tbuckley/cabot-search huggingface dataset:
Ticlopidine and Clopidogrel
Authors: Martin J. Quinn, Desmond J. Fitzgerald
Journal: Circulation (1999)

Abstract —The thienopyridines ticlopidine and clopidogrel are inhibitors of platelet function in vivo. Their mode of action has not been defined, but it appears that they require conversion to as yet unidentified metabolites that are noncompetitive antagonists of the platelet ADP receptor. Inhibition of platelet aggregation with these compounds is delayed until 24 to 48 hours after administration. Maximum inhibition occurs after 3 to 5 days, and recovery is slow after drug withdrawal. Ticlopidine is effective in preventing cardiovascular events in cerebrovascular, cardiovascular, and peripheral vascular disease, with an efficacy that is similar to aspirin. However, its use is associated with significant and sometimes fatal adverse reactions, specifically neutropenia and bone marrow aplasia. Gastrointestinal side effects and skin rashes are common and result in discontinuation of therapy in up to 10% of patients. Clopidogrel is at least as effective as aspirin in preventing cardiovascular events in patients with a history of vascular disease. It appears to be safer than ticlopidine, although its efficacy in acute coronary syndromes or post–coronary-stent insertion has not been reported. Important outstanding issues are whether clopidogrel adds to the benefit of aspirin and whether the combination of these agents is safe. If so, this combination may become the standard for antithrombotic therapy in cardiovascular disease.
Abstract 977: Elevated MDM2 protein contributes to activity of MDM2 antagonists by enabling p53 induction of antitumor microRNAs
Authors: Mingxuan Xia, Baoying Huang, Wei Chu, Lyubomir T. Vassilev
Journal: Cancer Research (2012)

Abstract Small-molecule inhibitors of p53-MDM2 binding, the nutlins, can free p53 from MDM2 control and effectively activate its growth suppressive and pro-apoptotic activity in cancer cells (Vassilev et al., Science, 2004, 303, 844). Optimized members of this family of molecules are currently under clinical investigation as novel therapeutic modality for cancers expressing wild-type p53. We have shown previously that MDM2 antagonists are most effective in cancer cells that overproduce MDM2 as a result of mdm2 gene amplification (Tovar et al., PNAS, 2006, 103, 1888). Here, we show that reduction of MDM2 protein by RNA interference decreases the effectiveness of nutlin-3a in osteosarcoma cells with mdm2 gene amplification, suggesting that MDM2 protein contributes to antitumor activity of MDM2 antagonists. In search of the mechanism behind this phenomenon, we found that nutlin-induced p53 activates the transcription of a specific subset of microRNAs in cancer cells with mdm2 amplification but not in cells expressing normal levels of MDM2 protein. Five specific members of the class (miR1, miR133, miR141, miR184, miR375) were studied and showed that their p53-dependent transcription is also dependent on the presence of high levels of MDM2 protein, generated by continuous p53 activation of MDM2 in the presence of nutlin. Weak p53 response elements were found in the promoter regions of all five miRs and p53 binding was conformed by ChIP analysis of cell lysates and p53 reporters in experiments with miR375. Transcriptional cofactor p300 was found elevated in cancer cells with mdm2 gene amplification and dependent on the presence of high MDM2 protein levels. Our experimental data suggests that in the presence of high p300, and high MDM2, generated by nutlin treatment, p53 acquires the ability to activate weak p53-responsive miR promoters in MDM2-amplified cells. Interestingly, miR mimics of two of the five p53-induced miRs showed growth suppressive effects in cancer cells and enhanced the activity of low dose nutlin-3a. These findings reveal a novel mechanism for modulation of p53 transcriptional activity and indicate that the high levels of MDM2, generated in mdm2-amplified cancer cells in the presence of nutlin, contribute to its antitumor. 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 977. doi:1538-7445.AM2012-977
URINARY SODIUM EXCRETION PREDICTS ARTERIAL STIFFNESS IN NEWLY DIAGNOSED HYPERTENSIVE PATIENTS: A 6-YEAR FOLLOW-UP STUDY
Authors: C. Thomopoulos, K. Tsioufis, E. Andrikou, D. Syrseloudis, D. Tsiachris, D. Roussos, E. Stefanadi, I. Tatsis, A. Kasiakogias, C. Stefanadis
Journal: Journal of the American College of Cardiology (2011)
Tuberculosis
Authors: Paul T. Davidson
Journal: New England Journal of Medicine (1985)

