tbuckley/cabot-search huggingface dataset:
Sex hormones and gynaecological cancer.
Authors: J S Scott
Journal: BMJ (1982)

The opportunities for preventing cancer of the sex organs in women tend to differ greatly from those arising with other cancers.  For example avoidance of sexual intercourse would probably almost eliminate carcinoma of the cervix.  With cancers of the breast ovary and endometrium sexual activity (in so far as it is measured by numbers of pregnancies) appears to be protective.  The action may be hormonally mediated and of these cancers endometrial carcinoma has the clearest endocrine relation:  estrogens unopposed by progestogens predispose to it while progestogens can inhibit established tumors and may also act prophylactically.  A recent report suggests that the progestogen in oral contraceptives (OCs) may have such a protective effect.  The numbers were small and analysis of the total data gave results that did not reach statistical significance but the calculated relative risk of 0.44 is in keeping with other estimates.  Apart from comparison with controls the pattern of the data is persuasive:  protection appears greater with use over 5 years with recent use and with more progestogenic preparations.  Minor modifications of OC regimens should be examined in the hope of enhancing any cancer-inhibiting effect without increasing their adverse effects.  The sequential regimen seems not to protect against endometrial cancer while combined estrogen and progestogen for 21 out of 28 days may give some protection.  So daily progestogen alone may be more protective.  In regard to hormonal replacement for postmenopausal women unopposed estrogen has been found to increase the risk of endometrial cancer but adding progestogen may counteract the effect.  Cancer of the ovary seems to be less frequent in users of OCs.  An inevitable consequence of OC is more coitus without barrier contraception so that cervical cancer would be expected to be more common in women taking the pill.  In practice no evidence has emerged of a substantial increase in invasive tumors in OC users although intraepithelial lesions are more common.  Far from disposing to gynecological cancer OCs (or at least their progestogen component) seem to be having an overall favorable influence on the incidence of neoplasms.  Such a balance of risks and benefits is more difficult to assess for cardiovascular effects.  Inevitably any longterm change in the physiological state such as that pronounced with OCs and postmenopausal hormone replacement will result in a change in disease pattern.
Expression of CYP3A4 as a predictor of response to chemotherapy in peripheral T-cell lymphomas
Authors: Cristina Rodríguez-Antona, Susanna Leskelä, Magdalena Zajac, Marta Cuadros, Javier Alvés, Maria Victoria Moneo, Carmen Martín, Juan Cruz Cigudosa, Amancio Carnero, Mercedes Robledo, Javier Benitez, Beatriz Martínez-Delgado
Journal: Blood (2007)
Successful Treatment of Anti-Caspr2 Syndrome by Interleukin 6 Receptor Blockade Through Tocilizumab
Authors: Christos Krogias, Robert Hoepner, Andre Müller, Christiane Schneider-Gold, Alexandra Schröder, Ralf Gold
Journal: JAMA Neurology (2013)

<h3>Importance</h3> A patient with a Caspr2 autoantibodies–associated syndrome had an unusual clinical triad and an excellent response to B-cell–anergizing therapy using the humanized monoclonal antibody tocilizumab directed against the interleukin 6 (IL-6) receptor. <h3>Observations</h3> A 55-year-old man had an atypical clinical triad of epilepsy, dysarthria, and paroxysmal kinesigenic dystonia, and a high titer of Caspr2 antibodies was detected in his serum and cerebrospinal fluid. Screening for underlying neoplasias was negative. With initial methylprednisolone sodium succinate and alternate treatment using plasma exchange and immunoabsorption as well as subsequent IL-6 receptor blockade through tocilizumab, a complete and stable remission of symptoms has been achieved throughout the follow-up period of 7 months. <h3>Conclusions and Relevance</h3> In our patient, the implementation of a B-cell–anergizing therapy using tocilizumab, a humanized monoclonal antibody against the IL-6 receptor, has shown an excellent response. Larger case series or even controlled studies are needed to confirm the efficacy of tocilizumab in autoimmune synaptic or presynaptic diseases.
Outcomes of Older Patients Receiving Chronic Dialysis
Authors: Glenn M. Chertow
Journal: JAMA (1994)

