tbuckley/cabot-search huggingface dataset:
Abstract 578: Apigenin blocks medroxyprogesterone acetate-dependent progression of BT-474 human breast tumor xenografts by inducing apoptosis
Authors: Benford Mafuvadze, Yayun Liang, Cynthia L. Besch-Williford, Salman M. Hyder
Journal: Cancer Research (2012)

Abstract Recent clinical and epidemiological evidence suggests that hormone replacement therapy (HRT) containing both estrogen and progestin increases the risk of metastatic breast cancer in post-menopausal women compared with estrogen monotherapy or placebo treated women. The biological mechanisms behind this phenomenon remain obscure. We showed that medroxyprogesterone acetate (MPA), a commonly used progestin in HRT, increases the production of the potent angiogenic growth factor VEGF in breast cancer cells. The anti-progestin RU-486 blocks this effect, suggesting the involvement of progesterone receptors in the process (Int J Cancer, 2001, 92:469). This led to our hypothesis that progestins increase the angiogenic potential of latent tumorigenic cells in the breast, leading to development of palpable tumors. Using a xenograft model that was developed in our laboratory (Cancer Res., 2007, 67:9929), we previously showed that progestins promote the growth and development of BT-474 human xenograft tumors, as well as increasing BT-474 cell metastasis. In this study, we sought to determine whether apigenin, a low molecular weight flavonoid with known anti-carcinogenic properties, inhibits MPA-induced growth of BT-474 xenografts in nude mice. BT-474 human breast cancer cells were inoculated in immune-deficient mice that had been pre-inoculated with estradiol pellets. As was previously reported with this model, estradiol supported a short burst of tumor cell growth, which was followed by tumor regression. Implantation of MPA pellets rescued and stimulated further tumor growth. Administration of apigenin (50 mg/kg i.p.) inhibited the MPA-induced progression and development of BT-474 xenograft tumors. Immunohistochemical analysis revealed that the anti-tumor effects of apigenin occur through induction of tumor cell apoptosis, as measured using TUNEL assay, and also in part by suppression of cell proliferation (Ki67). Apigenin therefore appears to have therapeutic potential against progestin-dependent breast cancer and might be considered as a neutraceutical for treating progestin-dependent tumors in women already exposed to progestins. This study was supported by a COR award from the College of Vet Medicine, and research funds from RADIL, University of Missouri. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 578. doi:1538-7445.AM2012-578
Benzodiazepines and Zolpidem for Chronic Insomnia
Authors: Peter D. Nowell
Journal: JAMA (1997)

<h3>Objective.</h3> —To evaluate the efficacy of benzodiazepines and zolpidem tartrate in chronic insomnia based on a quantitative review of literature. <h3>Data Sources.</h3> —Articles from 1966 to 1996 were identified using MEDLINE, by a manual review of relevant journals, and from bibliographies of identified articles. <h3>Study Selection.</h3> —Studies using randomized, double-blind, placebo-controlled, parallel or crossover designs with benzodiazepines or zolpidem in adults younger than 65 years with chronic insomnia (modified<i>Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition</i>criteria for primary insomnia) were selected for review. Self-report and polysomnographic measures of sleep-onset latency, total sleep time, number of awakenings, and sleep quality were selected as outcomes. <h3>Data Extraction.</h3> —Twenty-two studies met the selection criteria. A combined test of<i>P</i>values was performed, pooling broadly from the 22 studies to determine whether medication was superior to placebo. A combined test of effect sizes was performed on the subset of studies that reported effect size information to determine the magnitude of medication effect. <h3>Data Synthesis.</h3> —A homogeneous sample of studies summarized 1894 patients treated for a median duration of 7 days. The combined test of P values demonstrated that medication was superior to placebo in all 4 outcome measures. Treatment response was moderate in magnitude by the combined test of effect sizes. <h3>Conclusions.</h3> —Benzodiazepines and zolpidem produced reliable improvements in commonly measured parameters of sleep in patients with chronic insomnia. Relative to the chronic and recurring course of insomnia, both the limited duration of treatments studied and the lack of follow-up data from controlled trials represent challenges for developing evidence-based guidelines for the use of hypnotics in the management of chronic insomnia.
Cost-effectiveness of Combined Statin-Resin Therapy
Authors: Dennis L. Sprecher
Journal: Annals of Internal Medicine (1994)

