tbuckley/cabot-search huggingface dataset:
Evidence of Interaction between Polychlorinated Biphenyls and Phthalates in Relation to Human Sperm Motility
Authors: Russ Hauser, Paige Williams, Larisa Altshul, Antonia M. Calafat
Journal: Environmental Health Perspectives (2005)

Previously, we reported evidence of inverse associations between exposure to some polychlorinated biphenyls (PCBs) and some phthalate monoesters in relation to semen parameters, specifically sperm motility. Because humans are exposed to both phthalates and PCBs and because experimental studies suggest that PCBs may interact with glucuronidative enzymes that are responsible for phthalate metabolism, we explored the potential interaction between phthalates and PCBs in relation to human semen quality. We studied 303 men who were partners in subfertile couples seeking infertility diagnosis from the andrology laboratory at Massachusetts General Hospital. Semen parameters were dichotomized based on World Health Organization reference values, and phthalate and PCB levels were dichotomized at their respective medians. After adjusting for age and abstinence time, for below reference sperm motility there was a greater than additive interaction between monobenzyl phthalate and PCB-153 [relative excess risk due to interaction (RERI) = 1.40; 95% confidence interval (CI), 0.41-3.22], sum of PCBs (RERI = 1.24; 95% CI, 0.15-2.94), and cytochrome P450 (CYP450)-inducing PCBs (RERI = 1.30; 95% CI, 0.21-3.06). For below-reference sperm motility, there was also a greater than additive interaction between monobutyl phthalate (MBP) and PCB-153 (RERI = 1.42; 95% CI, 0.09-3.76) and CYP450-inducing PCBs (RERI = 1.87; 95% CI, 0.56-4.52) and a suggestive interaction between MBP and sum of PCBs (RERI = 1.35; 95% CI, -0.11 to 3.48). In conclusion, because there are important risk assessment and public health implications of interactions between these two ubiquitous classes of compounds, further studies need to be conducted to confirm these results and identify potential mechanisms of interactions.
AN ANALYSIS OF THE STATISTICS OF FORTY-ONE THOUSAND FIVE HUNDRED CASES OF EPIDEMIC INFLUENZA.Read before the American Academy of Medicine, Philadelphia, December 4, 1890.
Authors: BENJAMIN LEE
Journal: JAMA (1891)

It is not difficult to understand why, in the extreme south-eastern portion of Europe, doubts should have been entertained as to the diagnosis of the disease, which during the past year has not only overspread that continent, but crossing the ocean, has swept over this country so generally and attacked the population so universally that we are justified in calling it a<i>pandemic.</i> It is evidently due to the fact that one of the prominent symptoms, which is, however, by no means an essential symptom, namely: coughing and sneezing, indicating catarrh of the air passages, has been mistaken in the minds of the people, and to some extent also of the medical profession, for the disease itself. To such an extent is this true, that one medical author of considerable reputation has designated it<i>Epidemic Acute Bronchitis.</i> The first intimation which we had of its presence in Europe was that
Instruments for Assessing the Quality of Drug Studies Published in the Medical Literature
Authors: Mildred K. Cho
Journal: JAMA (1994)

To develop valid and reliable instruments to assess the methodologic quality and clinical relevance of drug studies.We developed an instrument to assess the methodologic quality of articles reporting clinical research and an instrument to measure nonmethodologic measures of quality, such as clinical relevance, generalizability, and adherence to ethical standards. Each instrument was pretested by seven independent, masked reviewers and modified based on interrater agreement and content validity of individual items. We determined correlational validity of the final methodologic quality instrument by comparing quality scores assigned to 10 articles by means of our instrument and a previously published one.Clinical drug studies published in symposium proceedings and peer reviewed biomedical literature.Interrater reliability of overall quality scores, measured by intraclass correlation (r) and Kendall's coefficient of concordance (W), and interrater reliability of individual items, by percentage agreement.The interrater reliability of the pretest methodologic quality instrument was high (r = .89 [95% confidence interval, .73 to .96]; W = 0.64). Correlational validity of the final instrument was suggested by the high degree of concordance with another previously published one (W = 0.74). The interrater reliability of the pretest clinical relevance instrument was moderate (r = .41 [95% confidence interval, .18 to .64]; W = 0.47). Reviewers confirmed the content validity of both instruments.The two instruments we developed, one measuring methodologic quality and one measuring clinical relevance of articles reporting clinical research, are reliable, valid, and applicable to a variety of research designs.
Left Atrial Appendage Occlusion Does Not Eliminate the Need for Warfarin
Authors: Richard P. Whitlock, Jeff S. Healey, Stuart J. Connolly
Journal: Circulation (2009)