To the Editor.  —Medicare's end-stage renal disease (ESRD) program has been subject to renewed critical interest in recent years. The effectiveness of the program has been judged largely by patient survival and less so by objective measures of quality of life such as employment status; neither of these have reached physician or societal expectations. The article by Dr Ifudu and colleagues 1 describes dismal rehabilitation in geriatric inner-city hemodialysis patients. Despite the authors' claim to the contrary, we are concerned that this article may present a short-sighted interpretation of the data and provide ammunition for those who wish to institute age-based rationing of hemodialysis. 1   As determined by modified Karnofsky scores, the authors report a significant reduction in overall functional status compared with 2 years before the initiation of maintenance hemodialysis (mean, 5.3 years; up to 11 years previously). It is unclear how much of this decline in functional status
PLK1shRNA and doxorubicin co-loaded thermosensitive PLGA-PEG-PLGA hydrogels for osteosarcoma treatment
Authors: Hecheng Ma, Chaoliang He, Yilong Cheng, Dongsong Li, Yubao Gong, Jianguo Liu, Huayu Tian, Xuesi Chen
Journal: Biomaterials (2014)
Routine Urinalysis: Is the Dipstick Enough?
Authors: Christopher Fung
Journal: JAMA (1985)

To the Editor.—  We agreed with the conclusions and recommendations of the article Routine Urinalysis by Shaw et al, 1 but we would like to comment on one aspect of the article. The authors stated that many of these patients suffered from more than one disease process. Thus, the total false-negative rate of the Chemstrip may be considerably lower in other settings where relatively more healthy individuals, or those in the early stages of a single disease, are seen. This is certainly true, because their false-negative rate is derived by dividing the number of false-negatives by total number of cases tested. If the proportion of healthy individuals is increased in the tested population, clearly this false-negative rate must decrease. Obviously, among the healthy there can be no false-negatives; there can only be true-negatives and false-positives. If testing had been done on a relatively healthy population, the false-negative rate of 3.3%
On Writing (5): Fabrication, Falsification and Plagerism in Medical Research and Publishing
Authors: J. Baillie
Journal: Endoscopy (2004)

This is the fifth in a series of articles on medical writing and publishing. In this one we look at the “Dark Side” of research and publishing, namely fraud. When I recently looked at a textbook on medical writing published 25 years ago, this issue was covered in a few short paragraphs. Unfortunately, despite their honorable “calling”, members of the medical profession are not immune to the temptations of scientific fraud, as evidenced by a series of spectacular and well-publicized cases over the years. In 1974, Dr William Summerlin claimed to have shown that skin taken from a black mouse could be transplanted into a white one. It turned out that he had used a black felt-tip marker to color a graft of white skin! In another infamous case, American researcher John Darsee was shown to have fabricated the results of over 100 published studies. His work came under scrutiny when colleagues wondered how anyone could publish a new research paper approximately every 10 days! As pointed out by other commentators, accusations of scientific fraud are not new: dark rumors still circulate that famous scientists in history, from Sir Isaac Newton to Gregor Mendel and Louis Pasteur, must have manipulated their data to get such good results! Outright fraud in research and publication comes in a variety of guises, including fabrication (making up data), falsification (changing data), plagiarism (copying the work of others and perhaps “piracy” (stealing others’ ideas). However, other abuses, such as duplicate (or multiple) publication and “gift authorship” (making colleagues who have not contributed to the work authors) may also be considered fraudulent. Needless to say, the exposure of fraud has serious consequences for the perpetrators: their reputations are irreversibly tarnished, they can face civil - and even criminal - penalties, and their promising research careers are ruined (along with any hope of academic promotion and tenure). As the potential for “collateral damage” (e. g. adverse publicity, censure by government agencies) is enormous when cases of scientific fraud are exposed, institutions where basic and/or clinical research take place are strongly motivated to detect fraud and prevent its dissemination.
Oligonucleotide therapeutic approaches for Huntington disease
Authors: Dinah W.Y. Sah, Neil Aronin
Journal: Journal of Clinical Investigation (2011)

Huntington disease is an autosomal dominant neurodegenerative disorder caused by a toxic expansion in the CAG repeat region of the huntingtin gene. Oligonucleotide approaches based on RNAi and antisense oligonucleotides provide promising new therapeutic strategies for direct intervention through reduced production of the causative mutant protein. Allele-specific and simultaneous mutant and wild-type allele–lowering strategies are being pursued with local delivery to the brain, each with relative merits. Delivery remains a key challenge for translational success, especially with chronic therapy. The potential of disease-modifying oligonucleotide approaches for Huntington disease will be revealed as they progress into clinical trials.
Decreased leukotriene B4 synthesis in smokers' alveolar macrophages in vitro.
Authors: M Laviolette, R Coulombe, S Picard, P Braquet, P Borgeat
Journal: Journal of Clinical Investigation (1986)

