tbuckley/cabot-search huggingface dataset:
Pollution in Alaska
Authors: Arthur N. Wilson
Journal: JAMA (1971)

To the Editor.—  We were interested in Dr. Lotspeich's article Air and Water Pollution in Alaska ( 214 :-829,1970).  My brother and I are both physicians practicing in Ketchikan and grew up in this community, arriving here in 1932. We are not intimate with the problem of ice fog other than having been in the North and been witness to many of its problems. However, I feel we can speak with authority on our local environment.  The author states, Dying trees in the vicinity of these mills suggests that some constituents of the gases must be toxic to vegetation. This is just not so. For years prior to the construction of the Ketchikan Pulp Mill at Ward Cove, Alaska, I fished for salmon in the cove and we picnicked at Wacker City which existed at the site of the present mill. This whole area was the site of a relatively large
Investigations on CXCL13 in Anti–<i>N</i>-Methyl-<scp>D</scp>-Aspartate Receptor Encephalitis
Authors: Frank Leypoldt, Romana Höftberger, Maarten J. Titulaer, Thaís Armangue, Nuria Gresa-Arribas, Holger Jahn, Kevin Rostásy, Wolfgang Schlumberger, Thomas Meyer, Klaus-Peter Wandinger, Myrna R. Rosenfeld, Francesc Graus, Josep Dalmau
Journal: JAMA Neurology (2014)

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe but treatable autoimmune encephalitis affecting mainly young adults and children. The lack of suitable biomarkers of disease activity makes treatment decisions and identification of relapses challenging.To determine the levels of the B-cell-attracting C-X-C motif chemokine 13 (CXCL13) in serum samples and cerebrospinal fluid (CSF) of patients with anti-NMDAR encephalitis and whether they can be used as biomarkers of treatment response and outcome.Retrospective cohort study of 167 patients consecutively diagnosed as having anti-NMDAR encephalitis between May 1, 2008, and January 31, 2013. Concentration of CXCL13 was determined with enzyme-linked immunosorbent assay in all available patients' samples (272 CSF and 55 serum samples). Samples from 25 patients with noninflammatory neurological disorders and 9 with neuroborreliosis served as controls. Expression of CXCL13 in the brain biopsy of a patient with anti-NMDAR encephalitis was determined by immunohistochemistry.Percentage of patients with anti-NMDAR encephalitis and elevated CXCL13 in CSF.Compared with control individuals, 70% of patients with early-stage anti-NMDAR encephalitis had increased CXCL13 in CSF (>7 pg/mL; P < .001) but none in serum samples (>1047 pg/mL; P > .99). High concentration of CSF CXCL13 was associated with the presence of prodromal fever or headache (P = .01), limited response to therapy (P = .003), clinical relapses (P = .03), and intrathecal NMDAR-antibody synthesis (P < .001). Among patients with monophasic disease assessed 2 to 6 months after starting treatment, 10 of 15 with limited treatment response vs 0 of 13 with favorable response had increased CSF CXCL13 (specificity, 100%; 95% CI, 75-100 and sensitivity, 67%; 95% CI, 38-88; P = .02). Six of 12 patients had elevated CSF CXCL13 at relapse including 3 with previously normal levels. In brain, abundant mononuclear cells in perivascular infiltrates and scattered intraparenchymal microglia expressed CXCL13.Seventy percent of patients with early-stage anti-NMDAR encephalitis had increased CSF CXCL13 concentration that correlated with intrathecal NMDAR-antibody synthesis. Prolonged or secondary elevation of CXCL13 was associated with limited response to treatment and relapses. CXCL13 is a potentially useful biomarker of treatment response and outcome in anti-NMDAR encephalitis.
Eliminating Racial Disparities in Colorectal Cancer in the Real World: It Took a Village
Authors: Stephen S. Grubbs, Blase N. Polite, John Carney, William Bowser, Jill Rogers, Nora Katurakes, Paula Hess, Electra D. Paskett
Journal: Journal of Clinical Oncology (2013)

