tbuckley/cabot-search huggingface dataset:
Sir Vidia's ‘racism’
Authors: Ethan Taub
Journal: Journal of the Royal Society of Medicine (2009)

I was surprised to read in the JRSM, of all places, a gratuitous reference to VS Naipaul's ‘racism’ from Jim Thornton,1 who has just read a new biography of the great writer.2 The biographer, Patrick French, indeed pulls no punches (like Naipaul himself), yet he does not call his subject a racist or show him to be one. If the charge is levelled with tiresome regularity by certain PC critics, this is because Naipaul has not fallen for the fallacy of ‘the superior virtue of the oppressed’, as Bertrand Russell, not a racist either, once called it. To read Naipaul's works with both eyes open is to understand that they are one long and masterful plea for human dignity and freedom. His knighthood and Nobel Prize are an honour, not just to him, but to Britain and the world.
Miriam Claire Ogden
Authors: N. Rane
Journal: BMJ (2009)

The lives of many were turned upside down when Miriam Claire Ogden was found dead in Cambridge in spring last year. A dark day, a shining star prematurely lost. Her tragic suicide was two days before her 24th birthday.

Miriam excelled through her school days to take up a place at Newnham College, Cambridge, to read medicine in 2002. It was uncertain where her passion for medicine stemmed from, however, it was clear to all that she …
Thyroid Stimulating Antibodies, Thyroglobulin Antibodies and Serum Proteins during Treatment of Graves’ Disease with Radioiodine or Propylthouracil
Authors: Ulla Feldt‐Rasmussen, Karine Bech, John Date, Per Hyltoft Pedersen, Klaus Johansen, Stig Nistrup Madsen
Journal: Allergy (1982)

The relation between serum concentrations of thyroglobulin antibodies (TgAb), thyroid-stimulating antibodies (TSAb) and serum immunoglobulins during treatment of Graves' disease was studied in 36 consecutive patients treated randomly with 131-iodine (n = 16) or propylthiouracil (n = 20). The patients were investigated before treatment was started and on seven occasions within the following year. In the entire patient group 78% were positive for TSAb and 47% for TgAb. There was a significant correlation between TSAb and TgAb in 15 patients concomitantly positive. There were no significant changes in serum immunoglobulins during treatment in either group of patients. In the radioiodine-treated group of patients TgAb was reduced after 1 week, whereas TSAb showed insignificant variations. After 5-10 weeks both antibodies increased, for TgAb with a median peak level 3 time above the initial concentration. Of 16 patients treated with radioiodine five developed myxoedema and four of these were positive for TgAb. There was a relation between the development of myxoedema and the ratio between increases of TSAb and TgAb. Increase in TSAb was not related to serum thyroglobulin (Tg) measured in TgAb-negative patients. Propylthiouracil showed minor effects on the studied variables, but with lower mean values of Tg, TgAb and TSAb at the end of the observation period. The results indicate an immunological relation between TSAb and TgAb, although differences between their course exist in some situations.
Abstract 2978: DNA methylation changes during epithelial-to-mesenchymal transition in ovarian cancer cells.
Authors: Horacio Cardenas, Chirayu Goswami, Kenneth P. Nephew, Daniela Matei
Journal: Cancer Research (2013)

Abstract Epithelial-to-mesenchymal transition (EMT) is a required step in the process of metastasis and has been linked to cancer cell stemness. We hypothesized that aside from defined genetic changes associated with EMT, epigenetic mechanisms are also involved. We determined DNA methylation changes in SKOV3 ovarian cancer (OC) cells undergoing TGFβ-induced EMT by using the Infinium HumanMethylation450 array. Methylation of sites was expressed as ß-values ranging from 0 (completely unmethylated) to 1 (completely methylated). Methylation of 468 and 390 sites changed significantly (P&amp;lt;.01, ANOVA and FDR&amp;lt;0.05) after 48h and 120h of TGFβ stimulation, of which 31 and 72 sites changed &amp;gt;1.25-fold. The majority of changes (∼66%) reflected TGFβ-induced demethylation. Methylation of 160 sites changed similarly at 48 and 120h indicating that approximately 40% of changes were sustained. PCA analysis demonstrated that the removal of TGFβ was associated with reversal of DNA methylation changes at most sites and restitution of the baseline methylome. Pathway analysis identified DNA methylated genes involved in functional networks relevant to EMT and cancer progression, including: 1) cell morphology and development (39 genes), 2) cell growth and proliferation, and cell death and survival (34 genes), 3) cellular assembly and organization (22 genes), 4) DNA replication, recombination and repair (17 genes), and 5) gene expression, cell signaling, and cellular movement (15 genes). Validation of the relevant genes is ongoing. Treatment of OC cells with the DNA methyl transferase inhibitor SGI-110 prevented TGFβ-induced EMT and reduced by two-fold the number of cells with stem cell characteristics (ALDH1+). These results demonstrate that DNA methylation is a dynamic process involved in regulation of genes implicated in EMT and metastasis. Citation Format: Horacio Cardenas, Chirayu Goswami, Kenneth P. Nephew, Daniela Matei. DNA methylation changes during epithelial-to-mesenchymal transition in ovarian cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2978. doi:10.1158/1538-7445.AM2013-2978
Prognosis of subsequent pregnancies after recurrent spontaneous abortion in first trimester.
Authors: W Vlaanderen, P E Treffers
Journal: BMJ (1987)

