tbuckley/cabot-search huggingface dataset:
Lack of health insurance leads to 45 000 excess deaths in US
Authors: J. Lenzer
Journal: BMJ (2009)

Researchers at Harvard University report that lack of health insurance is taking a huge toll on US citizens and is associated with 45 000 excess deaths annually among those aged 18 to 64 years, even after controlling for factors such as smoking, obesity, race and ethnicity, income, and alcohol use.

The study, published on 17 September in the American Journal of Public Health, (www.ajph.org/) updates a 2002 report by the Institute of Medicine …
Dichotomous pattern of coronary atherosclerosis 1 to 9 years after transplantation: Insights from systematic intravascular ultrasound imaging
Authors: E.Murat Tuzcu, Anthony C. De Franco, Marlene Goormastic, Robert E. Hobbs, Gustavo Rincon, Corinne Bott-Silverman, Patrick McCarthy, Robert Stewart, Ellen Mayer, Steven E. Nissen
Journal: Journal of the American College of Cardiology (1996)
Wither the Platelet?
Authors: John W. Adamson
Journal: New England Journal of Medicine (1988)

THE number of circulating platelets in normal persons is maintained within a narrow range. The factors regulating the platelet count are poorly understood, however. Two thirds to three quarters of all platelets are in the peripheral circulation, but in dynamic equilibrium with a pool of platelets within the spleen. Extreme alterations in platelet number — either too few or too many — may be associated with bleeding, although the clinical manifestations of bleeding generally differ in the two instances. Because of its more predictable morbidity, thrombocytopenia has attracted considerable investigative interest, both in its mechanisms and in its treatment. Thrombocytopenia . . .
Abstract P6-04-19: Neutralizing antibody to human GP88 (progranulin) restores sensitivity to tamoxifen and inhibits breast tumor growth in mouse xenografts
Authors: G Serrero, J Dong, J Hayashi
Journal: Cancer Research (2012)

Abstract The 88 kDa glycoprotein GP88 (Progranulin, PCDGF, acrogranin) is the largest member of the granulin/epithelin family of growth modulators characterized by 7.5 cysteine-rich granulin/epithelin repeats. Our laboratory has demonstrated that GP88 represents an ideal therapeutic and diagnostic target in breast cancer. Our published studies have demonstrated that: 1) GP88 expression increases with tumorigenesis; 2) inhibition of GP88 expression by antisense transfection in MDA-MB-468 cells inhibited by 90% tumor formation in nude mice; 3) in ER+ breast cancer cells, GP88 stimulates proliferation and its overexpression confers estrogen independence and resistance to several anti-estrogens and aromatase inhibitor; 4) In Her-2 overexpressing breast tumors, GP88 stimulated Her-2 phosphorylation and conferred trastuzumab resistance; 5) GP88 is expressed in 80% invasive ductal carcinoma and 60% of ductal carcinoma whereas it is negative in lobular carcinoma, benign lesions and normal mammary epithelial cells; 6) pathological studies with 530 cases of ER+ invasive ductal carcinoma showed that GP88 tumor expression measured by immunohistochemistry (IHC) is a prognostic indicator of recurrence in early stage breast cancer patients; High GP88 tissue expression was associated with a 4-fold increase in risk of recurrence at 5 years; 7) GP88 is secreted and can be detected in the serum of breast cancer patients at an increased level when compared to healthy subjects. Based on these results, we developed a neutralizing anti-GP88 antibody AG1. AG1 was expressed in a high yield CHO cell line and formulated. AG1 inhibits GP88 biological effect (proliferation and migration) in a dose-dependent fashion in vitro. Here we will report the results of studies investigating the effect of AG1 on the tumor development of tamoxifen sensitive (MCF-7) and resistant (TamR) estrogen receptor positive breast cancer cells lines injected in nude mice. We show that AG1 alone (5mg/kg) inhibited tumor growth of MCF-7 cells injected into nude mice in a similar efficacy as tamoxifen. Interestingly, in tamoxifen resistant cells derived from MCF-7, the anti-GP88 antibody AG1 inhibited by more than 50% tumor formation of TamR cells in combination with tamoxifen, whereas tamoxifen only had no effect. These data suggest that inhibiting GP88 provides a novel and alternative therapeutic pathway for the restoration of tamoxifen sensitivity in ER+ breast cancer. This works is supported by grant 2R44CA124179 from the National Cancer Institute and 02–2010-010 from the Avon Foundation for Women. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-04-19.
A Rare Complication of a Ventriculoperitoneal Shunt Resolved by Colonoscopy
Authors: E. Pikoulis, N. Psallidas, P. Daskalakis, K. Kouzelis, A. Leppäniemi, P. Tsatsoulis
Journal: Endoscopy (2003)

