tbuckley/cabot-search huggingface dataset:
Ethical perspectives for public and environmental health: fostering autonomy and the right to know.
Authors: Timothy William Lambert, Colin L Soskolne, Vangie Bergum, James Howell, John B Dossetor
Journal: Environmental Health Perspectives (2002)

In this paper we develop an ethical perspective for public and environmental health practice in consideration of the "right to know" by contrasting consequential and deontological perspectives with relational ethics grounded in the concept of fostering autonomy. From the consequential perspective, disclosure of public and environmental health risks to the public depends on the expected or possible consequences. We discuss three major concerns with this perspective: respect for persons, justice, and ignorance. From a deontological perspective, the "right to know" means that there is a "duty" to communicate about all public health risks and consideration of the principles of prevention, precaution, and environmental justice. Relational ethics develops from consideration of a mutual limitation of the traditional perspectives. Relational ethics is grounded in the relationship between the public and public/environmental health providers. In this paper we develop a model for this relationship, which we call "fostering autonomy through mutually respectful relationships." Fostering autonomy is both an end in public health practice and a means to promote the principles of prevention, precaution, and environmental justice. We discuss these principles as they relate to practical issues of major disasters and contaminants in food, such as DDT, toxaphene, chlordane, and mercury.
Prediction of therapy-related acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) after autologous bone marrow transplant (ABMT) for lymphoma
Authors: Robert D. Legare, John G. Gribben, Marlon Maragh, Anne Hermanowski-Vosatka, Sheila Roach, Ramana Tantravahi, Lee M. Nadler, D. Gary Gilliland
Journal: American Journal of Hematology (1997)

Therapy-related acute myelogenous leukemia and myelodysplastic syndrome (t-AML/MDS) are being reported with increasing frequency as a complication of ABMT for Hodgkin's disease and non-Hodgkin's lymphoma. At present there is no method available to predict who is at risk or is destined to develop this nearly universally fatal disorder. We therefore investigated whether clonal growth of cells is predictive of the development of t-AML/MDS. In a patient who developed secondary AML/MDS 18 months after ABMT, X-linked clonality analysis at the human androgen receptor locus was performed on serial banked samples, and documented transition from polyclonal to clonal hematopoiesis. Clonal cells could be identified 6 months after transplant (1 year prior to the diagnosis of t-AML/MDS), at a time when there was no morphologic or clinical evidence of disease. Clonality analysis can be predictive of the development of t-AML/MDS after ABMT and may offer important insights into associated risk factors and strategies to minimize the risk of t-AML/MDS. Am. J. Hematol. 56:45–51, 1997. © 1997 Wiley-Liss, Inc.
An exercise program for hands and arms improved hand function in RA controlled with medication
Authors: Lyn March
Journal: Annals of Internal Medicine (2015)

Source Citation Lamb SE, Williamson EM, Heine PJ, et al; Strengthening and Stretching for Rheumatoid Arthritis of the Hand Trial (SARAH) Trial Team. Exercises to improve function of the rheumatoid hand (SARAH): a randomised controlled trial. Lancet. 2015. (Epub ahead of print) 25308290
Symptomatic prescribing reappraised
Authors: P. Hays
Journal: BMJ (1996)

At the University of Alberta we focus our history, examine pointedly, diagnose specifically, eradicate the cause, and educate the patient prophylactically. For completely ideal care we should also include (what was omitted from the dreamlike opening sequence) symptomatic treatment, the judicious management of distress.

Until recently symptomatic treatment was virtually our entire stock in trade, but the profession prospered. Then science and serendipidity provided us with a range of specifics, and we began to dismiss other treatments as merely symptomatic and to note their capacity to obscure diagnosis or to cause dependence. I have seen calamities arising from thoughtless symptomatic prescribing and, because I am a fastidious academic, I shudder at the memory.

Why, then, do I not shudder when I look at my own prescribing patterns and those of the senior professors who are my closest colleagues?

Lorazepam is recommended for the short term relief of anxiety neurosis. Five years is commonplace at this centre, mostly not for anxiety neuroses. Diazepam should be discontinued after a few weeks at the most. Twenty five years does not raise an eyebrow round here. I draw a veil over amphetamines and congeners; symptomatic medicine thrives where you would least expect it.

