tbuckley/cabot-search huggingface dataset:
Colorado Tick Fever Simulating Acute Myocardial Infarction
Authors: Hugh I. Schade
Journal: JAMA (1972)

<h3>To the Editor.—</h3> A report by W. J. Hierholzer and D. W. Barry ("Colorado Tick Fever Pericarditis," 217:825, 1971) has prompted us to report a case of Colorado tick fever (CTF) in which disease manifestations referable to the heart were prominent. <h3>Report of a Case.—</h3> A 49-year-old white, male, truck driver was admitted on June 4, 1965, to a hospital in Santa Clara County, Calif, with the complaint of chest pain for the past week. He first noted pain and a sense of heavy substernal pressure after strenuous exertion while vacationing in Colorado at an elevation of 9,000 feet. On returning home, he developed chills, recurrent fever, profuse diaphoresis, and as the sensation of substernal pressure persisted, he sought medical attention. Results of examination revealed the following: temperature, 38.5 C (101.4 F); blood pressure, 124/78 mm Hg; respirations, 25; pulse rate, 68 beats per minute and regular; no cardiac murmurs;
Abstract 5490: In vitro and in vivo evaluation of LipoFufol, a new triple stealth liposomal formulation of modulated 5-FU: impact on efficacy and toxicity
Authors: Joseph Ciccolini, Raphaelle Fanciullino, Sarah Giacometti, Joël Vacus, Caroline Mignard, Zina Koob, Athanassios Iliadis
Journal: Cancer Research (2010)

Abstract 5-FU is a mainstay for treating various solid tumors in adults, including digestive cancers. At bedside, treatment efficacy is often hampered by drug resistance and severe toxicities, mostly due to impaired liver detoxification related to dihydropyrimidine dehydrogenase (DPD) deficiency. We have developed a stealth liposomal formulation of 5-FU combined with two modulators (2′-deoxy-inosine and folinic acid) designed to exhibit higher antiproliferative properties while being less affected by liver uptake and subsequent DPD-related dysregulations. Lipofufol is a 100 nm diameter, pegylated liposome that proved to be stable at room temperature for at least 4 weeks. When used in vitro in the highly 5-FU-resistant human colorectal cell line SW620, mean IC50 values for standard 5-FU, 5-FU + folinic acid and LipoFufol were 29 µM, 14µM and 2µM respectively, indicative of a greater antiproliferative effect. Pharmacokinetics study was performed in rodents after I.V. administration and showed that liposomal 5-FU clearance was strongly reduced by 62% (e.g. 0.087 l/h VS. 0.231 l/h), as compared with standard 5-FU. Toxicity study was undertaken to check whether Lipofufol could be less toxic in DPD-deficient individuals, and confirmed that milder (e.g., neutrophils count: −75% VS. −96%) and shorter (e.g., 6 VS. 11 days) neutropenia was observed in DPD-deficient rats treated with liposomal 5-FU, as compared with deficient animals exposed to standard 5-FU. Tolerance studies and search for MTD were further performed in tumor-bearing mice and showed that LipoFufol could be administered safely up to 20 mg/kg I.V. on a 3QW basis for 3 consecutive weeks. In mice bearing LS174t human colorectal orthotopic xenografts, longer survival was achieved in animals treated with 20 mg/kg Lipofufol, as compared with animals treated with 80 mg/kg of standard 5-FU (e.g., 80% VS. 40% survival at 3 weeks). Overall, our data show that Lipofufol exhibits a greater anticancer efficacy both in vitro and in vivo, including in highly resistant models, with an optimized and safer pharmacokinetics profile skipping, at least in part, the DPD deficiency issue. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 5490.
Reducing the “Risk” of Chemoprevention: Defining and Targeting High Risk—2005 AACR Cancer Research and Prevention Foundation Award Lecture
Authors: Scott M. Lippman, J. Jack Lee
Journal: Cancer Research (2006)

