tbuckley/cabot-search huggingface dataset:
P5-11-14: Flat Epithelial Atypia of the Breast: A Single Institution Experience.
Authors: JE Joh, G Acs, JV Kiluk, C Laronga, N Khakpour, MC Lee
Journal: Cancer Research (2011)

Abstract Background: Flat epithelial atypia of the breast is a relatively new entity of unknown significance. Our objective is to evaluate our surgical experience with this diagnosis. Methods: A single institution database of breast patients from 2005–2010 was used to identify women who were diagnosed with flat epithelial atypia on core biopsy and subsequently underwent surgical excision. Patient data regarding history, type and reason for biopsy, and associated pathology was collected. Individuals diagnosed with flat epithelia atypia and cancer on core biopsies in the same breast were excluded. Results: There were 52 patients who underwent surgical excision for the primary diagnosis of flat epithelial atypia. There were 3 (6%) patients with a personal history of breast cancer, 14 (27%) patients with a family history of breast cancer, and 11 (21%) patients with a concurrent new diagnosis of breast cancer in the contralateral breast. Core biopsy was recommended in most (81%) cases because of suspicious calcifications on mammography. Twenty-eight (54%) patients were found to have flat epithelial atypia associated with other atypical breast hyperplasia and 24 (46%) had flat epithelial atypia as the most significant lesion on core biopsy. In 8 (15%) patients, there was a sonographic correlate that was biopsied; 5 had only flat epithelial atypia and 3 had flat epithelial atypia associated with other atypical hyperplasia. Of the 52 patients there were 4 (8%) patients who upstaged to ductal carcinoma in-situ on surgical excision. There were no cases of invasive carcinoma. All ductal carcinoma in-situ cases were associated with other atypical breast hyperplasia, not flat epithelial atypia alone. Conclusion: Though flat epithelial atypia may be associated with an increased risk of breast cancer, surgical excision of pure flat epithelial atypia may not be necessary. Larger studies are needed to corroborate these findings. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-11-14.
Searching for sporting excellence: talent identification and development
Authors: Carlton Cooke, Steve Cobley, Kevin Till, Nicholas Wattie
Journal: British Journal of Sports Medicine (2010)

The systems, models and programmes designed to identify and provide for the development of talented young people in sport continue to evolve in their complexity and comprehensiveness, often driven by national interests of doing well in sport. The influences of the approach developed in the German Democratic Republic still remain, with a continued focus on the physical determinants of performance in sport. However, such influences are now complemented by due consideration for the holistic development of young people who happen to be talented in sport. As a field of enquiry talent identification and development demands a multidisciplinary approach and those that work directly with young people require a sound interdisciplinary understanding of the key disciplinary contributions. Selection for performance with a focus on the immediate or short term goals and aspirations of important others are still too often confused with talent identification and development. In contrast, some of the most comprehensive examples of talent identification and development programmes in sport analyse the performer's activity from end to start (ie, they start from an accessible result and work backwards in terms of understanding the processes of preparation and development that are the required building blocks in order to get an individual young performer to their accessible endpoint). This presentation will draw on a range of theoretical and disciplinary perspectives, as well as providing some examples from sport, to identify the contemporary issues in talent identification and development of concern to those who plan and practice it, but mostly importantly for those young people that experience it.
Misclassification of subjects with insulin resistance and associated cardiovascular risk factors by homeostasis model assessment index. Utility of a postprandial method based on oral glucose tolerance test
Authors: Sergio Martinez-Hervas, Carlos Argente, Javier Garcia-Jodar, Antonia Priego, Jose T. Real, Arturo Carratala, Rafael Carmena, Juan F. Ascaso
Journal: Metabolism (2010)
Polarity Index of Psychological Interventions in Maintenance Treatment of Bipolar Disorder
Authors: Dina Popovic, Maria Reinares, Jan Scott, Alessandra Nivoli, Andrea Murru, Isabella Pacchiarotti, Eduard Vieta, Francesc Colom
Journal: Psychotherapy and Psychosomatics (2013)

