tbuckley/cabot-search huggingface dataset:
Approaches to developing alternative and predictive toxicology based on PBPK/PD and QSAR modeling.
Authors: R S Yang, R S Thomas, D L Gustafson, J Campain, S A Benjamin, H J Verhaar, M M Mumtaz
Journal: Environmental Health Perspectives (1998)

Systematic toxicity testing, using conventional toxicology methodologies, of single chemicals and chemical mixtures is highly impractical because of the immense numbers of chemicals and chemical mixtures involved and the limited scientific resources. Therefore, the development of unconventional, efficient, and predictive toxicology methods is imperative. Using carcinogenicity as an end point, we present approaches for developing predictive tools for toxicologic evaluation of chemicals and chemical mixtures relevant to environmental contamination. Central to the approaches presented is the integration of physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) and quantitative structure--activity relationship (QSAR) modeling with focused mechanistically based experimental toxicology. In this development, molecular and cellular biomarkers critical to the carcinogenesis process are evaluated quantitatively between different chemicals and/or chemical mixtures. Examples presented include the integration of PBPK/PD and QSAR modeling with a time-course medium-term liver foci assay, molecular biology and cell proliferation studies. Fourier transform infrared spectroscopic analyses of DNA changes, and cancer modeling to assess and attempt to predict the carcinogenicity of the series of 12 chlorobenzene isomers. Also presented is an ongoing effort to develop and apply a similar approach to chemical mixtures using in vitro cell culture (Syrian hamster embryo cell transformation assay and human keratinocytes) methodologies and in vivo studies. The promise and pitfalls of these developments are elaborated. When successfully applied, these approaches may greatly reduce animal usage, personnel, resources, and time required to evaluate the carcinogenicity of chemicals and chemical mixtures.
Lepers of New York Turned Loose by the Board of Health.
Authors: Albert S. Ashmead
Journal: JAMA (1897)

New York, Oct. 20, 1897. <h3>To the Editor:</h3> —The public be d—! Whether leprosy is contagious or not does not seem to be the question with our New York Board of Health. The point is to escape responsibility, care and trouble. Let the leper go; we are glad to get rid of him on any terms! It is a lamentable circumstance that such devil-may-carelessness should exist just on the point where it can do the most evil. New York is the most important port of our country. The lepers are foreigners; most of them come from Norway, Sweden, Iceland, South America and the West Indies to New York. Most of the lepers who live in Minnesota and Wisconsin came through New York. Had they remained here instead of going to those far-off States, would the New York Board of Health dare to have let them run loose? Horrified public opinion
A novel apolipoprotein E mutation, E2 (Arg25Cys), in lipoprotein glomerulopathy
Authors: Akira Matsunaga, Jun Sasaki, Takeo Komatsu, Kazuro Kanatsu, Emiko Tsuji, Kengo Moriyama, Takafumi Koga, Kikuo Arakawa, Shinichi Oikawa, Takao Saito, Toru Kita, Toshio Doi
Journal: Kidney International (1999)
Conversion of FDG PET Activity of Fibrous Dysplasia of the Skull Late in Life Mimicking Metastatic Disease
Authors: David Bonekamp, Heather Jacene, Detlef Bartelt, Nafi Aygun
Journal: Clinical Nuclear Medicine (2008)

Fibrous dysplasia (FD) accounts for 7% of benign bone tumors. It is a developmental disorder of unclear etiology. The lamellar cancellous bone of the medullary cavity is replaced with immature fibroosseous tissue. We describe a case of FD of the skull in a patient of advanced age (69 years) with recent diagnosis of colon cancer, which changed its FDG activity and CT appearance within 10 months of follow-up. Surgical biopsy confirmed FD. Several case reports describe FDG-avid FD, but conversion of metabolic activity late in life is probably unusual.
Labetalol-induced toxic myopathy.
Authors: A Teicher, T Rosenthal, E Kissin, I Sarova
Journal: BMJ (1981)