Two large-scale, phase III cancer prevention trials, the Breast Cancer Prevention Trial (BCPT) of tamoxifen and Prostate Cancer Prevention Trial (PCPT) of finasteride, concluded with strikingly positive and simultaneously problematic results: reduced cancer risks but a major adverse finding with each agent that prevented its widespread use in the community. For most moderate-risk people, such as those studied in the BCPT and PCPT, the benefit of reduced breast or prostate cancer does not outweigh the major risk of tamoxifen (endometrial cancer in the BCPT) or apparent risk of finasteride (high-grade prostate cancer in the PCPT). Promising interventions with biologically active substances are likely to have adverse, perhaps unforeseen effects, especially with long-term preventive use. Acceptance of such agents will depend heavily on the level of cancer risk of the target population. This article outlines research in molecularly identified high-risk oral intraepithelial neoplasia that creates the clinical opportunity for optimizing the risk-benefit ratio of agents to prevent oral cancer. Two other major research efforts focused on improving preventive agent risk-benefit ratios are molecular-targeted research designed to target away from known adverse signaling pathways and multidisciplinary research based on the PCPT that will develop comprehensive models of prostate cancer risk (especially of aggressive prostate cancer) and pharmacoecogenetic models for identifying high-risk men most likely to benefit from (and not be harmed by) finasteride or similar (5alpha-reductase inhibiting) agents. Defining and targeting high-risk populations, developing molecular-targeted approaches, and developing accurate pharmacoecogenetic models promise to reduce the risk of chemoprevention and ultimately to reduce the risk and burden of major cancers.
Plasma zinc in psoriatic in-patients treated with local zinc applications
Authors: M. E. IMOGEN MORGAN, MARTINE A. HUGHES, E. M. MCMILLAN, I. KING, RONA M. MACKIE
Journal: British Journal of Dermatology (1980)

Zinc is a major component of many local skin applications. An investigation into its systemic absorption in thirty-one psoriatic hospital in-patients is reported. Plasma zinc, copper and whole blood delta-aminolaevulinic acid dehydratase were followed before and during in-patient treatment over 14 days. No significant alteration in these parameters was detected. Significantly reduced plasma zinc levels were found in the patients compared to a matched control population.
Case of Meningeal Apoplexy
Authors: G. F. Hodgson
Journal: BMJ (1875)

new flap like a watch-glass.The skin required for the formation of this eyelid was two inches in length and one inch in breadth, which I took from the forearm.To test the principles above indicated, I divided my flap into three portions.The first I removed, along with the cellular tissue, as close to the dermis as compatible with the in-
Abstract 4916: Systems biology analysis of subpopulation-based heterogeneity for cellular radiosensitivity modeling
Authors: Yoonseok Kam, Katarzyna A. Rejniak, Haiyan Zhao, Javier F. Torres-Roca
Journal: Cancer Research (2011)

