tbuckley/cabot-search huggingface dataset:
Physician Preferences and Knowledge Gaps Regarding the Care of Childhood Cancer Survivors: A Mailed Survey of Pediatric Oncologists
Authors: Tara O. Henderson, Fay J. Hlubocky, Kristen E. Wroblewski, Lisa Diller, Christopher K. Daugherty
Journal: Journal of Clinical Oncology (2009)

PURPOSE Little is known about physicians' attitudes and knowledge regarding the health care needs of childhood cancer survivors (CCS). We sought to obtain pediatric cancer physicians' self-reported attitudes and knowledge regarding this population. METHODS A mailed survey was sent to 1,159 pediatric oncologists in the United States. Results A total of 655 surveys were returned (ie, 57% response rate). Median age of respondents was 47 years (range, 31 to 82 years); 57% were men. Respondents practiced for a median 14 years (range, 1 to 50 years) and reported seeing a median of 21 patients per week (range, 0 to 250 patients per week). When comfort levels in caring for CCS were described (ie, 1 = very uncomfortable; 7 = very comfortable), respondents were most comfortable with survivors < or = 21 years (mean +/- standard deviation, 6.2 +/- 1.3 level), were less comfortable (5.0 +/- 1.5 level) with those older than 21 years but less than 30 years old, and were uncomfortable with CCS > or = 30 years (2.9 +/- 1.7 level). In response to a clinical vignette of a 29-year-old woman treated with mantle radiation for Hodgkin's lymphoma at 16 years of age, and on the basis of available guidelines, 34% of respondents did not appropriately recommend yearly breast cancer surveillance; 43% of respondents did not appropriately recommend cardiac surveillance; and 24% of respondents did not appropriately recommend yearly thyroid surveillance. Those with greater self-reported familiarity with available long-term follow-up (LTFU) guidelines (odds ratio [OR], 1.33; 95% CI, 1.15 to 1.54) and with receipt of training in the care of CCS (OR, 1.73; 95% CI, 1.18 to 2.52) were more likely to have answered all three questions correctly. CONCLUSION Pediatric oncologists express a range of preferences with regard to LTFU of CCS. Many appear unfamiliar with LTFU surveillance guidelines.
F<scp>c</scp>RECEPTOR BIOLOGY
Authors: Marc Daëron
Journal: Annual Review of Immunology (1997)

This review deals with membrane Fc receptors (FcR) of the immunoglobulin superfamily. It is focused on the mechanisms by which FcR trigger and regulate biological responses of cells on which they are expressed. FcR deliver signals when they are aggregated at the cell surface. The aggregation of FcR having immunoreceptor tyrosine-based activation motifs (ITAMs) activates sequentially src family tyrosine kinases and syk family tyrosine kinases that connect transduced signals to common activation pathways shared with other receptors. FcR with ITAMs elicit cell activation, endocytosis, and phagocytosis. The nature of responses depends primarily on the cell type. The aggregation of FcR without ITAM does not trigger cell activation. Most of these FcR internalize their ligands, which can be endocytosed, phagocytosed, or transcytosed. The fate of internalized receptor-ligand complexes depends on defined sequences in the intracytoplasmic domain of the receptors. The coaggregation of different FcR results in positive or negative cooperation. Some FcR without ITAM use FcR with ITAM as signal transduction subunits. The coaggregation of antigen receptors or of FcR having ITAMs with FcR having immunoreceptor tyrosine-based inhibition motifs (ITIMs) negatively regulates cell activation. FcR therefore appear as the subunits of multichain receptors whose constitution is not predetermined and which deliver adaptative messages as a function of the environment.
TCT-573 Quantitative Chemical Analysis and Antimicrobial Activity of a Novel Triple-Antimicrobial-Bonded Graft for Preventing Perioperative Aortic Infection
Authors: Ibrahim Aboshady, Issam Raad, Deborah Vela, Kamal G. Khalil, L. Maximilian Buja
Journal: Journal of the American College of Cardiology (2014)
Transforming growth factor-beta induces senescence in hepatocellular carcinoma cells and inhibits tumor growth
Authors: Serif Senturk, Mine Mumcuoglu, Ozge Gursoy-Yuzugullu, Burcu Cingoz, Kamil Can Akcali, Mehmet Ozturk
Journal: Hepatology (2010)