A trial fibrillation (AF) is the most common sustained heart rhythm disorder.2][3] It is estimated to affect 1% to 1.5% of the developed world, and the incidence increases with age to a rate of 19.2 per 1000 patient-years in those 65 years of age and older.The most important aspect of the treatment of patients with AF is the prevention of stroke.The average annual stroke rate across risk groups is 5%, and AF-associated strokes confer worse outcomes than those occurring in the absence of AF. 1,4 Furthermore, Stroke Prevention in Nonrheumatic Atrial Fibrillation (SPINAF) data suggest that 15% of patients with AF suffer silent cerebral infarctions on computed tomography, the implications of which are unknown.
Residential Pesticides and Childhood Leukemia: A Systematic Review and Meta-Analysis
Authors: Michelle C. Turner, Donald T. Wigle, Daniel Krewski
Journal: Environmental Health Perspectives (2009)

We conducted a systematic review and meta-analysis of previous observational epidemiologic studies examining the relationship between residential pesticide exposures during critical exposure time windows (preconception, pregnancy, and childhood) and childhood leukemia.Searches of MEDLINE and other electronic databases were performed (1950-2009). Reports were included if they were original epidemiologic studies of childhood leukemia, followed a case-control or cohort design, and assessed at least one index of residential/household pesticide exposure/use. No language criteria were applied.Study selection, data abstraction, and quality assessment were performed by two independent reviewers. Random effects models were used to obtain summary odds ratios (ORs) and 95% confidence intervals (CIs).Of the 17 identified studies, 15 were included in the meta-analysis. Exposures during pregnancy to unspecified residential pesticides (summary OR = 1.54; 95% CI, 1.13-2.11; I2 = 66%), insecticides (OR = 2.05; 95% CI, 1.80-2.32; I2 = 0%), and herbicides (OR = 1.61; 95% CI, 1.20-2.16; I2 = 0%) were positively associated with childhood leukemia. Exposures during childhood to unspecified residential pesticides (OR = 1.38; 95% CI, 1.12-1.70; I2 = 4%) and insecticides (OR = 1.61; 95% CI, 1.33-1.95; I2 = 0%) were also positively associated with childhood leukemia, but there was no association with herbicides.Positive associations were observed between childhood leukemia and residential pesticide exposures. Further work is needed to confirm previous findings based on self-report, to examine potential exposure-response relationships, and to assess specific pesticides and toxicologically related subgroups of pesticides in more detail.
Molecular characterization of human Ro/SS-A antigen. Amino terminal sequence of the protein moiety of human Ro/SS-A antigen and immunological activity of a corresponding synthetic peptide.
Authors: T S Lieu, M M Newkirk, J D Capra, R D Sontheimer
Journal: Journal of Clinical Investigation (1988)

The Ro/SS-A antigen was purified from an Epstein-Barr virus-transformed human B lymphoblastoid cell line. The amino terminal amino acid sequence of the 60-kD polypeptide bearing this antigenic epitope was determined to be: (formula; see text) A peptide composed of residue 6-19 was synthesized by the solid-phase method. Immunodiffusion-defined monospecific autoimmune sera to Ro/SS-A reacted with this synthetic peptide in ELISA, whereas autoantibodies with other specificities such as anti-La/SS-B and anti-Sm, as well as normal human sera, were not reactive. In addition, rabbit anti-peptide 6-19 antisera reacted specifically with native human Ro/SS-A antigen in ELISA. Furthermore, this synthetic peptide inhibited the binding of rabbit anti-peptide antiserum to native human Ro/SS-A. An additional synthetic peptide corresponding to residues 7-24 partially inhibited the binding of a patient anti-Ro/SS-A serum to native Ro/SS-A. These results suggest that the amino terminal portion of the molecule represents a major epitope of Ro/SS-A. The determination of the amino acid sequence of Ro/SS-A and the availability of synthetic peptide(s) bearing this antigen should provide additional approaches to further characterize the autoimmune response to this antigen.
Leukemia surfaceome analysis reveals new disease-associated features
Authors: Paulina Mirkowska, Andreas Hofmann, Lukasz Sedek, Lucie Slamova, Ester Mejstrikova, Tomasz Szczepanski, Maike Schmitz, Gunnar Cario, Martin Stanulla, Martin Schrappe, Vincent H. J. van der Velden, Beat C. Bornhauser, Bernd Wollscheid, Jean-Pierre Bourquin
Journal: Blood (2013)
Transport of fluorescent bile acids by the isolated perfused rat liver: Kinetics, sequestration, and mobilization
Authors: Fernando Holzinger, Claudio D. Schteingart, Huong-Thu Ton-Nu, Carolina Cerrè, Joseph H. Steinbach, Hong-Zen Yeh, Alan F. Hofmann
Journal: Hepatology (1998)