Abstract Intrinsic cellular radiosensitivity is a key parameter used in radiotherapy modeling. Our previous studies showed that a cellular model based on the in vitro clonogenic assay measuring survival fraction at 2Gy (SF2) accurately predicts tumor response in patients treated with radiotherapy. However, SF2 as determined from a heterogeneous cell population represents its averaged sensitivity, whilst we have shown, using live cell imaging, that cultured tumor cell populations include colonies of varying sizes, cell numbers and growth rates. In order to link this subpopulation-based heterogeneity to the parental cell line radiosensitivity, and to build an integrative predicting model, we designed a novel systems biology approach that combines SF2 clonogenic assay experimentation, high-content screening and image analysis together with a quantitative bio-mathematical study. We integrated a 96-well plate-based SF2 assay with a semi-automated image analysis using CellProfilerTM, and measured morphological parameters including SF2, colony tightness index (colony density), and colony growth rate. We have also developed new algorithms to complement those implemented in CellProfilerTM to identify some highly dispersed colonies. As a preliminary trial, we analyzed five non-small cell lung cancer (NSCLC) cell lines characterized by different levels of radiosensitivity in vitro. We observed several common phenotypic shifts after irradiation, such as reduction in growth rate and cell density. However, the response patterns for each subpopulation was highly heterogenous across cell lines. Interestingly, the variability in morphological response was better correlated to radiosensitivity than the average colony density. In order to further assess subpopulation heterogeneity, we isolated 15 random sub-clones from H460 cells and found significant intrinsic SF2 heterogeneity. In addition to morphology, we examined the intrinsic variability in the expression level of several molecular biomarkers including STAT1, a molecular maker in our prediction model, and CD44, a cancer stem cell marker proposed to be related with radioresistance. Both markers showed significant variability, which was negatively correlated with the colony density. In conclusion, we propose a novel systems-based approach that integrates high content phenotypic information at a single cell level to study tumor-intrinsic heterogeneity and its contribution to clinically-relevant radioresistance. 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 4916. doi:10.1158/1538-7445.AM2011-4916
Abstract B59: The dual effect of therapy-induced IL-1β expression on tumor progression: Role of tumor-associated macrophages
Authors: Tali Voloshin, Dror Alishekevitz, Valeria Miller, Lika Isakov, Rotem Bril, Moran Benhar, Roney Apte, Yuval Shaked
Journal: Cancer Research (2013)

Abstract A major obstacle in clinical oncology is that tumors eventually acquire resistance to therapy. The mechanism by which resistance arises is usually associated with changes made in tumor cells in response to the therapy, however, little is known about the effect of the host which may also contribute to tumor resistance. Previous studies from our lab suggest that the induction of host cellular and molecular events following therapy may promote tumor re-growth, angiogenesis and metastasis. In this study we uncovered the possible role IL-1β - a proinflammatory cytokine - has on the growth of primary tumor and its impact on metastasis following paclitaxel (PTX) chemotherapy. We found that plasma and spleen from PTX-treated mice exhibited elevated expression of IL-1β. Furthermore, plasma from PTX-treated mice induced tumor cell invasion, an effect which was abrogated in plasma from mice treated with PTX and Anakinra, an IL-1 receptor antagonist. Consequently, mice inoculated with Lewis lung carcinoma (LLC) cells pre-exposed to plasma from mice treated with the combined therapy survived longer than mice inoculated with tumor cells pre-exposed to plasma from mice treated with PTX or Anakinra monotherapy. We next determined whether treatment efficacy of PTX is enhanced by the combination of PTX and Anakinra using 4T1 metastatic breast cancer model in mice. Tumors treated with the combined therapy were significantly smaller than tumors treated with PTX or Anakinra monotherapy. Surprisingly, although the primary tumors were smaller, such mice succumb to metastasis earlier than mice in any of the other treated groups. Furthermore, an increased number of M2 macrophages colonizing 4T1 primary tumors treated with the combined therapy was observed when compared to their number in PTX treated tumors, indicating a possible pro-metastatic role of M2 macrophages in post treatment IL-1β deprived microenvironment. Parallel results were observed when LLC bearing IL-1β deficient mice, were treated with PTX. Taken together, these findings demonstrate that although treatment outcome is enhanced following the blockade of host-induced IL1β at the primary tumor level, at the metastatic level it may serve as a double-edge sward and can lead to metastatic spread. Citation Format: Tali Voloshin, Dror Alishekevitz, Valeria Miller, Lika Isakov, Rotem Bril, Moran Benhar, Roney Apte, Yuval Shaked. The dual effect of therapy-induced IL-1β expression on tumor progression: Role of tumor-associated macrophages. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B59.
Multiple Innate Inflammatory Responses Induced after Systemic Adenovirus Vector Delivery Depend on a Functional Complement System
Authors: Anne Kiang, Zachary C. Hartman, Ruth S. Everett, Delila Serra, Haixiang Jiang, Michael M. Frank, Andrea Amalfitano
Journal: Molecular Therapy (2006)

