS concentration. In symptomatic subjects from nonurban areas, no consistent associations between air pollution and health indicators were observed. However, the differences in effect estimates between urban and nonurban symptomatic panels were small and nonsignificant. In nonsymptomatic adults from both areas, no consistent pattern of associations with air pollution was found. In conclusion, air pollution effects were only found in symptomatic adults in the urban areas.
Does Crossing the Legs Decrease Arterial Pressure In Diabetic Patients With Peripheral Vascular Disease?
Authors: Marvin E Levin, Gregorio A Sicard, Dirk S Baumann, Barbara Loechl
Journal: Diabetes Care (1993)

To evaluate the effect of crossing the legs at the knee and the ankle on peripheral arterial pressures.A prospective study of 6 diabetic patients with known peripheral vascular disease and 5 nondiabetic control subjects without peripheral vascular disease was conducted. Peripheral arterial pressures were taken at the ankle and at the great toe before and after crossing the legs at the knees and ankles. Comparisons were made of measurements obtained in the supine and sitting positions. All crossed leg measurements were taken in the sitting position.Ankle arm indexes and digital arm indexes pressures taken in the sitting position were equal to or higher than supine pressures, with the exception of one subject, GB. In this patient, ankle arm indexes and digital arm indexes on the right extremity were lower in the sitting position, but increased with the legs crossed at the knees and ankles compared with the uncrossed sitting position. In all patients, lower extremity pressures that decreased slightly with crossing the legs remained higher than pressures obtained in the supine position. Statistical analyses showed no significant differences. Wave forms did not change even when there was a slight decrease in ankle arm indexes or digital arm indexes. Control subjects without peripheral vascular disease showed no change in pressures with crossing the legs.Crossing the legs at the knees and ankles does not result in a significant decrease in peripheral arterial pressures in diabetic patients with peripheral vascular disease.
IMMUNITY AGAINST TULAREMIA: PASSIVE PROTECTION OF MICE BY TRANSFER OF IMMUNE TISSUES
Authors: William Peter Allen
Journal: The Journal of Experimental Medicine (1962)

Acquired resistance to fully virulent strains of P. tularensis was passively transferred to normal mice by viable spleen cells or peritoneal leucocytes from donors that recovered from infection with an attenuated strain of P. tularensis. This passively transferred resistance was reflected in survival or delayed death after challenge of the recipients. The degree of passively transferred resistance was dependent upon the immune status of the donors and the number of viable immune cells transferred. There were indications that this resistance persisted only as long as the transferred tissues were compatible with the tissues of the recipient. The results support the hypothesis that immunity of mice against fully virulent strains of P. tularensis is associated with an altered state of the tissues.
Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial
Authors: Maria Rosario Capeding, Ngoc Huu Tran, Sri Rezeki S Hadinegoro, Hussain Imam H J Muhammad Ismail, Tawee Chotpitayasunondh, Mary Noreen Chua, Chan Quang Luong, Kusnandi Rusmil, Dewa Nyoman Wirawan, Revathy Nallusamy, Punnee Pitisuttithum, Usa Thisyakorn, In-Kyu Yoon, Diane van der Vliet, Edith Langevin, Thelma Laot, Yanee Hutagalung, Carina Frago, Mark Boaz, T Anh Wartel, Nadia G Tornieporth, Melanie Saville, Alain Bouckenooghe
Journal: The Lancet (2014)
Strong, sustained hepatocellular proliferation precedes hepatocarcinogenesis in hepatitis B surface antigen transgenic mice
Authors: Shao-Nan Huang, Francis V. Chisari
Journal: Hepatology (1995)

Hepatocyte turnover rates were studied in two lineages of transgenic mice that overproduce the hepatitis B virus (HBV) large envelope protein and retain filamentous hepatitis B surface antigen (HBsAg) particles in the endoplasmic reticulum, resulting in the formation of ground glass hepatocytes. The high producer lineage (50-4) develops a necroinflammatory liver disease that progresses to hepatocellular carcinoma (HCC), whereas the low producer lineage (107-5) displays no histopathologic changes other than ground glass hepatocytes. Bromodeoxyuridine (BrdU)-labeling studies of S-phase hepatocytes provide quantitative evidence for a strong, sustained proliferative response in the hepatocytes in lineage 50-4 that occurs after the onset of hepatocellular injury but long before the development of liver cell tumors. In contrast, the level of hepatocellular proliferation in lineage 107-5 is the same as nontransgenic controls. The findings support the concept that sustained hepatocellular proliferation plays an important role in the development of hepatocellular carcinoma (HCC).
PTU-108 Azathioprine Pharmacogenetics in Autoimmune Hepatitis
Authors: H Dhaliwal, E McFarlane, D Gleeson, L Lennard
Journal: Gut (2013)

<h3>Introduction</h3> Azathioprine (AZA) is widely used to treat autoimmune hepatitis (AIH). However, 20% of patients are intolerant of AZA and a further 18% are unresponsive. AZA metabolism is complex and in childhood leukaemia, genetic polymorphisms in thiopurine methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) have been associated with AZA toxicity and differences in active metabolite production. This has been little studied in AIH. We aimed to assess the association of these polymorphisms with AZA toxicity and with accumulation of AZA derived thioguanine nucleotide (TGN) and methylmercaptopurine metabolites (MeMPNs) in AIH. <h3>Methods</h3> We studied 151 patients with AIH (123 female; median age at diagnosis 55 (range 2–81) years). Subjects were genotyped for the presence of <i>TPMT *3</i>, <i>TPMT *2</i> and ITPA (94C &gt; A and IVS2+21A &gt; C) variant alleles. TGNs and and MeMPNs were measured in patients who remained on AZA. <h3>Results</h3> For TPMT, 138 patients were wildtype and 13 (9%) were heterozygous (1 <i>TPMT*2</i>, 11 <i>TPMT*3A</i> and 1 <i>TPMT*3C</i>). For ITPA, 95 were wildtype, 50(33%) heterozygous (10 94C &gt; A and 40 IVS2+21A &gt; C) and 6 homozygous/compound heterozygous. There were 57 adverse events (AE) in 54(36%) patients – in 32 (21%) AZA was withdrawn. TPMT wildtype and heterozygous patients had a similar incidence of leucopenia (18 vs 17%, p = 0.9 ) and of non-myelotoxic AEs (21 vs 8% p = 0.5). Likewise, ITPA wildtype, heterozygous and homozygous patients had a similar incidence of leucopenia (19, 10 and 16% respectively, p = 0.2) and of non-myelotoxic AEs (20, 39 and 15%, p = 0.2). Compared to wildtype patients, TPMT heterozygotes accumulated higher concentrations of TGNs (413 vs 212 pmol/8x108RBCs, p = 0.009) and lower MeMPNs (111 vs. 1000 pmol/8x108RBCs, p &lt; 0.001), despite being a lower doses of AZA (1.0 vs. 1.7 mg/kg/day, p &lt; 0.001). Comparing IPTA wildtype, heterozygous and homozygous patients, there was no difference in TGNs (222, 212 and 176 pmol/8x108 RBCs respectively, p = 0.76) and MeMPNs (957, 957 and 713 pmol/8x108RBCs respectively, p = 0.7) <h3>Conclusion</h3> TPMT and ITPA polymorphisms do not predict the occurrence of adverse events in AIH. However, TPMT genotyping may be clinically useful as heterozygous patients may require a lower dose of AZA. <h3>Disclosure of Interest</h3> None Declared