Abstract Senescence induction could be used as an effective treatment for hepatocellular carcinoma (HCC). However, major senescence inducers (p53 and p16Ink4a) are frequently inactivated in these cancers. We tested whether transforming growth factor-β (TGF-β) could serve as a potential senescence inducer in HCC. First, we screened for HCC cell lines with intact TGF-β signaling that leads to small mothers against decapentaplegic (Smad)-targeted gene activation. Five cell lines met this condition, and all of them displayed a strong senescence response to TGF-β1 (1-5 ng/mL) treatment. Upon treatment, c-myc was down-regulated, p21Cip1 and p15Ink4b were up-regulated, and cells were arrested at G1. The expression of p16Ink4a was not induced, and the senescence response was independent of p53 status. A short exposure of less than 1 minute was sufficient for a robust senescence response. Forced expression of p21Cip1 and p15Ink4b recapitulated TGF-β1 effects. Senescence response was associated with reduced nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) induction and intracellular reactive oxygen species (ROS) accumulation. The treatment of cells with the ROS scavenger N -acetyl-L-cysteine, or silencing of the NOX4 gene, rescued p21Cip1 and p15Ink4b accumulation as well as the growth arrest in response to TGF-β. Human HCC tumors raised in immunodeficient mice also displayed TGF-β1–induced senescence. More importantly, peritumoral injection of TGF-β1 (2 ng) at 4-day intervals reduced tumor growth by more than 75%. In contrast, the deletion of TGF-β receptor 2 abolished in vitro senescence response and greatly accelerated in vivo tumor growth. Conclusion: TGF-β induces p53-independent and p16Ink4a-independent, but Nox4-dependent, p21Cip1-dependent, p15Ink4b-dependent, and ROS-dependent senescence arrest in well-differentiated HCC cells. Moreover, TGF-β–induced senescence in vivo is associated with a strong antitumor response against HCC.
Recurrent Salmonella enteritidis sepsis and hepatic tuberculosis.
Authors: M Trauner, E Grasmug, R E Stauber, H F Hammer, G Hoefler, E C Reisinger
Journal: Gut (1995)

A 33 year old woman with recurrent Salmonella enteritidis sepsis is described. Penicillins, ceftriaxone, ciprofloxacin, and chloramphenicol could not eradicate the salmonellas but a combination of high dose ciprofloxacin and ceftriaxone for the eighth episode successfully cured the infection. The combination of ciprofloxacin and ceftriaxone may be a valuable therapeutic regimen in patients with recurrent salmonella sepsis. Prolonged intrahepatic cholestasis resulting from granulomatous hepatitis in this patient improved considerably with empiric ursodeoxycholic acid treatment. A liver biopsy specimen showing non-caseating epitheloid granulomas was positive for mycobacterial DNA by polymerase chain reaction. Repeated bronchoscopy with multiple biopsies eventually revealed caseating granulomas with acid fast bacilli in the lung biopsy specimens. Therefore, tuberculosis was diagnosed as the underlying disease and the cause of granulomatous hepatitis in this patient and tuberculostatic treatment was started. Polymerase chain reaction for mycobacterial DNA may be helpful in the differential diagnosis of hepatic granulomas when routine histological examination and culture of biopsy specimens are not diagnostic. Tuberculosis should be considered as one of the diseases predisposing to recurrent salmonella sepsis.
Switching from conventional to extrafine aerosol beclomethasone dipropionate therapy in children: A 6-month, open- label, randomized trial
Authors: Stanley J Szefler, John Warner, Doris Staab, Ulrich Wahn, Muriel Le Bourgeois, Elisabeth E M van Essen-Zandvliet, Sujata Arora, Søren Pedersen
Journal: Journal of Allergy and Clinical Immunology (2002)
Patient reported outcome measures in practice
Authors: Eugene C Nelson, Elena Eftimovska, Cristin Lind, Andreas Hager, John H Wasson, Staffan Lindblad
Journal: BMJ (2015)

Scores of tools to measure outcomes that matter to patients have been developed over the past 30 years but few are used routinely at the point of care. <b>Nelson and colleagues</b> describe examples where they are used in primary and secondary care and argue for their wider uptake to improve quality of care
Protein Tyrosine Phosphatase Receptor Type γ Is a Functional Tumor Suppressor Gene Specifically Downregulated in Chronic Myeloid Leukemia
Authors: Marco Della Peruta, Giovanni Martinelli, Elisabetta Moratti, Davide Pintani, Marzia Vezzalini, Andrea Mafficini, Tiziana Grafone, Ilaria Iacobucci, Simona Soverini, Marco Murineddu, Fabrizio Vinante, Cristina Tecchio, Giovanna Piras, Attilio Gabbas, Maria Monne, Claudio Sorio
Journal: Cancer Research (2010)