Excessive complement activation can result in extreme tissue damage and systemic inflammatory responses, similar to innate immune responses rapidly elicited after systemic adenovirus (Ad) injections. To determine if Ad interactions with the complement system impact upon Ad-induced innate immune responses, we injected Ad into complement-deficient, C3-knockout mice (C3-KO) or wild-type mice (WT) and quantitatively compared multiple anti-Ad innate immune responses in both strains of mice. In Ad-treated WT mice, we noted rapid increases in plasma KC levels (1 h post injection), followed by increases in IL-6, IFN-γ, RANTES, IL-12(p40), IL-5, G-CSF, and GM-CSF and subsequently thrombocytopenia. Conversely, in Ad-treated C3-KO mice, many of these inflammatory responses were significantly blunted, including the avoidance of Ad-induced thrombocytopenia. Global liver transcriptome responses in Ad-treated WT mice were assessed by RT-PCR-validated gene array analysis and were found to be also significantly affected by the lack of complement activity in Ad-treated C3-KO mice. Finally, our results confirmed the ability of high dose Ads to transduce hepatocytes despite a lack of complement activity. In summary, Ad interactions with the mammalian complement system are significant and likely initiate and/or exacerbate many of the inflammatory responses noted after systemic Ad injections.
Acute Primary HIV Infection
Authors: Thomas C. Quinn
Journal: JAMA (1997)

<h3>CASE PRESENTATIONS</h3><h3>Patient 1</h3> A 31-year-old bisexual man presented to the Johns Hopkins Hospital emergency department complaining of progressive headaches, confusion, myalgia, vivid nightmares, and diarrhea. For many years he had traveled extensively throughout sub-Saharan Africa and had recently spent 2 years in Madagascar. He had returned to the United States 1 month before admission. Once home, he developed diffuse myalgia and malaise. Stool analysis showed hookworm and<i>Entamoeba histolytica</i>, and he was treated with mebendazole and metronidazole 1 week before admission. During that week, he developed flulike symptoms of fever, chills, cough, and persistent diarrhea. Three days before admission, he developed a stiff neck, headaches, confusion, and vivid nightmares. His medical history included an inguinal hernia repair 12 years before admission and hepatitis A infection 7 years before admission. For the past 2 years, he had taken prophylactic chloroquine against malaria. Within the past 6 months, he had been
Lives saved by breast screening outnumber cases of overdiagnosis, review says
Authors: N. Hawkes
Journal: BMJ (2012)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Lives saved by breast screening outnumber cases of overdiagnosis, review says Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Detachable Snare Versus Epinephrine Injection in the Prevention of Postpolypectomy Bleeding: a Randomized and Controlled Study
Authors: P. Di Giorgio, L. De Luca, G. Calcagno, G. Rivellini, M. Mandato, B. De Luca
Journal: Endoscopy (2004)

Background and Study Aims: Several endoscopic techniques have been developed to prevent bleeding after the removal of large pedunculated polyps. Patients and Methods: From January 1995 to December 2002, 488 consecutive patients with pedunculated colorectal polyps, the heads of which were larger than 10 mm in diameter, were randomly assigned to three groups. In group A (163 patients), detachable snares were placed at the base of the stalk and standard snares were then used for polypectomy. In group B (161 patients), the polyp stalk was injected with a 0.01 % epinephrine solution before conventional snare polypectomy. Group C (a control group including 164 patients) underwent conventional snare polypectomy without preventive measures. Early (< 24 h) and late (> 24 h - 30 days) bleeding complications were assessed. Each group was divided into two subgroups relative to the polyp size (polyps 1.0 - 1.9 cm and polyps ≥ 2 cm). Results: Overall bleeding complications occurred after 4.3 % of the polypectomies. Bleeding was successfully controlled in all patients, and no blood transfusions were required. There were three cases of bleeding in group A (1.8 %), five in group B (3.1 %), and 13 in group C (7.9 %). Early bleeding was more frequent than late bleeding (15 vs. six patients). In polyps ≥ 2 cm (207 patients), postpolypectomy bleeding occurred in 14 patients (6.7 %): two (2.7 %) in the detachable snare group, two (2.9 %) in the epinephrine injection group, and 10 (15.1 %) in the control group. Conclusions: These results show that polypectomy of large pedunculated polyps is associated with a higher incidence of bleeding. Particularly in polyps larger than 2 cm, preventive measures can significantly reduce bleeding complications after polypectomy. This can be achieved with similar efficacy either by placing Endoloops or by injecting epinephrine.
H-2 I-region encoded targets in allograft rejection.
Authors: J E Gose, F H Bach
Journal: The Journal of Experimental Medicine (1979)