Recent studies have shown that alveolar macrophages (AM) are able to release leukotrienes (LTs). Since cigarette smoking inhibits the cyclooxygenase pathway of arachidonic acid metabolism in the AM, we evaluated the LT production by AM from smokers and nonsmokers. AM were obtained from 35 volunteers, 16 nonsmokers, and 19 smokers. The cells were incubated under various conditions including stimulation with 30 microM arachidonic acid, 2 microM ionophore A23187, or both. Each experiment was performed in parallel using cells from a smoker and a nonsmoker. Lipoxygenase products were analyzed by reverse-phase high performance liquid chromatography. After stimulation, nonsmokers' AM produced LTB4 and 5-hydroxy-eicosatetraenoic acid (5-HETE). In incubations of AM with arachidonic acid and ionophore, the amounts of products formed were: LTB4, 317 +/- 56 pmol/10(6) cells and 5-HETE, 1,079 +/- 254, mean +/- SEM. No metabolites were generated under control conditions (no stimulation). In all incubations performed, the peptido-LTs (LTC4, LTD4, and LTE4) were undetectable. In comparison with AM from nonsmokers, those from smokers showed a 80-90% reduction of 5-HETE and LTB4 synthesis (P less than 0.05 to P less than 0.001 according to stimulatory conditions). This defective lipoxygenase metabolite production in AM from smokers was observed over a wide range of stimuli concentrations and incubation times; AM from smokers also had lower levels of intracellular (esterified) 5-HETE than nonsmokers' AM. We also studied blood polymorphonuclear leukocytes (PMNL) and no difference in the synthesis of 5-lipoxygenase products in these cells was noticed between smokers and nonsmokers. These data show that cigarette smoking causes a profound inhibition of the 5-lipoxygenase pathway in AM but not in blood PMNL.
Cysteinyl Leukotrienes Modulate Both Bone Marrow Eosinophilia and T Cells Numbers in a Murine Model of Allergen-induced Airway Remodeling.
Authors: M.B. Hogan, S. Khaiboulina, K.S. Landreth, R.A. Van Andel, L.A. Welniak
Journal: Journal of Allergy and Clinical Immunology (2009)
Gas-liquid chromatography in the analysis of mercury (II) compounds.
Authors: P Mushak
Journal: Environmental Health Perspectives (1973)

Gas-liquid chromatography (GLC) in recent years has found application in the analysis of various metals, either singly (1) or in tandem function with mass spectrometry (2), and presently is gaining wide acceptance in the analysis of organomercury(II) compounds.Since increasing use of GLC in mercury analysis may be anticipated for both research and monitoring purposes, it is of value at this point in time to review critically the status of GLC analysis of mercury compounds, in- cluding the relevant chemistry and biocoordi- nation chemistry of mercury in its various chemical forms.Gueral Consideradon of Gas-Uquid Chroma- tography of Msmury(ill Compounds As GLC analysis usually requires that an analyte be simultaneously thermally stable and possess volatility, GLC analyses of mercury compounds have involved primarily volatile organomercurials possessing a variety of alkyl, substituted alkyl, or aryl groups.Isolated reports of inorganic mercury(II) analysis by GLC do exist in the literature, however, and have involved idealized condi- *tions without analytical application.
Release Kinetics of Circulating Muscle-Enriched MicroRNAs in Patients Undergoing Transcoronary Ablation of Septal Hypertrophy
Authors: Christoph Liebetrau, Helge Möllmann, Oliver Dörr, Sebastian Szardien, Christian Troidl, Matthias Willmer, Sandra Voss, Luise Gaede, Johannes Rixe, Andreas Rolf, Christian Hamm, Holger Nef
Journal: Journal of the American College of Cardiology (2013)
Intestinal obstruction caused by splenosis at the rectosigmoid junction, mimicking malignant pelvic tumor
Authors: V. Gincu, P. Kornprat, F. Thimary, S. Jahn, H. Mischinger
Journal: Endoscopy (2011)