Hepatocyte transport of six fluorescent bile acids containing nitrobenzoxadiazolyl (NBD) or a fluorescein derivative on the side chain was compared with that of natural bile acids using the single-pass perfused rat liver. Compounds were infused at 40 nmol/g liver · min for 15 minutes; hepatic uptake and biliary recovery were measured; fractional extraction, intrinsic basolateral clearance, and sequestration (nonrecovery after 45 minutes of additional perfusion) were calculated. Fluorescent bile acids were efficiently extracted during the first 3 minutes (70%-97%), but net extraction decreased with time mostly because of regurgitation into the perfusate. For cholylglycine and ursodeoxycholylglycine (UDC-glycine), extraction was 94% to 99%, and regurgitation did not occur. Intrinsic hepatic clearance of fluorescent bile acids (2-7 mL/g liver · min) was lower than that of cholylglycine (9.0 ± 0.6; mean ± SD) and UDC-glycine (21.4 ± 0.4). Sequestration at 60 minutes was 8% to 26% for fluorescent bile acids with a cholyl moiety (cholylglycylaminofluorescein [CGamF], cholyllysylfluorescein [C-L-F], cholyl-[Nε-NBD]-lysine [C-L-NBD], and cholylaminofluorescein [CamF]), 32% for ursodeoxycholylaminofluorescein (UDCamF), and 88% for ursodeoxycholyl-(Nε-NBD)-lysine (UDC-L-NBD). Cholylglycine and UDC-glycine had &lt;3% retention. Biliary secretion of sequestered UDCamF, but not of UDC-L-NBD, was induced by adding dibutyryl cyclic adenosine monophosphate (DBcAMP) to the perfusate, possibly by translocation to the canaliculus of pericanalicular vesicles containing fluorescent bile acids. Biliary secretion of UDC-L-NBD, but not of UDCamF, was induced by adding cholyltaurine or UDC-taurine, possibly by inhibition of binding to intracellular constituents or of transport into organelles. It is concluded that fluorescent bile acids are efficiently transported across the basolateral membrane, but in contrast to natural conjugated bile acids, are sequestered in the hepatocyte (UDC derivatives &gt; cholyl derivatives). Two modes of hepatic sequestration of fluorescent bile acids were identified. Fluorescent bile acids may be useful to characterize sequestration processes during bile acid transport through the hepatocyte.
Use of time interval histographic output from echo-Doppler to detect left-to-right atrial shunts.
Authors: S J Goldberg, J C Areias, S E Spitaels, V H de Villeneuve
Journal: Circulation (1978)

The primary purpose of this study was to attempt to select, by examination of the time interval histogram (TIH) output of a range gated pulsed Doppler (RGPD), all children with left-to-right shunt at the atrial level from a pool of 57 children. Fifty-four of the children had various forms of acyanostic cardiac disease. A secondary purpose was to identify any associated lesions in those children with atrial defects. Examiners were unfamiliar with the children and their diagnoses. Results were interpreted independently by two examiners. Detection of diastolic TIH dispersion was used when studying the right atrial outflow tract to separate children with atrial left-to-right shunts from control children. All controls were judged negative by this technique, and 13 of 14 children with atrial shunts were detected by both examiners; the 14th was detected by one examiner. Of a total of 308 TIH decisions on the atrial shunt group, 298 were made identically by both examiners for a 97.7% agreement, demonstrating the objectivity of the method. This study demonstrated the usefulness of the TIH evaluation, indicating that continued investigation and equipment improvements are warranted.
Use of Mechanical Ventilation by Patients With and Without Dementia, 2001 Through 2011
Authors: Tara Lagu, Marya D. Zilberberg, Jennifer Tjia, Penelope S. Pekow, Peter K. Lindenauer
Journal: JAMA Internal Medicine (2014)