Labetalol has been successful in treating hypertension, and few side effects have been reported, although there have been cases of muscle pain during treatment. A patient with essential hypertension treated with labetalol 600 mg daily complained of muscle pains, particularly in the legs. No neurological abnormality was found, but the activity of muscle enzymes in the blood was high. Findings on electromyography were compatible with myositis and electron microscopical findings suggested toxic myopathy. Labetalol was stopped for 10 days, and the muscle pain disappeared and enzyme activity returned to normal. When labetalol was restarted the pain returned and enzyme activities rose. Myopathy should be considered in patients experiencing muscle pain after treatment with labetalol.
RANKing c-Jun in osteoclast development
Authors: Steven L. Teitelbaum
Journal: Journal of Clinical Investigation (2004)

Pathological bone loss always reflects enhanced net osteoclastic activity. Recognition and binding of the receptor activator of NF-κB (RANK) by RANK ligand (RANKL) is the key osteoclastogenic event, and the signaling cascades induced by this reaction therefore contain potential anti-osteoporosis therapeutic targets. A study reported in this issue of the JCI documents that a pivotal component of RANKL/RANK-mediated osteoclast recruitment involves sequential induction of the transcription factors c-Jun and nuclear factor of activated T cells 2 .
Serious adverse events associated with perinatal drugs
Authors: S. Gottlieb
Journal: BMJ (2002)

An average of 243 children under the age of 2 years die each year in the United States as a result of drugs used during the perinatal period. Seventeen drugs accounted for more than half of all cases of serious and fatal adverse events in children treated directly with them.

The analysis was based on 7111 reports of adverse drug reactions in infants and children between November 1997 and December 2000. The reports were culled from more than 500 000 MedWatch adverse event reports that doctors and drug companies are required to file …
Averting a world food shortage: tighten your belts for CAIRO II
Authors: M. King, C. Elliott
Journal: BMJ (1996)

We are going to have to eat what the world will produce with all its failings, not what it could produce without them. Trends in global food production are therefore all important. These are now giving cause for anxiety, in that the rate of increase of global grain yields has been slowing seriously. Locally, the food security of some demographically trapped communities is so dire that, like China, they need one child families. The 1994 Cairo population conference (Cairo I) took future food supplies for granted and took no account of demographic entrapment: the conference should be recalled urgently as CAIRO II.This article discusses the prospects for world food shortages. It is argued that the 1994 Cairo International Conference on Population and Development evaded the issue of local demographic conditions and global food security. The authors urge a Cairo II conference on food security and carrying capacity that would include China, as a country which needs one-child families; Japan, as the largest provider of foreign aid; and the following groups: trapped communities, the agronomists, the green revolution people, and demographers. The conference should occur before the next planned conference in 2004. The important messages are that the percentage rate of increase in grain yields is seriously "slowing," and grain yields will need to double or triple in order to meet the needs of future population growth. Other countries besides China may need one-child families. Countries, such as the UK, that propose one-child families should also promote one-child families within their own boundaries. In order to assure global adoption of the one-child family norm, preparations need to be made to develop strategies that avoid the human rights abuses of China and that avoid the lack of concern for population control in places such as Rwanda. The UN must consider how much grain it can provide to trapped communities that are working to reduce population growth, to improve their economies, and to increase their exports. Cairo II must address the issue of sustainable life style among developed countries that is balanced with the needs of the South and the planet's resources. Trapped communities are ones whose rising agricultural population exceeds the carrying capacity of the local ecosystem. This may occur when the economy fails to develop sufficiently and migration is inadequate. Trapped communities are likely to be in sub-Saharan Africa and parts of South Asia.
Chemotherapy for Liver Cancer by Protracted Ambulatory Infusion
Authors: Robert D. Sullivan
Journal: JAMA (1965)

A method of treatment for cancer of the liver (primary and secondary) and the biliary tract, which consists of the protracted infusion of anticancer drugs through a plastic catheter inserted directly into the hepatic artery, was investigated. Long-term infusion was conducted for periods of weeks to months. A portable infusion apparatus was developed to permit ambulatory outpatient infusion treatment, rendering long-term infusion more practical. Eighty-one patients with neoplasms of the liver were accepted for treatment and 73 patients achieved an adequate trial of therapy. Objective response was noted in 43 patients. Survival was prolonged in patients with advanced metastatic liver cancer from primary tumors of the colorectum. Average survival was increased from the expected survival of 2.1 months to 9.4 months in this latter group. It was concluded that protracted hepatic artery infusion is of significant practical value in the management of patients with cancer of the liver.
611 DIFFERENT CHANGES OF PERIPHERAL BLOOD CD19CD5 COUNT AND TH1/TH2 CYTOKINES CONCENTRATION DURING THERAPY OF CHRONIC HEPATITIS C PATIENTS DEPENDING ON TREATMENT RESPONSE
Authors: V. Liakina, D. Speiciene, A. Siaurys, J. Jakutiene, B. Titova, A. Irnius, J. Valantinas
Journal: Journal of Hepatology (2008)
Safety of Long-Acting β-Agonists
Authors: Mats Jacob Lindberg
Journal: Annals of Internal Medicine (2006)

