tbuckley/cabot-search huggingface dataset:
Women Physicians Target Barriers
Authors: Paul Cotton
Journal: JAMA (1993)

GYNECOLOGY is virtually nonexistent at the National Institutes of Health (NIH), Bethesda, Md, the nation's preeminent medical research funder and facility. Significant progress has been made in addressing the lack of attention to women in medical research since a 1990 Congressional General Accounting Office report documented the great extent to which women have been ignored by the NIH. Yet veterinarians still outnumber manyfold the half dozen or so gynecologists on staff, says Florence Haseltine, MD, PhD, director of the NIH Center for Population Research. Despite an estimated $10 billion NIH budget, there is "no input from the group of people that takes care of women in the reproductive years," says Haseltine. "This says that in our major research institution, women's health is not observed." This and other structural impediments to equality for women in medicine were discussed at a round table sponsored by the Society for the Advancement of Women's
Inhibition of lipolysis by adenosine is potentiated with age.
Authors: B B Hoffman, H Chang, Z Farahbakhsh, G Reaven
Journal: Journal of Clinical Investigation (1984)

The ability of a variety of hormones to activate cells declines with age. We have investigated the mechanism for the reduced ability of beta adrenergic stimulation to activate lipolysis in fat cells from older rats. Previously, we have found that these cells have an intact lipolytic response to a cAMP analogue but diminished cAMP accumulation after isoproterenol stimulation, suggesting that the blunted cAMP response is rate limiting. In the present study we have tested the hypothesis that enhanced inhibition of lipolysis by endogenously released adenosine accounts for the diminished lipolysis. Adenosine deaminase was added to media containing the adipocytes from older rats to remove endogenous adenosine. Under these conditions beta adrenergic stimulation of lipolysis is intact in fat cells from older rats. The adenosine analogue N6-phenylisopropyladenosine more effectively inhibited lipolysis in the older group (77 +/- 6%) than in the younger group (46 +/- 5%), suggesting that enhanced efficacy of endogenous adenosine may account for the reduced lipolytic response to catecholamines. When pertussis vaccine was used to functionally inactivate adenosine receptors in adipocytes from the younger and older rats, the ability of isoproterenol to activate lipolysis was restored in the older group. All the data are consistent with the hypothesis that enhanced inhibitory effects of adenosine explain the diminished ability of beta adrenergic agonists to activate lipolysis. It is possible that enhanced inhibitory pathways may be involved in blunting responses to stimulatory hormones in other tissues from older animals.
MicroRNA down-regulated in human cholangiocarcinoma control cell cycle through multiple targets involved in the G1/S checkpoint
Authors: Alexandru V. Olaru, Gabriel Ghiaur, Sumitaka Yamanaka, Delgermaa Luvsanjav, Fangmei An, Irinel Popescu, Sorin Alexandrescu, Sarah Allen, Timothy M. Pawlik, Michael Torbenson, Christos Georgiades, Lewis R. Roberts, Gregory J. Gores, Anne Ferguson-Smith, Maria I. Almeida, George A. Calin, Esteban Mezey, Florin M. Selaru
Journal: Hepatology (2010)

Abstract MicroRNAs (miRs) recently emerged as prominent regulators of cancer processes. In the current study we aimed at elucidating regulatory pathways and mechanisms through which miR-494, one of the miR species found to be down-regulated in cholangiocarcinoma (CCA), participates in cancer homeostasis. miR-494 was identified as down-regulated in CCA based on miR arrays. Its expression was verified with quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR). To enforce miR expression, we employed both transfection methods, as well as a retroviral construct to stably overexpress miR-494. Up-regulation of miR-494 in cancer cells decreased growth, consistent with a functional role. mRNA arrays of cells treated with miR-494, followed by pathway analysis, suggested that miR-494 impacts cell cycle regulation. Cell cycle analyses demonstrated that miR-494 induces a significant G1/S checkpoint reinforcement. Further analyses demonstrated that miR-494 down-regulates multiple molecules involved in this transition checkpoint. Luciferase reporter assays demonstrated a direct interaction between miR-494 and the 3′-untranslated region of cyclin-dependent kinase 6 (CDK6). Last, xenograft experiments demonstrated that miR-494 induces a significant cancer growth retardation in vivo . Conclusion: Our findings demonstrate that miR-494 is down-regulated in CCA and that its up-regulation induces cancer cell growth retardation through multiple targets involved in the G1-S transition. These findings support the paradigm that miRs are salient cellular signaling pathway modulators, and thus represent attractive therapeutic targets. miR-494 emerges as an important regulator of CCA growth and its further study may lead to the development of novel therapeutics. (Hepatology 2011)
Cost of Medical Care-Reply
Authors: George B. Markle
Journal: JAMA (1978)