The outcome of subsequent pregnancies was studied in 24 women with a history of three or more consecutive spontaneous abortions in the first trimester. Twenty one of the women agreed to forgo active treatment during the study period and three received progestogens or surgical intervention. As the outcome of their first pregnancy after recurrent abortion 18 of the 24 women delivered a liveborn infant after 28 weeks or more. Of all 49 pregnancies in the untreated group during the study, 10 ended in abortion. Only one woman in the study failed to achieve a live birth. Except in exceptional cases encouraging women with recurrent abortion to keep trying for a successful outcome is just as effective as currently recommended treatments.
Abstract A04: Endothelial FAK activity controls vascular permeability and tumor metastasis
Authors: Christine Jean, Xiao Lei Chen, Isabelle Tancioni, Sean Uryu, Christine Lawson, Nichol Miller, Patric Turowski, Elisabetta Dejana, Sara Weis, David Cheresh, David D. Schlaepfer
Journal: Cancer Research (2015)

Abstract Tumor spread remains a primary cause of cancer mortality. Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase co-activated by integrin and growth factor receptors in the control of vascular permeability. As FAK inhibitors are being tested in clinical trials, it is important to determine whether FAK signaling plays distinct roles in tumor versus stromal cell biology. Herein, we elucidate a new mechanism for endothelial cell (EC) FAK activity in the regulation of blood vessel barrier integrity and the passage of tumor cells through an EC barrier. We show that vascular endothelial cadherin (VEC) tyrosine (Y) 658 is phosphorylated by FAK in tumor-associated ECs. Conditional kinase-dead FAK knockin within ECs inhibited recombinant vascular endothelial growth factor (VEGF-A) and tumor-induced VEC Y658 phosphorylation in vivo. Adherence of VEGF-expressing tumor cells to ECs triggered FAK-dependent VEC Y658 phosphorylation. Both FAK inhibition and VEC Y658F mutation within ECs prevented VEGF-initiated paracellular permeability and tumor cell transmigration across EC barriers. In mice, EC FAK inhibition prevented VEGF-dependent tumor cell extravasation and melanoma dermal to lung metastasis without affecting primary tumor growth. Although it is known that Src tyrosine kinase activity is important in controlling VEC tyrosine phosphorylation downstream of VEGF, we find that pharmacological Src inhibition prevents FAK activation. Moreover, FAK inhibition prevents both Src and FAK translocation to EC adherens junctions, but does not alter Src activation. Together, these results identify EC FAK as a key intermediate between Src and the regulation of EC barrier function controlling tumor metastasis. Citation Format: Christine Jean, Xiao Lei Chen, Isabelle Tancioni, Sean Uryu, Christine Lawson, Nichol Miller, Patric Turowski, Elisabetta Dejana, Sara Weis, David Cheresh, David D. Schlaepfer. Endothelial FAK activity controls vascular permeability and tumor metastasis. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr A04. doi:10.1158/1538-7445.CHTME14-A04
How mad are we?
Authors: L. Henderson
Journal: BMJ (2008)

Television is often blamed for helping to fuel rather than challenge the stigma associated with mental illness, and people with acute mental disorders are often depicted as frightening and potentially violent. So it was with enormous interest that I tuned into the Horizon special “How Mad are You?” The programme had generated many column inches on the back of its provocative title and unhelpful strap lines, such as “They’re coming to take me away.” Some commentators wondered whether the show might be tasteless, a sort of I’m a Nutter Get Me out of Here . 