Increasing demand for US critical care resources, including beds, intensivists, and invasive mechanical ventilation (IMV),1,2 has placed substantial strain on the critical care system. Since 2000, elderly patients treated in the intensive care unit have received higher intensity care (and have experienced lower mortality rates) than historical cohorts.3 Yet certain populations of elderly patients exposed to intensive care experience substantial long-term adverse effects, including functional decline and excess mortality. Patients with dementia receiving IMV, for example, are at high risk for delirium, which confers a 3.2-fold increased risk of 6-month mortality.4 The increasing use of aggressive therapies suggests that demand for IMV in elderly populations will increase in the future, both among patients that are likely to benefit and among those with terminal illness. We examined temporal trends in IMV use by older patients with and without dementia and projected future use.
Alteration of lysophosphatidylcholine content in low density lipoprotein after oxidative modification: relationship to endothelium dependent relaxation
Authors: S-Y Liu, X Lu, S Choy, T C Dembinski, G M Hatch, D Mymin, X Shen, A Angel, P C Choy, R Y K Man
Journal: Cardiovascular Research (1994)

Objective: The aim was to examine the formation of lipid peroxidation products and the alteration in phospholipid content in low density lipoprotein (LDL) after oxidative modification by CuSO4, and subsequently, to determine the ability of the modified LDL to impair endothelium dependent relaxation in rat aortic rings. Methods: Blood samples were obtained from normal human volunteers. LDL was prepared by sequential ultracentrifugation and it was oxidatively modified in the presence of 5 μM CuSO4. Lipid peroxidation products (thiobarbituric acid reactive substancec, TBARS), and alterations in electrophoretic mobility and phospholipid content were determined in normal (native) and oxidised LDL. Endothelium dependent relaxation was produced by acetylcholine (10−8-10−5 M) in phenylephrine precontracted rat aortic rings. Results: LDL incubated for 24 h with 5 μM CuSO4, at 20°C and 37°C with constant agitation displayed higher amounts of TBARS than the respective native LDL. While the amounts of TBARS in LDL modified at 20°C and 37°C were similar, the former condition resulted in statistically smaller changes of phospholipid contents. LDL with higher lysophosphatidylcholine content showed greater impairment of endothelium dependent relaxation in rat aortic rings than LDL with lower lysophosphatidylcholine content. Conclusions: The raised lysophosphatidylcholine level in oxidatively modified LDL was related to the ability of the LDL to impair endothelium dependent relaxation. However, lipid peroxidation products assessed by TBARS did not relate to the phospholipid changes in LDL and therefore cannot be used to predict the vascular effects of LDL after oxidative modification. Cardiovascular Research 1994;28:1476-1481
Nonmutagenic carcinogens induce intrachromosomal recombination in dividing yeast cells.
Authors: R H Schiestl
Journal: Environmental Health Perspectives (1993)

A large number of animal and human carcinogens without apparent genotoxic activity exist (nonmutagenic carcinogens) that are difficult or impossible to detect with the currently used short-term tests. Because of the association of carcinogenesis with genome rearrangement, a system selecting for intrachromosomal recombination (DEL recombination) that results in genome rearrangement has been constructed in the yeast Saccharomyces cerevisiae. Because DEL recombination is under different genetic control than interchromosomal recombination and meiotic recombination, it is probably due to a different mechanism. It has been found that DEL recombination is readily inducible by 10 mutagenic carcinogens and 17 nonmutagenic carcinogens that are not detectable (false negatives) with the Ames assay. In addition, three out of four mutagens that do not cause cancer (false positives in the Ames assay) do not induce DEL recombination. DEL recombination is inducible by UV only in dividing cells but not in cells synchronized in the G1 or G2 phase of the cell cycle. Interchromosomal recombination, on the other hand, is inducible in G1 but not in G2. The nonmutagenic carcinogens induce DEL recombination only in actively growing cells, which may give some indication as to their mechanism. Further characterization of the mechanism involved in induction of DEL recombination may contribute to the understanding of the biological activity of nonmutagenic carcinogens.
Global Levels of Histone Modifications in Peripheral Blood Mononuclear Cells of Subjects with Exposure to Nickel
Authors: Adriana Arita, Jingping Niu, Qingshan Qu, Najuan Zhao, Ye Ruan, Arthur Nadas, Yana Chervona, Fen Wu, Hong Sun, Richard B. Hayes, Max Costa
Journal: Environmental Health Perspectives (2011)