What happens …
Regional left ventricular deafferentation increases baroreflex sensitivity following myocardial infarction
Authors: A MINISI, T NASHED, M QUINN
Journal: Cardiovascular Research (2003)

Objective: Depressed baroreflex sensitivity (BRS) has been observed following MI and has adverse prognostic implications. The mechanism for this finding is unknown. We tested the hypothesis that depressed BRS following myocardial infarction (MI) is related to augmented input from afferent receptors in the left ventricle. Methods: Conscious, chronically-instrumented dogs were trained to undergo BRS testing. This testing was performed before and 4 weeks after creation of experimental anterior MI. Animals were then randomized to undergo regional deafferentation or sham thoracotomy. One week later, BRS testing was repeated. Results: Animals with reduced BRS post-MI showed slight increases in sensitivity values after regional deafferentation. Following sham thoracotomy, animals with reduced BRS post-MI exhibited further decreases in sensitivity values. The differences in mean BRS values measured after regional or sham deafferentation were significant (17.4±2.0 ms/mmHg vs. 11.7±1.4 ms/mmHg; P<0.05). Conclusions: In animals with reduced BRS post-MI, deafferentation of the infarcted region prevented the progressive decline in sensitivity values that was noted in the control group. These data suggest that depressed BRS following MI is related to augmented afferent input from left ventricular receptors.
DPYD Variants as Predictors of 5-fluorouracil Toxicity in Adjuvant Colon Cancer Treatment (NCCTG N0147)
Authors: Adam M. Lee, Qian Shi, Emily Pavey, Steven R. Alberts, Daniel J. Sargent, Frank A. Sinicrope, Jeffrey L. Berenberg, Richard M. Goldberg, Robert B. Diasio
Journal: JNCI Journal of the National Cancer Institute (2014)

Previous studies have suggested the potential importance of three DPYD variants (DPYD*2A, D949V, and I560S) with increased 5-FU toxicity. Their individual associations, however, in 5-FU-based combination therapies, remain controversial and require further systematic study in a large patient population receiving comparable treatment regimens with uniform clinical data. We genotyped 2886 stage III colon cancer patients treated adjuvantly in a randomized phase III trial with FOLFOX or FOLFIRI, alone or combined with cetuximab, and tested the individual associations between functionally deleterious DPYD variants and toxicity. Logistic regressions were used to assess univariate and multivariable associations. All statistical tests were two-sided. In 2594 patients with complete adverse event (AE) data, the incidence of grade 3 or greater 5FU-AEs in DPYD*2A, I560S, and D949V carriers were 22/25 (88.0%), 2/4 (50.0%), and 22/27 (81.5%), respectively. Statistically significant associations were identified between grade 3 or greater 5FU-AEs and both DPYD*2A (odds ratio [OR] = 15.21, 95% confidence interval [CI] = 4.54 to 50.96, P < .001) and D949V (OR = 9.10, 95% CI = 3.43 to 24.10, P < .001) variants. Statistical significance remained after adjusting for multiple variables. The DPYD*2A variant statistically significantly associated with the specific AEs nausea/vomiting (P = .007) and neutropenia (P < .001), whereas D949V statistically significantly associated with dehydration (P = .02), diarrhea (P = .003), leukopenia (P = .002), neutropenia (P < .001), and thrombocytopenia (P < .001). Although two patients with I560S had grade≥3 5FU-AEs; a statistically significant association could not be demonstrated because of its low frequency (P= .48). In the largest study to date, statistically significant associations were found between DPYD variants (DPYD*2A and D949V) and increased incidence of grade 3 or greater 5FU-AEs in patients treated with adjuvant 5-FU-based combination chemotherapy.
Why the gender difference in susceptibility to rheumatoid arthritis?
Authors: P Brennan, A Silman
Journal: Annals of the Rheumatic Diseases (1995)