In addition to the two most frequent complications of obstruction and infection, ventriculoperitoneal (VP) shunts have been associated with a pseudocyst, mesenteric pseudotumor, metastasis of cerebral tumors via the shunt, and protrusion of the distal catheter through the scrotum or vagina [1] [2]. Bowel perforation, especially of the colon, has been previously described in about 30 cases, usually in children [2].
Phthalate Excretion Pattern and Testicular Function: A Study of 881 Healthy Danish Men
Authors: Ulla Nordström Joensen, Hanne Frederiksen, Martin Blomberg Jensen, Mette Petri Lauritsen, Inge Ahlmann Olesen, Tina Harmer Lassen, Anna-Maria Andersson, Niels Jørgensen
Journal: Environmental Health Perspectives (2012)

Background: In animals, some phthalates impair male reproductive development and function. Epidemiological studies have reported inconsistent evidence of associations between phthalates and markers of human testicular function.Objectives: We aimed to provide estimates of the effects of phthalate exposure on reproductive hormone levels and semen quality in healthy men.Methods: A total of 881 men gave urine, serum, and semen samples. Serum levels of testosterone, estradiol (E2), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and inhibin-B; semen quality; and urinary concentrations of 14 phthalate metabolites, including metabolites of di(2-ethylhexyl) phthalate (DEHP) and diisononyl phthalate (DiNP), were assessed. The proportions of DEHP and DiNP excreted as their respective primary metabolites [mono(2-ethylhexyl) phthalate (MEHP) and mono-isononyl phthalate (MiNP)] were calculated and expressed as percentages (%MEHP and %MiNP, respectively).Results: The free androgen index was 15% lower [95% confidence interval (CI): –23, –8%] for men in the highest %MiNP quartile compared to the lowest quartile (p < 0.001) after adjusting for confounders, and 9% lower (95% CI: –16, –1%) in the highest %MEHP quartile (p = 0.02). %MEHP and %MiNP were negatively associated with the ratio of testosterone/LH and testosterone/FSH. %MEHP was negatively associated with total testosterone, free testosterone, and ratio of testosterone/E2. %MiNP was positively associated with SHBG. There was little evidence of associations between urinary phthalate metabolites or sums of phthalates with reproductive hormones or semen qualityConclusion: Our data suggest that both testosterone production and pituitary–hypothalamic feedback may be compromised in individuals excreting a high proportion of primary metabolites of long-chained phthalates relative to the proportion of secondary metabolites.
THE TREATMENT OF DEPRESSIVE STATES WITH G 22355 (IMIPRAMINE HYDROCHLORIDE)
Authors: ROLAND KUHN
Journal: American Journal of Psychiatry (1958)

Over a three-year period, more than 500 psychiatric patients of various diagnostic categories were treated with imipramine hydrochloride. It was demonstrated that the compound has potent antidepressant action. Best responses were obtained in cases of endogenous depression showing the typical symptoms of mental and motor retardation, fatigue, feeling of heaviness, hopelessness, guilt, and despair. The condition is furthermore characterized by the aggravation of symptoms in the morning with a tendency to improvement during the day. Treatment with imipramine hydrochloride resulted in full or social recovery in a high percentage of the patients. As a rule, the initial response was evident within 2 to 3 days, while in some cases 1 to 4 weeks of therapy were required. In view of the symptomatic nature of the action of imipramine hydrochloride, therapy must be maintained as long as the illness lasts. The side effects noted were relatively slight, and with the exception of one case of severe allergic exanthema necessitating discontinuance of treatment, no serious complications were encountered. In some cases of depression, particularly those associated with organic brain damage or schizophrenic psychosis, transitory states of agitation or exacerbation of the psychotic features were noted. These observations suggest the importance of a proper selection of the patients as to type and etiology of depression. While in a number of instances, neurotic, schizophrenic or other depressions were also benefited by the drug, particularly when used in combination with chlorpromazine, electroshock or psychotherapy, it is concluded that imipramine hydrochloride is primarily indicated and effective in the treatment of endogenous depression.
Genetically determined resistance to 3-methylcholanthrene-induced lymphoma is expressed at the level of bone marrow-derived cells.
Authors: S T Ishizaka, F Lilly
Journal: The Journal of Experimental Medicine (1987)

