tbuckley/cabot-search huggingface dataset:
Estrogenic Properties of 3,9-Dihydroxy-7,12-dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene in rats&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Charles E. Morreal, Sara L. Schneider, Dilip K. Sinha, Robert E. Bronstein
Journal: JNCI Journal of the National Cancer Institute (1979)

Previously, the 3,9-dihydroxy derivative of benz[a]-anthracene was shown to be weakly estrogenic. The availability of the related diol of the mammary carcinogen dimethylbenz[a]-anthracene, i.e., 3,9-dihydroxy-7,12-dimethylbenz[a]anthracene (3,9-diOHDMBA), prompted a similar study of its estrogenic properties. The competitive binding studies of 3,9-diOHDMBA with 17beta-estradiol in the uterine cytosol of immature SD rats gave a Ka of 1.7 x 10(8) M-1. 17beta-Estradiol (10(-9) M) binding to the 8S binding protein was inhibited by 3,9-diOHDMBA at concentrations similar to those of nafoxidine HCl (1 x 10(-5) M). Bioassay demonstrated that the diol possesses 1/4,464 the activity of 17beta-estradiol.
SP0207 Scleroderma-Like Sclerosing Diseases
Authors: A. Tyndall
Journal: Annals of the Rheumatic Diseases (2015)

Juvenile localised scleroderma and juvenile SSc have both have recently undergone classification revision. Essential to their diagnosis is the exclusion of other sclerosing disorders, most of which are rare. Eosinophilic fasciitis (Schulman9s disease) is usually symmetrical and tends to spare the face and hands, The absence of Raynauds, vascular changes and ANA distinguish it from scleroderma. Deep biopsy to and including muscle are required and peripheral eosinophilia is not always present. Also sparing the face, but variable in distribution is nephrogenic systemic fibrosis due to gadolinium in renal impaired patients including children. Scleredema of Buschke is mostly symmetrical, often involves the back (unlike scleroderma) and in children may follow respiratory infections. It often resolves spontaneously. It should be distinguished histologically from the neonatal panniculitides; sclerodema neonatorum (often fatal) and subcutaneous fat necrosis of the newborn. Sclerodema-like syndromes also may be seen in poorly controlled IDDM. Other metabolic/endocrine disorders with skin thickening include thyroid dysfunction and porphyria cutanea tarda. Stiff skin syndrome starts in childhood with insidious onset of stony-hard skin, often with associated contractures, joint restriction and hypertrichosis. Biopsy shows fascial sclerosis and/or subcutaneous septa with increased fibroblast cellularity with sclerotic collagen bundles in the deep reticular dermis and no inflammation. Scleroderma-like skin changes in infants, associated with growth retardation and dysmorphic features, suggest premature aging syndromes (Werners, Hutchinson Gilford, restrictive dermopathy), requiring genetic testing and counselling of asymptomatic carriers of LMNA mutations. Infections (e.g.borrelia burgdorferi) and exposure to toxins should be excluded in all skin thickening syndromes. <h3>Disclosure of Interest</h3> None declared
Growth hormone response to growth hormone-releasing hormone in schizophrenic patients
Authors: D I Mayerhoff, J A Lieberman, C Z Lemus, S Pollack, B S Schneider
Journal: American Journal of Psychiatry (1990)

Ten schizophrenic patients and five normal control subjects were challenged with growth hormone-releasing hormone in a pilot study investigating growth hormone secretion from the pituitary. The results suggest suprapituitary dysfunction in schizophrenia, but replication in a larger study is needed.
Prospective study of prodromal symptoms in schizophrenic relapse
Authors: D W Heinrichs, W T Carpenter
Journal: American Journal of Psychiatry (1985)

The authors examined the type and frequency of prodromal symptoms in 47 cases of schizophrenic relapse during which 30 patients were drug free and 17 were medicated. The findings indicate that clinicians who use patient and family reports can identify prodromal symptoms as they occur.
Temperature modulates calcium homeostasis and ventricular arrhythmias in myocardial preparations
Authors: G. Gambassi, E. Cerbai, M. Pahor, M. C Capogrossi, P. Carbonin, A. Mugelli
Journal: Cardiovascular Research (1994)