Although several adjunctive psychological interventions are effective in the maintenance of bipolar disorders (BD), no attempt has been made to classify them according to their ability to prevent manic versus depressive episodes. Our study aims to rank the adjunctive psychotherapies for the prophylaxis of BD by means of their polarity index (PI).Randomized controlled trials comparing the efficacy of a psychological intervention with a comparator in BD maintenance treatment in patients aged over 18 were systematically reviewed. Exclusion criteria were a small sample size, a study sample not exclusively composed of bipolar patients and the absence of a control group. PI is a novel metric indicating the relative antimanic versus antidepressive preventive efficacy of treatments. PI was retrieved by calculating the ratio of the number needed to treat (NNT) for prevention of depression and the NNT for prevention of mania. PI >1.0 indicates a relatively higher antimanic prophylactic efficacy and PI <1.0 a greater antidepressive efficacy.A total of 9 studies were included. PI was 0.33, 0.63 and 0.89 for cognitive-behavioral therapy, 0.42 for family-focused therapy, 0.73 and 0.78 for psychoeducation, 1 for enhanced relapse prevention, 1.78 for caregiver group psychoeducation and 3.36 for brief technique-driven interventions. With regard to the PI for 1 cognitive-behavioral study, enhanced relapse prevention and brief technique-driven interventions may not be reliable since those trials were negative.The PI provides a measure of how much depression-preventive or (hypo) mania-preventive an intervention is and may guide the choice of adjunctive psychotherapy in the context of individualized long-term treatment of BD.
Current cancer concepts. The place of chemotherapy in management
Authors: J. Hadfield
Journal: JAMA (1967)

Chemotherapy is not specific. It differs fundamentally from hormone therapy which is directly dependent on the hormone sensitivity of the tumor. This lack of specificity depresses the mitotic activity of all rapidly multiplying normal cells such as those of the hemopoietic bone marrow and the epithelium of the gastrointestinal tract. The magnitude of this antimitotic activity on normal cells can be serious and is often unpredictable. The choice of methods of administration is dictated by the widespread nature of the disease. Isolated perfusion for recurrence in the breast area or a previously untreated primary lesion is of little value, as there is no major cannulable arterial supply to the breast and innominate or subclavian cannulation<sup>21</sup>is even too localized for the distribution of the disease. It might, however, be an adjunct to parenteral therapy when there is a concentration of metastases at a site or in an organ with
Hypokalemic Periodic Paralysis Induced by Thymic Hyperplasia and Relieved by Thymectomy
Authors: Renrong Yang, Karin Jurkat-Rott, Jinlin Cao, Guofeng Wang, Hans-Peter Seelig, Changping Yang, Guibao Liu, Lin Pan, Haiyan Zheng, Frank Lehmann-Horn
Journal: JAMA Neurology (2013)

Hypokalemic periodic paralysis is a muscle channelopathy based on mutations or predisposing variants or secondary to potassium wasting. In contrast to myasthenia gravis, an association with thymic hyperplasia has not yet been reported, to our knowledge.We report a male patient in his mid-20s with progressive episodes of flaccid muscle weakness, associated low serum potassium levels, and a pathologic decrement in the long exercise test. Because the familial inheritance in the family was initially unknown, thorough diagnostic tests were performed including contrast-enhanced computed tomography scan, which displayed a mass in the anterior mediastinum. The test results for autoantibodies against myasthenia gravis (acetylcholine receptor, muscle-specific tyrosine kinase, and low-density lipoprotein receptor-related protein 4) and other end plate channelopathies were negative, and test results for hypokalemia-inducing hormones (thyroid, corticotropin, and cortisol) were negative. Surgery identified a thymus of 13 × 8 × 3 cm(3). Histologic analysis was consistent with thymic hyperplasia of the follicular subtype and immunohistologic analysis showed cytokeratin 5/6 in hyperplastic epithelial cells. A 2-year follow-up revealed the postoperative absence of weakness episodes. As in 30% of familial cases, molecular genetics testing failed to identify a mutation in periodic paralysis genes.Thymic hyperplasia can clinically manifest susceptibility to hypokalemic periodic paralysis. For patients with late onset or increasing weakness episodes, we recommend imaging to assess for thymic enlargement and thymectomy at thymic hyperplasia.
Obesity as a determinant for response to antihypertensive treatment.
Authors: R E Schmieder, C Gatzka, H Schachinger, H Schobel, H Ruddel
Journal: BMJ (1993)