Reciprocal bone marrow transfers were performed between mouse strains sensitive or resistant to 3-methylcholanthrene-induced thymic lymphoma. Sensitivity and resistance are properties inherent in bone marrow, and cannot be altered by maturation of marrow in an environment of the opposite phenotype.
Nonobese population in a developing country has a high prevalence of nonalcoholic fatty liver and significant liver disease
Authors: Kausik Das, Kshaunish Das, Partha S. Mukherjee, Alip Ghosh, Sumantra Ghosh, Asit R. Mridha, Tapan Dhibar, Bhaskar Bhattacharya, Dilip Bhattacharya, Byomkesh Manna, Gopal K. Dhali, Amal Santra, Abhijit Chowdhury
Journal: Hepatology (2010)

There is a paucity of community-based epidemiological data on nonalcoholic fatty liver (NAFL) among nonaffluent populations in developing countries. Available studies are radiological and/or biochemical and lack histological assessment, limiting their strength. We conducted a prospective epidemiological study comprising a 1:3 subsample of all adult (&gt;18 years) inhabitants of a rural administrative unit of West Bengal, India. Subjects positive for hepatitis B virus and/or hepatitis C virus infection and consuming any amount of alcohol were excluded. Diagnosis of NAFL was by dual radiological screening protocol consisting of ultrasonographic and computed tomographic examination of the liver. Transient elastographic examination and liver biopsy were performed in a subset to identify significant liver disease. The risk factors of having NAFL were analyzed. A total of 1,911 individuals were analyzed, 7% of whom were overweight and 11% of whom had abdominal obesity. The prevalence of NAFL, NAFL with elevated alanine aminotransferase, and cryptogenic cirrhosis was 8.7%, 2.3%, and 0.2%, respectively. Seventy-five percent of NAFL subjects had a body mass index (BMI) &lt;25 kg/m2, and 54% were neither overweight nor had abdominal obesity. The subjects with the highest risk of having NAFL were those with a BMI &gt;25 kg/m2 (odds ratio 4.3, 95% confidence interval 1.6-11.5). Abdominal obesity, dysglycemia (fasting plasma glucose &gt;100 mg/dL or elevated homeostatic model assessment of insulin resistance), and higher income were the other risk factors. Even having a normal BMI (18.5-24.9 kg/m2) was associated with a 2-fold increased risk of NAFL versus those with a BMI &lt;18.5 kg/m2. Conclusion: There is a significant prevalence of NAFL and potentially significant liver disease, including cryptogenic cirrhosis, in this predominantly nonobese, nonaffluent population in a developing country. NAFL will be a major determinant of future liver disease burden in countries of the developing world. (Hepatology 2010)
LOCALIZATION OF RIBONUCLEIC ACID IN THE CYTOPLASM OF LIVER CELLS
Authors: Eugene L. Opie, George I. Lavin
Journal: The Journal of Experimental Medicine (1946)

The attempt has been made to determine the character of the basophile material that occurs normally in the cytoplasm of liver cells and accumulates in association with the hyperplasia of liver cells and of newly formed bile ducts when the azo dye butter yellow is administered to white rats. This substance in the normal liver cells, in the parenchymatous foci of basophile hyperplasia that are precursors of hepatomas, and in the hyperplastic basophile ducts that precede the cholangiomas produced by butter yellow has the characteristics of ribonucleic acid. It absorbs ultraviolet radiation of wave length 2537 A. It does not, like desoxyribonucleic acid, give the Feulgen reaction. It is removed from the cytoplasm by ribonuclease, and precipitation with lanthanum acetate protects it against the enzyme.
Consider Tanning Motivations and Counsel AccordinglyTANNING, SKIN CANCER, SEASONAL AFFECTIVE DISORDER
Authors: June K. Robinson
Journal: JAMA (2010)