Clearly the programme is a departure from Horizon’s traditional approach as a flagship science documentary series with an established reputation for measured scientific debate, talking heads, and “voice of God” commentary. Nevertheless we are told that this programme was inspired by the 1973 scientific controversy when the US psychologist David Rosenhan, along with seven associates, managed to be admitted to psychiatric hospital and in so doing challenged “science’s ability to judge the fine line between sanity and insanity.”

We …
Selective Inhibition of Histone Deacetylase 2 Silences Progesterone Receptor–Mediated Signaling
Authors: Elona Biçaku, Douglas C. Marchion, Morgen L. Schmitt, Pamela N. Münster
Journal: Cancer Research (2008)

Abstract Several histone deacetylases (HDAC) are involved in estrogen receptor (ER)–mediated gene transactivation, and HDAC inhibitors have been reported to restore sensitivity to antihormonal therapy. The modulation of ER is the most promising approach to ER-expressing breast cancers. Recent studies further suggest a critical role of the progesterone receptor (PR) on ER signaling. Although HDAC inhibitors modulate ER, little is known about their effects on PR. We evaluated the roles of specific HDAC isoenzymes and their inhibition on both ER and PR signaling and their importance in response to endocrine therapy. The roles of individual HDAC isoenzymes on ER and PR expression and their functions were evaluated by depletion of select HDAC enzymes using siRNA or pharmacologic inhibition. Cotreatment of breast cancer cell lines with HDAC inhibitors and the antiestrogen, tamoxifen, resulted in synergistic antitumor activity with simultaneous depletion of both ER and PR. Selective inhibition of HDAC2, but not HDAC1 or HDAC6, was sufficient to potentiate tamoxifen-induced apoptosis in ER/PR-positive cells. Depletion of HDAC1 and HDAC6 was associated with down-regulation of ER but not PR. Only the selective depletion of HDAC2 siRNA down-regulated both ER and PR expression, and was sufficient to potentiate tamoxifen. Selective depletion of HDAC2 resulted in simultaneous depletion of ER and PR, and potentiated the effects of antihormonal therapy in ER-positive cells. A more effective pharmacologic inhibition of HDAC2 and evaluation of HDAC2 and PR as therapeutic targets or as predictive markers in hormonal therapy may be considered when combining HDAC inhibitors and hormonal therapy. [Cancer Res 2008;68(5):1513–9]
The Effect of Inhaled Chromium on Different Exhaled Breath Condensate Biomarkers among Chrome-Plating Workers
Authors: Andrea Caglieri, Matteo Goldoni, Olga Acampa, Roberta Andreoli, Maria Vittoria Vettori, Massimo Corradi, Pietro Apostoli, Antonio Mutti
Journal: Environmental Health Perspectives (2005)

Chromium is corrosive, cytotoxic, and carcinogenic for humans and can induce acute and chronic lung tissue toxicity. The aim of this study was to investigate Cr levels in exhaled breath condensate (EBC) of workers exposed to Cr(VI) and to assess their relationship with biochemical changes in the airways by analyzing EBC biomarkers of oxidative stress, namely, hydrogen peroxide (H2O2) and malondialdehyde (MDA). EBC samples were collected from 24 chrome-plating workers employed in a chrome-plating plant both before and after the Friday work shift and before the work shift on the following Monday. Cr-EBC levels increased from the beginning (5.3 μg/L) to the end of Friday (6.4 μg/L) but were considerably lower on Monday morning (2.8 μg/L). A similar trend was observed for H2O2-EBC levels (which increased from 0.36 μM to 0.59 μM on Friday and were 0.19 μM on Monday morning) and MDA-EBC levels (which increased from 8.2 nM to 9.7 nM on Friday and were 6.6 nM on Monday). Cr-EBC levels correlated with those of H2O2-EBC (r = 0.54, p &lt; 0.01) and MDA-EBC (r = 0.59, p &lt; 0.01), as well as with urinary Cr levels (r = 0.25, p &lt; 0.05). The results of this study demonstrate that EBC is a suitable matrix that can be used to investigate both Cr levels and biomarkers of free radical production sampling the epithelial-lining fluid of workers exposed to Cr(VI).
Analogies in medicine
Authors: J. D R Rose
Journal: BMJ (2003)

A nurse once told me that my patient would need a PhD in analogy to understand the explanation that I had given. She probably had a point; I have been known to overdo it, but analogies do have their uses. They can explain, mislead, and provide illuminating insights.