A 74-year-old woman presented with an incidental finding on computed tomography (CT) scanning of a tumor in the lesser pelvis of unclear origin. Questioning of the patient revealed a history of long-term, intermittent constipation and splenectomy 18 years previously after a car accident. A contrast-enhanced CT scan showed a solid expansive process with marked contrast enhancement ([Fig. 1]). Magnetic resonance imaging (MRI) revealed a 2.5-cm clearly demarcated nodular lesion at the rectal fold, directly adjacent to the rectum ([Fig. 2]). Our suspicion was that this lesion was a neoplasm.
PU.1 is not strictly required for B cell development and its absence induces a B-2 to B-1 cell switch
Authors: Min Ye, Olga Ermakova, Thomas Graf
Journal: The Journal of Experimental Medicine (2005)

In this paper, we describe the unexpected outgrowth of B lineage cells from PU.1−/− fetal liver cultures. The cells express all early B cell genes tested, including the putative PU.1 target genes IL-7R and EBF but not B220, and can produce immunoglobulin M. However, we observed a delay in the PU.1−/− B cell outgrowth and reduced precursor frequencies, indicating that although PU.1 is not strictly required for B cell commitment, it facilitates B cell development. We also ablated PU.1 in CD19-expressing B lineage cells in vivo, using a Cre-lox approach that allows them to be tracked. PU.1 excision resulted in a shift from B-2 cells to B-1–like cells, which dramatically increased with the age of the mice. Our data indicate that this shift is predominantly caused by a B-2 to B-1 cell reprogramming. Furthermore, we found that B-2 cells express substantially more PU.1 than B-1 cells, which is consistent with the idea that maintenance of the B-2 cell phenotype requires relatively high levels of PU.1, but B-1 cells require little.
Malaria is on the rise in Pakistan, health workers warn
Authors: N. Siva
Journal: BMJ (2010)

As floods continued to ravage the south of Pakistan last week, health workers have expressed concern about the rise in the number of suspected malaria cases that have been reported.

World Health Organization data show that 3.7 million people have been treated in areas affected by the floods since they began on 29 July. The cases include just over 500 000 of acute diarrhoea (13% of the total number of cases), 520 000 of acute respiratory …
Immunosurveillance against Cancer and Immunotherapy — Synergy or Antagonism?
Authors: Thierry Boon, Nicolas van Baren
Journal: New England Journal of Medicine (2003)

Immunologists have long been alert to the possibility that the immune system eliminates many cancers at an early stage and slows down the progress of others.1 In recent years, the concept of immune surveillance against cancer has received support from experiments in mice. An increased incidence of spontaneous or methylcholanthrene-induced tumors was observed in mice lacking interferon-γ, interferon-γ receptors, or perforin and also in mice deficient in recombinase-activating gene 2, which have severe immunodeficiency.2 Processes other than immune rejection of tumor cells may contribute to these results,3 but it is likely that in mice, the immune system can eliminate incipient . . .
Case in Which the Urachus Remained Pervious after Birth
Authors: T. H. Starr
Journal: BMJ (1844)

2 8 IPERVIOUS URACHUS.-TREATMENTOF ASPHYXIA.answered best (in the erysipelatous form) in my prac- tice has been hot, dry applications to the belly and extremities, and large doses of calomel, opium, and tartar emetic.
Living Longer, Contributing Longer
Authors: Robert N. Butler
Journal: JAMA (1997)

IN 1988, the image of the "Greedy Geezer" was born. Depicted on the cover of<i>The New Republic</i>magazine, the advancing army of angry-faced older persons wielding garden trowels, fishing poles, and golf clubs looked menacing, poised to assault America. The essay inside by Henry Fairlie<sup>1</sup>described what the cover expressed visually: Older people are selfish and drain the country of resources that might otherwise be channeled elsewhere, especially to children. There have been other similar negative attacks on older people in this country. The Concord Coalition, for example—a membership organization dedicated to federal deficit reduction—has, in its concern over the solvency of public entitlement programs, scapegoated older people. The image of the affluent Greedy Geezer and his or her arrogant sense of entitlement has become a powerful symbol in this time of negative attitudes toward government and increased tax resistance, and it is helping to foment an artificially
Pressure Transients Occurring in Diastole in the Central Aorta
Authors: Thomas E. Piemme, Lewis Dexter
Journal: Circulation Research (1963)