Letters7 November 2006Safety of Long-Acting β-AgonistsMats Jacob Lindberg, MD, MHAMats Jacob Lindberg, MD, MHAFrom Institute for Rational Pharmacotherapy, Copenhagen, Denmark.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-145-9-200611070-00018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR: The meta-analysis by Salpeter and colleagues (1) is interesting and important; however, I have 2 concerns. My first concern is about the trial inclusion in their primary analysis. I have found 2 trials that I think should have been included: Pauwels and colleagues' 1997 trial from the New England Journal of Medicine(2) and Woolcock and colleagues' 1996 trial from the American Journal of Respiratory and Critical Care Medicine(3). Why weren't these trials included in the primary analysis?My second concern is about Salpeter and colleagues' separate evaluation of trials in which more than 75% of participants were ...References1. Salpeter SR, Buckley NS, Ormiston TM, Salpeter EE. Meta-analysis: effect of long-acting beta-agonists on severe asthma exacerbations and asthma-related deaths. Ann Intern Med. 2006;144:904-12. [PMID: 16754916] LinkGoogle Scholar2. Pauwels RA, Löfdahl CG, Postma DS, Tattersfield AE, O'Byrne P, Barnes PJ, et al. Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. N Engl J Med. 1997;337:1405-11. [PMID: 9358137] CrossrefMedlineGoogle Scholar3. Woolcock A, Lundback B, Ringdal N, Jacques LA. Comparison of addition of salmeterol to inhaled steroids with doubling of the dose of inhaled steroids. Am J Respir Crit Care Med. 1996;153:1481-8. [PMID: 8630590] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Institute for Rational Pharmacotherapy, Copenhagen, Denmark.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoMeta-Analysis: Effect of Long-Acting β-Agonists on Severe Asthma Exacerbations and Asthma-Related Deaths Shelley R. Salpeter , Nicholas S. Buckley , Thomas M. Ormiston , and Edwin E. Salpeter Safety of Long-Acting β-Agonists Dermot Ryan Safety of Long-Acting β-Agonists Shelley R. Salpeter Safety of Long-Acting β-Agonists Graeme P. Currie Safety of Long-Acting β-Agonists Stuart W. Stoloff Safety of Long-Acting β-Agonists Harold S. Nelson and Paul M. Dorinsky Metrics 7 November 2006Volume 145, Issue 9Page: 706-707KeywordsConflicts of interestCorticosteroid therapyCritical careSafety ePublished: 7 November 2006 Issue Published: 7 November 2006 CopyrightCopyright © 2006 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
P4-08-03: Serum Autoantibodies to Breast Cancer Associated Antigens Reflect Tumor Biology: An Opportunity for Early Detection &amp; Prevention?
Authors: W Eiermann, L Jackson, A Murray, CJ Chapman, LJ Peek, P Widschwendter, J Allen, H Graham, JF Robertson
Journal: Cancer Research (2011)