Chronic myelogenous leukemia (CML) is the most common myeloproliferative disease. Protein tyrosine phosphatase receptor type γ (PTPRG) is a tumor suppressor gene and a myeloid cell marker expressed by CD34(+) cells. Downregulation of PTPRG increases colony formation in the PTPRG-positive megakaryocytic cell lines MEG-01 and LAMA-84 but has no effect in the PTPRG-negative cell lines K562 and KYO-1. Its overexpression has an oncosuppressive effect in all these cell lines and is associated with myeloid differentiation and inhibition of BCR/ABL-dependent signaling. The intracellular domain of PTPRG directly interacts with BCR/ABL and CRKL, but not with signal transducers and activators of transcription 5. PTPRG is downregulated at the mRNA and protein levels in leukocytes of CML patients in both peripheral blood and bone marrow, including CD34(+) cells, and is reexpressed following molecular remission of disease. Reexpression was associated with a loss of methylation of a CpG island of PTPRG promoter occurring in 55% of the patients analyzed. In K562 cell line, the DNA hypomethylating agent 5-aza-2'-deoxycytidine induced PTPRG expression and caused an inhibition of colony formation, partially reverted by downregulation of PTPRG expression. These findings establish, for the first time, PTPRG as a tumor suppressor gene involved in the pathogenesis of CML, suggesting its use as a potential diagnostic and therapeutic target.
New recommendations for duration of respiratory isolation based on time to detect Mycobacterium tuberculosis in liquid culture
Authors: S. R. Ritchie, A. C. Harrison, R. H. Vaughan, L. Calder, A. J. Morris
Journal: European Respiratory Journal (2007)

It was hypothesised that the time to detect Mycobacterium tuberculosis in liquid culture of sputum from patients with pulmonary tuberculosis may be a better indicator for the duration of respiratory isolation than sputum smear status. Pre-treatment and during-treatment sputum acid-fast bacilli (AFB) smear and culture results were reviewed in 284 patients with pulmonary tuberculosis. The time to detect M. tuberculosis in liquid culture (TTD-TB) was the number of days from inoculation of the Mycobacterial Growth Indicator Tube to culture detection and visualisation of AFB. The median (interquartile range) TTD-TB for smear group 0 (no bacilli seen) was 14 (12–20) days. This value was used as the standard at which release from isolation could be permitted. In smear group 4 (&gt;9 AFB per high-power field (hpf) in sputum specimens before treatment) patients, the TTD-TB exceeded 14 days after a median of 25 days of treatment. The current authors recommend that patients in smear groups 1 and 2 (1–9 AFB per 100 hpf and 1–9 AFB per 10 hpf in sputum specimens before treatment, respectively) receive treatment in respiratory isolation for 7 days, provided the risk of drug resistance is low. Smear group 3 (1–9 AFB per hpf) and 4 patients should receive treatment in respiratory isolation for 14 and 25 days, respectively. These criteria would have reduced the duration of respiratory isolation by 1,516 days in the 143 study participants with sputum smear-positive pulmonary tuberculosis. Provided clinical and radiographical criteria are satisfactory, use of the time to detect Mycobacterium tuberculosis in liquid culture could enable the duration of respiratory isolation to be predicted from the pre-treatment sputum smear grade. The recommendations enable isolation to end well before sputum becomes smear negative, with considerable benefits to patients and healthcare providers.
Marijuana as medicine
Authors: R. W. Bennetts
Journal: JAMA (1995)