Joel Hillhouse, PhD; Rob Turrisi, PhD; Jerod Stapleton, BS; June Robinson, MDObjective: To evaluate the robustness of an appearance-focused intervention to prevent skin cancer in individuals reporting seasonal affective disorder (SAD) symptoms and pathological tanning motives.Design: Randomized, controlled clinical trial.Setting: College campus.Participants: Four hundred thirty adult female indoor tanners (200 in the intervention group and 230 control participants).Intervention: A booklet discussing the history of tanning, current tanning norms, UV radiation's effects on skin, recommendations for indoor tanning use focusing on abstinence and harm reduction recommendations, and information on healthier, appearance-enhancing alternatives to tanning.Main Outcome Measures: Self-reported attitudes, intentions, and tanning behaviors; pathological tanning motives assessed by a questionnaire developed for this study; and SAD symptoms assessed by the Seasonal Pattern Assessment Questionnaire.Results: Two of the 4 pathological tanning scales, opiatelike reactions to tanning and dissatisfaction with natural skin tone, were significant moderators demonstrating stronger treatment effects for individuals scoring higher on these scales. Treatment effects were equivalently positive (ie, no significant moderator effects) for all levels of SAD symptoms and all levels of the other 2 pathological tanning motive scales (ie, perceiving tanning as a problem and tolerance to the effects of tanning).Conclusions: The appearance-focused skin cancer prevention intervention is robust enough to reduce indoor tanning among tanners who exhibit SAD symptoms or pathological tanning motives. Tailored interventions may address individuals' motivations for tanning and their relation to maladaptive behavior, such as dissatisfaction with appearance or the need for relaxation because of anxiety.
Management of High-Risk Pregnancy
Authors: Alex S. Tulsky
Journal: JAMA (1986)

Although I frequently pick up a new book with a jaundiced eye and an almost combative attitude—a "so what" approach—I happily report that not to be true in the case of the second edition of Queenan's<i>Management of High-Risk Pregnancy</i>. From the vantage point of many years and the perusal of many books in this specialty, it is refreshing to see a multiauthored volume so well organized, so simply written with a minimum of verbiage, and so uniform in its presentation. I can see the editor's firm hand in the demands made on the contributors, familiar from his writings in<i>Contemporary Obstetrics and Gynecology</i>. Each presentation is made particularly clear, where possible, by the interesting method of an appropriate case report followed by editorial comment. No complication of pregnancy, labor, delivery, or the postpartum state seems to have been omitted, and the authors are recognized authorities in their various fields.
Outcomes of Endovascular Repair of Ruptured Descending Thoracic Aortic Aneurysms
Authors: Frederik H.W. Jonker, Hence J.M. Verhagen, Peter H. Lin, Robin H. Heijmen, Santi Trimarchi, W. Anthony Lee, Frans L. Moll, Husam Athamneh, Bart E. Muhs
Journal: Circulation (2010)

Thoracic endovascular aortic repair offers a less invasive approach for the treatment of ruptured descending thoracic aortic aneurysms (rDTAA). Due to the low incidence of this life-threatening condition, little is known about the outcomes of endovascular repair of rDTAA and the factors that affect these outcomes.We retrospectively investigated the outcomes of 87 patients who underwent thoracic endovascular aortic repair for rDTAA at 7 referral centers between 2002 and 2009. The mean age was 69.8+/-12 years and 69.0% of the patients were men. Hypovolemic shock was present in 21.8% of patients, and 40.2% were hemodynamically unstable. The 30-day mortality rate was 18.4%, and hypovolemic shock (odds ratio 4.75; 95% confidence interval, 1.37 to 16.5; P=0.014) and hemothorax at admission (odds ratio 6.65; 95% confidence interval, 1.64 to 27.1; P=0.008) were associated with increased 30-day mortality after adjusting for age. Stroke and paraplegia occurred each in 8.0%, and endoleak was diagnosed in 18.4% of patients within the first 30 days after thoracic endovascular aortic repair. Four additional patients died as a result of procedure-related complications during a median follow-up of 13 months; the estimated aneurysm-related mortality at 4 years was 25.4%.Endovascular repair of rDTAA is associated with encouraging results. The endovascular approach was associated with considerable rates of neurological complications and procedure-related complications such as endoleak.
Exposure to measles in utero and Crohn's disease: Danish register study
Authors: L. L. W Nielsen, N. M. Nielsen, M. Melbye, M. Sodermann, M. Jacobsen, P. Aaby
Journal: BMJ (1998)