From the observations noted and from physical considerations, the following may be concluded: Cardiac events of sufficient energy content to cause sudden displacement of the heart and great vessels give rise to pressure transients that may be seen in all chambers if carefully looked for. These are, in reality, "acceleration" waves superimposed upon otherwise smooth pressure functions. Such an oscillation occurs normally at the time of isometric ventricular contraction. The energy content of isometric ventricular contraction results in an induced pressure wave in all chambers, but is most prominently seen in the low pressure atria as the "c wave, " and in the aorta and pulmonary artery as small, relatively high frequency, presystolic impulses. The event is obscured in the ventricles by the rapidly rising intraventricular pressure but may be identified when the ventricular pressure is differentiated. Under pathological circumstances, atrial contraction and early ventricular filling may result in peripherally recordable pressure deflections.
Abstract 3473: Prolonged exposure to zinc chromate induces numerical chromosome instability via centrosome amplification in human lung cells
Authors: Amie L. Holmes, Sandra S. Wise, Stephen Pelsue, Wilma Lingle, Jeffery Salisbury, Jamie Gallagher, John P. Wise
Journal: Cancer Research (2010)

Abstract Lung cancers are often characterized by numerical chromosome instability. Hexavalent chromium (Cr(VI)) is a well-known human lung carcinogen; however, its carcinogenic mechanism remains unknown. Studies show that solubility plays a key role in its carcinogenicity, with the particulate, or insoluble, compounds being the most potent carcinogens. Epidemiological and whole animal studies pinpoint particulate zinc chromate as the most potent Cr(VI) carcinogen; however, few studies have investigated its carcinogenic mechanism. Therefore, the goal of this study was to determine if zinc chromate induces numerical chromosome instability in human lung cells. We found that exposure to zinc chromate for 24 h did not induce aneuploidy but longer exposures induced both concentration- and time-dependent increases in aneuploid metaphases. For example, exposure to 0.1, 0.15 and 0.2 ug/cm2 zinc chromate for 120 h induced 28, 40 and 44 percent aneuploid metaphases, respectively, with increases in hypodiploid, hyperdiploid and tetraploid metaphases. Consistent with the aneuploidy data, a 24 h exposure to zinc chromate did not induce centrosome amplification but more chronic exposures induced concentration- and time-dependent increases in centrosome amplification in both interphase and mitotic cells. Exposure to 0.1, 0.15 and 0.2 ug/cm2 zinc chromate for 120 h induced centrosome amplification in 13.9, 18 and 21.3 percent of interphase cells and 21, 33 and 46 percent of mitotic cells. In order to determine the mechanism of centrosome amplification, we investigated the number of centrioles in each centrosome and found that cells with amplified centrosomes exhibited centrosomes with normal centriole pairs and centrosomes with centriolar defects indicating multiple mechanisms are involved in zinc chromate-induced centrosome amplification. Lastly, we found that chronic exposure to zinc chromate induced a prolonged G2 arrest. All together, these data indicate that chronic exposure to zinc chromate induces numerical chromosome instability via centrosome amplification in human lung cells. This work was supported by NIEHS grant ES016893 (J.P.W.), cooperative agreement #EP-08-01 through the Maine Space Grant Consortium (J.P.W.), EPA GRO Fellowship MA-91685401 (A.L.H.) and the Maine Center for Toxicology and Environmental Health at the University of Southern Maine. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3473.
Small bowel enema in non-responsive coeliac disease.
Authors: N Mike, U Udeshi, P Asquith, J Ferrando
Journal: Gut (1990)

A small bowel enema was performed in patients with non-responsive coeliac disease, in coeliac patients on a normal diet (untreated) and those who had shown a good response to a gluten free diet, and in control subjects to determine whether there were any specific radiological features of the non-responsive state. A significant reduction in the average number of jejunal folds and an increase in the number of ileal folds (reversal of the jejunoileal fold pattern) was found in eight of nine non-responsive coeliac patients, one of seven untreated coeliac patients, and in none of the good responders or control subjects. This pattern identifies coeliac patients with a poor response to a gluten free diet who are likely to suffer major complications.
Mutation of tyrosine 145 of lymphocyte cytosolic protein 2 protects mice from anaphylaxis and arthritis
Authors: Laurie E. Lenox, Taku Kambayashi, Mariko Okumura, Christopher Prieto, Karsten Sauer, Ralph M. Bunte, Martha S. Jordan, Gary A. Koretzky, Kim E. Nichols
Journal: Journal of Allergy and Clinical Immunology (2009)
Book Review From Faust to Strangelove: Representations of the scientist in western literature By Roslynn D. Haynes. 417 pp. Baltimore, Johns Hopkins University Press, 1994. $55 (cloth); $19.95 (paper). 0-8018-4801-6 (cloth); 0-8018-4983-7 (paper).
Authors: Edward W. Campion
Journal: New England Journal of Medicine (1995)