tbuckley/cabot-search huggingface dataset:
The Troubled Profession: Is Medicine's Glass Half Full or Half Empty?
Authors: Steven A. Schroeder
Journal: Annals of Internal Medicine (1992)

Abundant evidence that medicine is in trouble includes serious career dissatisfaction among practicing and would-be physicians as well as steeply declining interest in generalist careers, especially internal medicine. Medicine is threatened by ever-rising health care expenditures and ineffectual but vexing administrative efforts to contain them. Additional problems challenge internal medicine in particular: the clinical complexity of practice, lower income potential, and incomplete clinical experiences for medical students. Yet, in the past 25 years, spectacular advances in science and technology enabled improved patient care and outcomes; more women and minorities entering the profession brought it into better demographic balance; relative physician incomes rose; and access to physician services improved with Medicare and Medicaid and the desegregation of southern hospitals. Despite an unfinished agenda, never before has medicine held so much promise for improving the health of the public. Despite various professional problems, no other career offers the unique blend of state-of-the-art science and humanism that epitomizes internal medicine—medicine's integrating specialty.
Myxedema Coma and Cardiac Arrest-Reply
Authors: Vicenzo Bacci
Journal: JAMA (1982)

<h3>In Reply.—</h3> We appreciate the comments of Drs Georgitis and Hofeldt. In response to their question, the time relationships were as follows: At 7 PM, the pH was 7.33; Pco<sub>2</sub>, 48 mm Hg; Po<sub>2</sub>, 51 mm Hg. At 7:10 PM oxygen therapy was begun. At 8 PM, pH was 7.31; Pco<sub>2</sub>, 46 mm Hg; Po<sub>2</sub>, 72 mm Hg. At 11:45 PM the patient was alert and responsive. At 2 AM the patient was lethargic, and levothyroxine was administered intravenously (IV). At 2:10 AM, after cardiopulmonary resuscitation, pH was 7.34; Pco<sub>2</sub>, 42 mm Hg; Po<sub>2</sub>, 58 mm Hg. The Pco<sub>2</sub>, was measured at 37 °C and not corrected for the patient's temperature. With the appropriate correction for hypothermia, the Pco<sub>2</sub>at 8 PM after one hour on oxygen becomes 41.3 mm Hg. Thus, it does not appear that in this instance oxygen therapy
Etanercept, mycophenolate, denileukin, or pentostatin plus corticosteroids for acute graft-versus-host disease: a randomized phase 2 trial from the Blood and Marrow Transplant Clinical Trials Network
Authors: Amin M. Alousi, Daniel J. Weisdorf, Brent R. Logan, Javier Bolaños-Meade, Shelly Carter, Nancy DiFronzo, Marcelo Pasquini, Steven C. Goldstein, Vincent T. Ho, Brandon Hayes-Lattin, John R. Wingard, Mary M. Horowitz, John E. Levine
Journal: Blood (2009)
Identifying Target Areas of Treatment for Depressed Early Inflammatory Arthritis Patients
Authors: Patricia L. Dobkin, Marta Filipski, Karl Looper, Orit Schieir, Murray Baron
Journal: Psychotherapy and Psychosomatics (2008)

&lt;i&gt;Background:&lt;/i&gt; The goal of this study was to identify target areas for psychosocial intervention for depressed patients with earlyinflammatory arthritis. &lt;i&gt;Methods:&lt;/i&gt;One hundred and sixty-five patients with early inflammatory arthritis (≧1 joint with synovitis for ≧6 weeks and &lt;1 year with a diagnosis of either rheumatoid or undifferentiated inflammatory arthritis) were referred to the McGill Early Arthritis Registry (McEAR) by their rheumatologist. McEAR patients agree to periodic physical exams and to completing questionnaires. Demographic, disease and psychosocial factors were compared between patients screening positive and negative for depression using independent samples t tests and Pearson’s χ&lt;sup&gt;2&lt;/sup&gt; test and then were entered into a logistic regression model examining the likelihood of screening positive for depression. &lt;i&gt;Results:&lt;/i&gt; Thirty-eight (23%) patients screened positive for depressive symptoms. Patients with symptoms of depression had significantly worse disease severity, disability, and pain, engaged in more emotional preoccupation coping, had less self-efficacy for pain and other arthritis-related symptoms, smaller social networks and were less satisfied with social support than the nondepressed group. In logistic regression analyses, pain and emotional preoccupation coping were positively related to the likelihood of screening positive for depression, while satisfaction with social support was negatively related to the likelihood of screening positive for depression &lt;i&gt;Conclusion:&lt;/i&gt; Higher pain levels, emotional preoccupation coping and dissatisfaction with social support were related to depressive symptoms in this study. This suggests that the optimal care of depressed patients with inflammatory arthritis would include a psychosocial approach that addresses these specific target areas.
Quantitative in situ evaluation of telomeres in fluorescence in situ hybridization-processed sections of cutaneous melanocytic lesions and correlation with telomerase activity
Authors: C. Miracco, M. Margherita De Santi, K. Schurfeld, R. Santopietro, A.V. Lalinga, M. Fimiani, M. Biagioli, M. Brogi, C. De Felice, P. Luzi, L. Andreassi
Journal: British Journal of Dermatology (2002)