P = 0.017) and was highest for infants found supine.Unconditional analysis showed that quilt use attenuated the protective effect of sleeping supine compared with sleeping on the side (common odds ratio test, P = 0.03).
Improvement of maternal and newborn health through midwifery
Authors: Petra ten Hoope-Bender, Luc de Bernis, James Campbell, Soo Downe, Vincent Fauveau, Helga Fogstad, Caroline S E Homer, Holly Powell Kennedy, Zoe Matthews, Alison McFadden, Mary J Renfrew, Wim Van Lerberghe
Journal: The Lancet (2014)
Abstract 1531: BCR-Abl tyrosine kinase inhibitor Nilotinib (Tasigna®) reverses ABCB1/Pgp- and ABCG2/BCRP-mediated multidrug resistance
Authors: Amit K. Tiwari, Kamlesh Sodani, Sirong Wang, Ye-Hong Kuang, Wen Deng, Xiang Chen, Kevin Chen, Charles R. Ashby, Zhe-Sheng Chen
Journal: Cancer Research (2010)

Abstract Over-expression of ABC transporters are involved in the extrusion of therapeutic drugs, leading to MDR, which can eventually produce cancer chemotherapy failure. Previously, it was shown that specific TKIs could modulate several human multidrug resistance (MDR) ATP-binding cassette (ABC) proteins. Recently discovered second generation, BCR-Abl tyrosine kinase inhibitor (TKI), Nilotinib was developed to surmount resistance or intolerance to imatinib in patients with Philadelphia positive chronic myelogenous leukemia. Here, we report for the first time that nilotinib not only potentiates the cytotoxicity of widely used therapeutic substrates of ABCB1, such as colchicine, vincristine, and paclitaxel, but also that of ABCG2 substrates such as mitoxantrone and doxorubicin. Nilotinib also significantly enhances the intracellular accumulation of methotrexate (MTX) in cells transfected with ABCG2. Similarly, nilotinib significantly increases the accumulation of paclitaxel in cell lines overexpressing ABCB1. Furthermore, nilotinib produces a concentration-dependent inhibition of the ABCG2-mediated transport of MTX, as well as E217βG a physiological substrate of ABCG2. Uptake studies in membrane vesicles over-expressing ABCG2 have indicated that nilotinib inhibits ABCG2 similar to other established TKIs as well as fumitremorgin C. In addition, the kinetic analysis demonstrated that nilotinib is a potent competitive inhibitor of MTX transport by ABCG2 with a Ki value of 0.69+/-0.083 μM. To sum it up, our results indicate that nilotinib could reverse ABCB1- and ABCG2-mediated MDR by blocking the efflux function of these transporters. These findings may be useful in clinical practice for cancer combination therapy with nilotinib and may be vital to the design of present and future clinical trials with nilotinib, elucidating potential pharmacokinetic interactions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1531.
Abstract 2109: Tumor progression locus 2 (Tpl2) knockout mice have a dysregulation in COX-2 signaling in two-stage skin carcinogenesis
Authors: Kathleen L. DeCicco-Skinner, Sabrina Nolan, Taylor Dempsey, Erika Trovato, Jonathan Weist
Journal: Cancer Research (2011)

Abstract Skin cancer is the most common form of cancer in the United States, with an estimated two million cases diagnosed annually. Inflammation is believed to be a critical component in skin cancer progression, and therefore understanding genes controlling inflammation is beneficial. MAP3K8 (Tpl2) is a protein kinase in the MAP Kinase signal transduction cascade. Previous research using a two-stage skin carcinogenesis model has revealed that Tpl2 -/- mice have significantly higher tumor incidence and inflammation than wild-type (WT) controls. Mechanistically, dysregulation in NF-κB signaling is a major contributor to the high degree of inflammation and tumorigenesis found in the Tpl2 -/- mice. Knockout animals have heightened NF-κB reporter activity, increased NF-κB dependent edema, and increased NF-κB nuclear localization. This study investigates how cyclooxygenase-2 (COX-2), an NF-κB regulated gene known to contribute to skin carcinogenesis, and COX-2 downstream factors might play a role in inflammation-mediated skin carcinogenesis in Tpl2 -/- mice. Keratinocytes from newborn WT or Tpl2 -/- mice were treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) for varying times over 24 hours. Western analysis revealed significant differences in COX-2 and COX-2 dependent prostanoids and prostanoid receptors. Additionally, in vivo experiments confirmed that COX-2 and COX-2 downstream factors were elevated in TPA-treated Tpl2 -/- skin, as well as in papillomas and squamous cell carcinomas from Tpl2-/- mice. These experiments illustrate that COX-2 induction in the absence of Tpl2 may be responsible for the increased tumorigenesis found in Tpl2-/- mice. 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 2109. doi:10.1158/1538-7445.AM2011-2109