The aim was to evaluate the effect of temperature on reoxygenation induced ventricular arrhythmias in isolated hearts, on delayed afterdepolarisations and Iti current in Purkinje fibres, and on sarcoplasmic reticular function and Ca2+ handling of single cardiac myocytes.Isolated guinea pig hearts were retrogradely perfused at 37 degrees C with a hypoxic medium for 15 min and reoxygenated for 10 min either at 33 degrees C or at 37 degrees C. Intracellular microelectrodes were used to assess the presence of delayed afterdepolarisations and triggered activity in sheep Purkinje fibres exposed to strophanthidin at different temperatures. Iti current was evaluated in voltage clamp experiments. In rat cardiomyocytes, loaded with the fluorescent Ca2+ dye, indo-1, the sarcoplasmic reticular Ca2+ content was assessed at 30 degrees C and at 37 degrees C, either by a caffeine spritz puffed onto a cell from a patch pipette or by a post-rest contraction.Hypothermic reoxygenation reduced the incidence of ventricular arrhythmias in isolated hearts (30%, n = 10, at 33 degrees C and 75%, n = 30, at 37 degrees C, p < 0.05). In Purkinje fibres, hypothermia decreased the amplitude of delayed afterdepolarisations. Moreover, at 32 degrees C, the amplitude of Iti current was decreased to 59.2(SEM 2.6)% of the normothermic value [27.5(6.7) nA, n = 4, p < 0.005] and time to peak increased to 159.7(10.2)% [value at 37 degrees C = 470(41) ms, n = 4, p < 0.01]. In cardiac cells, sarcoplasmic reticular Ca2+ release induced by caffeine spritz or by post-rest contraction was increased at 30 degrees C. However, following a pacing period at 1 Hz, hypothermia prolonged the time to onset of the first spontaneous Ca2+ oscillation [59(14) s at 30 degrees C and 27(9) s at 37 degrees C, n = 5, p < 0.05] and reduced the oscillation frequency [1.1(0.4) min-1 at 30 degrees C and 3.1(0.9) min-1 at 37 degrees C, n = 5, p < 0.05].Mild hypothermia increases sarcoplasmic reticular Ca2+ content but decreases the likelihood of spontaneous Ca2+ release. This may explain the reduction of delayed afterdepolarisations and Iti current amplitude in Purkinje fibres and it could represent a mechanism for the protection provided by hypothermia against ventricular arrhythmias.
Contribution of transmission in HIV-positive men who have sex with men to evolving epidemics of sexually transmitted infections in England: an analysis using multiple data sources, 2009–2013
Authors: R Malek, H Mitchell, M Furegato, I Simms, H Mohammed, A Nardone, G Hughes
Journal: Eurosurveillance (2015)

Binary file ES_Abstracts_Final_ECDC.txt matches
Abstract P5-02-04: Plasma autoantibodies associated with basal-like breast cancers
Authors: J Wang (Student), JD Figueroa, G Wallstrom, K Barker, JG Park, G Demirkan, J Lissowska, K Anderson, J Qiu, J LaBaer
Journal: Cancer Research (2016)