Telomere length is correlated with cellular ageing and immortalization processes. In some human cancers telomere length measurement has proved to be of diagnostic and prognostic value. Results comparable with the traditional terminal restriction fragment length determination by Southern blotting have been obtained in metaphase and interphase cells in some studies by fluorescence in situ hybridization (FISH) analysis; FISH additionally allows for the quantification of telomeres at the cellular level.In this study, 32 melanocytic lesions were analysed by FISH, aiming at investigating possible telomere differences among various benign and malignant lesions and correlation with telomerase activity (TA) level.FISH was performed on paraffin sections from six common naevi, eight Spitz naevi, 12 melanomas, six melanoma metastases and nine control samples of normal skin. Telomere mean maximum diameter (Feret max), area and number per nuclear area were calculated by image analysis on fluorescent images elaborated through KS400 and in situ imaging system (ISIS) for FISH analysis programs. Mean TA level was also calculated in all lesions and correlated with telomere parameters.Telomere number per nuclear area was significantly lower in melanomas and metastases than in benign common and Spitz naevi and in control skin (7 small middle dot24 +/- 3.3; 6.11 +/- 3 vs. 14.46 +/- 5.6; 16.92 +/- 7.8; and 12.59 +/- 3.4, respectively; P < 0 .001). No significant differences were found for the other telomere parameters. In common and Spitz naevi, telomere number was positively correlated with Feret max (P = 0.046 and P < 0.0001, respectively). TA was significantly higher in melanomas and metastases than in the other groups (70.18 +/- 25.2; 105.07 +/- 30 vs. 2.16 +/- 2.4; 2 .99 +/- 2.1; 2 +/- 1.2, respectively; P< or = 0. 001) and it was inversely correlated with telomere number per nuclear area in melanomas (P = 0.0041). No other significant correlations were found.Encouraging results have been obtained from quantitative telomere evaluation in the diagnosis of melanocytic lesions, although an analysis of a larger number of cases would be necessary to provide more reliable data. An extreme shortening of some telomeres probably results in the decrease of telomeric signals and the lower mean number of detectable telomeres in melanomas and metastases. In melanomas, telomere number per nuclear area is also inversely correlated with TA levels. Quantitative FISH of melanocytic lesions could give more specific information at the cellular level in telomere and telomerase fields of investigation.
Insulin-like Growth Factor-I–Dependent Up-regulation of ZEB1 Drives Epithelial-to-Mesenchymal Transition in Human Prostate Cancer Cells
Authors: Tisheeka R. Graham, Haiyen E. Zhau, Valerie A. Odero-Marah, Adeboye O. Osunkoya, K. Sean Kimbro, Mourad Tighiouart, Tongrui Liu, Jonathan W. Simons, Ruth M. O'Regan
Journal: Cancer Research (2008)