Colorectal cancer (CRC) is the third most common cancer in the United States, with more than 102,000 new patients diagnosed per year. 1 It is, however, one of the few cancers that is highly preventable through the use of routine screening, 2 which can also prevent death resulting from CRC. 3,4 CRC is also one cancer that continues to demonstrate widening incidence and survival disparities between whites and African Americans. 1,5Although the reasons for these disparities are multifactorial, advanced stage at diagnosis may explain up to 50% of the survival disparity. 6his reality is not unique to CRC.Those who are poor, underserved, or minorities are more likely to get cancer and die as a result of it than those who are rich or white.This is a fact, and it is the current reality of cancer care in the United States, as documented in thousands of peer-reviewed articles, including the focus of an Institute of Medicine report.6a The shame for CRC is that the higher incidence rates and advanced stage of diagnosis are likely affected by differences in screening rates between whites and racial and ethnic minority populations.][9][10][11] Other studies have also found lower rates of follow-up for abnormalities detected on screening among minorities. 12Lack of insurance and usual sources of care certainly contribute to these disparities, but even when screening is universally provided, such as in the Medicare program, screening rates and follow-up after abnormal findings are still lower among African Americans compared with whites. 7,13,14][22] In Journal of Clinical Oncology, Robbins et al 23 reported on a study that identified disparities in CRC mortality rates among African American patients with late-stage disease.In an editorial, Paskett 24 suggested three steps to reduce CRC disparities: one, increase CRC
Combination chemoimmunotherapy with monthly cycles of 5-fluorouracil + interferon-alfa-2b in previously-treated advanced cancer
Authors: Walter Quan, Vivek Khemka, Laura S Martell, Marci J Pierog
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts The in vitro antineoplastic activity of the combination of 5-fluorouracil (5-FU) and interferon-alfa (IFN) has been attributed to multiple mechanisms including enhanced thymidylate synthase inhibition (Elias) and increased susceptibility to interferon-stimulated natural killer
Armed conflict as a public health problem
Authors: C J L Murray
Journal: BMJ (2002)

Armed conflict is a major cause of injury and death worldwide, but we need much better methods of quantification before we can accurately assess its effect

Armed conflict between warring states and groups within states have been major causes of ill health and mortality for most of human history. Conflict obviously causes deaths and injuries on the battlefield, but also health consequences from the displacement of populations, the breakdown of health and social services, and the heightened risk of disease transmission. Despite the size of the health consequences, military conflict has not received the same attention from public health research and policy as many other causes of illness and death. In contrast, political scientists have long studied the causes of war but have primarily been interested in the decision of elite groups to go to war, not in human death and misery.

We review the limited knowledge on the health consequences of conflict, suggest ways to improve measurement, and discuss the potential for risk assessment and for preventing and ameliorating the consequences of conflict.

#### Summary points

Conflict related death and injury are major contributors to the global burden of disease

Information systems break down during conflict, leading to great uncertainty in the magnitude of mortality and disability

The World Health Survey may provide a reliable and valid basis for assessing conflict related mortality and disability

Forecasting models may provide a plausible basis for assessing risk of conflict and thus prevention

Improved collaboration between political scientists and experts in public health would benefit measurement, prediction, and prevention of conflict related death

The impact of war on populations arises both from the direct effects of combat—namely, battle deaths—and from the indirect consequences of war, which may occur for several years after a conflict ends.1 Indirect effects of conflict on mortality can be formally …
Germline p53 Gene Mutations in Subsets of Glioma Patients
Authors: A. P. Kyritsis, M. L. Bondy, M. Xiao, E. L. Berman, J. E. Cunningham, P. S. Lee, V. A. Levin, H. Saya
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Germline p53 Gene Mutations in Subsets of Glioma Patients Get access Athanassios P. Kyritsis, Athanassios P. Kyritsis * 1Department of Neuro-oncology, The University of Texas M.D. Anderson Cancer CenterHouston * Athanassios P. Kyritsis, Department of Neuro Oncology, Box 100. The University Of Texas M. D. Anderson Cancer Center. Houston. TX 77030. Search for other works by this author on: Oxford Academic PubMed Google Scholar Melissa L. Bondy, Melissa L. Bondy 2Department of Epidemiology, The University of Texas M.D. Anderson Cancer CenterHouston Search for other works by this author on: Oxford Academic PubMed Google Scholar Mi Xiao, Mi Xiao 1Department of Neuro-oncology, The University of Texas M.D. Anderson Cancer CenterHouston Search for other works by this author on: Oxford Academic PubMed Google Scholar Elise L. Berman, Elise L. Berman 2Department of Epidemiology, The University of Texas M.D. Anderson Cancer CenterHouston Search for other works by this author on: Oxford Academic PubMed Google Scholar Joan E. Cunningham, Joan E. Cunningham 2Department of Epidemiology, The University of Texas M.D. Anderson Cancer CenterHouston Search for other works by this author on: Oxford Academic PubMed Google Scholar Polly S. Lee, Polly S. Lee 1Department of Neuro-oncology, The University of Texas M.D. Anderson Cancer CenterHouston Search for other works by this author on: Oxford Academic PubMed Google Scholar Victor A. Levin, Victor A. Levin 1Department of Neuro-oncology, The University of Texas M.D. Anderson Cancer CenterHouston Search for other works by this author on: Oxford Academic PubMed Google Scholar Hideyuki Saya Hideyuki Saya 1Department of Neuro-oncology, The University of Texas M.D. Anderson Cancer CenterHouston Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 5, 2 March 1994, Pages 344–349, https://doi.org/10.1093/jnci/86.5.344 Published: 02 March 1994 Article history Received: 12 July 1993 Revision received: 02 December 1993 Accepted: 07 December 1993 Published: 02 March 1994
Prospective comparison of different gastric motility tests in dyspeptic patients
Authors: M. F. Jaboli, J. Bell, C. Clayman, J. Buscombe, L. Marelli, O. Epstein
Journal: Gut (2011)