Abstract Background: Basal-like breast cancer (BLBC) is a rare aggressive subtype that is less likely to be detected through mammographic screening. Identification of circulating markers associated with BLBC could have promise in detecting and managing this deadly disease. Methods: Using samples from the Polish Breast Cancer study, a high-quality population-based case-control study of breast cancer, we screened 10,000 antigens on protein arrays using 45 BLBC patients and 45 controls, and identified 748 promising plasma autoantibodies (AAbs) associated with BLBC. ELISA assays of promising markers were performed on a total of 145 BLBC cases and 145 age-matched controls. Sensitivities at 98% specificity were calculated and a BLBC classifier was constructed. Results: We identified a 13-AAbs (CTAG1B, CTAG2, TP53, RNF216, PPHLN1, PIP4K2C, ZBTB16, TAS2R8, WBP2NL, DOK2, PSRC1, MN1, TRIM21) that distinguished BLBC from controls with 33% sensitivity and 98% specificity. We also discovered a strong association of TP53 AAb with its protein expression (p=0.009) in BLBC patients. In addition, MN1 and TP53 AAbs were associated with worse survival (MN1 AAb marker HR=2.25 95%CI= 1.03-4.91 p=0.04; TP53, HR=2.02, 95%CI 1.06-3.85, p=0.03). We found limited evidence that AAb levels differed by demographic characteristics. Conclusions: These AAbs warrant further investigation in clinical studies to determine their value for further understanding the biology of BLBC and possible detection. Currently, they are also being tested in a large national blind validation trial using a well characterized independent sample set. Citation Format: Wang (Student) J, Figueroa JD, Wallstrom G, Barker K, Park JG, Demirkan G, Lissowska J, Anderson K, Qiu J, LaBaer J. Plasma autoantibodies associated with basal-like breast cancers. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-02-04.
Randomized trial of active cellular immunotherapy with sipuleucel-T in androgen dependent prostate cancer (ADPC)
Authors: T. M. Beer, G. T. Bernstein, J. M. Corman, M. L. Glode, S. Hall, W. L. Poll, P. F. Schellhammer, Y. Xu, L. Yu, M. W. Frohlich
Journal: Journal of Clinical Oncology (2007)

5059 Background: Sipuleucel-T is an investigational, active cellular immunotherapy product for prostate cancer. To explore the potential benefit in ADPC, sipuleucel-T was studied in a randomized, double blind, multicenter, placebo controlled study, P-11. Methods: ADPC patients with a rise in serum prostate specific antigen (PSA) as the only sign of disease recurrence after prostatectomy were randomized (2:1) to sipuleucel-T or placebo, administered in weeks 0, 2, and 4, following 3-months of hormonal therapy. PSA kinetics were evaluated by time to biochemical failure (BF), defined as any PSA = 3 ng/mL (primary endpoint), as well as PSA doubling time (PSADT). Clinical endpoints included time to distant metastases (DF) and survival. The effect of a single booster infusion of sipuleucel-T on the immune system was also evaluated. Results: 176 patients were randomized (117 sipuleucel-T:59 placebo) and analyzed by intent to treat. Median time to BF was 18.0 months for sipuleucel-T and 15.4 months for placebo (hazard ratio (HR)=0.94 [95% confidence interval (CI): 0.64, 1.38]; p&gt;0.05, log rank). The hazard ratio for BF was 0.80 in favor of sipuleucal-T ([95%CI: 0.53, 1.20], p&gt;0.05) when the analysis was restricted to patients with a confirmed BF. An analysis of PSADT calculated from 90 days following randomization to BF or the initiation of systemic therapy demonstrated that patients randomized to sipuleucel-T had a 35% increase in PSADT (125 vs 91 days; p=0.046, F-test). PSADT calculated after testosterone recovery to baseline levels demonstrated a 48% increase in PSADT for the sipuleucel-T arm (155 vs 105 days; p=0.038). Only 16% of patients developed distant metastases. The hazard ratio for time to DF was 0.78 (95%CI: 0.34, 1.58, p&gt;0.05, log rank). Patients are still being followed for DF and survival. The most common treatment-associated adverse events were chills, fatigue, headache, and pyrexia, which were primarily Grade 1–2. Conclusions: Time to BF was not different between the two study arms. The effect on PSADT, an important prognostic indicator in ADPC, may suggest the biologic activity of sipuleucel-T in this population. Additional follow-up for clinical endpoints of DF and survival is of interest. No significant financial relationships to disclose.
The Prospective Analysis Of Clinical Efficacy and Adverse Events In Chronic Myeloid Leukemia In Chronic Phase (CML-CP) Patients With Imatinib Resistance Or Intolerance, Evaluated By European Leukemia Net (ELN) 2013 Criteria
Authors: Kazunori Murai, Tomoaki Akagi, Kenji Shimosegawa, Kenichi Ishizawa, Tomohiro Sugawara, Hisayuki Yokoyama, Hideyoshi Noji, Kazuei Ogawa, Katsushi Tajima, Koji Oba, Junichi Sakamoto, Koumei Kubo, Hisashi Sakamaki, Hideo Harigae, Yoji Ishida
Journal: Blood (2013)
Danazol Treatment for Telomere Diseases
Authors: Danielle M. Townsley, Bogdan Dumitriu, Delong Liu, Angélique Biancotto, Barbara Weinstein, Christina Chen, Nathan Hardy, Andrew D. Mihalek, Shilpa Lingala, Yun Ju Kim, Jianhua Yao, Elizabeth Jones, Bernadette R. Gochuico, Theo Heller, Colin O. Wu, Rodrigo T. Calado, Phillip Scheinberg, Neal S. Young
Journal: New England Journal of Medicine (2016)