Abstract The epithelial-to-mesenchymal transition (EMT) is crucial for the migration and invasion of many epithelial tumors, including prostate cancer. Although it is known that ZEB1 overexpression promotes EMT primarily through down-regulation of E-cadherin in a variety of cancers, the soluble ligands responsible for the activation of ZEB1 have yet to be identified. In the present study, we investigated the role of insulin-like growth factor-I (IGF-I) in the regulation of ZEB1 during EMT associated with prostate tumor cell migration. We found that ZEB1 is expressed in highly aggressive prostate cancer cells and that its expression correlates directly with Gleason grade in human prostate tumors (P &amp;lt; 0.001). IGF-I up-regulates ZEB1 expression in prostate cancer cells exhibiting an epithelial phenotype. In prostate cancer cells displaying a mesenchymal phenotype, ZEB1 inhibition reverses the suppression of E-cadherin protein and down-regulates the expression of the mesenchymal markers N-cadherin and fibronectin. Furthermore, ZEB1 blockade decreases migratory and invasive potential in ARCaPM compared with the control. These results identify ZEB1 as a key transcriptional regulator of EMT in prostate cancer and suggest that the aberrant expression of ZEB1 in prostate cancer cells occurs in part in response to IGF-I stimulation. [Cancer Res 2008;68(7):2479–88]
Assessment of Paracervical Nerve Block Anaesthesia during Labour
Authors: P. J. Murphy, J. D. Wright, T. B. Fitzgerald
Journal: BMJ (1970)

An assessment of paracervical nerve block anaesthesia was made in 118 women during labour using 0.5% bupivacaine with 1:200,000 parts of adrenaline added. The 82 multiparae were each given a single block and the 36 primigravidae a continuous block to try to provide the sole means of analgesia throughout the first stage of labour.Only 48% of the primigravidae required no other form of analgesia, as against 72% of the multiparae.Complications included a 17% incidence of maternal haemorrhage during insertion of the continuous needle, an overall fetal bradycardia rate of 11%, and two perinatal deaths following single paracervical block. It is concluded that the use of continuous paracervical block should be discontinued, and that amide-type local anaesthetic agents should not be used for single paracervical block.
Reflex Increase in Coronary Vascular Resistance in Patients with Ischemic Heart Disease
Authors: Gilbert H. Mudge, William Grossman, Roger M. Mills, Michael Lesch, Eugene Braunwald
Journal: New England Journal of Medicine (1976)

To assess possible coronary vasoconstriction in patients with ischemic heart disease, we measured coronary vascular resistance in 12 patients with normal hearts and 12 with coronary disease before and during the initial 50 seconds of cold pressor test, a stimulus known to produce systemic vasoconstriction. Control coronary vascular resistance was similar in the two groups, and although it did not change in patients with normal vessels, it rose by 27 per cent (P less than 0.005) in the group with coronary disease during the cold pressor test. In three of 12 patients with coronary disease coronary flow actually declined despite an increase in arterial pressure; in four, angina was precipitated. Phentolamine abolished increases in arterial pressure and coronary vascular resistance during the test in three patients with coronary disease. Adrenergically mediated coronary vascular tone may be an important determinant of coronary blood flow and may contribute to ischemia in patients with coronary disease.
Increase in the expression of a family of small guanosine triphosphate-binding proteins, rab proteins, during induced phagocyte differentiation.
Authors: I Maridonneau-Parini, C Z Yang, M Bornens, B Goud
Journal: Journal of Clinical Investigation (1991)

Rab is a newly identified family of small G-proteins that share 35-70% homology with the yeast Sec4p and Ypt1p involved in the regulation of the secretory pathway. Mature phagocytes display functions requiring organized intracellular traffic and, for this reason, we questioned whether phagocyte differentiation could correlate with the increased expression of rab proteins. Rabbit antisera raised against the recombinant proteins rab1Ap, 2p, 4p, and 6p were able to detect the corresponding proteins in the human monoblast leukemic cell line U937. When these cells were induced to differentiate into monocyte/macrophage-like cells displaying functional characteristics of a normal phagocyte, rab1Ap, 2p, 4p, and 6p were increased and this correlated with an increase in the rab transcripts. Using a rab5 probe, we also observed an increased expression of the rab5 gene in differentiated cells. Similarly, differentiation of the human leukemic myeloblast HL60 cell line along either monocyte or granulocyte pathways induced an increased expression of the rab proteins. Rab proteins were also detected in human neutrophils and in guinea pig alveolar macrophages. As degranulation is one of the phagocyte functions acquired in the late stage of differentiation, we investigated whether rab proteins would be involved in this process. Although rab proteins were tightly membrane bound, none of them was detected in the specific or azurophil granules purified from human neutrophils. The increased expression of rab proteins in mature phagocytes suggests that they may promote functions highly developed in these cells.
Korotkoff Sounds
Authors: ERNEST P. MCCUTCHEON, ROBERT F. RUSHMER, O. Jacobson, Harold Sandier
Journal: Circulation Research (1967)

