tbuckley/cabot-search huggingface dataset:
SURGICAL TREATMENT OF GOITER.
Authors: ROBERT WALLACE HARDON
Journal: JAMA (1906)

<h3>PATHOLOGY.</h3> For a proper understanding of the subject it is necessary to give a short review of the various pathologic conditions which affect the thyroid gland, together with a brief description of the clinical pictures presented by each. Normally, the thyroid gland, a ductless body, is composed of a vascular stroma supporting acini which are lined with a single layer of epithelial cells. The acini contain colloid material which keeps the epithelial cells from contact. <h3>Simple Goiter.</h3> —In simple goiter there is found only increased colloid material, causing greater distention of the acini. <h3>Exophthalmic Goiter.</h3> —In this variety we not only find a greater amount of colloid material, but an increase of the epithelial cells causing an irregular invagination of the lining of the acini. These two varieties may be considered hypertrophies, as they represent normal thyroid conditions exaggerated. Both of these varieties show a fairly symmetrical enlargement of gradual
Gagging clauses outlawed
Authors: J. Warden
Journal: BMJ (1997)

A more relaxed attitude to whistleblowing in the NHS was signalled last week by the health minister, Alan Milburn, in what he called a “fairer deal for NHS staff” that will also include better standards of food and accommodation for junior doctors on call.

Mr Milburn told a conference of health service managers at Keele University that he is outlawing all gagging clauses in employment contracts so that …
Changes of mitral regurgitation severity under altered loading conditions and its relationship to pulmonary venous flow
Authors: Hua Yang, Michael Jones, Takahiro Shiota, None Jian Xin Qin, None Yong Jin Kim, D.Wesley Daugherty, Zoran Popovic, Neil L. Greenberg, Min Pu, Lisa A. Cardon, Arthur D. Zetts, James D. Thomas
Journal: Journal of the American College of Cardiology (2002)
The addition of medium-chain triglycerides to a purified fish oil-based diet alters inflammatory profiles in mice
Authors: Sarah J. Carlson, Prathima Nandivada, Melissa I. Chang, Paul D. Mitchell, Alison O’Loughlin, Eileen Cowan, Kathleen M. Gura, Vania Nose, Bruce R. Bistrian, Mark Puder
Journal: Metabolism (2014)
679 COMPARISON OF HISTOPATHOLOGICAL FEATURES OF HEPATOCELLULAR CARCINOMA RISING FROM NONALCOHOLIC FATTY LIVER DISEASE WITH THOSE OF HEPATOCELLULAR CARCINOMA RISING FROM HEPATITIS C-VIRUS-RELATED CHRONIC LIVER DISEASE
Authors: M. Taniai, S. Chishima, K. Kodama, M. Tobari, N. Matsushita, T. Kogiso, N. Torii, K. Tokushige, E. Hashimoto
Journal: Journal of Hepatology (2013)
Proinflammatory and cytotoxic effects of Mexico City air pollution particulate matter in vitro are dependent on particle size and composition.
Authors: Alvaro R Osornio-Vargas, James C Bonner, Ernesto Alfaro-Moreno, Leticia Martínez, Claudia García-Cuellar, Sergio Ponce-de-León Rosales, Javier Miranda, Irma Rosas
Journal: Environmental Health Perspectives (2003)