To the Editor.  —The plea by Dr Grinspoon and Mr Bakalar 1 to expend precious research dollars on potential uses of cannabis in medicine is weak given their admission that after 5000 years of common and controlled use of these agents they have no place in our armamentarium and given the length of time it has taken us to gradually reduce average daily alcohol consumption and to restrict the use of tobacco in the workplace. In a time of shrinking formularies and reduced budget for medical care, I see no reason to displace better agents currently in use in my practice with cannabis.  I would make a counterplea that the National Organization for the Reform of Marijuana Laws use its talents, political leverage, and finances to help the many orphan drugs that do not have such potent advocates. There are equally as many nonchemical approaches to relief of distress that
Brain Volumes, RBC Status, and Hepatic Function in Alcoholics After 1 and 4 Weeks of Sobriety: Predictors of Outcome
Authors: Adolf Pfefferbaum, Margaret J Rosenbloom, Kathleen L Serventi, Edith V Sullivan
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The authors asked if hematological indices of RBC status and hepatic function in newly sober alcoholic men are related to abnormalities in brain morphology, change with normalization of brain function during short-term sobriety, and predict prolonged sobriety. METHOD: Alcoholic men received brain magnetic resonance imaging and laboratory assessments on admission and before discharge from an inpatient treatment program. Healthy comparison men were similarly tested. RESULTS: On admission, RBC count, hemoglobin level, and hematocrit were significantly lower in alcoholic subjects than comparison subjects; mean corpuscular volume, SGOT, SGPT, and γ-glutamyl transpeptidase were significantly higher. By discharge, all measures had improved, although RBC count, mean corpuscular volume, and γ-glutamyl transpeptidase levels remained significantly different from those of comparison subjects. Upon admission, alcoholic men had smaller cortical white and gray matter and larger lateral and third ventricle volumes, with reduced lateral ventricle and increased anterior cortical gray matter volumes by discharge. Lower RBC count, hemoglobin level, and hematocrit were associated with lower white matter and higher ventricular volumes at admission. Change in these measures was related to reduction in ventricular volume with treatment. By discharge, associations among RBC count, hemoglobin level, and hematocrit and white matter and ventricular volumes were less marked than at admission. Discharge hemoglobin value and hematocrit discriminated patients who maintained sobriety from those who relapsed. Hepatic function showed limited association with brain measures at admission and discharge. CONCLUSIONS: Hemograms reflect alcohol-related abnormalities in brain morphology, improvement over short-term sobriety, and liability to relapse after treatment.
Hbo1 Is a Cyclin E/CDK2 Substrate That Enriches Breast Cancer Stem-like Cells
Authors: MyLinh T. Duong, Said Akli, Sira Macalou, Anna Biernacka, Bisrat G. Debeb, Min Yi, Kelly K. Hunt, Khandan Keyomarsi
Journal: Cancer Research (2013)

Expression of cyclin E proteolytic cleavage products, low-molecular weight cyclin E (LMW-E), is associated with poor clinical outcome in patients with breast cancer and it enhances tumorigenecity in mouse models. Here we report that LMW-E expression in human mammary epithelial cells induces an epithelial-to-mesenchymal transition phenotype, increases the CD44(hi)/CD24(lo) population, enhances mammosphere formation, and upregulates aldehyde dehydrogenase expression and activity. We also report that breast tumors expressing LMW-E have a higher proportion of CD44(hi)/CD24(lo) tumor cells as compared with tumors expressing only full-length cyclin E. In order to explore how LMW-E enriches cancer stem cells in breast tumors, we conducted a protein microarray analysis that identified the histone acetyltransferase (HAT) Hbo1 as a novel cyclin E/CDK2 substrate. The LMW-E/CDK2 complex phosphorylated Hbo1 at T88 without affecting its HAT activity. When coexpressed with LMW-E/CDK2, wild-type Hbo1 promoted enrichment of cancer stem-like cells (CSC), whereas the T88 Hbo1 mutant reversed the CSC phenotype. Finally, doxorubicin and salinomycin (a CSC-selective cytotoxic agent) synergized to kill cells expressing LMW-E, but not full-length cyclin E. Collectively, our results suggest that the heightened oncogenecity of LMW-E relates to its ability to promote CSC properties, supporting the design of therapeutic strategies to target this unique function.
THE PROGRESS OF SURGERY.
Authors: HERMAN E. PEARSE
Journal: JAMA (1899)

Standing on the threshold of the twentieth century, and looking with the eyes of hope at the future of our noble profession, let us remember that the splendid progress of the past fifteen years has been made possible only by the solid foundation builded by those whose hands have laid down their scalpels forever; who watch us now from the great unknown, let us hope, in our feeble struggles to attain perfection in our art. These surgeons who upheld the profession in the long past struggled against a series of obstacles, and with a succession of handicaps that are appalling to contemplate at the present day. They had no method of controlling hemorrhage save by the cautery or direct pressure. They were compelled to operate without anesthesia. Their knowledge of anatomy was as limited as one would expect from the strenuous opposition offered to human body dissection. They knew nothing of infection as applied to
Toll gates to periodontal host modulation and vaccine therapy
Authors: George Hajishengallis
Journal: Periodontology 2000 (2009)

