tbuckley/cabot-search huggingface dataset:
The National Cancer Institute Audit of the National Surgical Adjuvant Breast and Bowel Project Protocol B-06
Authors: Michaele C. Christian, Mary S. McCabe, Edward L. Korn, Jeffrey S. Abrams, Richard S. Kaplan, Michael A. Friedman
Journal: New England Journal of Medicine (1995)

The National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-06, a clinical trial sponsored by the National Cancer Institute (NCI), has provided evidence of the value of lumpectomy and breast irradiation for treating women with breast cancer in an early stage. Publicity generated by the discovery that the study included fraudulent data on patients enrolled by St. Luc Hospital in Montreal aroused concern about the overall accuracy of the data and conclusions. To address this concern, the NCI conducted an audit of other participating institutions.
SAFETY OF ORAL DOFETILIDE LOADING FOR RHYTHM CONTROL OF ATRIAL ARRHYTHMIAS
Authors: JoEllyn Carol Moore M. Abraham, Carolyn Vekstein, David Lawrence, Mandeep Bhargava, David Janiszewski, Michael Militello, Steven Nissen, Stacy Poe, Walid Saliba, Christine Tanaka-Esposito, Kathy Wolski, Bruce Wilkoff
Journal: Journal of the American College of Cardiology (2014)
Reportitis: Not So Trivial a Disorder
Authors: Daniel S. Greenberg
Journal: New England Journal of Medicine (1979)

An overburdened journalist acquaintance recently pointed to a thick, newly issued government report and said, not altogether wryly, "I can either read this or write about it. I can't do both."The remark stuck in my mind because health-related matters — along with the innumerable other objects of official Washington's attention — are routinely the subject of Brobdingnagian salvos of findings and recommendations. Whether the subject is radiation safety, drug-regulation reform, the peer-review system, national health insurance or whatever, it is a certainty that not only are reports already on the shelves but others are in the works. Emanating from . . .
Ethylene glycol monomethyl ether and propylene glycol monomethyl ether: metabolism, disposition, and subchronic inhalation toxicity studies.
Authors: R R Miller, E A Hermann, J T Young, T D Landry, L L Calhoun
Journal: Environmental Health Perspectives (1984)

Short-term and subchronic vapor inhalation studies have shown that there are pronounced differences in the toxicological properties of ethylene glycol monomethyl ether (EGME) and propylene glycol monomethyl ether (PGME). Overexposure to EGME has resulted in adverse effects on testes, bone marrow and lymphoid tissues in laboratory animals. PGME does not affect these tissues, and instead, overexposure to PGME has been associated with increases in liver weight and central nervous system depression. EGME is primarily oxidized to methoxyacetic acid in male rats, while PGME apparently undergoes O-demethylation to form propylene glycol. Since methoxyacetic acid has been shown to have the same spectrum of toxicity as EGME in male rats, the observed differences in the toxicological properties of EGME and PGME are thought to be due to the fact that the two materials are biotransformed via different routes to different types of metabolites.
G-protein-coupled receptor kinase activity in human heart failure: Effects of β-adrenoceptor blockade
Authors: K LEINEWEBER, P ROHE, A BEILFUS, C WOLF, H SPORKMANN, H BRUCK, H JAKOB, G HEUSCH, T PHILIPP, O BRODDE
Journal: Cardiovascular Research (2005)

In human end-stage heart failure as well as in experimental animal models of heart failure, G-protein-coupled receptor kinase activity (GRK) is increased while beta-adrenoceptor responsiveness is diminished. In animal studies, beta-adrenoceptor blockers reverse the GRK-mediated desensitization and down-regulation of myocardial beta-adrenoceptors. The aim of this study was to investigate whether alterations in GRK activity are an early or late accompaniment of human heart failure and whether also in humans beta-adrenoceptor blocker treatment is able to influence myocardial GRK activity.We assessed in right atria, obtained from patients at different stages of heart failure, treated with or not treated with beta-adrenoceptor blockers, and in the four chambers of explanted hearts, obtained from patients with end-stage heart failure, beta-adrenoceptor density (by (-)-[(125)I]-iodocyanopindolol binding) and GRK activity (by an in vitro rhodopsin phosphorylation assay).With increasing severity of heart failure, plasma noradrenaline levels increased while myocardial beta-adrenoceptor density decreased with a maximum in GRK activity in end-stage heart failure. However, in relation to the progression of heart failure, we found that GRK activity transiently increased at an early stage of heart failure (NYHA I and II) but decreased back to control values in patients at NYHA III and IV. beta-Adrenoceptor blockers were able to reduce the early increase in GRK activity at NYHA I and II to control levels, whereas in those patients who did not have increased GRK activity (NYHA III and IV), they had only a marginal effect.According to our results, an increase in GRK activity is an early and transient event in the course of heart failure that can be prevented by beta-adrenoceptor blocker treatment.
More weapons in the arsenal against ischemic retinopathy
Authors: Eli Keshet
Journal: Journal of Clinical Investigation (2001)