Exposure to urban airborne particulate matter (PM) is associated with adverse health effects. We previously reported that the cytotoxic and proinflammatory effects of Mexico City PM10 (less than or equal to 10 micro m mean aerodynamic diameter) are determined by transition metals and endotoxins associated with these particles. However, PM2.5 (less than or equal to 2.5 micro m mean aerodynamic diameter) could be more important as a human health risk because this smaller PM has the potential to reach the distal lung after inhalation. In this study, we compared the cytotoxic and proinflammatory effects of Mexico City PM10 with those of PM2.5 using the murine monocytic J774A.1 cell line in vitro. PMs were collected from the northern zone or the southeastern zone of Mexico City. Elemental composition and bacterial endotoxin on PMs were measured. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) production by J774A.1 cells was measured in the presence or absence of recombinant endotoxin-neutralizing protein (rENP). Both northern and southeastern PMs contained endotoxin and a variety of transition metals. Southeastern PM10 contained the highest endotoxin levels, 2-fold higher than that in northern PM10. Northern and southeastern PM2.5 contained the lowest endotoxin levels. Accordingly, southeastern PM10 was the most potent in causing secretion of the proinflammatory cytokines TNF-alpha and IL-6. All PM2.5 and PM10 samples caused cytotoxicity, but northern PMs were the most toxic. Cytokine secretion induced by southeastern PM10 was reduced 50-75% by rENP. These results indicate major differences in PM10 and PM2.5. PM2.5 induces cytotoxicity in vitro through an endotoxin-independent mechanism that is likely mediated by transition metals. In contrast, PM10 with relatively high levels of endotoxin induces proinflammatory cytokine release via an endotoxin-dependent mechanism.
1045 PIRFENIDONE MAINTAINS NUCLEAR NRF2 ACTIVATION AND REDUCES PROINFLAMMATORY AND FIBROGENIC EFFECTS INDUCED BY OXIDATIVE STRESS IN HUMAN HEPATIC STELLATE CELLS (HSC)
Authors: J. Macias, A. Caligiuri, E. Novo, M. Parola, J. Armendáriz-Borunda, M. Pinzani
Journal: Journal of Hepatology (2011)
Relationship Between Metabolic Risk Factor Clustering and Cardiovascular Mortality Stratified by High Blood Glucose and Obesity
Authors: Aya Kadota, Atsushi Hozawa, Tomonori Okamura, Takashi Kadowak, Koshi Nakmaura, Yoshitaka Murakami, Takehito Hayakawa, Yoshikuni Kita, Akira Okayama, Yasuyuki Nakamura, Atsunori Kashiwagi, Hirotsugu Ueshima
Journal: Diabetes Care (2007)

Metabolic syndrome is diagnosed according to several criteria. Of these, some require glucose intolerance and others require obesity for the diagnosis. We investigated the relationship between metabolic risk factor clustering and cardiovascular disease (CVD) mortality stratified by high blood glucose or obesity.We followed 7,219 Japanese men and women without a history of CVD for 9.6 years. We defined high blood pressure, high blood glucose, high triglycerides, low HDL cholesterol, and obesity as metabolic factors. The multivariate adjusted hazard ratio (HR) for CVD mortality according to the number of clustering metabolic factors was calculated using the Cox proportional hazards model.During follow-up, 173 participants died of CVD. The numbers of metabolic risk factors and CVD mortality were positively correlated (P(trend) = 0.07). The HR was obviously higher among participants with than among those without high blood glucose and clustering of > or =2 other metabolic risk factors (HR 3.67 [95% CI 1.49-9.03]). However, the risk increase was only modest in participants without high blood glucose even if they had > or =2 other metabolic risk factors (1.99 [0.93-4.28]). Conversely, metabolic risk factor clustering was related to CVD mortality irrespective of obesity.Our findings suggest that glucose tolerance plays an important role in CVD mortality. Because the prevalence of nonobese participants with several metabolic risk factors was quite high and their CVD risk was high, excluding them from the diagnosis of metabolic syndrome because of the absence of obesity might overlook their risk.
Relationship of Prenatal Diagnosis and Pregnancy Termination to Overall Infant Mortality in Canada
Authors: Shiliang Liu
Journal: JAMA (2002)