OBJECTIVE--To test the hypothesis that beta blockers lower blood pressure more effectively than calcium entry blockers in obese hypertensive patients and that calcium entry blockers are more effective in lean patients. DESIGN--Double blind, randomised controlled trial of treatment over six weeks. SETTING--Tertiary referral centre. SUBJECTS--42 white men with uncomplicated mild to moderate essential hypertension (World Health Organisation stage I or II); 36 completed the study. INTERVENTION--Patients were randomised to metoprolol 50-100 mg twice daily or isradipine 2.5-5.0 mg twice daily for six weeks after a two week run in phase. MAIN OUTCOME MEASURE--Blood pressure after six weeks of treatment. RESULTS--When stratified according to treatment and presence of obesity (body mass index &lt; or = 27 kg/m2), the mean (SD) fall in blood pressure in the beta blocker group was 24 (13)/18 (10) mm Hg in obese patients and 18 (19)/12 (13) mm Hg in lean patients. In the calcium entry blocker group, the fall in blood pressure was 21 (15)/17 (6) mm Hg in lean patients and 18 (11)/8 (10) mm Hg in obese patients. After taking age and blood pressure before treatment into account there was a significant interaction between obesity and drug therapy (p = 0.019) with a better diastolic blood pressure response to calcium entry blockers in lean patients and to beta blockers in obese hypertensive patients. CONCLUSION--Obesity affects the efficacy of metoprolol and isradipine in reducing blood pressure.
Fortnightly review: Treatment of schizophrenia
Authors: J. McGrath, W B. Emmerson
Journal: BMJ (1999)

This selective review on the treatment of schizophrenia provides an update on two important issues. Firstly, new antipsychotic drugs have improved the quality of life for people with schizophrenia. This review outlines some practical issues surrounding the use of these drugs Secondly, evidence suggests that the prompt identification and treatment of people with psychoses (including schizophrenia and affective psychoses) results in improved clinical outcomes.1 The important role that general practitioners can play in reducing the duration of untreated psychosis is also discussed.

#### Summary points

Drug treatment is effective in managing acute psychosis and in reducing the risk of relapse

Newer antipsychotics, apart from clozapine, seem to be as effective in treating positive symptoms as traditional antipsychotics but have fewer, less severe side effects

Clozapine is more effective than traditional antipsychotics and should be offered to patients who have not responded to other antipsychotic drugs

Health services and community agencies need to collaborate to reduce the amount of time that patients with psychosis remain untreated

General practitioners are playing increasingly prominent roles in new models of delivering services to people with schizophrenia

In writing this review, we collated the advice given in clinical practice guidelines for the management of schizophrenia that had been published in the past three years.2–6 Relevant reviews in the Cochrane Library were inspected.

The schizophrenic disorders are a group of illnesses characterised by various combinations of neuropsychiatric symptoms. Modern diagnostic classifications also include criteria related to the duration of symptoms, declines in functioning, and an absence of comorbid neurological disease. Problems with attention and memory may be prominent in psychoses, for example some patients have difficulties with novel tasks that require flexibility and planning. The so called positive symptoms of schizophrenia include hallucinations, delusions, and disorganised communication. The so called negative symptoms of schizophrenia include …
Ophthalmology: Principles and Concepts
Authors: Arnall Patz
Journal: JAMA (1965)

Dr. Newell has prepared a superb text. There is a carefully balanced presentation of the basic sciences related to ophthalmology and the clinical material. The author has intentionally avoided detailed emphasis on specialized aspects of ophthalmology, such as refraction and optics. Instead of weakening the text, this omission has made his book much more useful to the nonspecialist. In the section on "Systemic Diseases and the Eye," a considerable amount of new information is included that is not readily available in other texts. This, together with the emphasis that is placed on the fundamental aspects of the primary disease, makes this portion of the book valuable both to the resident and the practicing ophthalmologist. The author has used 34 tables, each one a condensation of a considerable amount of information about the subject under discussion. The tables on "Classification of Autonomic Drugs" and "Virus Diseases" are especially useful. The chapters
Pharmacokinetics of Gonadotropin-Releasing Hormone and Its Analogs
Authors: DAVID J. HANDELSMAN, RONALD S. SWERDLOFF
Journal: Endocrine Reviews (1986)