Tuberculosis is perceived by many as a rare disease of quaint historical interest. The ubiquitous county and state sanatoriums are long gone, as are the mobile chest-film units. The tuberculin skin test is used infrequently as a general surveillance tool, and when used as a diagnostic procedure, it is often part of a search for the cause of an unexplained obscure condition. Health departments point to a dramatic drop in the number of patients listed in the tuberculosis case registries. And so it goes.Nevertheless, the reality is that nearly 25,000 new cases were reported in the United States for . . .
Hormonal Control of Cardiac Myosin Adenosine Triphosphatase in the Rat
Authors: Michael J. Rovetto, Åke C. Hjalmarson, Howard E. Morgan, Michael J. Barrett, Richard A. Goldstein
Journal: Circulation Research (1972)

Cardiac function was impaired in hearts from hypophysectomized rats. Corresponding to the decrease in performance, myosin from the hearts of these rats exhibited a decreased Ca 2+ -activated ATPase activity. Myosin ATPase activated by K + or NH 4 + was not different in any of the preparations studied. The decreased Ca 2+ -activated ATPase was observed in cardiac myosin but not in red or white skeletal muscle myosin. Treatment with thyroxine, but not with growth hormone, restored cardiac myosin ATPase and performance to normal. Hypothyroidism produced a decrease in cardiac myosin ATPase activity comparable to that seen after hypophysectomy, suggesting that the absence of thyroid hormone was responsible for the alterations. However, hyperthyroidism did not increase ATPase activity above normal values. Adrenalectomy failed to alter myosin ATPase. Anion exchange chromatography of the myosins and addition of various concentrations of Na + , Ca 2+ , and Mg 2+ did not abolish the differences in myosin ATPase. The results strongly suggest that the lower myosin ATPase activity in the absence of thyroid hormone was the result of a change in the myosin molecule per se and that the lower enzymatic activity was involved in the lower cardiac performance in these rats.
Two closely related simulations provide weak limits on Residual Normality
Authors: Richard P. Cooper
Journal: Behavioral and Brain Sciences (2002)

Thomas &amp; Karmiloff-Smith (T&amp;K-S) correctly identify Residual Normality (RN) as a critical assumption of some theorising about mental structure within developmental psychology. However, their simulations provide only weak support for the conditions under which RN may occur because they explore closely related architectures that share a learning algorithm. It is suggested that more work is required to establish the limits of RN.
TINEA CAPITIS IN A PRIMARY SCHOOL.
Authors: SUZANNE ALEXANDER, YVONNE M. CLAYTON, W. C. NOBLE
Journal: British Journal of Dermatology (1965)

Journal Article TINEA CAPITIS IN A PRIMARY SCHOOL. Get access SUZANNE ALEXANDER, SUZANNE ALEXANDER St. John's Hospital for Diseases of the Skin, Lisle St., London, W.C.2 Search for other works by this author on: Oxford Academic Google Scholar YVONNE M. CLAYTON, YVONNE M. CLAYTON St. John's Hospital for Diseases of the Skin, Lisle St., London, W.C.2 Search for other works by this author on: Oxford Academic Google Scholar W. C. NOBLE W. C. NOBLE St. John's Hospital for Diseases of the Skin, Lisle St., London, W.C.2 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 77, Issue 7, 1 July 1965, Pages 373–376, https://doi.org/10.1111/j.1365-2133.1965.tb14663.x Published: 01 July 1965
Thyroid Dysfunction During Interferon Alpha Therapy for Chronic Hepatitis C
Authors: Lily Shen, Chuong Bui, Robert Mansberg, Diep Nguyen, Sharon Alam-Fotias
Journal: Clinical Nuclear Medicine (2005)

Interferon-alpha therapy is well known to induce a wide range of thyroid dysfunction. A 22-year-old woman with chronic hepatitis C developed overt hyperthyroidism while on interferon-alpha and ribavirin therapy. Tc-99m thyroid scintigraphy demonstrated virtually absent tracer uptake consistent with subacute thyroiditis. Ten months after starting antiviral therapy, overt hyperthyroidism recurred. Repeat thyroid scintigraphy revealed diffusely increased tracer uptake throughout the thyroid gland consistent with Graves disease. This is an unusual case of 2 forms of hyperthyroidism-confirmed scintigraphically and occurring in the same patient over time while on interferon-alpha therapy.
The Value of High Fidelity Electrocardiography Using the Cathode Ray Oscillograph and an Expanded Time Scale
Authors: PAUL H. LANGNER
Journal: Circulation (1952)