Occupational exposure to nickel (Ni) is associated with an increased risk for lung and nasal cancers. Ni compounds exhibit weak mutagenic activity, cause gene amplification, and disrupt cellular epigenetic homeostasis. However, the Ni-induced changes in global histone modification levels have only been tested in vitro.This study was conducted in a Chinese population to determine whether occupational exposure to Ni is associated with alterations of global histone modification levels and to evaluate the inter- and intraindividual variance of global histone modification levels.Forty-five subjects with occupational exposure to Ni and 75 referents were recruited. Urinary Ni and global H3K4 trimethylation, H3K9 acetylation, and H3K9 dimethylation levels were measured in peripheral blood mononuclear cells (PBMCs) of subjects.H3K4me3 was elevated in Ni-exposed subjects (0.25% ± 0.11%) compared with referents (0.15% ± 0.04%; p = 0.0004), and H3K9me2 was decreased (Ni-exposed subjects, 0.11% ± 0.05%; referents, 0.15% ± 0.04%; p = 0.003). H3K4me3 was positively (r = 0.4, p = 0.0008) and H3K9ac was negatively (r = 0.1, p = 0.01) associated with urinary Ni. Interindividual variances of H3K4me3, H3K9ac, and H3K9me2 were larger compared with intraindividual variance in both exposure test groups, resulting in reliability coefficients (an estimate of consistency of a set of measurements) of 0.60, 0.67, and 0.79 for H3K4me3, H3K9ac, and H3K9me2, respectively, for Ni-exposed subjects and of 0.75, 0.74, and 0.97, respectively, for referent subjects.The results of this study indicate that occupational exposure to Ni is associated with alterations of global histone modification levels and that measurements of global levels of histone modifications are relatively stable over time in human PBMCs.
Book: Medication Errors: Lessons for Education and Healthcare
Authors: T. Avery
Journal: BMJ (2003)

Robert Naylor Radcliffe Medical Press, £29.95, pp 344 ISBN 1 85775 956 7 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> Like many who have made an in-depth examination of medical error, Robert Naylor seems to have been profoundly affected by his explorations. This is a book that charts the literature on medication errors and displays a passion shared by Harvard professor Lucian Leape and others in arguing that we can and must do more to stop harming patients ( BMJ 2000;320:725-6). Naylor notes that his concern “to report and then reduce drug-induced adverse … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Prospective randomised trial in 1062 infants of diet low in saturated fat and cholesterol
Authors: H. Lapinleimu, P. Salo, T. Routi, H. Lapinleimu, E. Jokinen, I. Välimäki, O. Simell, J. Viikari, T. Rönnemaa
Journal: The Lancet (1995)
Effect of a Decision Aid on Knowledge and Treatment Decision Making for Breast Cancer Surgery
Authors: Timothy Whelan, Mark Levine, Andrew Willan, Amiram Gafni, Ken Sanders, Doug Mirsky, Shelley Chambers, Mary Ann O'Brien, Susan Reid, Sacha Dubois
Journal: JAMA (2004)

ContextThe long-term results of randomized trials have demonstrated equivalent survival rates for mastectomy and breast-conserving therapy for the treatment of early stage breast cancer. Consequently, the choice of treatment should be based on a patient's preferences.ObjectiveTo evaluate the impact of a decision aid regarding the different surgical treatment options on patient decision making.Design and SettingA cluster randomized trial for which general surgeons in the communities of central-west, and eastern Ontario, Canada, were randomly assigned to use the decision aid or not in the surgical consultation. Patients received the decision aid or not based on the surgeon seen.ParticipantsTwenty surgeons participated in the study. Of the 208 eligible women with newly diagnosed clinical stage I or II breast cancer seen by study surgeons, 201 agreed to be evaluated: 94 were assigned to the decision board and 107 to usual practice. Patients were recruited from November 1999 to April 2002.InterventionThe decision board is a decision aid designed to help physicians inform their patients about different treatment options and to enable patients to express a preference for treatment.Main Outcome MeasuresPatient knowledge about the surgical treatment of breast cancer; decisional conflict; satisfaction with decision making; and the treatment decision following the consultation.ResultsPatients in the decision board group had higher knowledge scores about their treatment options (66.9 vs 58.7; P&lt;.001), had less decisional conflict (1.40 vs 1.62, P = .02), and were more satisfied with decision making (4.50 vs 4.32, P = .05) following the consultation. Patients who used the decision board were more likely to choose BCT (94% vs 76%, P = .03).ConclusionsThe decision board was helpful in improving communication and enabling women to make a choice regarding treatment. Such instruments should be considered by surgeons when communicating the different surgical options to women with breast cancer.
Interleukin 15–mediated survival of natural killer cells is determined by interactions among Bim, Noxa and Mcl-1
Authors: Nicholas D Huntington, Hamsa Puthalakath, Priscilla Gunn, Edwina Naik, Ewa M Michalak, Mark J Smyth, Hyacinth Tabarias, Mariapia A Degli-Esposti, Grant Dewson, Simon N Willis, Noboru Motoyama, David C S Huang, Stephen L Nutt, David M Tarlinton, Andreas Strasser
Journal: Nature Immunology (2007)