<h3>Introduction</h3> Up to 60% of dyspeptic patients have a normal upper endoscopy. Endoscopy is unable to diagnose myoelectrical disorders which can cause dyspeptic symptoms including epigastric discomfort, early satiety, bloating, nausea and vomiting. Although patients with functional dyspepsia complain of epigastric symptoms, the relation between these symptoms and gastric motility remains controversial. Electrogastrography (EGG) is a simple, non-invasive method for assessing the gastric pacemaker slow wave. Gastric emptying study (GES) is typically the first test in evaluation of gastric motor function using a radiolabelled test meal. The ultrasound of the stomach (USS) is a recent non-invasive and cheap modality to evaluate gastroduodenal motility. We wanted to compare the information given by three different gastric motility tests in patients with endoscopy negative dyspepsia (END). <h3>Methods</h3> A series of 77 dyspeptic helicobacter pylori negative patients (60 female: 17 male, ages 18–65 years) diagnosed according to the Roman III criteria and a normal upper endoscopy, underwent a standard fasting and postprandial EGG, a technetium labelled mashed potato GES and an ultrasound of the stomach given a soup test meal. The EGG was considered abnormal if &lt;70% of slow wave activity was recorded at 3 cycles/min. Delayed or increased gastric emptying was diagnosed if the T½ for the test meal was outside the normal range for our unit (&lt;15 or &gt;45 min, respectively). The USS was considered normal if the gastric emptying rate was between 45% and 78%. <h3>Results</h3> Thirty-one (40%) patients had both GES and USS test showing gastroparesis with mainly symptoms of nausea and vomiting (20/31, 64%). Eighty per cent (25/31) of these patients had an abnormal EGG, having as a predominant pattern an abnormal pre and post prandial test (12/31, 38%). Interestingly 17 people (22%) had normal GES and USS, with abnormal EGG in 82% of patients (14/17). Ten of these patients (58%) were experiencing nausea and vomiting as well. Only 2 (2.5%) patients had findings of dumping syndrome on GES and USS. There was more heterogeneity in the results of these tests with patients referring bloating and epigastric discomfort. <h3>Conclusion</h3> In patients with endoscopy negative dyspepsia, gastroparesis is very common and particularly with symptoms like nausea and vomiting. GES and USS can provide a firm diagnosis and possibly influence treatment strategies. We think these investigations should be incorporated into dyspepsia guidelines at the point where endoscopy is reported as normal. We are currently investigating the role of EGG for the poor correlation with the other tests.
The dependence of electrophysiological derangements on accumulation of endogenous long-chain acyl carnitine in hypoxic neonatal rat myocytes.
Authors: M T Knabb, J E Saffitz, P B Corr, B E Sobel
Journal: Circulation Research (1986)