Genetic defects in telomere maintenance and repair cause bone marrow failure, liver cirrhosis, and pulmonary fibrosis, and they increase susceptibility to cancer. Historically, androgens have been useful as treatment for marrow failure syndromes. In tissue culture and animal models, sex hormones regulate expression of the telomerase gene.In a phase 1-2 prospective study involving patients with telomere diseases, we administered the synthetic sex hormone danazol orally at a dose of 800 mg per day for a total of 24 months. The goal of treatment was the attenuation of accelerated telomere attrition, and the primary efficacy end point was a 20% reduction in the annual rate of telomere attrition measured at 24 months. The occurrence of toxic effects of treatment was the primary safety end point. Hematologic response to treatment at various time points was the secondary efficacy end point.After 27 patients were enrolled, the study was halted early, because telomere attrition was reduced in all 12 patients who could be evaluated for the primary end point; in the intention-to-treat analysis, 12 of 27 patients (44%; 95% confidence interval [CI], 26 to 64) met the primary efficacy end point. Unexpectedly, almost all the patients (11 of 12, 92%) had a gain in telomere length at 24 months as compared with baseline (mean increase, 386 bp [95% CI, 178 to 593]); in exploratory analyses, similar increases were observed at 6 months (16 of 21 patients; mean increase, 175 bp [95% CI, 79 to 271]) and 12 months (16 of 18 patients; mean increase, 360 bp [95% CI, 209 to 512]). Hematologic responses occurred in 19 of 24 patients (79%) who could be evaluated at 3 months and in 10 of 12 patients (83%) who could be evaluated at 24 months. Known adverse effects of danazol--elevated liver-enzyme levels and muscle cramps--of grade 2 or less occurred in 41% and 33% of the patients, respectively.In our study, treatment with danazol led to telomere elongation in patients with telomere diseases. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01441037.).
Tc-99m DMSA and Tc-99m DTPA imaging in the diagnosis of crossed renal ectopia.
Authors: G Büyükdereli, B Hazar, O Sargin, R Tuncer
Journal: Clinical Nuclear Medicine (2001)

BÜYÜKDERELI, GÜLGÜN M.D.,*; HAZAR, BURHAN M.D.,†; SARGIN, ÖZOGUL M.D.*; TUNCER, RECEP M.D.‡ Author Information
Failed publications: the medical model
Authors: T. Albert
Journal: BMJ (1998)

Next time you see a newsletter or an annual report from a distinguished medical body, look for the anodyne bureaucratic phrases and the pseudoscientific gobbledygook, the pompous initial capitals, and the photo booth “repertory company” photographs. Then reflect that in all probability a lot of highly paid academics put in a lot of expensive hours making the publication that bad.

Earlier this year I gave up that part of my business which produced newsletters for medical and academic organisations. While most of my clients were charming, stimulating, and able, they were working within a culture that encouraged a type of behaviour that has serious implications for the relation between medicine and the media.