The cathode ray is practically free from inertia and therefore an ideal instrumentality for studying variations in electrical potential. A cathode ray oscilloscope with an amplifier system of high frequency response and an expanded time scale, 330 mm. per second, were employed to record electrocardiograms. Such tracings revealed considerable notching, slurring, and other peculiarities not seen in the conventional electrocardiographic records on the same individuals. An instrument should have a frequency response curve flat to well over 330 cycles per second to record faithfully the human electrocardiogram. This is much higher than the frequency response of instruments usually used for electrocardiography.
‘Positive’ and ‘Negative’ Aspects of the ‘Altered States of Consciousness’ Induced by Autogenic Training, Zen and Yoga
Authors: Yujiro Ikemi, Hitoshi Ishikawa, J.R.M. Goyeche, Y. Sasaki
Journal: Psychotherapy and Psychosomatics (1978)

As practices of altered states of consciousness (ASC) have become more widely used among psychotherapists who have become aware of the limitations of psychoanalytic, educational and behavioral approaches, negative aspects ('Makyo') of ASC have drawn their special attention. For the purpose of controlling or preventing these side-effects, (1) the problem of indication is most important, (2) and evaluation of the patient's personality is indispensable, (3) preparatory education about ASC methods and (4) guidance by experienced leaders are most helpful, (5) appropriate use of tranquilizers and (6) the mere presence of a supportive therapist at the place of practice can also be helpful.
Interleukin-6 Signaling Drives Fibrosis in Unresolved Inflammation
Authors: Ceri A. Fielding, Gareth W. Jones, Rachel M. McLoughlin, Louise McLeod, Victoria J. Hammond, Javier Uceda, Anwen S. Williams, Mark Lambie, Thomas L. Foster, Chia-Te Liao, Christopher M. Rice, Claire J. Greenhill, Chantal S. Colmont, Emily Hams, Barbara Coles, Ann Kift-Morgan, Zarabeth Newton, Katherine J. Craig, John D. Williams, Geraint T. Williams, Simon J. Davies, Ian R. Humphreys, Valerie B. O’Donnell, Philip R. Taylor, Brendan J. Jenkins, Nicholas Topley, Simon A. Jones
Journal: Immunity (2014)

Highlights•Repeated acute resolving inflammation leads to excessive tissue damage•IL-6 regulates profibrotic IFN-γ-secreting T cells•IFN-γ increases detrimental STAT1 signaling in stromal tissue•STAT1 activity alters homeostatic control of extracellular matrix to promote fibrosisSummaryFibrosis in response to tissue damage or persistent inflammation is a pathological hallmark of many chronic degenerative diseases. By using a model of acute peritoneal inflammation, we have examined how repeated inflammatory activation promotes fibrotic tissue injury. In this context, fibrosis was strictly dependent on interleukin-6 (IL-6). Repeat inflammation induced IL-6-mediated T helper 1 (Th1) cell effector commitment and the emergence of STAT1 (signal transducer and activator of transcription-1) activity within the peritoneal membrane. Fibrosis was not observed in mice lacking interferon-γ (IFN-γ), STAT1, or RAG-1. Here, IFN-γ and STAT1 signaling disrupted the turnover of extracellular matrix by metalloproteases. Whereas IL-6-deficient mice resisted fibrosis, transfer of polarized Th1 cells or inhibition of MMP activity reversed this outcome. Thus, IL-6 causes compromised tissue repair by shifting acute inflammation into a more chronic profibrotic state through induction of Th1 cell responses as a consequence of recurrent inflammation.
Assessment of 1,3-butadiene exposure in polymer production workers using HPRT mutations in lymphocytes as a biomarker.
Authors: M M Ammenheuser, W E Bechtold, S Z Abdel-Rahman, J I Rosenblatt, D A Hastings-Smith, J B Ward
Journal: Environmental Health Perspectives (2001)