Why the gender difference in susceptibility to rheumatoid arthritis?A recent Norwich observati 'rheumatoid arthritis in men (E) and women (U) in why infertility and reduced fecundity are associated with ?a1thAuthority during 1990-91.RA, given their relationship to hyperprolactinaemia.
Human health hazards associated with chemical contamination of aquatic environment.
Authors: J F Stara, D Kello, P Durkin
Journal: Environmental Health Perspectives (1980)

Given the finite supply of water available for human use, continued chemical contamination of the aquatic environment may pose a significant human health hazard. Consequently, an effort must be made to develop ambient water quality criteria to protect human health and preserve the integrity of the aquatic environment. In developing water quality criteria based on human health effects, information on sources of exposure, pharmacokinetics, and adverse effects must be carefully evaluated. Information on sources of exposure is needed to determine the contribution of exposure from water relative to all other sources. Pharmacokinetic data are used in inter- and intraspecies extrapolation and in characterizing the mode of toxic action. Information on toxic effects includes data on acute, subchronic, and chronic toxicity, mutagenicity, teratogenicity, and carcinogenicity. In analyzing such information, a distinction is made between threshold and nonthreshold effects. Currently, carcinogenicity and mutagenicity are considered to be nonthreshold effects. For carcinogens and mutagens, criteria are calculated by postulating an
How effective are some common treatments for traumatic brain injury?
Authors: K. Ker, P. Perel, K. Blackhall, I. Roberts
Journal: BMJ (2008)

Surveys show that mannitol, hyperventilation, cerebrospinal fluid drainage, and barbiturates are commonly used in the United Kingdom, Europe, and the United States to treat traumatic brain injury.1 2 3 Yet the effects of such treatments are uncertain.Traumatic brain injury is a major cause of death and disability worldwide.Every year at least 10 million people sustain a traumatic brain injury serious enough to result in death or admission to hospital.4Bearing in mind that almost half of all patients with traumatic brain injury experience long term disability5 6 and that most injury occurs in young adults, the medical, social, and financial burden is clear.1/8/2016 How effective are some common treatments for traumatic brain injury?| The BMJ http://www.bmj.com/content/
TCTAP A-098 The Clinical Outcomes of EVT for Restenosis of Superficial Femoral Artery Stent with Jailed Deep Femoral Artery
Authors: Takahiro Tokuda, Keisuke Hirano, Toshiya Muramatsu, Hiroshi Ishimori, Masatsugu Nakano, Masahiro Yamawaki, Motoharu Araki, Norihiro Kobayashi, Hideyuki Takimura, Yasunari Sakamoto, Shinsuke Mori, Masakazu Tsutsumi, Hiroya Takafuji, Takuro Takama, Yohsuke Honda
Journal: Journal of the American College of Cardiology (2015)
Hepatopulmonary syndrome: Favorable outcomes in the MELD exception era
Authors: Vivek N. Iyer, Karen L. Swanson, Rodrigo Cartin-Ceba, Ross A. Dierkhising, Charles B. Rosen, Julie K. Heimbach, Russell H. Wiesner, Michael J. Krowka
Journal: Hepatology (2012)

Hepatopulmonary syndrome (HPS) is a pulmonary vascular disorder occurring as a consequence of advanced liver disease, characterized by hypoxemia due to intrapulmonary vascular dilatations. HPS independently increases mortality, regardless of the cause or severity of liver disease. Liver transplantation (LT) improves survival in HPS. We present the largest consecutive series of HPS patients specifically addressing long-term survival relative to the degree of hypoxemia and the era in which LT was conducted. We evaluated 106 HPS patients at the Mayo Clinic from 1986 through 2010. Survival was assessed using Kaplan-Meier methodology. LT was accomplished in 49 HPS patients. Post-LT survival (1, 3, 5, and 10 years) did not differ between groups based on baseline partial pressure of arterial oxygen (PaO2 ) obtained at the time of HPS diagnosis. Improvements in overall survival at 1, 3, and 5 years post-LT in those HPS patients transplanted after January 1 2002 (n = 28) (92%, 88%, and 88%, respectively) as compared with those transplanted prior to that time (n = 21) (71%, 67%, and 67%, respectively) did not reach statistical significance (5-year P = 0.09). Model for Endstage Liver Disease (MELD) exception to facilitate LT was granted to 21 patients since January 1 2002 with post-LT survival of 19/21 patients and one wait-list death.Long-term outcome after LT in HPS is favorable, with a trend towards improved survival in the MELD exception era since 2002 as compared to earlier HPS transplants. Survival after LT was not associated with PaO2 levels at the time of HPS diagnosis. (HEPATOLOGY 2012).
Genetic Deletion of AEG-1 Prevents Hepatocarcinogenesis
Authors: Chadia L. Robertson, Jyoti Srivastava, Ayesha Siddiq, Rachel Gredler, Luni Emdad, Devaraja Rajasekaran, Maaged Akiel, Xue-Ning Shen, Chunqing Guo, Shah Giashuddin, Xiang-Yang Wang, Shobha Ghosh, Mark A. Subler, Jolene J. Windle, Paul B. Fisher, Devanand Sarkar
Journal: Cancer Research (2014)