Letters1 October 1994Cost-effectiveness of Combined Statin-Resin TherapyDennis L. Sprecher, MD and Leonard Jokubaitis, MDDennis L. Sprecher, MDSearch for more papers by this author and Leonard Jokubaitis, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-121-7-199410010-00027 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:The comments of Dr. Katz regarding cost-effectiveness and its value in reports on new drugs are well advised. However, his suggestion that pharmaceutical company sponsorship of this clinical trial was the rationale for nondisclosure of cost is unfounded. Our manuscript [1] was submitted to Annals before the Food and Drug Administration approved fluvastatin for clinical use. The determination of pharmaceutical pricing is a labile phenomenon, and the specific price of fluvastatin was not available to the authors at the time of submission.Table 1 provides a simple cost-effectiveness comparison of various therapeutic regimens, based on currently available pricing ...References1. Sprecher DL, Abrams J, Allen JW, Keane WF, Chrysant SG, Ginsberg H, et al. Low-dose combined therapy with fluvastatin and cholestyramine in hyperlipidemic patients. Ann Intern Med. 1994; 120:537-43. Google Scholar2. Bradford RH, Shear CL, Chremos AN, Dujovne C, Downton M, Franklin FA, et al. Expanded clinical evaluation of Lovastatin (EXCEL) study results. I. Efficacy in modifying plasma lipoproteins and adverse event profile in 8245 patients with moderate hypercholesterolemia. Arch Intern Med. 1991; 151:43-9. Google Scholar3. The Lovastatin Pravastatin Study Group. A multicenter comparative trial of lovastatin and pravastatin in the treatment of hypercholesterolemia. Am J Cardiol. 1993; 71:810-5. Google Scholar4. Full prescribing information for Zocor (simvastatin; Merck, Sharp & Dohme, West Point, Pennsylvania). In: Physician's Desk Reference. Montvale, New Jersey: Medical Economics Data. Google Scholar5. Lescol (fluvastatin). East Hanover, New Jersey: Sandoz Pharmaceuticals. U.S. package insert; 1994. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1994Volume 121, Issue 7Page: 548-549KeywordsCholesterolClinical trialsDrug therapyFamilial hypercholesterolemiaFood and Drug AdministrationHemoglobinLipoproteinsLow density lipoproteinRandomized trials Issue Published: 1 October 1994 CopyrightCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Fenestration of the Oval Window Four-Year Report
Authors: John J. Shea
Journal: JAMA (1960)

In this operation for otosclerosis the entire stapes is removed, and a fenestra is created in the oval window by drilling away the otosclerotic bone at the margins with a small cutting bur. The fenestra is then covered with a thin piece of vein graft removed from the back of the patient's hand. The sound-conducting mechanism of the middle ear is rebuilt with a length of polyethylene-90 tubing inserted between the lenticular process of the incus and the center of the vein graft. The eardrum is then put back into place, and the middle ear is closed. In more than 1,400 such operations done during the past four years, about 94% of the patients have improved to the extent that the disparity between air and bone conduction has been reduced to 10 decibels or less.
Antenatal prophylaxis with anti-D immunoglobulin.
Authors: R. Hussey
Journal: BMJ (1989)

BCG immunisationSIR,-The Department of Health, in circular EL(89)P/93, asked health authorities to postpone their regular BCG programme for schoolchildren this autumn because the British supplier of the vaccine is in the throes of moving to a new site.I wonder if others share my view that this request is unacceptable.As district vaccination coordinator I hear much stout talk "from on high" about targets and accountability, and I feel that the department must now be seen to meet the standards it lays down for others.No target date for resumption of supply has been offered-is the problem for a week, a month, a year?Or is the hope that the programme will quietly wither away?The department should be held to account for this avoidable disruption to the immunisation programme.I also do not understand why, in a health service increasingly exposed to market forces, the market cannot be allowed to provide a solution.There is more than one reput- able manufacturer of BCG vaccine.We are already threatened with a resurgence of tuberculosis thanks to HIV, increasing poverty, and the possibility of a wave of refugees from Hong Kong and Indo-China.The last thing we need is departmental own goals.
Congenital Mesoblastic Nephroma and Polyhydramnios
Authors: Eugene Blank
Journal: JAMA (1978)