1,3-Butadiene (BD), which is used to make styrene-butadiene rubber, is a potent carcinogen in mice and a probable carcinogen, associated with leukemia, in humans. We have previously used HPRT mutation as a biomarker to evaluate exposures to BD in a monomer production plant. We now report on a study of 49 workers in a styrene-butadiene rubber plant in which we used the concentration of the BD metabolite 1,2-dihydroxy-4-(N-acetylcysteinyl-S)-butane (M1) in urine as a biomarker of exposure and the frequency of HPRT variant (mutant) lymphocytes (Vf) as a biomarker of effect. Workers were assigned to high- and low-exposure groups based on historical information about work areas and jobs. Personal exposure to BD for one work shift was measured using a passive badge dosimeter. Each participant provided a urine specimen and blood sample at the end of the work shift and completed a questionnaire providing information on lifestyle, health, and work activities. The average BD exposures in the high- and low-exposure groups were significantly different, even after excluding two extreme values, (high 1.48 ppm; low 0.15 ppm, p &lt; 0.002). This study was done in 1994 and 1995 before the establishment, in 1996, of the new permissible exposure limit of 1 ppm. Both the mean M1 and the HPRT Vf were more than three times greater in the high-exposure group than in the low-exposure group (p &lt; 0.0005). The three end points correlated with each other, with sample correlation coefficients between 0.4 and 0.6. The correlations among BD exposure and the biomarkers of internal exposure and genotoxicity suggest that occupational exposure to BD, in the range of 1-3 ppm, may be associated with adverse biological effects.
Smoking, drinking and psoriasis
Authors: E.M. Higgins, T.J. Peters, A.W.P. du Vivier
Journal: British Journal of Dermatology (1993)

Journal Article Smoking, drinking and psoriasis Get access E.M. Higgins, E.M. Higgins Department of Dermatology, King's College Hospital, London SE5 9RS U.K. Search for other works by this author on: Oxford Academic Google Scholar T.J. Peters, T.J. Peters Clinical Biochemistry, King's College Hospital, London SE5 9RS U.K. Search for other works by this author on: Oxford Academic Google Scholar A.W.P. du Vivier A.W.P. du Vivier Department of Dermatology, King's College Hospital, London SE5 9RS U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 129, Issue 6, 1 December 1993, Pages 749–750, https://doi.org/10.1111/j.1365-2133.1993.tb03349.x Published: 01 December 1993
P3-14-01: Panitumumab in Combination with FEC 100 (5-Fluorouracile, Epirubicin, Cyclophosphamide) Followed by Docetaxel (T) in Patients with Operable, Triple Negative Breast Cancer (TNBC): Final Results of a Multicentre Neoadjuvant Pilot Phase II Study.
Authors: J-M Nabholtz, B Weber, J Gligorov, M-A Mouret-Reynier, O Tredan, L Vanlemmens, T Petit, F Mayer, Praagh-Doreau I Van, P Dubray-Longeras, B Nayl, J-P Ferriere, C Jouannaud, H Devaud, N Tubiana-Mathieu, C Abrial, F Kwiatkowski, E Planchat, N Chalabi, F Penault-Llorca, P Chollet
Journal: Cancer Research (2011)

Abstract Background: Panitumumab is an antibody targeting the epidermal growth factor receptor (EGFR) to which a role has been suggested in TNBC. Consequently, we evaluated the combination of a standard chemotherapy (FEC 100 followed by T) with panitumumab as neoadjuvant therapy of oprable TNBC. Methods: 60 patients with stage II-IIIA disease were prospectively included in this multicentre pilot study. Systemic therapy (ST) consisted of 4 cycles of FEC 100 (500/100/500 mg/m2) q.3 weeks followed by 4 cycles of T (100 mg/m2) q.3 weeks, in combination with panitumumab (9 mg/kg) for 8 cycles q.3 weeks. All patients underwent surgery at completion of ST. Complete pathologic response (pCR) was the primary endpoint (Sataloff/J Am Coll Surg 1995; Chevallier: Am J Clin Oncol 1993), with toxicity and biologic ancillary studies as secondary endpoints. Results: Patients characteristics are as follows: mean age 47 [27-72]; T2: 74%, T3: 26%, (mean tumor size: 40 mm [20-120]); N0: 65%, N1: 28% and N2: 7%; invasive ductal carcinoma: 96%; Scarff-Bloom-Richardson Grade III: 72%, grade II: 28%. The median number of cycles was: FEC 100: 4 [2-4], T: 4 [0-4], Panitumumab: 7 [1-8]. Pathological response showed a pCR according to Sataloff's classification of 57.1% [95% IC: 40.7−73.5] and according to Chevallier's classification of 51.4% [95% IC: 34.8−68.0] with an overall clinical response rate of 60% (29% CR) [95% IC: 43.8−76.2]. Conservative surgery was performed in 79% of cases. Skin toxicity was the main side-effect: Cutaneous toxicity grade IV: 12%, grade III: 26%, grade II: 23%. No ocular complications have been reported. Neutropenia grade IV: 23.7%; febrile neutropenia: 4.2%. Infection: 0%. Hand-foot syndrome grade III: 4%. Ungueal toxicity grade IV: 2.5%, grade II: 25 .5%. Conclusions: These results suggest that Panitumumab in combination with FEC100 followed by T appears efficacious with acceptable toxicity in the neoadjuvant therapy of operable TNBC. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-01.
Mucormycosis in Severely Burned Patients
Authors: Erwin R. Rabin, George D. Lundberg, Elmer T. Mitchell
Journal: New England Journal of Medicine (1961)