Abstract Activation of the oncogene AEG-1 (MTDH, LYRIC) has been implicated recently in the development of hepatocellular carcinoma (HCC). In mice, HCC can be initiated by exposure to the carcinogen DEN, which has been shown to rely upon activation of NF-κB in liver macrophages. Because AEG-1 is an essential component of NF-κB activation, we interrogated the susceptibility of mice lacking the AEG-1 gene to DEN-induced hepatocarcinogenesis. AEG-1–deficient mice displayed resistance to DEN-induced HCC and lung metastasis. No difference was observed in the response to growth factor signaling or activation of AKT, ERK, and β-catenin, compared with wild-type control animals. However, AEG-1–deficient hepatocytes and macrophages exhibited a relative defect in NF-κB activation. Mechanistic investigations showed that IL6 production and STAT3 activation, two key mediators of HCC development, were also deficient along with other biologic and epigenetics findings in the tumor microenvironment, confirming that AEG-1 supports an NF-κB–mediated inflammatory state that drives HCC development. Overall, our findings offer in vivo proofs that AEG-1 is essential for NF-κB activation and hepatocarcinogenesis, and they reveal new roles for AEG-1 in shaping the tumor microenvironment for HCC development. Cancer Res; 74(21); 6184–93. ©2014 AACR.
Methohexital Anesthesia In Office Practice
Authors: Frank A. Straccia
Journal: JAMA (1966)

To the Editor:—  Methohexital has proven extremely helpful in the office treatment of selective emotional disorders, thus making hospitalization unnecessary in many instances. Methohexital is a rapid and shortacting anesthetic, giving prompt recovery and having minimal, if any, aftereffects. It has greatly facilitated electroconvulsive therapy and can be used as an office procedure. It is superior to thiopental sodium, which is slower acting, gives a slower rate of recovery, and is associated with a greater incidence of side effects.  Procedure:—  patients are instructed to abstain from food and liquid on the morning treatment is to be given.  Atropine, 1/75 grains, is administered subcutaneously approximately one hour prior to treatment. A 1% solution of methohexital is prepared by dissolving 500 mg in 50 cc of distilled water. The solution is administered intravenously by the drip method; occasionally a syringe is used. The amount required for satisfactory induction varies between 6 and
Regular Use of Laxatives by Schoolchildren
Authors: J. J. A. Reid
Journal: BMJ (1956)