<h3>In Reply.—</h3> I am extremely gratified that there is an increasing number of physicians like Dr Rodney who are not only concerned about the costs of health care, but who are doing something about them. I thoroughly agree that traditional training in our medical educational institutions is biased toward extravagant use of expensive technology, more costly medications and therapies, and overuse of hospitals and medical personnel. Residents in training and those physicians who have recently finished their training may be quicker to use pulmonary function studies than their stethoscopes, intravenous aminoglycosides instead of oral penicillin, or an operating room instead of the office for a minor procedure. Fear of malpractice suits has something to do with this of course, but in many cases the young physicians just have never been shown how to practice in any other way. They appear to believe that anything that is more expensive, more time-consuming,
Paraquat poisoning in a pregnant woman.
Authors: J. J. Fennelly, J. T. Gallagher, R. T. Carroll
Journal: BMJ (1968)

Preliminary Communications and mental changes occurred in one or other of the patients; all resolved within a few days, pective of the drug tratment gin.There were no complications, and all patients made a very satisfactory and uneventful recovery. ---*Chloramphenicoltreated group ---x---Trhmethoprim /sul phametboxazoletreated group
The Alteration of Aspart Insulin Pharmacodynamics When Mixed With Detemir Insulin
Authors: Eda Cengiz, Karena L. Swan, William V. Tamborlane, Jennifer L. Sherr, Melody Martin, Stuart A. Weinzimer
Journal: Diabetes Care (2012)

Mixing rapid acting insulin analogs with detemir insulin to minimize daily injections has been adopted as a common regimen, especially for some children with type 1 diabetes, despite the manufacturing company's caution against mixing these analogs in the same syringe. The effect of this practice on the pharmacodynamics (PD) of rapid-acting insulin has not been widely studied. This crossover, randomized study was undertaken to determine whether mixing aspart with detemir insulin has an adverse effect on the early glucodynamic action of rapid-acting insulin analog in humans.Eight adolescents with type 1 diabetes (age 17.3 ± 0.6 years and A1C 7.3 ± 0.3%) had two euglycemic glucose clamps during which 0.2 units/kg aspart and 0.4 units/kg detemir insulin were injected either as a separate or single mixed injection in random order.Mixing the two insulins diminished the peak and overall early aspart insulin action with significantly lower maximum glucose infusion rate (GIR(max) separate 6.1 ± 0.7 mg/kg/min vs. mix 4.5 ± 0.5 mg/kg/min; P = 0.03) values and the area under curve for GIR during the first 3 h of the insulin action study (separate 757 ± 105 mg/kg vs. mix 491 ± 66 mg/kg; P = 0.04).These data demonstrate that mixing aspart with detemir insulin markedly lowers the early PD action of aspart and prolongs its time-action profile as compared with the separate injection of these analogs. These changes in insulin PD should be weighed against the added convenience of mixing when considering such unlicensed use of these insulins in youth with type 1 diabetes.
Primary Lymphoma of the Gastrointestinal Tract
Authors: Raymond S. Bush
Journal: JAMA (1974)

PRIMARY lymphoma of the gastrointestinal tract is diagnosed when tumor involvement of the intestine is the principal anatomic site of disease. The patient has abdominal symptoms that may be acute. Involvement of mesenteric nodes alone is not sufficient to place a patient in this classification. <h3>Nature of the Disease</h3><h3>General.—</h3> A number of characteristics are summarized in Table 5.<sup>31-33</sup> <h3>Staging.—</h3> A very simple staging was used for this discussion, ie, localized or extensive. Bowel perforations, or systemic symptoms, such as fever, weight loss or anemia, that are compatible with the local disease process do not change the staging in localized cases. The localized classification was used for those patients in whom the lymphoma involved the gastrointestinal tract alone or had spread to the regional mesenteric nodes only. There was no difference in the survival of those adult patients who did or did not have proven involvement of the regional
Isolation and immunocytochemical characterization of human bone marrow stromal macrophages in hemopoietic clusters.
Authors: S H Lee, P R Crocker, S Westaby, N Key, D Y Mason, S Gordon, D J Weatherall
Journal: The Journal of Experimental Medicine (1988)