Toll-like receptors (TLRs) are central mediators of innate antimicrobial and inflammatory responses and play instructive roles in the development of the adaptive immune response.Thus when stimulated by certain agonists, TLRs serve as adjuvant receptors that link innate and adaptive immunity.However, when excessively activated or inadequately controlled during an infection, TLRs may contribute to immunopathology associated with inflammatory diseases, such as periodontitis.Moreover, certain microbial pathogens appear to exploit aspects of TLR signalling in ways that enhance their adaptive fitness.The diverse and important roles played by TLRs suggest that therapeutic manipulation of TLR signalling may have implications in the control of infection, attenuation of inflammation, and the development of vaccine adjuvants for the treatment of periodontitis.Successful application of TLR-based therapeutic modalities in periodontitis would require highly selective and precisely targeted intervention.This would in turn necessitate precise characterization of TLR signalling pathways in response to periodontal pathogens, as well as development of effective and specific agonists or antagonists of TLR function and signalling.This review summarizes the current status of TLR biology as it relates to periodontitis, and evaluates the potential of TLR-based approaches for host-modulation therapy in this oral disease. Toll-like receptors and potential for periodontal host modulationPeriodontitis can be defined as an infection-driven chronic inflammatory disease that affects the integrity of tooth-supporting tissues (179).Several oral bacteria within the subgingival dental plaque biofilm have been implicated in the initiation and progression of the disease.These include the "red complex" bacteria, Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola, as well as other organisms, such as Aggregatibacter actinomycetmcomitans, Prevotella intermedia, and Eikenella corrodens (99,212).Although periodontal bacteria are essential for disease initiation, host susceptibility, as determined by various genetic, environmental, and other risk factors, is also implicated in the etiopathogenesis of periodontitis (65,121).In fact, it is the host inflammatory reaction to uncontrolled bacterial challenge that primarily mediates tissue damage (9,120,219).The discovery of the Toll-like receptor (TLR) family of pattern recognition receptors in the late 1990s (2) has filled a great mechanistic gap in our understanding of inflammatory mechanisms in infectious diseases such as periodontitis (68,85,151,220).Indeed, at the molecular level, TLRs have emerged as central mediators of innate immunity and inflammation with an instructive role in adaptive immunity and polarization of the T cell responses (73, 175).Although TLRs can induce critical antimicrobial responses (34,183), it has become
A Multicenter, Phase I, Dose-Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of Etirinotecan Pegol in Patients with Refractory Solid Tumors
Authors: Gayle S. Jameson, John T. Hamm, Glen J. Weiss, Carlos Alemany, Stephen Anthony, Michele Basche, Ramesh K. Ramanathan, Mitesh J. Borad, Raoul Tibes, Allen Cohn, Ioana Hinshaw, Robert Jotte, Lee S. Rosen, Ute Hoch, Michael A. Eldon, Robert Medve, Katrina Schroeder, Erica White, Daniel D. Von Hoff
Journal: Clinical Cancer Research (2012)

This study was designed to establish the maximum tolerated dose (MTD) and to evaluate tolerability, pharmacokinetics, and antitumor activity of etirinotecan pegol.Patients with refractory solid malignancies were enrolled and assigned to escalating-dose cohorts. Patients received 1 infusion of etirinotecan pegol weekly 3 times every 4 weeks (w × 3q4w), or every 14 days (q14d), or every 21 days (q21d), with MTD as the primary end point using a standard 3 + 3 design.Seventy-six patients were entered onto 3 dosing schedules (58-245 mg/m(2)). The MTD was 115 mg/m(2) for the w × 3q4w schedule and 145 mg/m(2) for both the q14d and q21d schedules. Most adverse events related to study drug were gastrointestinal disorders and were more frequent at higher doses of etirinotecan pegol. Late onset diarrhea was observed in some patients, the frequency of which generally correlated with dose density. Cholinergic diarrhea commonly seen with irinotecan treatment did not occur in patients treated with etirinotecan pegol. Etirinotecan pegol administration resulted in sustained and controlled systemic exposure to SN-38, which had a mean half-life of approximately 50 days. Overall, the pharmacokinetics of etirinotecan pegol are predictable and do not require complex dosing adjustments. Confirmed partial responses were observed in 8 patients with breast, colon, lung (small and squamous cell), bladder, cervical, and neuroendocrine cancer.Etirinotecan pegol showed substantial antitumor activity in patients with various solid tumors and a somewhat different safety profile compared with the irinotecan historical profile. The MTD recommended for phase II clinical trials is 145 mg/m(2) q14d or q21d.