Context Prenatal diagnosis and termination of affected pregnancies can prevent infant deaths due to congenital anomalies, but an effect at the population level has not been shown. ObjectiveTo examine the impact of recent changes in congenital anomaly-related fetal and infant deaths on overall population-based infant mortality.Design, Setting, and Subjects Birth cohort-based study of all live births, stillbirths, and infant deaths in Canada (excluding Ontario) for 1991-1998. Main Outcome MeasuresCause-specific infant mortality rates and gestational agespecific fetal death rates. ResultsThe birth cohort-based infant mortality rate fluctuated between 6.4 and 6.1 per 1000 live births between 1991 and 1995, then dropped to 5.4 per 1000 in 1996 and 5.5 per 1000 in 1997.The rate of infant death from congenital anomalies was stable between 1991 and 1995 but declined by 21% (95% confidence interval, 19%-32%) from 1.86 per 1000 in 1995 to 1.47 per 1000 in 1996 and 1997.Fetal deaths due to pregnancy termination at 20 to 23 weeks' gestation increased dramatically in 1994, while fetal deaths due to congenital anomalies at 20 to 21 weeks increased in 1995 and subsequently.Provinces/territories with high rates of fetal death due to pregnancy termination/congenital anomalies at 20 to 23 weeks had fewer infant deaths due to congenital anomalies. ConclusionA large decrease in infant deaths due to congenital anomalies was associated with the most recent decline in infant mortality in Canada, suggesting that increases in prenatal diagnosis and pregnancy termination for congenital anomalies are related to decreases in overall infant mortality at the population level.
The case for resurrecting the long case
Authors: Narci C Teoh, Francis J Bowden
Journal: BMJ (2008)

In adult mice, monocular enucleation (ME) results in an immediate deactivation of the contralateral medial monocular visual cortex. An early restricted reactivation by open eye potentiation is followed by a late overt cross-modal reactivation by whiskers (Van Brussel et al., 2011). In adolescence (P45), extensive recovery of cortical activity after ME fails as a result of suppression or functional immaturity of the cross-modal mechanisms (Nys et al., 2014). Here, we show that dark exposure before ME in adulthood also prevents the late cross-modal reactivation component, thereby converting the outcome of long-term ME into a more P45-like response. Because dark exposure affects GABAergic synaptic transmission in binocular V1 and the plastic immunity observed at P45 is reminiscent of the refractory period for inhibitory plasticity reported by Huang et al. (2010), we molecularly examined whether GABAergic inhibition also regulates ME-induced cross-modal plasticity. Comparison of the adaptation of the medial monocular and binocular cortices to long-term ME or dark exposure or a combinatorial deprivation revealed striking differences. In the medial monocular cortex, cortical inhibition via the GABA<sub>A</sub> receptor α1 subunit restricts cross-modal plasticity in P45 mice but is relaxed in adults to allow the whisker-mediated reactivation. In line, <i>in vivo</i> pharmacological activation of α1 subunit-containing GABA<sub>A</sub> receptors in adult ME mice specifically reduces the cross-modal aspect of reactivation. Together with region-specific changes in glutamate acid decarboxylase (GAD) and vesicular GABA transporter expression, these findings put intracortical inhibition forward as an important regulator of the age-, experience-, and cortical region-dependent cross-modal response to unilateral visual deprivation. <b>SIGNIFICANCE STATEMENT</b> In adult mice, vision loss through one eye instantly reduces neuronal activity in the visual cortex. Strengthening of remaining eye inputs in the binocular cortex is followed by cross-modal adaptations in the monocular cortex, in which whiskers become a dominant nonvisual input source to attain extensive cortical reactivation. We show that the cross-modal component does not occur in adolescence because of increased intracortical inhibition, a phenotype that was mimicked in adult enucleated mice when treated with indiplon, a GABA<sub>A</sub> receptor α1 agonist. The cross-modal versus unimodal responses of the adult monocular and binocular cortices also mirror regional specificity in inhibitory alterations after visual deprivation. Understanding cross-modal plasticity in response to sensory loss is essential to maximize patient susceptibility to sensory prosthetics.
NUMBER OF VULNERABLE PLAQUE CHARACTERISTICS THAT ARE REQUIRED IN A SINGLE NON-CALCIFIED PLAQUE ON CT TO BE AT HIGH RISK OF CAUSING MAJOR ADVERSE CARDIOVASCULAR EVENTS
Authors: Hiroyuki Takaoka, Nobusada Funabashi, Masae Uehara, Koya Ozawa, Yoshio Kobayashi
Journal: Journal of the American College of Cardiology (2013)
Networking for health
Authors: F. Godlee
Journal: BMJ (2008)

Contagion has been the curse of human health for centuries. Medicine has dedicated itself to preventing it. But what if diseases aren’t the only things that can be caught? What if good things can also be transmitted from one person to another—happiness for example? This is the hypothesis explored in this week’s BMJ .