Stromal macrophages (M phi) have been localized in situ and isolated within erythroid clusters from human marrow. Stromal M phi arborize in an extensive network uniformly distributed throughout marrow interstitium, and express the phenotype CD4+, CD11a+, CD11c+, CD13+, CD14+, CD16+, CD18+, CD31+, CD32+, FcRI+, HLA-DR+, and CD35-, transferrin receptor-negative, and CD11b (weak). They express endocytic receptor antigens, but show significant differences in myeloid antigen expression compared with freshly harvested or cultured monocytes. Human stromal M phi are therefore specialized mature marrow M phi that are accessible for further investigations in infectious, storage, or hemopoietic disorders.
Targeted and Untargeted CD137L Fusion Proteins for the Immunotherapy of Experimental Solid Tumors
Authors: Nan Zhang, Rebecca E. Sadun, Robyn S. Arias, Meg L. Flanagan, Suzanne M. Sachsman, Yu-Chih Nien, Leslie A. Khawli, Peisheng Hu, Alan L. Epstein
Journal: Clinical Cancer Research (2007)

Abstract Introduction: CD137L is a member of the tumor necrosis factor superfamily that provides a costimulatory signal to T cells. In this study, two novel CD137L fusion proteins were produced and compared with the CD137 agonist antibody 2A. Materials and Methods: Murine CD137L was linked to the COOH terminus of either the Fc fragment of immunoglobulin (untargeted version) or TNT-3 (targeted version), an antibody that binds to necrotic regions of tumors. Groups of mice bearing established Colon 26 tumors were then treated daily ×5 with each fusion protein or 2A to determine their immunotherapeutic potential. Results: Both fusion proteins retained CD137L activity in vitro and TNT-3/CD137L showed tumor-binding activity by biodistribution analysis in tumor-bearing mice. The fusion proteins also produced similar responses in vivo at the 1 nmol per dose range and showed a 60% (TNT-3/CD137L) or 40% (Fc/CD137L) survival of treated mice at 150 days after tumor implantation, similar to the effects of 2A. Morphologic and immunohistochemical analyses showed massive central necrosis and infiltration of granzyme B–positive cells in necrotic areas and viable peripheral regions of treated tumors. Finally, cell depletion studies showed that CD137L-mediated tumor regression was CD8+ T cell dependent. Conclusions: From these studies, it was determined that both targeted and untargeted CD137L fusion proteins showed effective antitumor activity, but that the targeted version was more potent. Therefore, the use of the natural CD137 ligand is a promising approach to the treatment of solid tumors by virtue of its ability to produce physiologic costimulation within the tumor, limiting side effects often seen with agonist antibody therapies.
Antithrombosis stockings must have non-slip soles
Authors: R. Gillon, A. Cullum, E. Pimm, S. Andersen, A. Andersen, D. Bacon
Journal: BMJ (2012)

A doctor patient died last year after slipping on a hospital floor and sustaining a cerebral bleed. He was wearing antithrombosis stockings but no slippers.1 Informally, a clinician at a different hospital said …
When Law and Ethics Collide — Why Physicians Participate in Executions
Authors: Atul Gawande
Journal: New England Journal of Medicine (2006)

Interview with Dr. Carlo Musso on the participation of physicians in capital punishment. (09:31)Download On February 14, 2006, a U.S. District Court issued an unprecedented ruling concerning the California execution by lethal injection of murderer Michael Morales. The ruling ordered that the state have a physician, specifically an anesthesiologist, personally supervise the execution, or else drastically change the standard protocol for lethal injections.1 Under the protocol, the anesthetic sodium thiopental is given at massive doses that are expected to stop breathing and extinguish consciousness within one minute after administration; then the paralytic agent pancuronium is given, followed by a fatal dose of potassium chloride.The judge found, however, that evidence from execution logs showed . . .
Localized Pretibial Myxedema
Authors: Gordon N. French
Journal: New England Journal of Medicine (1949)