The Korotkoff sounds which serve as criteria for sphygmomanometry are composed of at least two components, (1) an initial transient (K i ), and (2) a more prolonged "compression murmur" (K c ). In this experimental survey, the Doppler flow detection device was used to acquire evidence indicating that K i occurs at the very onset of flow under the cuff and probably represents an acceleration transient producing abrupt displacement of the arterial wall and surrounding tissues distal to the point of compression. It is nonspecific in nature and can be simulated by tapping the skin of the hand. K c follows the initial transient and appears to represent audible sounds from turbulence or eddies in the blood flowing from the constricted artery under the cuff. Muffling seems attributable to the attenuation of frequencies between 60 and 180 cycle/sec, as the initial transient sound disappears, leaving the "compression murmur" as the muffled sound. Studies of cineangiograms and casts of arteries demonstrated that the arterial lumen under the cuff is primarily tapered and that the circumference of the artery shrinks considerably as the wall is unloaded by decreased transmural pressure. In contrast, rubber tubes become unstable and flatten into a binodal configuration when externally compressed. It seems doubtful that rubber tubes constitute adequate models for arteries in situ in the study of the genesis of Korotkoff sounds.
Comparison of Geostatistical Interpolation and Remote Sensing Techniques for Estimating Long-Term Exposure to Ambient PM<sub>2.5</sub>Concentrations across the Continental United States
Authors: Seung-Jae Lee, Marc L. Serre, Aaron van Donkelaar, Randall V. Martin, Richard T. Burnett, Michael Jerrett
Journal: Environmental Health Perspectives (2012)

A better understanding of the adverse health effects of chronic exposure to fine particulate matter (PM2.5) requires accurate estimates of PM2.5 variation at fine spatial scales. Remote sensing has emerged as an important means of estimating PM2.5 exposures, but relatively few studies have compared remote-sensing estimates to those derived from monitor-based data.We evaluated and compared the predictive capabilities of remote sensing and geostatistical interpolation.We developed a space-time geostatistical kriging model to predict PM2.5 over the continental United States and compared resulting predictions to estimates derived from satellite retrievals.The kriging estimate was more accurate for locations that were about 100 km from a monitoring station, whereas the remote sensing estimate was more accurate for locations that were > 100 km from a monitoring station. Based on this finding, we developed a hybrid map that combines the kriging and satellite-based PM2.5 estimates.We found that for most of the populated areas of the continental United States, geostatistical interpolation produced more accurate estimates than remote sensing. The differences between the estimates resulting from the two methods, however, were relatively small. In areas with extensive monitoring networks, the interpolation may provide more accurate estimates, but in the many areas of the world without such monitoring, remote sensing can provide useful exposure estimates that perform nearly as well.
Abstract 5026: Targeting non-canonical Wnt signaling in acute myeloid leukemia.
Authors: Jasper de Boer, Vanessa Walf-Vorderwulbecke, Sarah J. Horton, Owen Williams
Journal: Cancer Research (2013)