PHARMACOLOGICAL therapy must be based on a therapeutic aim coupled with an understanding of relevant normal physiology. As reviewed elsewhere in this issue, pituitary gonadotropes exposed to GnRH pulses outside the physiological range of 0.5–1 pulses/h fail to sustain gonadotropin output. Consequently, clinical applications of GnRH are designed to stimulate gonadal function when endogenous GnRH pulsatility is deficient (hypogonadism, delayed puberty) by mimicking physiological patterns using exogenous GnRH pulse frequencies of 0.5–1 pulses/h (1). Conversely, GnRH analog (superactive agonists or pure antagonists) treatment is intended to suppress gonadal function via pituitary desensitization as a result of sustained pituitary overexposure to GnRH effects by continuous or quasi-continuous administration (2, 3). Thus treatment regimens with GnRH or the analogs will have different optimal modes of application based on the pharmacokinetics of the compound and pharmacodynamics of the target physiological systems. This article will review the pharmacokinetics of GnRH and its analogs and the relevance to regimens designed to stimulate or suppress gonadal function.
Drug screen in patient cells suggests quinacrine to be repositioned for treatment of acute myeloid leukemia
Authors: A Eriksson, A Österroos, S Hassan, J Gullbo, L Rickardson, M Jarvius, P Nygren, M Fryknäs, M Höglund, R Larsson
Journal: Blood Cancer Journal (2015)

To find drugs suitable for repositioning for use against leukemia, samples from patients with chronic lymphocytic, acute myeloid and lymphocytic leukemias as well as peripheral blood mononuclear cells (PBMC) were tested in response to 1266 compounds from the LOPAC(1280) library (Sigma). Twenty-five compounds were defined as hits with activity in all leukemia subgroups (<50% cell survival compared with control) at 10 μM drug concentration. Only one of these compounds, quinacrine, showed low activity in normal PBMCs and was therefore selected for further preclinical evaluation. Mining the NCI-60 and the NextBio databases demonstrated leukemia sensitivity and the ability of quinacrine to reverse myeloid leukemia gene expression. Mechanistic exploration was performed using the NextBio bioinformatic software using gene expression analysis of drug exposed acute myeloid leukemia cultures (HL-60) in the database. Analysis of gene enrichment and drug correlations revealed strong connections to ribosomal biogenesis nucleoli and translation initiation. The highest drug-drug correlation was to ellipticine, a known RNA polymerase I inhibitor. These results were validated by additional gene expression analysis performed in-house. Quinacrine induced early inhibition of protein synthesis supporting these predictions. The results suggest that quinacrine have repositioning potential for treatment of acute myeloid leukemia by targeting of ribosomal biogenesis.
Relationship between Diuretic and Antihypertensive Effects of Chlorothiazide and Mercurial Diuretics
Authors: WILLIAM HOLLANDER, ARAM V. CHOBANIAN, ROBERT W. WILKINS
Journal: Circulation (1959)

Both chlorothiazide and parenteral mercurial diuretics have an antihypertensive as well as a natriuretic action. Previous observations have suggested that the antihypertensive effect is not due solely to sodium depletion. This paper expands these observations on a larger group of normotensive and hypertensive subjects and presents new studies on the effects of fluorohydrocortisone and SC-8109 (a "steroidal antagonist"), upon the sodium excretion and blood pressure of hypertensive patients during treatment with one of the diuretics.
Simultaneous Multiple Early Cancers of Esophagus and Stomach Treated by Endoscopic Mucosal Resection
Authors: N. Ando, Y. Niwa, N. Ohmiya, B. Ito, Y. Sasaki, H. Goto
Journal: Endoscopy (2002)

Endoscopic mucosal resection (EMR) has been accepted as a completely curative treatment of gastrointestinal mucosal cancers. With advances in diagnostic techniques, the tendency to detect simultaneous multiple primary cancers is increasing. Patients with another cancer coexisting with esophageal cancer have had a poor prognosis, but if both cancers are detected in the early stage, complete treatment consisting only of endoscopic surgery, with a good prognosis, is expected. We describe two cases of simultaneous multiple early cancers of the stomach and esophagus, treated by EMR.
VAGINO-UTERINE PROLAPSE AND ITS EFFECTIVE TREATMENT
Authors: E. E. MONTGOMERY
Journal: JAMA (1913)

Vagino-uterine prolapse is a form of hernia through the vaginal outlet which may involve respectively the bladder and anterior vaginal wall, the anterior vaginal wall or the bladder and the cervix uteri; or the eversion may comprise cervix, or uterus, and the entire vaginal structure. The protrusion of the anterior pelvic segment is frequently a sliding of the bladder, pushing it before the anterior vaginal wall and dragging on the cervix where the uterus is firmly fixed as by firm ligaments and resistant peritoneum. The traction on the cervix causes a hypertrophic elongation of the supravaginal portion of the cervix. The anterior and posterior vaginal walls are attached to the cervix at different levels so that such an elongation may occur in the vesical portion of the cervix with complete eversion of the anterior vaginal wall and the cervix, while the posterior vaginal, remains intact and presents its normal length.
EGF Receptor Activation Decreases Retroviral Gene Transfer through Protein Kinase C-δ
Authors: Raghvendra Singh, Stelios T Andreadis
Journal: Molecular Therapy (2007)