James Fowler and Nicholas Christakis have been studying the effects of social networks for some time. Now using a unique data set—the Framingham Heart Study cohort—they’ve analysed 20 years of data on nearly 5000 people, including measures of happiness (doi:10.1136/bmj.a2338). Within this social network they found non-random clustering …
Effects of a 'healthy' diet and of acute and long-term vitamin C on vascular function in healthy older subjects
Authors: Nivedita Singh, Jonathan Graves, Paul D Taylor, Raymond J MacAllister, Donald R J Singer
Journal: Cardiovascular Research (2002)

Objective: Aging is associated with endothelial dysfunction. We studied the acute and longer-term effects of vitamin C compared to a 'Mediterranean-type' diet on endothelial function in healthy older subjects. Methods: Bilateral venous occlusion plethysmography was used to measure forearm blood flow in subjects aged 57–80 years. Responses to cumulative intra-arterial doses of the endothelium-dependent dilator bradykinin (BK; n=56; 20, 40, 80 pmol/min) and the nitric oxide donor glyceryl trinitrate (GTN; n=54; 4, 8, 16 nmol/min), were determined alone and in the presence of vitamin C (25 mg/min). We then randomised 54 subjects to a 'healthy' diet (n=18), vitamin C (1 g/day; n=18) or placebo for 6 weeks and reassessed endothelial and smooth muscle function. Results: Acute intra-arterial vitamin C did not alter dilatation to BK or GTN. Similar increases in plasma vitamin C occurred on oral vitamin C (83±4 to135±8 μmol/l) and 'healthy' diet (84±5 to135±27 μmol/l; P<0.01 for both), with no change seen on placebo. Treatment with a 'healthy' diet but not oral vitamin C improved endothelium-dependent (P=0.043) and endothelium-independent dilatation (P=0.011). Conclusions: A 'Mediterranean-type' diet rich in vitamin C improves vascular function. Neither acute intra-arterial nor sustained administration of oral vitamin C improves vascular function in healthy older subjects.
LONG-TERM CLINICAL OUTCOMES OF SIROLIMUS ELUTING STENTS IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Shuichiro Sagara, Yusuke Fukushima, Yohei Inoue, Tatsuya Nakama, Daigo Mine, Kensaku Nishihira, Keiichi Ashikaga, Katsumasa Nomura, Nehiro Kuriyama, Akihiko Matsuyama, Yoshisato Shibata
Journal: Journal of the American College of Cardiology (2011)
Exploring the biological basis of hepatitis B e antigen in hepatitis B virus infection
Authors: David Milich, Jake T. Liang
Journal: Hepatology (2003)

The function of the hepatitis B e antigen (HBeAg) is largely unknown because it is not required for viral assembly, replication, or infection. In this report we chronicle clinical and experimental studies in an attempt to understand the role of HBeAg in natural infection. These studies largely have focused on clinical–pathologic features of HBeAg–negative variants in acute and chronic HBV infection, mutational analysis in animal models of hepadnavirus infection, and the use of transgenic murine models. The clinical and experimental data suggest that serum HBeAg may serve an immunoregulatory role in natural infection. To the contrary, cytosolic HBeAg serves as a target for the inflammatory immune response. These dual roles of the HBeAg and its ability to activate or tolerize T cells show the complexity of the interactions between the HBeAg and the host during HBV infection.
Pacing-Induced Dyssynchrony During Early Reperfusion Reduces Infarct Size
Authors: Ward Y. Vanagt, Richard N. Cornelussen, Tamara C. Baynham, Arne Van Hunnik, Quincy P. Poulina, Fawzi Babiker, Julio Spinelli, Tammo Delhaas, Frits W. Prinzen
Journal: Journal of the American College of Cardiology (2007)
Outcomes following an initial unsuccessful colonoscopy: a 5-year complete audit of teaching hospital colonoscopy practice
Authors: S. Sidhu, J. Geraghty, I. Karpha, L. Wark, C. Logan, S. Sarkar
Journal: Gut (2011)