Abstract Autoantibodies (AABs) are produced as an immune response to abnormal ('non-self') cancer antigens. Previous studies have reported that AABs can be measured in the blood long before cancers are presently diagnosed, e.g., up to 4 years before screening mammography identified breast cancers and up to 5 years before screening CT detected lung cancers. EarlyCDT™-Lung is currently available as an aid to early detection of lung cancer in high risk patients and measures a panel of seven AABs to general cancer antigens and also lung cancer (LC) specific antigens. These AABs have previously been reported to be associated with the two main types of LC i.e., non-small cell and small cell LC. This study looked at AABs to 4 general cancer antigens to evaluate whether their levels reflected different biology in primary breast tumors. Methods 770 patients presented with primary breast cancer to three centers (Nottingham, UK n=323; Munich, Germany n=320; Oklahoma, USA n=127); the median ages and ranges were 61 (26-82), 61 (20-88) &amp; 65 (54-84) years, respectively. All had serum samples taken post-diagnosis and pre-treatment. The tumors were well characterized for histological grade, estrogen receptor (ER), progesterone receptor (PgR) and HER2 status. Serum samples were tested for AABs to four generic cancer antigens(Ags) (p53, SOX2, NY-ESO-1 and Annexin1) originally included as part of Oncimmune's EarlyCDT™-Lung assay. The AABs were measured by ELISA on the Oncimmune platform, and the EarlyCDT™-Lung cutoffs were used to determine positivity. Results 131/770 (17%) of primary breast cancers showed elevated AAB levels to one or more of the limited panel of four generic antigens. Positivity for each AAB was correlated with histological grade, ER, PgR and HER2 status. The results, which were similar for each of the three centres, were combined, and the results are shown in Table 1 below. p53 AAB positive cancers tended to be hormone receptor negative and HER2 positive. NY-ESO-1 positive tumors were almost all higher grade with the majority hormone receptor and HER2 negative. SOX2 positive cancers tended to have a hormone sensitive phenotype (i.e., hormone receptor positive and HER2 negative). Annexin 1 positive cancers also tended to have a hormone sensitive phenotype as well as HER2 negative. The pattern was statistically different for the four AABs (p&amp;lt;0.001). The autoantibody profile for ER positive tumours was not statistically different from PgR positive tumors. Conclusions These data show that specific AABs measured in the serum reflected the biology of the breast cancers. Confirmation of this finding could, in the future, lead to using immuno-biomarkers such as these to guide early therapeutic intervention (e.g. prevention) in a targeted group of women. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-08-03.
Government's plans for foundation hospitals come under attack
Authors: Z. Kmietowicz
Journal: BMJ (2002)

NHS foundation hospitals could lead to a two tier health service, with hospitals competing for both patients and staff, critics warned this week.

Details of the proposed foundation hospitals, outlined in the Queen's speech, were unveiled in the House of Commons last week by the health secretary, Alan Milburn. He said there would be “no cap” on the number of hospitals that could become foundation trusts and that locally elected people would help run the hospitals, which would be free of government control.

But opponents of the scheme believe it could bring back competition into the health …
A 39-Year-Old Woman With Hypercholesterolemia
Authors: Murray A. Mittleman
Journal: JAMA (2006)

Ms T, a 39-year-old woman, has a total cholesterol level of 277 mg/dL (7.17 mmol/L) and well-controlled hypertension; her brother had a stroke in his 30s. She is primarily concerned with her mother's history of breast cancer, but she would like to know if she can take a dietary supplement or if she needs to take cholesterol-lowering medication, and if so, whether she will need to continue it as well as adhere to her diet for the rest of her life. Her estimated 10-year risk of developing coronary heart disease (CHD) is 1% to 2% using the Framingham Risk Score, but that may underestimate her true risk as an African American woman with a family history of CHD. Recommendations for her, her longer-term risk for CHD, and evidence for lipid-lowering therapies are discussed.
Single-Agent Pemetrexed or Sequential Pemetrexed/Gemcitabine as Front-Line Treatment of Advanced Non-small Cell Lung Cancer in Elderly Patients or Patients Ineligible for Platinum-Based Chemotherapy: A Multicenter, Randomized, Phase II Trial
Authors: Cesare Gridelli, Eckhard Kaukel, Vanessa Gregorc, Maria Rita Migliorino, Thomas R. Müller, Christian Manegold, Adolfo Favaretto, Andrea Martoni, Orazio Caffo, Alexander Schmittel, Antonio Rossi, Francesca Russo, Patrick Peterson, María Muñoz, Martin Reck
Journal: Journal of Thoracic Oncology (2007)
Rupture of an Infected Aortic Graft into Jejunum: Resection and Survival
Authors: Gordon Sproul
Journal: JAMA (1962)