Ischemia-induced retinopathy is the major cause of blindness world-wide. Diverse processes may lead to retinal ischemia, including a central retinal vein occlusion, a progressive deterioration of vascular function due to prolonged hyperglycemia, and obliteration of newly formed retinal vessels in premature neonates subjected to hyperoxia. The later two processes may culminate in the development of proliferative diabetic retinopathy (PDR) and retinopathy of prematurity (ROP), respectively. While different etiologies may lead to insufficient perfusion of the retina, once a critical level of ischemia has been achieved, the different forms of retinopathy seem to converge on a common sequela — the hypoxia-induced formation of morphologically abnormal vessels. Retinopathy-associated neovascularization is excessive and neo-vessels are abnormally leaky and tend to breach the inner limited membrane of the retina and invade the vitreous. Such pre-retinal vascular growth is perhaps the most devastating aspect of retinopathy, as it often leads to retina detachment and eventually to blindness.

Combating retinopathy can, in principle, be directed against the first pathogenic phase, the generation of a vascular deficit and the resultant ischemia, or against the second phase, the formation of surplus, abnormal vessels. At least for PDR, the former approach has been impossible because we lack sufficient insight into the mechanisms leading to progressive vessel dysfunction, or even a suitable animal model in which to study these events. For this reason, most of the studies outlined below have resorted to the use of an oxygen-induced retinopathy model (i.e., an ROP model) (1).
Astrocyte elevated gene‐1 and c‐Myc cooperate to promote hepatocarcinogenesis in mice
Authors: Jyoti Srivastava, Ayesha Siddiq, Rachel Gredler, Xue‐Ning Shen, Devaraja Rajasekaran, Chadia L. Robertson, Mark A. Subler, Jolene J. Windle, Catherine I. Dumur, Nitai D. Mukhopadhyay, Dawn Garcia, Zhao Lai, Yidong Chen, Uthra Balaji, Paul B. Fisher, Devanand Sarkar
Journal: Hepatology (2014)

Astrocyte elevated gene‐1 (AEG‐1) and c‐Myc are overexpressed in human hepatocellular carcinoma (HCC) functioning as oncogenes. AEG‐1 is transcriptionally regulated by c‐Myc, and AEG‐1 itself induces c‐Myc by activating the Wnt/β‐catenin–signaling pathway. We now document the cooperation of AEG‐1 and c‐Myc in promoting hepatocarcinogenesis by analyzing hepatocyte‐specific transgenic mice expressing either AEG‐1 (albumin [Alb]/AEG‐1), c‐Myc (Alb/c‐Myc), or both (Alb/AEG‐1/c‐Myc). Wild‐type and Alb/AEG‐1 mice did not develop spontaneous HCC. Alb/c‐Myc mice developed spontaneous HCC without distant metastasis, whereas Alb/AEG‐1/c‐Myc mice developed highly aggressive HCC with frank metastasis to the lungs. Induction of carcinogenesis by N‐nitrosodiethylamine significantly accelerated the kinetics of tumor formation in all groups. However, in Alb/AEG‐1/c‐Myc, the effect was markedly pronounced with lung metastasis. In vitro analysis showed that Alb/AEG‐1/c‐Myc hepatocytes acquired increased proliferation and transformative potential with sustained activation of prosurvival and epithelial‐mesenchymal transition–signaling pathways. RNA‐sequencing analysis identified a unique gene signature in livers of Alb/AEG‐1/c‐Myc mice that was not observed when either AEG‐1 or c‐Myc was overexpressed. Specifically, Alb/AEG‐1/c‐Myc mice overexpressed maternally imprinted noncoding RNAs (ncRNAs), such as Rian, Meg‐3, and Mirg, which are implicated in hepatocarcinogenesis. Knocking down these ncRNAs significantly inhibited proliferation and invasion by Alb/AEG‐1/c‐Myc hepatocytes. Conclusion : Our studies reveal a novel cooperative oncogenic effect of AEG‐1 and c‐Myc that might explain the mechanism of aggressive HCC. Alb/AEG‐1/c‐Myc mice provide a useful model to understand the molecular mechanism of cooperation between these two oncogenes and other molecules involved in hepatocarcinogenesis. This model might also be of use for evaluating novel therapeutic strategies targeting HCC. (H epatology 2015;61:915–929)
The critical role of toll-like receptor (TLR) 4 in alcoholic liver disease is independent of the common TLR adapter MyD88
Authors: Istvan Hritz, Pranoti Mandrekar, Arumugam Velayudham, Donna Catalano, Angela Dolganiuc, Karen Kodys, Evelyn Kurt‐Jones, Gyongyi Szabo
Journal: Hepatology (2008)