Abstract Childhood acute myeloid leukemia (AML) is a heterogeneous disease, with distinct cytogenetic sub-groups and responses to chemotherapy. Greater understanding of the molecular mechanisms underlying the different forms of this disease offers the possibility of developing novel therapies targeting disease-specific signaling pathways. We have recently analysed the role of non-canonical Wnt signaling induced Rac activation in the most frequent sub-type of childhood AML, associated with chromosomal translocations affecting the mixed lineage leukemia (MLL) gene. Our data indicate that MLL-fusions utilize non-canonical Wnt signaling, by inducing transcriptional activation of Frat gene expression and stimulating Rac activation through a signaling pathway involving GSK3 and DVL1 components. This pathway can be disrupted by shRNA-mediated silencing of Frat or Dvl expression, or by pharmacological inhibition of GSK3. Interestingly, the DVL-GSK3 signaling pathway can be disrupted by expression of a dominant negative FRATN mutant, that lacks the GSK3-binding domain, even in the absence of endogenous FRAT expression. FRATN inhibits growth, survival and disease progression of MLL-fusion expressing leukemic cells. These experiments have now been extended to the analysis of the anti-leukemia effects of FRATN expression in non-MLL-rearranged leukemia cell lines. This study highlights the potential of this novel signaling pathway as a target for future novel therapies of AML. Citation Format: Jasper de Boer, Vanessa Walf-Vorderwulbecke, Sarah J. Horton, Owen Williams. Targeting non-canonical Wnt signaling in acute myeloid leukemia. [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 5026. doi:10.1158/1538-7445.AM2013-5026
Quality reporting of endoscopic diagnostic studies in gastrointestinal journals: where do we stand on the use of the STARD and CONSORT statements?
Authors: M. Areia, M. Soares, M. Dinis-Ribeiro
Journal: Endoscopy (2010)

Background and study aims: Many papers have been published in the field of diagnostic endoscopy in the last few years. However, there are no reports on their quality. The aim of this study was to evaluate quality in recently published endoscopic articles.
Bile acids inhibit interleukin-6 signaling via gp130 receptor-dependent and -independent pathways in rat liver
Authors: Dirk Graf, Caroline Kohlmann, Katrin Haselow, Thor Gehrmann, Johannes G. Bode, Dieter Häussinger
Journal: Hepatology (2006)

Interleukin-6 (IL-6) is a major regulator of the acute phase reaction in the liver and is thought to mediate protective effects in response to hepatotoxins. In this study, the influence of bile acids on IL-6 signal transduction was analyzed. It was shown that hydrophobic bile acids such as glycochenodeoxycholate (GCDC) inhibited IL-6–induced tyrosine phosphorylation of signal transducer and activator of transcription (STAT) 3 in hepatocytes and in perfused rat liver. This inhibition was accompanied by GCDC-mediated downregulation of glycoprotein (gp) 130 expression, whereas gp130 and suppressor of cytokine signaling 3 messenger RNA and gp80 protein levels remained unaffected. The GCDC-induced downregulation of gp130 protein expression was insensitive to inhibition of proteasomal or lysosomal protein degradation but turned out to be sensitive to inhibition of caspase-3 or caspase-8 activity. Accordingly, treatment of cell extracts with active recombinant caspase-3 led to a decay of immunoreactive gp130. Moreover, activation of caspases by CD95 ligand or hyperosmotic stress also resulted in a downregulation of gp130 levels. This indicates that caspase activation antagonizes IL-6 signaling by decay of gp130 levels. However, caspase inhibition did not prevent GCDC-dependent inhibition of IL-6–induced STAT3 activation, which turned out to be at least partially sensitive to suppression of p38MAPK activation. In conclusion , hydrophobic bile acids compromise IL-6 signaling through both a caspase-mediated downregulation of gp130 and a p38MAPK-dependent inhibition of STAT3 phosphorylation. This may contribute to bile acid–induced hepatotoxicity in cholestasis through counteracting the known hepatoprotective effects of IL-6.
External cardiac compression. A randomized comparison of mechanical and manual techniques
Authors: George J. Taylor, Richard Rubin, Michael Tucker, H. Leon Greene, Michael T. Rudikoff, Myron L. Weisfeldt
Journal: JAMA (1978)

To compare the effectiveness of manual and mechanical chest compression during cardiopulmonary resuscitation, 50 patients who suffered cardiac arrest were randomly allocated to receive manual or mechanical chest compression. Randomization was performed after failure of initial resuscitative measures but within ten minutes after the onset of cardiac arrest (mean, 6.4 ±1.2 min). Ten patients from each group survived longer than one hour following resuscitation. Three from the mechanical group and two from the manual group were eventually able to leave the hospital. Thus mechanical compression appears comparable with manual compression when manual compression is performed under ideal conditions. Mechanical chest compression may be employed when trained personnel are not readily available or where manual compression is technically difficult to perform. (<i>JAMA</i>240:644-646, 1978)
Smoking and Hip Fractures
Authors: Rebecca Voelker
Journal: JAMA (1998)

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