tbuckley/cabot-search huggingface dataset:
Abstract P3-13-07: A-TaXel: Multicenter phase II combination of bevacizumab (A) with weekly paclitaxel (Ta) and capecitabine (Xel) in first line treatment for patients with triple negative metastatic or locally advanced breast cancer (TNMBC), a GINECO study
Authors: J-M Ferrero, A-C Hardy-Bessard, O Capitain, A Lortholary, B Salles, P Follana, R Herve, M Deblock, J Dauba, M Atlassi, R Largillier
Journal: Cancer Research (2013)

Abstract Background: Weekly paclitaxel and capecitabine intermittent regimen is a safe and effective combination in first line treatment of MBC including triple negative cancer (Lortholary et al, Breast Cancer Res Treat 2012). In TNMBC, the combination of A with first line Ta or Xel has been shown to improve response rate (RR) and progression-free survival (PFS) (Miller K et al., N Engl J Med 2007, Robert J et al., J Clin Oncol 2011). This phase II study is to evaluate the efficacy and safety of A-TaXel combination in TNMBC. Methods: Patients (pts) with measurable TNMBC were treated in first line until progression with q28 cycles of Ta (80 mg/m2 D1, 8, 15) + Xel (800 mg/m2 bid D1-5, 8-12, 15-19) + A (10 mg/kg D1, 14). Primary end point was best overall RR; secondary were safety, PFS, response duration and overall survival (OS). Results: From 04/2010 to 03/2012, 64 pts were accrued including 2 ineligible pts. Patients characteristics were: median age (56.7 yrs), ECOG PS 0 (55%), histological grade III (61%), previous adjuvant chemotherapy (74%), visceral disease (65%), &amp;gt; 1 metastatic sites (74%). Patients received a median of 6 cycles (1-6), mean 5.1. Grade 3-4 neutropenia, anemia and thrombopenia were 23%, 4% and 16% respectively with febrile neutropenia in 5% of pts. G-CSF support was observed in 7% of cycles. Most frequent non hematologic toxicities were alopecia (gr2 40%), hand-foot syndrome (gr2 27%, gr3 13%), nail toxicity (gr2 40%), hypertension (gr3 35%), neuropathy (gr2 26%, gr3 6%), mucositis (gr2 16%, gr3-4 9%), fatigue (gr3 18%, gr4 2%), nausea (gr2 15%, gr3 2%) and thrombosis (gr2 3%, gr3-4 5%). Treatment interruption due to toxicity was 22%, DPD deficiency in one patient, hospitalization 23%. RR was 77%, CR 19%, PR 58%, stable disease 14% and progressive disease 9%. Median response duration was 5.6 months. Median PFS was 7.9 months (6.7-9) and OS 19.2 months (17.3-21.1). Conclusion: A-TaXel is an effective regimen with high RR and manageable toxicity. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-13-07.
Hippocampal Volume and Depression: A Meta-Analysis of MRI Studies
Authors: Poul Videbech, Barbara Ravnkilde
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Several studies have found reduced hippocampal volume in patients with unipolar depression, but discrepancies exist. The authors performed a systematic review and meta-analysis of volumetric studies of the hippocampus in patients with mood disorders. METHOD: Studies of hippocampal volume in unipolar and bipolar patients were identified. A meta-analysis of the 12 studies of unipolar depression fulfilling specific criteria was performed. The sample comprised 351 patients and 279 healthy subjects. RESULTS: The studies were highly heterogeneous regarding age and gender distribution, age at onset of the disorder, average number of episodes, and responsiveness to treatment, but the pooled effect size of depression was significant in both hemispheres for the unipolar patients. The weighted average showed a reduction of hippocampal volume of 8% on the left side and 10% on the right side. The causes of the heterogeneity were analyzed, and a meta-regression showed that the total number of depressive episodes was significantly correlated to right but not left hippocampal volume reduction. CONCLUSIONS: Hippocampal volume is reduced in patients with unipolar depression, maybe as a consequence of repeated periods of major depressive disorder. Bipolar patients did not seem to show a reduction in hippocampal volume, but this has been much less investigated.
Septic arthritis complicating hip osteoarthritis.
Authors: S Donell, D M Williamson, D L Scott
Journal: Annals of the Rheumatic Diseases (1991)