The Toll-like receptor 4 (TLR4) that recognizes endotoxin, a trigger of inflammation in alcoholic liver disease (ALD), activates two signaling pathways utilizing different adapter molecules: the common TLR adapter, myeloid differentiation factor 88 (MyD88), or Toll/interleukin immune-response–domain-containing adaptor inducing interferon (IFN)-β. The MyD88 pathway induces proinflammatory cytokine activation, a critical mediator of ALD. Here we evaluated the role of MyD88 in alcohol-induced liver injury in wild-type, TLR2-deficient, TLR4-deficient, or MyD88-deficient (knockout [KO]) mice after administration of the Lieber-De-Carli diet (4.5% volume/volume ethanol) or an isocaloric liquid control diet for 5 weeks. Alcohol feeding resulted in a significant increase in serum alanine aminotransferase levels, liver steatosis and triglyceride levels suggesting liver damage in WT, TLR2-KO, and MyD88-KO but not in TLR4-KO mice. Expression of inflammatory mediators (tumor necrosis factor–α and interleukin-6) and TLR4 coreceptors (CD14 and MD2) was significantly higher in livers of alcohol-fed WT, TLR2-KO, or MyD88-KO, but not in TLR4-KO mice, compared to controls. Reactive oxygen radicals produced by cytochrome P450 and the nicotinamide adenine dinucleotide phosphate complexes contribute to alcoholic liver damage. Alcohol feeding–induced expression and activation of cytochrome P450 and the nicotinamide adenine dinucleotide phosphate complex were prevented by TLR4-deficiency but not by MyD88-deficiency. Liver expression of interferon regulatory factor 3 (IRF3), a MyD88-independent signaling molecule, was not affected by chronic alcohol treatment in whole livers of WT mice or in any of the KO mice. However, the induction of IRF7, an IRF3-inducible gene, was found in Kupffer cells of alcohol-fed WT mice. Alcohol feeding also induced nuclear factor–κB activation in a TLR4-dependent MyD88-independent manner. Conclusion: While TLR4 deficiency was protective, MyD88 deficiency failed to prevent alcohol-induced liver damage and inflammation. These results suggest that the common TLR adapter, MyD88, is dispensable in TLR4-mediated liver injury in ALD. (HEPATOLOGY 2008.)
Prevalence of Hereditary Hemochromatosis in 16 031 Primary Care Patients
Authors: Pradyumna D. Phatak
Journal: Annals of Internal Medicine (1998)