To determine whether accumulation of long-chain acyl carnitine contributes to electrophysiological abnormalities induced by hypoxia, we characterized effects of normoxic and hypoxic perfusion on the subcellular distribution of endogenous long-chain acyl carnitine and transmembrane potentials of cultured rat neonatal myocytes. Hypoxia increased long-chain acyl carnitine more than 5-fold. Sodium 2-[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (10 microM), a carnitine acyltransferase inhibitor, precluded accumulation of long-chain acyl carnitine induced by hypoxia. Tissue was processed for electron microscopy by a procedure specifically developed for selective extraction of endogenous short-chain and free carnitine but retention of endogenous long-chain acyl carnitine. In normoxic-perfused cells, long-chain acyl carnitine was concentrated in mitochondria and cytoplasmic membranous components. Only small amounts were present in sarcolemma. Hypoxia increased mitochondrial long-chain acyl carnitine by 10-fold and sarcolemmal long-chain acyl carnitine by 70-fold. After 60 minutes of hypoxia, sarcolemma contained 1.4 X 10(7) long-chain acyl carnitine molecules/micron 3 of membrane volume, a value corresponding to approximately 3.5% of total sarcolemmal phospholipid. Hypoxia also significantly decreased maximum diastolic potential, action potential amplitude and maximum upstroke velocity of phase 0. Sodium 2-[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate inhibited accumulation of long-chain acyl carnitine in each subcellular compartment and prevented the depression of electrophysiological function induced by hypoxia. These results strongly implicate endogenous long-chain acyl carnitine as a mediator of electrophysiological alterations induced by hypoxia.
Blockade of the Extracellular Signal-Regulated Kinase Pathway Enhances the Therapeutic Efficacy of Microtubule-Destabilizing Agents in Human Tumor Xenograft Models
Authors: Kazushi Watanabe, Susumu Tanimura, Aya Uchiyama, Toshiaki Sakamoto, Takumi Kawabata, Kei-ichi Ozaki, Michiaki Kohno
Journal: Clinical Cancer Research (2010)

Abstract Purpose: The extracellular signal-regulated kinase (ERK) pathway is upregulated in human cancers and represents a target for mechanism-based approaches to cancer treatment. However, specific blockade of the ERK pathway alone induces mostly cytostatic rather than proapoptotic effects, resulting in a limited therapeutic efficacy of inhibitors that target the mitogen-activated protein kinase/ERK kinase (MEK). Given the cytoprotective role of the ERK pathway, we examined whether its blockade by the MEK inhibitor PD184352 might enhance the therapeutic efficacy of anticancer drugs in human tumor xenograft models. Experimental Design: We recently showed that blockade of the ERK pathway by MEK inhibitors enhances the induction of apoptosis by microtubule-destabilizing agents, including TZT-1027 and vinorelbine, in various tumor cells with aberrant activation of the ERK pathway in vitro. We here examined the therapeutic efficacy of the combination of PD184352 with TZT-1027 or vinorelbine in nude mice harboring HT-29 or HT1080 tumor xenografts, in which the ERK pathway is activated as a result of mutations of BRAF and NRAS, respectively. Results: Coadministration of PD184352 markedly sensitized HT-29 or HT1080 tumor xenografts to TZT-1027–induced or vinorelbine-induced cytotoxicity. Low doses of TZT-1027 or vinorelbine that by themselves showed little or moderate cytotoxicity thus suppressed the growth of HT-29 xenografts almost completely and induced essentially complete regression of HT1080 xenografts when administered with PD184352. The enhanced therapeutic efficacy of the drug combinations was achieved by a relatively transient blockade of the ERK pathway. Conclusions: Administration of both a MEK inhibitor and a microtubule-destabilizing agent represents a promising chemotherapeutic strategy with improved safety for cancer patients. Clin Cancer Res; 16(4); 1170–8
Clinical trials in ovarian carcinoma: study methodology
Authors: J.B. Vermorken, M.K.B. Parmar, M.F. Brady, E.A. Eisenhauer, T. Hogberg, R.F. Ozols, J. Rochon, G.J.S. Rustin, S. Sagae, R.H.M. Verheijen
Journal: Annals of Oncology (2005)
Evaluation of breath holding in hypercapnia as a simple clinical test of respiratory chemosensitivity.
Authors: N N Stanley, E L Cunningham, M D Altose, S G Kelsen, R S Levinson, N S Cherniack
Journal: Thorax (1975)

Breath holding was used as the basis of a simple test of respiratory chemosensitivity. Breath holding was begun at selected degrees of hypercapnia produced by CO2 rebreathing. In 16 healthy control subjects there was a linear regression of the log of breath-holding time on the PCO2 at the start of breath holding. Breath-holding time (BHT) and the slope of a log BHT/Pco2 plot were closely correlated with the ventilatory response to CO2. In five cases of the idiopathic hypoventilation syndrome, CO2 retention and reduced ventilatory response to CO2 were accompanied by prolonged breath-holding time and the regression of log BHT on Pco2 was abnormally flat. However, in 17 patients with chronic airways obstruction, breath-holding time was never prolonged and the log BHT/Pco2 relationship was normal, even though 13 had a diminished ventilatory response to CO2 and four had chronic CO2 retention. It is concluded that the BHT/Pco2 relationship provides a useful index of respiratory chemosensitivity which is not influenced by airways obstruction. This may be helpful in the detection of impaired chemosensitivity as a cause of CO2 retention even when the ventilation CO2 response is reduced non-specifically by coexisting airways obstruction.
A new multiple dose powder inhaler, (Turbuhaler), compared with a pressurized inhaler in a study of terbutaline in asthmatics
Authors: G Persson, E Gruvstad, E Stahl
Journal: European Respiratory Journal (1988)