Polyhydramnios and premature delivery complicated the pregnancies of three women whose infants were born with renal tumors. In each case the tumor was a mesoblastic nephroma. The liquid of polyhydramnios enhances detection of masses in the fetal abdomen by ultrasound. In the future, mesoblastic nephroma may, therefore, be diagnosed antenatally. Tumors in these infants, which have proved in most cases to be benign, are usually cured by surgical removal. Occasionally, local infiltration and adhesions prevent removal. The fate of the infant with residual tumor is not known.
State Regulation of Managed Care and the Employee Retirement Income Security Act
Authors: W K Mariner
Journal: New England Journal of Medicine (1996)

The federal Employee Retirement Income Security Act (ERISA)1 is the federal law that governs employee-benefit plans offered by private employers and unions. ERISA has long hindered state efforts to expand access to health care, because it prohibits states from requiring all employers to offer benefits to their employees.2 States have shifted their attention from seeking universal insurance coverage for health care to regulating the benefits of people who already have health insurance. Reports describing how some managed-care organizations limit the care provided to their enrollees have prompted a rash of legislative efforts intended to protect patients from receiving substandard care. . . .
Three memorable consultations
Authors: Sylvia Potter
Journal: BMJ (2004)

Commentary: It's not just about rubbing-topical capsaicin and topical salicylates may be useful as adjuvants to conventional pain treatment Martin R TramèrDrugs can be injected (subcutaneously, intramuscularly, intravenously, intrathecally, epidurally); given by mouth (orally, sublingually), intranasally, or rectally; or inhaled.They can also be applied to the skin.The transdermal method is suitable for certain lipid soluble drugs and produces a steady rate of delivery for up to three days.Cutaneous administration is used when a local effect on the skin is required.Drugs may also be applied to the skin to achieve close proximity to the bones or muscles without flooding the organism; this is the case when, for instance, an analgesic cream is applied to a painful knee.The two reviews by Mason and coworkers (Oxford
XERODERMA PIGMENTOSUM..
Authors: H. EL-HEFNAWI, M. EL-NABAWI, M. F. S. EL-HAWARY
Journal: British Journal of Dermatology (1962)

Journal Article XERODERMA PIGMENTOSUM.: III: Studies of Serum Copper and Blood Glutathione. Get access H. EL‐HEFNAWI, M.D., Ch.B., D.V.D., H. EL‐HEFNAWI, M.D., Ch.B., D.V.D. Assistant Professor of Dermatology, Cairo University Search for other works by this author on: Oxford Academic Google Scholar M. EL‐NABAWI, M.D., Ch.B., D.C.H., M. EL‐NABAWI, M.D., Ch.B., D.C.H. Assistant Professor Paediatrics, Cairo University Search for other works by this author on: Oxford Academic Google Scholar M. F. S. EL‐HAWARY, Ph.D., B.Sc. M. F. S. EL‐HAWARY, Ph.D., B.Sc. Research Department, Serum and Vaccine Institute, Agouza, Cairo Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 74, Issue 6, 1 June 1962, Pages 218–221, https://doi.org/10.1111/j.1365-2133.1962.tb13494.x Published: 01 June 1962
Health and History in the Middle East
Authors: John L. Wilson
Journal: New England Journal of Medicine (1959)

THE pertinent comment was recently made that even the people of the Middle West are concerned about the Middle East. And well they may be. This strategic land bridge linking Eurasia and Africa now occupies a prominent place on the world stage — a position of importance that it has held many times during its seven thousand years of eventful history. Here, in an area larger than the United States, live 116,000,000 people.1 Their nations lie across the sea and air lanes between East and West, and beneath their feet are more than half the earth's known oil reserves. Critical . . .
Interleukin 10 pretreatment protects target cells from tumor- and allo-specific cytotoxic T cells and downregulates HLA class I expression.
Authors: M Matsuda, F Salazar, M Petersson, G Masucci, J Hansson, P Pisa, Q J Zhang, M G Masucci, R Kiessling
Journal: The Journal of Experimental Medicine (1994)