<i>INTRODUCTION:</i> This report demonstrates the spectrum of central nervous system (CNS) abnormalities observed on MR imaging and CT studies in 6 patients with clinical or pathologic diagnoses of acute retinal necrosis (ARN) and retrobulbar optic neuritis (RBON-H) resulting from Herpes Zoster Virus and Cytomegalovirus. We discuss the etiologic and pathophysiologic implications regarding these findings. <i>METHODS:</i> Standard MR imaging sequences of the whole brain and selected high-resolution images of the orbits and globes, from 6 patients, were reviewed by three neuroradiologists for consensus interpretation of the findings. Special sequences augmenting disease were obtained in individual cases. Axial CT images were obtained from two patients using 5mm sequential slices. <i>RESULTS:</i> MR imaging findings showed both T2 signal brightening and contrast enhancement in one or both optic nerves, optic tracts and lateral geniculate bodies, as well as the postsynaptic optic radiations and optic cortex. Similar findings were observed in the superior colliculus, lateral midbrain and cerebellum, with multiple potential etiologic possibilities regarding pathways of dissemination. Low T2* signal (indicating magnetic field susceptibility effects) and CT hyperdensity, consistent with prior hemorrhage, were also observed in the optic tracts, optic radiations and lateral geniculate bodies. Post-contrast enhancement was observed in the meninges and Meckle’s cave in one HIV negative patient. <i>CONCLUSION:</i> These cases demonstrate CNS imaging findings associated with RBON that are temporally-related to ARN. They support the hypothesis that RBON can either precede or follow ARN and implicate transneuronal, transsynaptic and/or transcerebrospinal fluid viral spread by the herpetic family.
Effect of acute hypercapnia on renal and proximal tubular total carbon dioxide reabsorption in the acetazolamide-treated rat.
Authors: J Winaver, K A Walker, R T Kunau
Journal: Journal of Clinical Investigation (1986)

The present study evaluates the effect of acute hypercapnia on renal total CO2 (tCO2) reabsorption after inhibition of renal carbonic anhydrase. Simultaneous renal clearance studies and free-flow micropuncture studies of the superficial proximal tubule were performed on plasma-repleted Sprague-Dawley rats treated with acetazolamide, 50 mg/kg body weight. Acute hypercapnia (arterial PCO2, 120 mmHg; blood pH, 7.02) was induced by ventilation with a 10% CO2-90% O2 gas mixture. Control rats (PCO2, 49.5 mmHg, pH 7.34) were ventilated with room air. The renal fractional excretion of tCO2 was approximately 20% lower in the hypercapnic group compared with the rats given acetazolamide alone. Acute hypercapnia reduced the fractional delivery of tCO2 to the late proximal tubule by a comparable amount. The absolute proximal reabsorption of tCO2 was increased by hypercapnia to 410 +/- 47 vs. 170 +/- 74 pmol X min-1, P less than 0.05. The single nephron glomerular filtration rate was 32.6 +/- 0.7 nl X min-1 in the hypercapnic group and 43.8 +/- 1.7 nl X min-1 in the rats given acetazolamide only, P less than 0.01. Acute hypercapnia enhances renal sympathetic nerve activity. To eliminate this effect, additional experiments were performed in which the experimental kidney was denervated before study. Denervation prevented the change in the single nephron filtration rate during acute hypercapnia, but absolute and fractional proximal tCO2 reabsorption remained elevated in comparison to denervated controls. The concentration of H2CO3 in the late proximal tubule, calculated from the measured luminal pH and bicarbonate concentration and the estimated cortical PCO2, was higher in the hypercapnic group, which was a finding compatible with H2CO3 cycling from lumen into proximal tubular cell, which provided a source of hydrogen ions for secretion.
Abstract A53: CXCR4 drives the metastatic phenotype in breast cancer through induction of CXCR2, transactivation of HER2/EGFR, and activation of MEK and PI3K pathways
Authors: Tammy Sobolik, Yingjun Su, Sam Wells, Ann Richmond
Journal: Cancer Research (2013)