In animal models of temporal lobe epilepsy (TLE), neurosteroid sensitivity of GABA<sub>A</sub> receptors on dentate granule cells (DGCs) is diminished; the molecular mechanism underlying this phenomenon remains unclear. The current study investigated a mechanism for loss of neurosteroid sensitivity of synaptic GABA<sub>A</sub> receptors in TLE. Synaptic currents recorded from DGCs of epileptic animals (epileptic DGCs) were less frequent, larger in amplitude, and less sensitive to allopregnanolone modulation than those recorded from DGCs of control animals (control DGCs). Synaptic currents recorded from epileptic DGCs were less sensitive to diazepam and had altered sensitivity to benzodiazepine inverse agonist RO 15-4513 (ethyl-8-azido-6-dihydro-5-methyl-6-oxo-4<i>H</i>-imidazo[1,5α][1,4]benzodiazepine-3-carboxylate) and furosemide than those recorded from control DGCs. Properties of synaptic currents recorded from epileptic DGCs appeared similar to those of recombinant receptors containing the α4 subunit. Expression of the α4 subunit and its colocalization with the synaptic marker GAD65 was increased in epileptic DGCs. Location of the α4 subunit in relation to symmetric (inhibitory) synapses on soma and dendrites of control and epileptic DGCs was examined with postembedding immunogold electron microscopy. The α4 immunogold labeling was present more commonly within the synapse in epileptic DGCs compared with control DGCs, in which the subunit was extrasynaptic. These studies demonstrate that, in epileptic DGCs, the neurosteroid modulation of synaptic currents is diminished and α4 subunit-containing receptors are present at synapses and participate in synaptic transmission. These changes may facilitate seizures in epileptic animals.
Endothelial Cell Metabolism in Normal and Diseased Vasculature
Authors: Guy Eelen, Pauline de Zeeuw, Michael Simons, Peter Carmeliet
Journal: Circulation Research (2015)

Higher organisms rely on a closed cardiovascular circulatory system with blood vessels supplying vital nutrients and oxygen to distant tissues. Not surprisingly, vascular pathologies rank among the most life-threatening diseases. At the crux of most of these vascular pathologies are (dysfunctional) endothelial cells (ECs), the cells lining the blood vessel lumen. ECs display the remarkable capability to switch rapidly from a quiescent state to a highly migratory and proliferative state during vessel sprouting. This angiogenic switch has long been considered to be dictated by angiogenic growth factors (eg, vascular endothelial growth factor) and other signals (eg, Notch) alone, but recent findings show that it is also driven by a metabolic switch in ECs. Furthermore, these changes in metabolism may even override signals inducing vessel sprouting. Here, we review how EC metabolism differs between the normal and dysfunctional/diseased vasculature and how it relates to or affects the metabolism of other cell types contributing to the pathology. We focus on the biology of ECs in tumor blood vessel and diabetic ECs in atherosclerosis as examples of the role of endothelial metabolism in key pathological processes. Finally, current as well as unexplored EC metabolism-centric therapeutic avenues are discussed.
Abstract LB-259: The gluconeogenic pathway is operative in lung cancer cells
Authors: Teresa WM Fan, Pawel Lorkiewicz, Richard M. Higashi, Andrew N. Lane
Journal: Cancer Research (2011)

Abstract Accelerated aerobic glycolysis has been a hallmark of cancer metabolism since Otto Warburg's seminal discovery [1]. Glucose oxidation via glycolysis and the pentose phosphate pathway (PPP) not only produces energy and reducing equivalents but also anabolic precursors to meet the demands of proliferation and many essential functions of cancer cells. Although many of the anabolic precursors can be obtained from alternative fuel substrates, the de novo synthesis of ribose and therefore nucleotides normally requires glucose metabolism. Thus, under glucose deficiency, cancer cells will cease proliferation due to a lack of new synthesis of nucleic acids. This can occur in poorly vascularized areas of a tumor. We now have direct evidence that lung cancer cells can circumvent this problem by making ribose from Gln using part of the gluconeogenic pathway. By using U-13C5,15N2-Gln as tracer, we tracked the fate of the 13C and 15N atoms simultaneously into various metabolites of A549 and H1299 cells using FT-ICR-MS and NMR. We found that both labels were incorporated into ATP and other nucleotides. Although the expected 15N labeling patterns were found based on the purine biosynthetic pathway, the 13C labeling patterns show that the adenine ring and/or ribosyl unit of ATP were also labeled. This can only occur through the metabolic sequence of glutaminolysis, Krebs cycle, pyruvate carboxylation, PEP carboxykinase (PEPCK) reaction, gluconeogenesis, and PPP. We believe this is the first time that gluconeogenesis is demonstrated for cancer cell lines not known to be gluconeogenic, which could have important implications for how cancer cells adapt to a glucose-limited microenvironment and the role of Gln in such adaptations. 1. Warburg, O., On the origin of cancer cells. Science, 1956. 123: p. 309–314. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-259. doi:10.1158/1538-7445.AM2011-LB-259