Twelve adult asthmatic patients participated in an open, randomized, cross-over comparison between cumulatively increasing doses of terbutaline sulphate administered via the multiple dose powder inhaler (Turbuhaler) or via a pressurized inhaler. Turbuhaler and the pressurized inhaler showed equipotency both with respect to bronchodilatation and side effects. Both treatments produced a significant increase in pulmonary function measurements, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). No increase in pulse rate was seen with either treatment but there was an increase in tremor at higher doses with both treatments. Inhalation of beta-agonists via Turbuhaler seems to be an effective way of treating asthma.
ANAPHYLACTIC SHOCK BY AZODYES
Authors: K. Landsteiner, J. van der Scheer
Journal: The Journal of Experimental Medicine (1933)

Experiments are described which show that anaphylactic shock can be induced in animals sensitized with azoproteins by injecting them with azodyes containing the same azo components as the sensitizing antigen. The anaphylactic reactions are specific and occur with quantities of the dyes as small as fractions of milligrams.
Microfabricated Microneedles for Gene and Drug Delivery
Authors: Devin V. McAllister, Mark G. Allen, Mark R. Prausnitz
Journal: Annual Review of Biomedical Engineering (2000)

By incorporating techniques adapted from the microelectronics industry, the field of microfabrication has allowed the creation of microneedles, which have the potential to improve existing biological-laboratory and medical devices and to enable novel devices for gene and drug delivery. Dense arrays of microneedles have been used to deliver DNA into cells. Many cells are treated at once, which is much more efficient than current microinjection techniques. Microneedles have also been used to deliver drugs into local regions of tissue. Microfabricated neural probes have delivered drugs into neural tissue while simultaneously stimulating and recording neuronal activity, and microneedles have been inserted into arterial vessel walls to deliver anti-restenosis drugs. Finally, microhypodermic needles and microneedles for transdermal drug delivery have been developed to reduce needle insertion pain and tissue trauma and to provide controlled delivery across the skin. These needles have been shown to be robust enough to penetrate skin and dramatically increase skin permeability to macromolecules.
The Generation, Detection, and Effects of Reactive Drug Metabolites
Authors: Andrew V. Stachulski, Thomas A. Baillie, B. Kevin Park, R. Scott Obach, Deepak K. Dalvie, Dominic P. Williams, Abhishek Srivastava, Sophie L. Regan, Daniel J. Antoine, Christopher E. P. Goldring, Alvin J. L. Chia, Neil R. Kitteringham, Laura E. Randle, Hayley Callan, J. Luis Castrejon, John Farrell, Dean J. Naisbitt, Martin S. Lennard
Journal: Medicinal Research Reviews (2012)

The decline in approval of new drugs during the past decade has led to a close analysis of the drug discovery process. One of the main reasons for attrition is preclinical toxicity, frequently attributed to the generation of protein-reactive drug metabolites. In this review, we present a critique of such reactive metabolites and evaluate the evidence linking them to observed toxic effects. Methodology for the characterization of reactive metabolites has advanced greatly in recent years, and is summarized first. Next, we consider the inhibition of key metabolic enzymes by electrophilic metabolites, as well as unfavorable drug–drug interactions that may ensue. One important class of protein-reactive metabolites, not linked conclusively to a toxic event, is acyl glucuronides. Their properties are discussed in light of the safety characteristics of carboxylic acid containing drugs. Many adverse drug reactions (ADRs) are known collectively as idiosyncratic events, that is, not predictable from knowledge of the pharmacology and pharmacokinetics of the parent compound. Observed ADRs may take various forms. Specific organ injury, particularly of the liver, is the most direct: we examine this in some detail. Moving to the cellular level, we also consider the upregulation of induced cellular processes. The related, but distinct, issue of hypersensitivity or allergic reactions to drugs and their metabolites, possibly via the immune system, is considered next. Finally, we discuss the impact of such data on the drug discovery process, both through early detection of reactive metabolites and informed synthetic design, which eliminates unfavorable functionality from drug candidates.