The story invariably goes something like this. …
BLVRB redox mutation defines heme degradation in a metabolic pathway of enhanced thrombopoiesis in humans
Authors: Song Wu, Zongdong Li, Dmitri V. Gnatenko, Beibei Zhang, Lu Zhao, Lisa E. Malone, Nedialka Markova, Timothy J. Mantle, Natasha M. Nesbitt, Wadie F. Bahou
Journal: Blood (2016)
Rectal Leiomyoma with Fibromuscular Obliteration Mimicking Adematous Lesion
Authors: H. Nakase, M. Ide, S. Yazumi, N. Watanabe, T. Itoh, M. Matsuura, C. Kawanami, K. Okazaki, T. Chiba
Journal: Endoscopy (2002)

Figure 1 A 54-year-old man with a main complaint of hematochezia underwent colonoscopic examination, which revealed a sessile elevated lesion with reddish mucosa on the surface at the rectum. Endoscopic mucosal resection was done without complications
Animal-human correlates of narcotic dependence: a brief review
Authors: B Stimmel, S D Glick
Journal: American Journal of Psychiatry (1978)

Knowledge of opiate action in laboratory animals can be of great value in developing a rational clinical approach to the treatment of narcotic dependence. Physiological alterations experimentally produced by narcotics have been confirmed in human subjects, and classical laboratory effects of conditioning and operant behavior also have clinical counterparts. Realization of animal-human correlates of narcotic dependence allows a better understanding of the strengths and weaknesses of existing therapeutic modalities.
Comparison of melphalan-prednisone-thalidomide (MP-T) to melphalan-prednisone (MP) in patients 75 years of age or older with untreated multiple myeloma (MM). Preliminary results of the randomized, double-blind, placebo controlled IFM 01–01 trial
Authors: C. Hulin, J. Virion, X. Leleu, P. Rodon, B. Pegourie, L. Benboubker, C. Doyen, M. Dib, G. Guillerm, P. Moreau
Journal: Journal of Clinical Oncology (2007)

8001 Background: The MP-T combination has been shown to be the standard treatment in newly diagnosed MM patients (pts) aged 65 to 75 years (Facon et al; JCO 2006; 24, A1). However, no specific therapeutic recommendation exists for pts older than 75 years regarding the benefit of adding Thalidomide to MP. Methods: The IFM 01–01 trial was initiated in 04/2002. Patients &gt; 75 years with untreated MM were randomized to receive MP (Melphalan 0.2mg/kg/d + Prednisone 2 mg/kg/d day1–4, 12 courses at 6-weeks intervals) + placebo (MP-placebo) vs MP + daily Thalidomide 100mg/d (MP-T). No anti-VTE prophylaxis was given. The primary end-point was overall survival (OS). Secondary end points were progression-free survival (PFS), response to treatment and toxicity. A first interim analysis was performed after the inclusion of 150 patients and a data safety monitoring board recommended a second analysis after the accrual of 200 patients. We here present the preliminary results of this analysis. Results: At the reference date of November 1, 2006, 232 pts were randomised. In all, 200 pts were analysed (100 per group), with 33.5% of pts &gt;80 years (median age, 78.4 years). There were no differences between the 2 groups regarding baseline characteristics. Data were analysed on an intent-to-treat basis. After the completion of therapy the rates of partial response and very good partial response were 31% and 8% respectively with MP-placebo vs 61% and 22% respectively with MP-T. The median PFS time was 19 months (95%-CI 14.6–21.5) with MP-placebo vs 24.1 months (95%-CI 19.4–29.7) with MP-T (p=0.004 log-rank test). In the MP-T arm, 43/100 pts stopped treatment due to toxicity (10 due to neuropathy) versus 11/100 in the MP-placebo arm. Toxicity (Grade 2–4) included peripheral neuropathy (18%), somnolence (7%) and DVT (7%) with MP-T, vs 6%, 6% and 1% respectively, with MP-placebo. Final results including OS data will be presented at the meeting. Conclusion: MPT is an effective combination with acceptable toxicity in patients with MM = 75 years of age, with a significant improvement in PFS. No significant financial relationships to disclose.
Second Biosimilar Approved
Authors: Rebecca Voelker
Journal: JAMA (2016)

The FDA has approved a second biosimilar drug, infliximab-dyyb, which is indicated for treating several rheumatic diseases. The drug is biosimilar to the tumor necrosis factor α inhibitor infliximab, which originally was licensed in 1998 (http://1.usa.gov/1RWO6BF).