IN ARTERIAL SURGERY there is no complication more feared or respected than infection and the resultant anastomotic disruption and hemorrhage that endangers life or limb. In situations that require multiple ligations, the surgeon must guard against complications that may result in the loss of a leg, or even the patient's life. In the past, various articles and editorials have emphasized the dangers of infection, and certainly arterial surgery is one field in which prophylactic antibiotics are indeed indicated. In recent years, some of the late complications of aortic grafting procedures have manifested themselves in gastrointestinal bleeding secondary either to aneurysmal breakdown of homografts or to suture line leaks of arterial prostheses. A rather nonaggressive attitude had been followed in the early experience with such cases. Several reports of resection and replacement of grafts under these conditions have made their way into the literature when the patient recovered; however, the majority
Persistent hyponatraemia complicating fibrosing alveolitis.
Authors: N J Snell, H L Coysh
Journal: Thorax (1978)

Two patients with fibrosing alveolitis, one associated with rheumatoid disease, the other cryptogenic, developed persistent hyponatraemia consistent with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH); this association has not previously been described. Case reportsPATIENT 1A previously healthy 70-year-old housewife pre- sented with dry cough and dyspnoea.She had finger clubbing, was dyspnoeic at rest, and had basal crackles.A chest radiograph showed bilateral reticulonodular shadowing.Spirometry showed a restrictive picture; transfer factor was very low at 3 55 ml/min/mm Hg (1 19 mmol min-' kPa-1).Pao2 at rest was 55 mm Hg (7 32 kPa), Paco, 40
Prevention of Sudden Cardiac Death by Dietary Pure ω-3 Polyunsaturated Fatty Acids in Dogs
Authors: George E. Billman, Jing X. Kang, Alexander Leaf
Journal: Circulation (1999)

Rat diets high in fish oil have been shown to be protective against ischemia-induced fatal ventricular arrhythmias. Increasing evidence suggests that this may also apply to humans. To confirm the evidence in animals, we tested a concentrate of the free fish-oil fatty acids and found them to be antiarrhythmic. In this study, we tested the pure free fatty acids of the 2 major dietary omega-3 polyunsaturated fatty acids in fish oil: cis-5,8,11,14, 17-eicosapentaenoic acid (C20:5omega-3) and cis-4,7,10,13,16, 19-docosahexaenoic acid (C22:6omega-3), and the parent omega-3 fatty acid in some vegetable oils, cis-9,12,15-alpha-linolenic acid (C18:3omega-3), administered intravenously on albumin or a phospholipid emulsion.The tests were performed in a dog model of cardiac sudden death. Dogs were prepared with a large anterior wall myocardial infarction produced surgically and an inflatable cuff placed around the left circumflex coronary artery. With the dogs running on a treadmill 1 month after the surgery, occlusion of the left circumflex artery regularly produced ventricular fibrillation in the control tests done 1 week before and after the test, with the omega-3 fatty acids administered intravenously as their pure free fatty acid. With infusion of the eicosapentaenoic acid, 5 of 7 dogs were protected from fatal ventricular arrhythmias (P<0.02). With docosahexaenoic acid, 6 of 8 dogs were protected, and with alpha-linolenic acid, 6 of 8 dogs were also protected (P<0.004 for each). The before and after control studies performed on the same animal all resulted in fatal ventricular arrhythmias, from which they were defibrillated.These results indicate that purified omega-3 fatty acids can prevent ischemia-induced ventricular fibrillation in this dog model of sudden cardiac death.
Extradural and Intrathoracic Lipoma Causing Spinal Cord Compression
Authors: Herbert C. Maier
Journal: JAMA (1962)

When a nonmalignant growth with rare features closely simulates a relatively common malignant neoplasm, proper therapy may unfortunately be delayed. If a benign tumor compressing the spinal cord is not promptly operated upon, irreversible neurological damage may ensue. This case of extradural and intrathoracic lipoma causing spinal cord compression in a child presented clinical and radiologic features most compatible with a diagnosis of neuroblastoma. Operation, however, revealed that the patient had a benign lipoma which could be excised by a 2-stage operation with resultant cure. To distinguish the erosion of ribs by benign tumors and vascular structures from the destruction of ribs by a malignant neoplasm is difficult; the pitfalls in differential radiologic diagnosis are discussed.