Fresh thyroids transplanted to I-region disparate recipients are, in most cases, rejected; in some instances fresh thyroids undergo periods of crisis followed by functional recovery. Cultured thyroids that are taken from donor animals pretreated with lymphocytotoxic drugs, gamma radiation and cultured for 10 d in vitro are not rejected by any normal allogenic recipient. If the recipient is sensitized with lymphoid cells syngeneic with an I-region disparate cultured thyroid donor, the cultured thyroid is rejected if I-A-subregion differences are included. We interpret these data to indicate that there exist I-region encoded perenchymal cell target determinants which are not, by themselves, immunogenic.
Latex-Induced Asthma Among Health Care Workers
Authors: Rebecca Voelker
Journal: JAMA (1995)

IN A NEW study, researchers in Belgium have shown that the prevalence rate among health care personnel of occupational asthma from latex exposure may be higher than 2%. Even though previous studies have reported that 8% to 17% of the health care workforce are sensitive to latex, data on the prevalence of asthma resulting from latex exposure are lacking. The researchers in Belgium studied 273 nurses, laboratory technologists, and cleaning staff working in a primary care hospital. In the first phase of the study, 13 (4.7%) displayed latex sensitivity during skin-prick testing. In the second phase using spirometry, 12 who were sensitive to skin pricks also showed bronchial hyperresponsiveness to histamine. After specific latex inhalation challenges, seven had asthmatic reactions, for a prevalence rate of 2.5%. "Widespread use of latex gloves should be considered a significant respiratory health hazard among hospital personnel. Every effort should therefore be made to reduce
Factors associated with mortality in Scottish patients receiving methadone in primary care: retrospective cohort study
Authors: C McCowan, B Kidd, T Fahey
Journal: BMJ (2009)

<b>Objective</b> To assess predictors of mortality in a population of people prescribed methadone. <b>Design</b> Retrospective cohort study. <b>Setting</b> Geographically defined population in Tayside, Scotland. <b>Participants</b> 2378 people prescribed and dispensed liquid methadone between January 1993 and February 2004. <b>Main outcome measures</b> All cause mortality (primary outcome) and drug dependent cause specific mortality (secondary outcome) by means of Cox proportional hazards models during 12 years of follow-up. <b>Results</b> Overall, 181 (8%) people died. Overuse of methadone (adjusted hazard ratio 1.67, 95% confidence interval 1.05 to 2.67), history of psychiatric admission (2.47, 1.67 to 3.66), and increasing comorbidity measured as Charlson index ≥3 (1.20, 1.15 to 1.26) were all associated with an increase in all cause mortality. Longer duration of use (adjusted hazard ratio 0.95, 0.94 to 0.96), history of having urine tested (0.33, 0.22 to 0.49), and increasing time since last filled prescription were protective in relation to all cause mortality. Drug dependence was identified as the principal cause of death in 60 (33%) people. History of psychiatric admission was significantly associated with drug dependent death (adjusted hazard ratio 2.41, 1.25 to 4.64), as was history of prescription of benzodiazepines (4.35, 1.32 to 14.30). <b>Conclusions</b> Important elements of care in provision of methadone maintenance treatment are likely to influence, or be a marker for, a person's risk of death.
New FDA Web Site for Health Care Professionals
Authors: Stuart L. Nightingale
Journal: JAMA (1998)

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