Interleukin 10 (IL-10) is a cytokine with a variety of reported effects including inhibition of monocyte major histocompatibility complex (MHC) class II-dependent antigen presentation, type 1 helper T cell cytokine production, and inhibition of T cell proliferation. Herein we report the effect of IL-10 pretreatment on antigen presentation to tumor- and allo-specific CD8+ cytotoxic T lymphocytes (CTL). Prior incubation of human melanoma cells with recombinant IL-10 (rIL-10) for 48-72 h resulted in a dose-dependent, up to 100% inhibition, of autologous CTL-mediated, HLA-A2.1-restricted, tumor-specific lysis. Allo-specific CTL cytotoxicity against Epstein-Barr virus-transformed lymphoblastoid cell lines (LCL) was also inhibited, demonstrating a protective effect also on lymphoid cells. In contrast, IL-10 pretreatment of allogeneic LCL or K562 targets had either no effect or slightly enhanced cytotoxic activity mediated by freshly isolated or IL-2-activated natural killer cells. Flow cytometric analysis with monoclonal antibodies against HLA-A2, or nonpolymorphic determinants of MHC class I proteins, revealed a 20-50% reduction in cell-surface expression, whereas intercellular adhesion molecules 1, and 2, and lymphocyte function-associated antigen 3 levels were not affected. In addition, relative to untreated target cells, IL-10 pretreated tumor cells were unaltered in their capacity to affect CTL-mediated lysis by cold target inhibition, demonstrating that the effect of IL-10 is unrelated to the initial binding of CTL to their targets. These results are compatible with an effect of IL-10 on the MHC class I antigen presentation pathway, and suggest a novel mechanism of immune tolerance, based on escape from CTL-mediated tumor and allo-transplant rejection.
Chronic Intermittent Juvenile Jaundice
Authors: A. P. H. Randle, M. J. H. Smith, B. W. Meade
Journal: BMJ (1952)

JOURNAL~~~~~~~~~~~~Ĩ n the present case the bilateral fractured patellae cannot be directly related to the cauda equina lesion, as no part of the reflex quadriceps arc was found defective.His frac- tures were undoubtedly due to faulty balance caused by muscular weakness below the knees.
Jessica in the Well: Ischemia and Reperfusion Injury
Authors: Paul J. Benke
Journal: JAMA (1988)

<h3>To the Editor.</h3> —The recent dramatic rescue of Jessica McClure from a Midland Texas well was a heroic measure that touched our hearts. After being immobilized and brought to the surface, Jessica was rushed to the hospital and received intravenous fluids and 90 minutes of hyperbaric oxygen to "save" an ischemic limb. The drillers and paramedics did excellent work. Creative therapy was provided by her physicians, who decided that if a little oxygen was good to treat a compromised leg, more oxygen was better. However, mechanisms of ischemic injury are now understood,<sup>1,2</sup>although not widely appreciated, and have been discussed in general medical journals.<sup>3</sup>Much damage does not take place during actual ischemia, but when blood flow is reestablished and toxic free radicals are formed. Following ischemia, the protective capacity of endogenous tissue superoxide dismutase therapy to break down free-radical oxygen is overwhelmed by increased xanthine oxidase activity,
Diagnostic systems as an aid to clinical decision making.
Authors: R P Knill-Jones
Journal: BMJ (1987)