Background: Despite evidence from screening studies in northern European populations, the prevalence of hemochromatosis in primary care populations in the United States remains speculative. Objective: To establish the feasibility of screening for hemochromatosis and to estimate the prevalence of hemochromatosis in a large primary care population. Design: Cross-sectional prevalence study. Setting: 22 primary care practices in the Rochester, New York, area. Patients: 16 031 ambulatory patients without a previous diagnosis of hemochromatosis. Intervention: Serum transferrin saturation screening tests were offered to all adult patients in participating primary care practices. Measurements: Patients with a serum transferrin saturation of 45% or more on initial testing had a serum transferrin saturation test done under fasting conditions and had serum ferritin levels measured. Those who had a fasting serum transferrin saturation of 55% or more and a serum ferritin level of 200 µg/L or more with no other apparent cause were presumed to have hemochromatosis and were offered liver biopsy to confirm the diagnosis. Results: 25 patients had biopsy-proven hemochromatosis; 22 patients met the clinical criteria for hemochromatosis but declined liver biopsy and were classified as having clinically proven hemochromatosis; and 23 patients had a serum transferrin saturation of 55% or more with no identifiable cause, indicating probable hemochromatosis. The prevalence of clinically proven and biopsy-proven hemochromatosis combined was 4.5 per 1000 (95% CI, 3.3 to 5.8 per 1000) in the total sample and 5.4 per 1000 (CI, 4.0 to 7.1 per 1000) in white persons. The prevalence was higher in men than in women (ratio, 1.8:1). Conclusions: Hemochromatosis is relatively common among white persons. Routine screening of white persons for hemochromatosis should be considered by primary care physicians.
Worldwide variations in the prevalence of symptoms of atopic eczema in the international study of asthma and allergies in childhood
Authors: Hywel Williams, Colin Robertson, Alistair Stewart, Nadia Aït-Khaled, Gabriel Anabwani, Ross Anderson, Innes Asher, Richard Beasley, Bengt Björkstén, Michael Burr, Tadd Clayton, Julian Crane, Philippa Ellwood, Ulrich Keil, Chris Lai, Javier Mallol, Fernando Martinez, Edwin Mitchell, Stephen Montefort, Neil Pearce, Jayant Shah, Bonnie Sibbald, David Strachan, Erika von Mutius, Stephan K. Weiland
Journal: Journal of Allergy and Clinical Immunology (1999)
A patient who changed my practice: To tell or not to tell
Authors: A N G Clark
Journal: BMJ (2001)

Whether it is correct to tell an elderly person how long he or she can expect to live, that is the question. In 50 years of work with elderly people, I have found it necessary only once to tell a patient that his expectation of life was short.

On my ward round I found a 72 year old man with a diagnosis of a large fungating carcinoma of the stomach busily engaged at the bedside with his bed covered in bits of paper bearing names and addresses. In reply to my inquiry as to what he was doing he said: “Doctor, I am planning to get married in two weeks' time and these are my wedding guests' invitations.”

In privacy I explained in as kind a way as I could that he had a serious, life threatening disease and that it would be wise for him to put all his affairs in order and not to make any radical plans for the future. A moment's silence followed, and then, to my surprise, he stood up and shook my hand warmly and said: “Thank you very much for telling me all this, doctor, but you must excuse me as I have a lot of invitations to send out about my wedding.” With that he hurried back to the bedside.

I learnt from this experience that the patient was totally unwilling to take in the horrible facts of his illness and was instead preoccupied with happy plans and thoughts of the future. In short, he preferred a fantasy of a happy future to the realities of death and dying.

I did not again attempt to tell an elderly patient the truth about a fatal illness, although I was always careful to inform the relatives. It would seem that many old people prefer to plan for a happy though unrealistic future rather than face a dismal fatal one. Many patients prefer to think about happy tomorrows as well as hope springing eternal. We should not take steps to change this unless patients ask directly for the truth for a good reason, which they seldom do.
Diagnosis of Metastatic Liver Cancer
Authors: Kenneth L. Jewel
Journal: JAMA (1984)

<h3>To the Editor.—</h3> In a letter by Dr Silberstein<sup>1</sup>concerning the study by Tempero et al,<sup>2</sup>the author states that the sensitivity of multiple liver biopsies averages 70% and does not exceed 82%. I would like to take exception to these statistical figures. In our institution, more than 250 image-guided percutaneous fine-needle aspiration biopsies have been performed. Of these, more than 50 liver biopsies have been undertaken with an overall accuracy of approximately 93%.<sup>3</sup>In addition, our specificity is 100% with a sensitivity of approximately 92%. We have encountered no complications in our series of liver biopsies. In addition, other interventional radiologists have reported the accuracy of image-guided liver biopsies performed under computed tomographic or ultrasonographic guidance to vary between 88%,<sup>4</sup>99%,<sup>5</sup>and 90%.<sup>6</sup> The references quoted by Dr Silberstein are rather outdated, from 1963 and 1972, and these biopsies were performed with so-called
Determinants of Agricultural Pesticide Concentrations in Carpet Dust
Authors: Robert B. Gunier, Mary H. Ward, Matthew Airola, Erin M. Bell, Joanne Colt, Marcia Nishioka, Patricia A. Buffler, Peggy Reynolds, Rudolph P. Rull, Andrew Hertz, Catherine Metayer, John R. Nuckols
Journal: Environmental Health Perspectives (2011)