Organisations have long been likened to organisms and can be seen as having disease 

Comparing heart failure from fast atrial fibrillation to the inefficiency of an over-revved engine helps patients with a mechanical background to understand what has gone wrong, as do many other mechanical analogies involving pumps, valves, and pipework of various sorts. However, one sometimes feels that there was more fun derived in developing the analogy than information actually imparted. Try working backwards from what patients say they were told to what the doctor actually said originally.

Analogies can also be subversive. You can derail any seminar threatening to uncover the true depths of your ignorance with a well timed obscure statement such as “So, the …
Beta-adrenergic agonist stimulated alveolar fluid clearance in ex vivo human and rat lungs.
Authors: T Sakuma, H G Folkesson, S Suzuki, G Okaniwa, S Fujimura, M A Matthay
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Because beta-adrenergic agonist therapy may be useful clinically as a treatment to hasten the resolution of alveolar edema, this study was designed to examine the dose-dependent effects of beta-adrenergic agonist therapy on alveolar epithelial fluid clearance. The studies were done by instilling an isosmolar 5% albumin solution into the distal air spaces of both ex vivo rat and ex vivo human lungs that were inflated with 8 to 10 cm H2O with 100% oxygen and placed in a 37 degrees C humid incubator. Alveolar fluid clearance was measured by the progressive increase in concentration of protein over 1 or 4 h. Salmeterol, a new long-acting lipophilic agent, was more potent than terbutaline in stimulating alveolar fluid clearance from the ex vivo human lung. Therefore, salmeterol was used for these studies. The results indicated that: (1) basal, unstimulated alveolar fluid clearance in rat lungs was significantly faster than in human lungs (24 +/- 4% over 4 h in rat lungs compared with 11 +/- 2% over 4 h in human lungs, p < 0.05); (2) comparison of equivalent doses of beta-adrenergic stimulation indicated that stimulated clearance rates were also faster in rat lungs than in human lungs; (3) very low doses of salmeterol were effective in ex vivo rat lungs (10(-8) M); and (4) relatively low doses were effective in the ex vivo human lungs (10(-6) M) as a treatment for increasing alveolar fluid clearance. In summary, there are significant differences in the basal and stimulated rates of alveolar epithelial fluid clearance in rat and human lungs, although the ex vivo human studies may have underestimated maximal alveolar fluid clearance in the intact human lung. The human lung responds well to relatively low doses of beta-adrenergic agonist therapy, a finding with potentially important clinical implications for hastening the resolution of alveolar edema.
Relation of Nonperfused Myocardial Volume and Surface Area to Left Ventricular Performance in Coronary Microembolization
Authors: Nasser M. Malyar, Lilach O. Lerman, Mario Gössl, Patricia E. Beighley, Erik L. Ritman
Journal: Circulation (2004)

After occlusion of an epicardial artery, left ventricular (LV) dysfunction is closely related to the volume of nonperfused myocardium (NPM). The impact of coronary microembolization (ME) on LV function, however, is larger relative to the total volume of NPM. We hypothesized that the total surface area (SA), rather than the total volume, of NPM is the major determinant of ME-induced LV dysfunction.We injected microspheres of 10-, 30-, or 100-microm diameter at each of 3 doses selectively into the left anterior descending coronary artery of 48 anesthetized pigs. Electron beam computed tomography (CT) was used to measure regional myocardial perfusion and changes in LV wall thickening (DeltaWT) and stroke volume (DeltaSV) after ME. At postmortem, a transmural "biopsy" of 1 to 2 cm3 of embolized myocardium was imaged by micro-CT, resulting in 3D images that provided volumes and SAs of the individual nonperfused foci. Additionally, in 9 pigs, creatine phosphokinase (CK) activity in embolized myocardium was measured as an index of washout of substances from the NPM. After ME, DeltaWT, DeltaSV, and CK washout were correlated more closely with the total SA (r=0.95, P<0.001; r=0.68, P<0.01; and r=0.88, P=0.01, respectively) than with the total NPM volume (r=0.59, P>0.05; 0.46, P>0.05; and r=0.69, P=0.04, respectively).After coronary ME, LV dysfunction is more closely related to the total SA than to the total volume of nonperfused microregions in the myocardium.
THE SIGNIFICANCE OF CARDIAC EXTRASYSTOLES IN CHILDHOOD
Authors: MURRAY H. BASS
Journal: JAMA (1926)