Although much progress has been made in the design of retrovirus vectors, the interactions of recombinant retrovirus with host cells remain largely elusive. The inability of recombinant retrovirus to transduce non-dividing cells prompted several studies to determine optimal cocktails of growth factors and/or extracellular matrix molecules to promote gene transfer to slowly diving cells and stem cells. In contrast to previous reports that growth factors increased gene transfer, we found that treatment of human epidermal keratinocytes and several cell lines with epidermal growth factor receptor (EGFR) ligands EGF, transforming growth factor-α, or heparin-binding-EGF decreased gene transfer. Conversely, treatment with an EGFR function-blocking antibody or inhibition of EGFR tyrosine phosphorylation enhanced gene transfer in a dose-dependent manner. In addition, blocking protein kinase C (PKC)-δ but not PKC-ζ, with chemical inhibitors or small interfering RNA reversed the effects of EGF and restored gene transfer, indicating that the effect of EGFR activation is mediated through PKC-δ. Lastly, cell cycle analysis showed that the effect of EGFR activation on retroviral gene transfer was independent of the cell cycle status of target cells. Our results implicate EGFR and PKC-δ in retroviral infection and may have implications for retrovirus gene transfer or design of antiretroviral therapies.
TCT-708 Predictors Of Left Ventricular Function Improvement After Transcatheter Aortic Valve Implantation In Patients With Moderate To Severe Left Ventricular Dysfunction
Authors: Freek Nijhoff, Pieter R. Stella, Vincent J. Nijenhuis, Nicolas M. Van Mieghem, Luca Testa, Mariam Samim, Patrizia Presbitero, Francesco Bedogni, Jurrien M. Ten Berg, Pierfrancesco Agostoni
Journal: Journal of the American College of Cardiology (2014)
MicroRNA Microarray Analysis of Human Adrenocortical Tumors Identifies miR-195 and miR-483-5p as Predictors of Poor Prognosis in Adrenocortical Cancer – Response
Authors: Patsy S.H. Soon, Lyndal J. Tacon, Roderick J. Clifton-Bligh, Bruce G. Robinson, Stan B. Sidhu, Peter R. Campbell, Anthony J. Gill, Christopher P. Bambach, Mark S. Sywak, Michael W. Yeh, Steven G. Wong
Journal: Clinical Cancer Research (2010)

We thank Dr. Tombol and colleagues for their interest in our article and their comments. As with our study, Dr. Tombol and colleagues also performed microRNA (miRNA) profiling of adrenocortical tumors. There were however only two miRNAs in common between the two studies. This is, of course,
Cardiorespiratory Toxicity Due to Miconazole
Authors: Victor Fainstein, Gerald P. Bodey
Journal: Annals of Internal Medicine (1980)

Seven patients with hematologic malignancies who were treated with miconazole for either suspected or proven fungal infections developed eight episodes of major adverse cardiorespiratory and anaphylactic reactions. All the episodes occurred after the first dose was administered, and the seven patients recovered without sequelae after the drug was withdrawn. None of them had a history of cardiac disease, and with the possible exception of one case of cardiac arrest, where the patient received doxorubicin, no predisposing factors could be found. The rate and length of administration, as well as the dose, should be carefully monitored to avoid these complications.
Lipoprotein Composition in Individuals with Impaired Glucose Tolerance
Authors: Brunella Capaldo, Loredana Tutino, Lidia Patti, Olga Vaccaro, Angela Rivellese, Gabriele Riccardi
Journal: Diabetes Care (1983)

The relationship between impaired glucose tolerance (IGT) and blood lipid levels was examined in 65 IGT individuals and in two control groups: control group I, composed of age-, sex-, and body weight-matched controls, and control group II, including normal subjects matched for sex and age but with normal body mass index. IGT individuals were found to have significantly higher total triglyceride (Tg) values compared with normal weight controls (P less than 0.001), while no difference was found between IGT and control group I. Total cholesterol levels were similar in IGT and each of the control groups. No significant correlation was found between serum lipoproteins and blood glucose levels either fasting or after load.