MUCORMYCOSIS has attracted much attention as a rapidly fatal fungous disease. Most cases have been reported in patients with chronic debilitating diseases, especially diabetes mellitus and malignant lymphoma. In a review of the English literature, McBride and his associates1 compiled 57 cases of mucormycosis; diabetes was present in 21, and lymphoma or leukemia in 13. The use of antibiotics, steroids, radiation therapy and antimetabolites in debilitated patients has been considered important in predisposing to mucormycosis.The organism responsible for this mycotic infection belongs to the class of nonseptate, true fungi, known as phycomycetes. The genera mucor and rhizopus of the . . .
Neuroendocrine mechanism of onset of puberty. Sequential reduction in activity of inhibitory and facilitatory N-methyl-D-aspartate receptors.
Authors: J P Bourguignon, A Gérard, M L Alvarez Gonzalez, P Franchimont
Journal: Journal of Clinical Investigation (1992)

In humans and in several animal species, puberty results from changes in pulsatile gonadotropin-releasing hormone (GnRH) secretion in the hypothalamus. In particular, the frequency of pulsatile GnRH secretion increases at the onset of puberty, as can be shown by using hypothalamic explants of male rats of 15 and 25 d. Previous observations from us and others suggested that the initiation of puberty could involve a facilitatory effect of excitatory amino acids mediated through N-methyl-D-aspartate (NMDA) receptors. We found that GnRH secretion could be activated through NMDA receptors only around the time of onset of puberty (25 d). The aim of this study was to clarify why this activation did not occur earlier (at 15 d) and could no longer be observed by the end of puberty (at 50 d). We studied GnRH secretion in the presence of MK-801, a noncompetitive antagonist of NMDA receptors or AP-5, a competitive antagonist. We showed that, in the hypothalamus of immature male rats (15 d), a highly potent inhibitory control of pulsatile GnRH secretion in vitro was mediated through NMDA receptors. These data were confirmed in vivo because administration of the antagonist MK-801 (0.001 mg/kg) to immature male rats resulted in early pubertal development. Onset of puberty (25 d) was characterized by the disappearance of that NMDA receptor-mediated inhibition, thus unmasking a facilitatory effect also mediated through NMDA receptors. During puberty, there was a reduction in activity of this facilitatory control which was no longer opposed by its inhibitory counterpart. We conclude that a sequential reduction in activity of inhibitory and facilitatory NMDA receptors provides a developmental basis for the neuroendocrine mechanism of onset of puberty.
Clinical and Neuropathological Correlates of Heroin Addiction.
Authors: Ralph W. Richter
Journal: Annals of Internal Medicine (1970)

Meeting Abstracts1 May 1970Clinical and Neuropathological Correlates of Heroin Addiction.Ralph W. Richter, M.D., Michael M. Baden, M.D., John Pearson, M.D.Ralph W. Richter, M.D.Search for more papers by this author, Michael M. Baden, M.D.Search for more papers by this author, John Pearson, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-808_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAlthough heroin addiction has become a major public health problem and is the leading cause of death in New York City in the 15- to 35-year age group, the neurologic sequelae are only now being defined. Almost 10% of medical admissions at Harlem Hospital, N. Y., are for complications of heroin addiction. These addicts were studied for neurological deficits. The clinical findings have included mononeuritis, polyneuritis and optic atrophy; acute myopathy with myoglobinuria and chronic myopathies; acute transverse myelitis; and acute and chronic brain syndromes with delirium, coma, convulsions, stroke and Parkinsonian-like syndromes. Infectious complications have included tetanus, bacterial, tuberculous,... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N.Y. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1970Volume 72, Issue 5Page: 808-808KeywordsAtrophyBrainComaConvulsionsDeliriumHeroinMononeuritisPrevention, policy, and public healthStrokeTetanus Issue Published: 1 May 1970 PDF DownloadLoading ...
Should clinicians edit Wikipedia to engage a wider world web?
Authors: M. Kint, D. P. Hart
Journal: BMJ (2012)

The “parents’ perspective” in the clinical review on the diagnosis and management of haemophilia highlights the responsibility of clinical teams to “coach and guide” people with a newly diagnosed rare genetic condition.1 The requirement for specialist teams to provide up to date information resources for the public is increasingly challenging, with the expectation of immediate availability, as offered online.

We …