Of the various arrhythmias encountered in the heart beat during childhood, that known as extrasystole is probably the least well understood. We find articles dealing with heart block, fibrillation, paroxysmal tachycardia and sinus arrhythmia, but there is very little in the literature dealing with the subject of extrasystole. In adults this particular form of irregularity is not uncommon; in fact, when one sees the table of age incidence of extrasystole given by Cowan and Ritchie, 1 one realizes that the condition is least common in childhood, comparatively rare below the age of 40, and not at all infrequent following that. Out of a total of 226 cases of extrasystole, only seven were present in individuals between the ages of 10 and 20, and none below the age of 10. This seeming rarity of the condition in childhood is only apparent, for if we deal with statistics concerning children only, we
Syndrome of Inappropriate Secretion of Antidiuretic Hormone
Authors: JEFFREY BODACK
Journal: Annals of Internal Medicine (1976)

Comments1 December 1976Syndrome of Inappropriate Secretion of Antidiuretic HormoneJEFFREY BODACK, M.D.JEFFREY BODACK, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-85-6-829_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In the recent paper by Vagenakis, Dole, and Braverman, "Pituitary Enlargement, Pituitary Failure, and Primary Hypothyroidism" (Ann Intern Med 85:195-198, 1976), the authors state that their second patient suffered from the inappropriate ADH syndrome (1), with sodium concentrations considerably below 130 meq/litre, elevated urine osmolality, and urine sodium in excess of 120 meq/litre. However, this patient's serum cortisols were undetectable, and his renal function was never clearly described.At our hospital, Dr. Albert, a nephrologist, states that adrenal function must be clearly delineated before the diagnosis of inappropriate ADH syndrome is made, as adrenocortical crisis might be...Reference1. BARTTERSCHWARTZ FW: The syndrome of inappropriate secretion of antidiuretic hormone. Am J Med 42:790-806, 1967 CrossrefMedlineGoogle Scholar1. AHMEDGEORGEAUVERT-GONZALES ABC: Increased plasma arginine vasosuppression in clinical adrenocortical insufficiency and its inhibition by glucosteroids. J Clin Invest 46:111, 1967 CrossrefMedlineGoogle Scholar2. AGUSGOLDBERG ZM: Role of antidiuretic hormone in the abnormal water diuresis of anterior hypopituitarism in man. J Clin Invest 50:1478, 1971 CrossrefMedlineGoogle Scholar3. SKOWSKYNIELSENFISHER RTD: Arginine vasosuppression kinetics in the thyroidectomized sheep. Program of the 56th Annual Meetings of the Endocrine Society, 1974 Google Scholar4. WILLIAMSROSEDLUHY GLR: Aldosterone response to sodium restriction and ACTH stimulation in panhypopituitarism. J Clin Endocrinol Metab 32:27, 1971 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Lankenau Hospital Philadelphia, PA 19151 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 December 1976Volume 85, Issue 6Page: 829-830KeywordsAntidiuretic hormoneAttentionCortisolHypothyroidismSodiumUrine Issue Published: 1 December 1976 PDF DownloadLoading ...
Reversible Pure Red Cell Hypoplasia in Pregnancy
Authors: Gary Lehman
Journal: JAMA (1982)

PREGNANCY is normally a state of erythroid hyperplasia. Increased erythropoiesis during pregnancy is controlled by erythropoietin, which is augmented by the action of placental lactogen and inhibited by high levels of estrogen.<sup>1</sup>We describe a case of a patient with pure red cell hypoplasia during pregnancy that resolved completely in the postpartum period. <h3>Report of a Case</h3> On Jan 22, 1981, a 23-year-old primigravida came to the obstetric clinic at Naval Regional Medical Center (NRMC), Charleston, SC, for an initial prenatal visit at approximately 24 weeks' gestation. A routine hemoglobin level and hematocrit reading were noted to be 9.0 g/dL and 27.1%, respectively. Administration of ferrous sulfate, 325 mg, one tablet three times a day, was begun. A follow-up visit four weeks later revealed a hemoglobin level of 7.1 g/dL and a hematocrit reading of 24.3%. The patient denied noncompliance with respect to self-administration of the prescribed medication. The
Firearm Injuries of Children and Adolescents in 2 Colorado Trauma Centers: 2000-2008
Authors: Angela Sauaia, Joshua I. Miller, Ernest E. Moore, David Partrick
Journal: JAMA (2013)

Given recent firearm-related fatalities combined with declining gun research funding,1 it is important to monitor firearm injuries in youths. Injury death rates are available but provide an incomplete picture of these potentially preventable injuries.2