THE term "myxedema" is frequently used as a synonym for "hypothyroidism." It is a matter of common experience, however, that the majority of patients with clinical hypothyroidism do not have either local or generalized mucinous changes in the skin. Local myxedema in euthyroid persons is a familiar entity to the dermatologist. Such lesions usually are not symmetrically placed and appear singly or multiply on the upper or lower extremities or on the trunk. Definite, local, myxedematous changes may also occur in patients with exophthalmic goiter. A few reviews1 2 3 4 and scattered case reports5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 have appeared. The concurrence of hyperthyroidism and local . . .
Fluorescence Cystoscopy with High-Resolution Optical Coherence Tomography Imaging as an Adjunct Reduces False-Positive Findings in the Diagnosis of Urothelial Carcinoma of the Bladder
Authors: Joerg Schmidbauer, Mesut Remzi, Tobias Klatte, Matthias Waldert, Julian Mauermann, Martin Susani, Michael Marberger
Journal: European Urology (2009)
Increased Risk for Vitamin A Toxicity in Severe Hypertriglyceridemia
Authors: JEROME K. ELLIS
Journal: Annals of Internal Medicine (1986)

A 48-year-old woman with malabsorption and type V hyperlipoproteinemia developed hypervitaminosis A with a total plasma vitamin A level of 871 µg/dL during therapy with an oral dosage of 18 000 retinol equivalents (60 000 IU) daily. Twelve percent of the total plasma retinol was found to be transported in the chylomicronvery low density lipoprotein (VLDL) fraction, which does not contain retinol-binding protein. For comparison, concentrations of retinyl esters and retinol were determined in nine patients with type V hyperlipoproteinemia and nine control subjects, none of whom were using vitamin A supplements. Both retinyl esters and retinol were significantly elevated in the group with hyperlipoproteinemia (p <0.0005 in both cases). Eight of these nine patients had retinol present in the chylomicron-VLDL fraction, whereas retinol was not detectable in this fraction in any of the nine normal controls. The data suggest that patients with severe hypertriglyceridemia associated with type V hyperlipoproteinemia are at increased risk for hypervitaminosis A.
Abstract 5324: Cathepsin E expression: A new potential target for pancreatic tumor imaging
Authors: Zobeida Cruz-Monserrate, Wael R. Abd-Elgaliel, Baoan Ji, Defeng Deng, Thiruvengadam Arumugan, Ching H. Tung, Craig D. Logsdon
Journal: Cancer Research (2011)

Abstract Purpose: Pancreatic ductal adenocarcinoma (PDAC) shows unique high expression of Cathepsin E (CTSE). Here we assessed the usefulness of detecting CTSE activity in vivo as a prognostic biomarker for PDAC using mouse xenografts and transgenic models of PDAC. Procedures: CTSE expression in human and mouse pancreases with/without cancer were assessed by immunohistochemistry. Transgenic animal models of PDAC and xenografts of primary human PDAC tumors or establish pancreatic cancer cell lines in nude mice were injected with the CTSE selective fluorescent probe via tail vein. CTSE expressions in transgenic pancreatic tumors and xenografts were imaged using IVIS-100 optical imaging system. Negative control tumors were imaged in parallel. Tumors, organs and tissues of interest were imaged ex vivo for their associated Cath E expression. Data: Results confirmed the over expression of CTSE in pancreatic cancer patients and transgenic mouse models of pancreatic cancer. Images illustrate the capability of detecting CTSE expression within pancreatic tumors in both transgenic and xenograft mice models. In vivo and ex vivo images of PDAC were possible by targeting CTSE expression. Conclusions: Results represent the usefulness of CTSE as a potential molecular target for pancreatic cancer imaging. The elevated CTSE expression in pancreatic tumors allows in vivo detection of human PDAC xenografts and ex vivo imaging of transgenic PDAC tumors in mice. The study demonstrates CTSE as a promising target for tumor imaging. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5324. doi:10.1158/1538-7445.AM2011-5324
The Treatment of Breast Cancer
Authors: William M. Cooper
Journal: JAMA (1975)