However denned, dyspepsia is a common condition that accounts for a considerable proportion of consultations in general practice, referrals to hospital, and working days lost to illness. Diagnosis is often difficult and negative results of investigations common,2 which leads to many patients having the symptoms but no evidence of an organic cause for them. An accurate history is therefore essential, yet one may not be taken because of lack of time, the easy availability of investigations such as endoscopy (which seems sometimes to be used as an alternative to a properly taken history), or a simple failure to appreciate the c?scriminating value of standardised questions. Several solutions to this problem have been explored, including the use of standard forms3 that can be entered on a computer,4 automated history taking,5 6 which can be used as a decision aid,7 * and simple weighting systems for symptoms.910 All these solutions aim to reduce the diagnostic uncertainty of the doctor so that more rational therapeutic, investigative, and referral procedures develop. Diagnostic uncertainty about patients who have dyspepsia is high in general practice and is probably equally high among junior hospital staff; despite such uncertainty, there is little teaching about which are the best questions to ask?that is, which are the Popperian searchlights alluded to by Macartney.1 What is required is a simple screening system that minimises unnecessary referrals and negative results of investigations. The development of such a system has many similarities to problems in other clinical specialties. For example, in the assessment of risk for ischaemic heart disease the use of weights (or scores) for each factor is becoming widespread.  In this instance the approach is a practical one for assessing risk, and it can help patients to reduce their own risk factors. In dyspepsia a similar approach should lead to better use of existing resources and in particular improve the overall management of patients when care is shared between the general practitioner and the hospital based specialist. This paper shows first how a simple weighting system for symptoms can be devised, given some carefully collected data. The method is clearly related to that described by Macartney1 but is expressed in a different way. For application in clinical practice this process has been partly automated: a computer asks the relevant questions of the patient and prints the results as a summary; this is effectively a screening process indicating which patients require referral and why, and, for those who do not indicating appropriate management to be carried out in general practice.
Radiolabeled Denatured RBC Scintigraphy in Autologous Splenic Transplantation
Authors: RAJNISH SHARMA, ANUPAM MONDAL, RAVI KASHYAP, SHYAMAL KUMAR CHAKRAVARTY, KRISHAN SAWROOP, THAKURI SINGH
Journal: Clinical Nuclear Medicine (1996)

An 18-year-old man underwent surgery for blunt abdominal trauma requiring a total splenectomy. Heterotopic splenic autotransplantation was done in the omentum. Immediate platelets counts, cell morphology, and serum immunoglobulin levels were suggestive of impaired splenic function. Radiolabeled denatured RBC splenic imaging showed evidence of functioning autotransplanted splenic tissue in the omentum. The blood parameters were found to be normal 4 weeks after transplant. Radionuclide denatured RBC imaging has been found to be useful in the localization of functional autotransplanted splenic tissue.
Web-based versus Paper Administration of Common Ophthalmic Questionnaires
Authors: Janine Austin Clayton, Malvina Eydelman, Susan Vitale, Zorayr Manukyan, Robert Kramm, Manuel Datiles, Alana Temple, Elizabeth Murphy, Jonghyeon Kim, Gene Hilmantel, Eva Rorer, Keri Hammel, Frederick Ferris
Journal: Ophthalmology (2013)
P84Pathway dissection in cardiac muscle cell death: MAP4K4 as a therapeutic target
Authors: LR Fiedler, K Chapman, E Maifoshie, R Sampson, C Low, C Traulau-Steward, MD Schneider
Journal: Cardiovascular Research (2014)

Cell death has been shown to be causative in progression to heart failure. However, no established pharmacological treatments directly address this problem in either acute or chronic settings. We previously identified MAP4K4/HGK as an activator of the TAK1 - JNK pathway in cardiac cell death, whose inhibition by dominant-negative mutations or shRNA knockdown confers protection in cultured rat neonatal cardiomyocytes. Confirming the relevance of MAP4K4 in a human setting, shRNAmir-mediated knockdown was protective against H202-induced cardiomyocyte cell death in human iPSC-derived cardiomyocytes. To address this therapeutic potential, we initiated a small molecule discovery programme. Screening of known kinase inhibitors for activity against recombinant MAP4K4 kinase domain identified four with a pIC50 > 7 (series 1). To generate novel compounds, features of similar charge distribution were analysed by pharmacophore field-point modeling and used to generate a consensus pharmacophore model for inhibition of MAP4K4. This model was then used to interrogate 2.5M structures in silico. The top 40 ranked compounds were synthesized and tested for activity against MAP4K4 and the most potent from each of two chemical series (series 2) taken forward. Series 2 had much improved selectivity (3-5 of 141 kinases inhibited > 50% at 1 μM) over series 1, and further, was more selective and equally potent (IC35-100 nM) as two small molecule inhibitors described by Pfizer. In addition, series 2 were not toxic to cardiomyocytes up to 10 μM, while those described by Pfizer, and two of series 1, were toxic (measured by hypodiploid DNA content, Caspase 3 activation and ATP production). Importantly, both compounds from series 2 showed protection against H202- or C2-ceramide mediated cell death in rat neonatal cardiomyocytes (measured by hypodiploid DNA content). Thus we have obtained promising lead compounds for optimization and experimental studies, and shown that inhibition of MAP4K4 in vitro, whether by knockdown of expression or pharmacological inhibition, is protective against cell death in cardiomyocytes.