Abstract Introduction: Aberrant expression of CXCR4 in human breast cancer correlates with metastasis and poor prognosis. Expression of a carboxyl-truncated CXCR4 (CXCR4ΔCTD) is associated with constitutive CXCR4 activity in MCF-7 breast cancer cells, increased motility, loss of E-cadherin, enhanced estrogen independent growth and lung metastasis in vivo. Here, we characterize the mechanism by which CXCR4 induces a mesenchymal phenotype with metastatic properties. Methods: MCF-7 cells expressing wild-type CXCR4 (CXCR4WT) or CXCR4ΔCTD were evaluated in two-dimensional (2D) and three-dimensional reconstituted basement membrane (3D rBM) cultures for cell morphology and expression of factors that regulate the epithelial to mesenchymal transition (EMT) and cell migration. Effects of inhibition of key cytokine/chemokine signaling pathways activated by CXCR4 were examined. Tumor cell migration within the tumor microenvironment was followed using intravital imaging. Results: In 2D culture, MCF-7 CXCR4ΔCTD but not CXCR4WT cells, exhibited EMT characterized by up-regulation of ZEB-1 and cadherin 11, loss of E-cadherin, p120 isoform switching, and activation of ERK1/2, and MMP-2. The up-regulation of ZEB-1 was coincident with down-regulation of miR-200b and miR200c. In contrast to the 2D environment, 3D rBM MCF-7 CXCR4WT cultures exhibited the same stellate morphology of CXCR4ΔCTD cells, while MCF-7 control cells formed round acinar clusters. Expression of CXCR4 resulted in induction of expression of CXCR2, CXCR7, CXCL1, CXCL8, CCL2, IL-6 and GM-CSF by MCF-7 cells in 3DrBM, but not 2D culture. CXCR4 expression also induced transactivation of HER2 and EGFR. CXCL1, CXCL8 and CXCR2 appear to signal through a CXCR2 autocrine loop. In 3D rBM culture combined inhibition of CXCR4 and MEK1, or PI3K and MEK1/2 resulted in a change in morphology of CXCR4 expressing cells from stellate to round acinar clusters resembling controls. Combined inhibition of CXCR2 with MEK1, PI3K, or CXCR4 inhibitors also resulted in reversion of the stellate phenotype in 3D rBM. In vivo studies revealed that MCF-7 CXCR4WT and MCF-7CXCR4ΔCTD tumor cells migrate in a collective manner capable of lymphatic spread in athymic nude mice. Conclusions: Elevated expression or constitutive activation of CXCR4 results in EMT that is accompanied by up-regulation of receptors and cytokines important in collective cell migration leading to lymphatic invasion and tumor metastasis. Citation Format: Tammy Sobolik, Yingjun Su, Sam Wells, Ann Richmond. CXCR4 drives the metastatic phenotype in breast cancer through induction of CXCR2, transactivation of HER2/EGFR, and activation of MEK and PI3K pathways. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr A53.
PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron
Authors: Neil V Morgan, Shawn K Westaway, Jenny E V Morton, Allison Gregory, Paul Gissen, Scott Sonek, Hakan Cangul, Jason Coryell, Natalie Canham, Nardo Nardocci, Giovanna Zorzi, Shanaz Pasha, Diana Rodriguez, Isabelle Desguerre, Amar Mubaidin, Enrico Bertini, Richard C Trembath, Alessandro Simonati, Carolyn Schanen, Colin A Johnson, Barbara Levinson, C Geoffrey Woods, Beth Wilmot, Patricia Kramer, Jane Gitschier, Eamonn R Maher, Susan J Hayflick
Journal: Nature Genetics (2006)