This small book edited by Sir Hedley Atkins has, as contributors, six physicians highly experienced in the treatment of breast cancer, in their special areas of expertise. In addition to their clinical experience, they have participated in both basic and clinical research. The presentations review the literature with excellent bibliographies and present the multiplicity of opinions and approaches now present in the field. Recommendations regarding management show the particular bias of the contributors. The most useful part of the book appeared to be the section on management of "Primary Cancer of the Breast," by A. P. M. Forrest of Edinburgh. For this condition he provided a full outline of treatment, which could provide a useful model for the practicing physician to follow. There are schemata of management for both premenopausal and postmenopausal breast cancer patients, presented by F. J. Ansfield of Madison, Wis. This could be useful even though the
Diabetes and Heart Disease
Authors: Elizabeth Barrett-Connor
Journal: Diabetes Care (2003)

Diabetes is a strong risk factor for coronary heart disease (CHD) and eradicates the usual delayed onset of fatal and nonfatal CHD in women (when compared with men) (1). Although nearly all observational studies have suggested that estrogen therapy reduces the risk of CHD in postmenopausal women (2), two large clinical trials, the Heart and Estrogen/Progestin Replacement Study (HERS) (3) and the Women’s Health Initiative (WHI) (4), compared daily conjugated equine estrogen plus medroxyprogesterone acetate with placebo and found an early increased risk of CHD and no evidence of long-term benefit. In HERS, a trial conducted in 2,763 women with known CHD, 19% were treated for diabetes at baseline. In WHI, a trial conducted in 16,608 women largely free of CHD at baseline, 4.4% were treated for diabetes at baseline. These subgroups were large enough to test for an interaction of hormone effects by diabetes status; these analyses showed no differential CHD risk or benefit among women with versus without diabetes in the HERS (5) or WHI (4) clinical trials.

These clinical trial results are in direct contrast to those reported by Newton et al. (6) in this issue of Diabetes Care , who report in yet another observational study that estrogen has a cardioprotective effect in women with diabetes. In this case-cohort study from a health maintenance organization (HMO), women with known diabetes who were current users of hormone therapy (with or without a progestin) had about half the …
NON-SECRETION OF ABO ANTIGENS PREDISPOSING TO INFECTION BY NEISSERIA MENINGITIDIS AND STREPTOCOCCUS PNEUMONIAE
Authors: C.C. Blackwell, K. Jónsdóttir, M. Hanson, W.T.A. Todd, A.K.R. Chaudhuri, B. Mathew, R.P. Brettle, D.M. Weir
Journal: The Lancet (1986)
Comprehensive Analysis of HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 Loci and Squamous Cell Cervical Cancer Risk
Authors: Margaret M. Madeleine, Lisa G. Johnson, Anajane G. Smith, John A. Hansen, Brenda B. Nisperos, Sue Li, Lue-Ping Zhao, Janet R. Daling, Stephen M. Schwartz, Denise A. Galloway
Journal: Cancer Research (2008)

Abstract Variation in human major histocompatibility genes may influence the risk of squamous cell cervical cancer (SCC) by altering the efficiency of the T-cell–mediated immune response to human papillomavirus (HPV) antigens. We used high-resolution methods to genotype human leukocyte antigen (HLA) class I (A, B, and Cw) and class II (DRB1 and DQB1) loci in 544 women with SCC and 542 controls. Recognizing that HLA molecules are codominantly expressed, we focused on co-occurring alleles. Among 137 allele combinations present at &amp;gt;5% in the case or control groups, 36 were significantly associated with SCC risk. All but one of the 30 combinations that increased risk included DQB1*0301, and 23 included subsets of A*0201-B*4402-Cw*0501-DRB1*0401-DQB1*0301. Another combination, B*4402-DRB1*1101-DQB1*0301, conferred a strong risk of SCC (odds ratio, 10.0; 95% confidence interval, 3.0–33.3). Among the six combinations that conferred a decreased risk of SCC, four included Cw*0701 or DQB1*02. Most multilocus results were similar for SCC that contained HPV16; a notable exception was A*0101-B*0801-Cw*0701-DRB1*0301-DQB1*0201 and its subsets, which were associated with HPV16-positive SCC (odds ratio, 0.5; 95% confidence interval, 0.3–0.9). The main multilocus associations were replicated in studies of cervical adenocarcinoma and vulvar cancer. These data confirm that T helper and cytotoxic T-cell responses are both important cofactors with HPV in cervical cancer etiology and indicate that co-occurring HLA alleles across loci seem to be more important than individual alleles. Thus, certain co-occurring alleles may be markers of disease risk that have clinical value as biomarkers for targeted screening or development of new therapies. [Cancer Res 2008;68(9):3532–9]