Background: Residential proximity to agricultural pesticide applications has been used as a surrogate for exposure in epidemiologic studies, although little is known about the relationship with levels of pesticides in homes.Objective: We identified determinants of concentrations of agricultural pesticides in dust.Methods: We collected samples of carpet dust and mapped crops within 1,250 m of 89 residences in California. We measured concentrations of seven pesticides used extensively in agriculture (carbaryl, chlorpyrifos, chlorthal-dimethyl, diazinon, iprodione, phosmet, and simazine). We estimated use of agricultural pesticides near residences from a statewide database alone and by linking the database with crop maps. We calculated the density of pesticide use within 500 and 1,250 m of residences for 180, 365, and 730 days before collection of dust and evaluated relationships between agricultural pesticide use estimates and pesticide concentrations in carpet dust.Results: For five of the seven pesticides evaluated, residences with use of agricultural pesticides within 1,250 m during the previous 365 days had significantly higher concentrations of pesticides than did residences with no nearby use. The highest correlation with concentrations of pesticides was generally for use reported within 1,250 m of the residence and 730 days before sample collection. Regression models that also accounted for occupational and home use of pesticides explained only a modest amount of the variability in pesticide concentrations (4–28%).Conclusions: Agricultural pesticide use near residences was a significant determinant of concentrations of pesticides in carpet dust for five of seven pesticides evaluated.
Prolactin modulates the naive B cell repertoire
Authors: Elena Peeva, Daniel Michael, James Cleary, Jeffrey Rice, Xian Chen, Betty Diamond
Journal: Journal of Clinical Investigation (2003)

Prolactin is a peptide hormone produced by the anterior pituitary gland that is critical in lactation. Prolactin can also be produced by lymphocytes, and both B and T cells express prolactin receptors. These findings have suggested that prolactin has immunomodulatory functions. Studies in spontaneously autoimmune hosts have demonstrated a role for prolactin in augmenting autoreactivity. We chose to analyze prolactin effects on anti-DNA B cells in nonspontaneously autoimmune female BALB/c mice transgenic for the heavy chain of an anti-DNA antibody. Treatment with prolactin for 4 weeks induced a lupus-like phenotype with an increased number of transgene-expressing B cells, elevated serum anti-DNA antibody titers, and glomerular immunoglobulin deposits. Prolactin caused a decrease in the population of transitional B cells and an increase in mature follicular and marginal zone B cells. The DNA-reactive B cells had a follicular cell phenotype. Anti-DNA hybridomas demonstrated that prolactin alters selection of the naive B cell repertoire. The expansion and activation of anti-DNA B cells in prolactin-treated R4A-gamma2b BALB/c mice was dependent on the presence of CD4(+) T cells. Finally, treatment with prolactin was unable to break tolerance in R4A-gamma2b transgenic C57Bl/6 mice, suggesting that responsiveness of the immune system to prolactin is genetically determined.
Sexual Aspects of Cardiovascular Disease
Authors: Judith A. Sutin
Journal: JAMA (1990)

Within an era of increasing specialization, time constraints, and fiscal accountability, the role of each medical practitioner logically narrows. The sense then evolves of an intense but circumscribed professional responsibility, whereby the outcome is either to effect remediation or cure or to render the most enlightened opinion for a problem or constellation of clinical problems. The consequence, however, is a tendency for compartmentalizing of patient needs and for failure of sensitive dialogue with each patient regarding the individual's perception of the problem. Somewhere between competence and intention, the more personal, intimate patient needs become submerged or subordinated, but ultimately are reflected as failures of compliance or treatment, or "doctor hopping."<i>Sexual Aspects of Cardiovascular Disease</i>is a consummate testament to these individual needs, concerns, and quality-of-life issues that must be satisfied in each case for treatment to be deemed successful. The scope of this compact, thoroughly referenced volume ranges from
German court rules that liquid nicotine is not a medicine
Authors: N. Stafford
Journal: BMJ (2013)

A court in the German state of North Rhine-Westphalia has struck down a state health ministry regulation classifying liquid nicotine used in electronic cigarettes as a medicine1 comparable to nicotine plasters, which in Germany can only be sold in pharmacies.

The court ruled that liquid nicotine used in e-cigarettes is not a medicine and therefore its sales cannot be regulated by Germany’s pharmaceutical laws.

North Rhine-Westphalia’s health minister, Barbara Steffen, said that the ministry would review the ruling before determining whether …