Approval of biosimilar products is based on evidence showing high-level similarity to an already approved biological product, known as the reference product. The FDA can approve a biosimilar product only if it has the same mechanism of action, route of administration, and dosage form and strength as the reference product. Facilities where biosimilars are manufactured also must meet FDA standards.
Surveillance of antimicrobial resistance of invasive pathogens: the Estonian experience
Authors: K Loivukene, K Kermes, E Sepp, V Adamson, P Mitt, Ü Kallandi, K Otter, P Naaber
Journal: Eurosurveillance (2006)

The aim of the present study was to evaluate the needs for surveillance of invasive Gram-negative pathogens in Estonia. The antimicrobial susceptibility data of invasive isolates of Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella spp, Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae and enterococci were collected in accordance with EARSS (European Antimicrobial Resistance Surveillance System) protocols. Despite the higher rate of Gram positive pathogens, their resistance to antimicrobials was low in contrast to the elevated resistance established for Gram negative pathogens. The higher resistance to antimicrobials was particularly associated with A. baumannii and P. aeruginosa. Also, the proportion of extended spectrum betalactamase (ESBL)-producing strains was 23% among Klebsiella spp. and 3.6% among E. coli. The inclusion of invasive Gram negative pathogens in antimicrobial resistance surveillance provides useful information concerning local pathogen susceptibility, as well as for the empirical treatment of suspected infections.
Abstract P2-03-06: Dysregulation of miR-34a-SIRT1 axis reduced breast cancer stemness
Authors: GG Xiao, W Ma, J Mao, L Li
Journal: Cancer Research (2016)

Abstract Recent studies show that enforced expression of miR-34a results in elimination of cancer stem cells (CSCs) in many malignant tumors. Sirtuin-1 (SIRT1) being confirmed as a direct target of miR-34a was reported to be involved in regulation of growth and survival of leukemia stem cells (LSCs). In this study, we aim to understand regulatory mechanism of miR-34a -SIRT1 axis in breast cancer stem cells (BCSCs). Lower endogenous level of miR-34a and higher level of Sirtuin1 (SIRT1) gene were identified in CD44+/CD24- BCSCs than breast cancer cells. Either ectopic expression of miR-34a or silenced SIRT1 in MCF-7 cells inhibited cellular proliferation, and led to cell apoptosis. Overexpression of miR-34a also suppressed expression of ALDH1, BMI1 and Nanog, and decreased capacity of mammosphere formation significantly.. Studies in vivo showed that stable expression of miR-34a reduced tumor burden significantly in nude mice xenografts. Taken together, our results showed that miR-34a inhibit the proliferative potential of BCSCs in vitro and in vivo, at least partially through downregulating SIRT1. miR-34a-SIRT1 axis may play an important role in self-renewal and stemness maintenance of BCSCs. This study may provide a novel BCSCs specific therapeutic strategy to improve breast cancer treatments. Citation Format: Xiao GG, Ma W, Mao J, Li L. Dysregulation of miR-34a-SIRT1 axis reduced breast cancer stemness. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-03-06.
Acquired Immune Deficiency Syndrome.
Authors: R Penny, R Marks, J Berger, D Marriott, D Bryant
Journal: Annals of Internal Medicine (1985)

The first Australian case of acquired immune deficiency syndrome (AIDS), which occurred in a 27-year-old homosexual man, is reported. The patient, an American citizen now resident in Sydney, presented with life-threatening pulmonary consolidation. AIDS is characterized by severe defects in cell-mediated immunity associated with infections and neoplasms (most commonly Pneumocystis carinii pneumonia and Kaposi's sarcoma). The cause of the syndrome is unknown, but it may be a new infectious agent.