Four patients with osteoarthritis of the hip, who developed septic arthritis of the affected joint, are reported. The septic arthritis developed insidiously and was diagnosed with difficulty. One patient died, two required subsequent joint excision, and one arthrodesis despite antibiotics. The presence of a recognised predisposing factor to septic arthritis, such as rheumatoid arthritis or a surgically replaced joint, can provide a diagnostic pointer. These cases suggest that osteoarthritis, similarly, is a predisposing factor. It is concluded that joint sepsis should be considered if a patient with osteoarthritis develops new symptoms from a single joint with associated systemic features.
CONVULSIVE SYNDROME IN RABBITS INJECTED WITH FAT EMULSION AND HEPARIN
Authors: Jozef Van den Bosch, Alfons Billiau
Journal: The Journal of Experimental Medicine (1963)

Functionally hepatectomized rabbits showed convulsions and coma within 2 hours after the intravenous injection of fat emulsion and heparin. Intravenous injection of the detergent triton prevented this syndrome, if given before the fat emulsion and heparin, and reversed it if given subsequently. Extremely high plasma non-esterified fatty acid levels were noted in rabbits showing the convulsive syndrome, but not in animals that received the detergent. The mechanism of the convulsions probably includes the toxicity of high amounts of non-esterified fatty acids.
Photoscanning of the Pancreas
Authors: Antonio Rodríguez-Antínez
Journal: JAMA (1968)

The early diagnosis of carcinoma of the pancreas is a difficult problem. The diagnostic procedures available today are based on the fact that the neoplasm, because of its size, produces indirect signs in the neighboring regions or viscera, such as the stomach or duodenum. Photoscanning with radioactive selenium (<sup>75</sup>Se) by means of selenomethione Se 75 has been used in the last four years to improve the diagnostic accuracy in regard to pancreatic disease. The selection of that radioactive substance is based on the following rationale. Physiologically, amino acids are the substratum for the pancreatic synthesis of digestive enzymes. The amino acid methionine contains sulfur in its molecule. Selenium, being similar to sulfur, can replace it in the methionine molecule without appreciably changing the properties of the amino acid. This substitution of selenium for sulfur has made selenomethionine Se 75 the preferred substance for pancreatic scanning. Blau et al<sup>1</sup>
Major peptide autoepitopes for nucleosome-specific T cells of human lupus
Authors: Liangjun Lu, Arunan Kaliyaperumal, Dimitrios T. Boumpas, Syamal K. Datta
Journal: Journal of Clinical Investigation (1999)

We tested 154 peptides spanning the entire length of core histones of nucleosomes for the ability to stimulate an anti-DNA autoantibody–inducing T helper (Th) clone, as well as CD4+ T-cell lines and T cells, in fresh PBMCs from 23 patients with lupus erythematosus. In contrast to normal T cells, lupus T cells responded strongly to certain histone peptides, irrespective of the patient’s disease status. Nucleosomal peptides in histone regions H2B10–33, H416–39 (and overlapping H414–28), H471–94, and H391–105 (and overlapping H3100–114) were recurrently recognized by CD4 T cells from the patients with lupus. Remarkably, these same peptides overlap with major epitopes for the Th cells that induce anti-DNA autoantibodies and nephritis in lupus-prone mice. We localized 2 other recurrent epitopes for human lupus T cells in H2A34–48 and H449–63. All the T-cell autoepitopes have multiple HLA-DR binding motifs, and the epitopes are located in histone regions recognized by lupus autoantibodies, suggesting a basis for their immunodominance. Native nucleosomes and their peptides H416–39, H471–94, and H391–105 induced a stronger IFN-γ response, whereas others, particularly, H2A34–48, favored an IL-10– and/or IL-4–positive T-cell response. The major autoepitopes may reveal the mechanism of autoimmune T-cell expansion and lead to antigen-specific therapy of human lupus.
Unstable minisatellite expansion causing recessively inherited myoclonus epilepsy, EPM1
Authors: Kimmo Virtaneva, Elena D'Amato, Jinmin Miao, Marjaleena Koskiniemi, Reijo Norio, Giuliano Avanzini, Silvana Franceschetti, Roberto Michelucci, Carlo A. Tassinari, Salah Omer, Len A. Pennacchio, Richard M. Myers, José L. Dieguez-Lucena, Ralf Krahe, Albert de la Chapelle, Anna-Elina Lehesjoki
Journal: Nature Genetics (1997)
P53 and p73 differ in their ability to inhibit glucocorticoid receptor (GR) transcriptional activity
Authors: Lili Zhang, Linghu Nie, Carl G Maki
Journal: Molecular Cancer (2006)

Abstract Background p53 is a tumor suppressor and potent inhibitor of cell growth. P73 is highly similar to p53 at both the amino acid sequence and structural levels. Given their similarities, it is important to determine whether p53 and p73 function in similar or distinct pathways. There is abundant evidence for negative cross-talk between glucocorticoid receptor (GR) and p53. Neither physical nor functional interactions between GR and p73 have been reported. In this study, we examined the ability of p53 and p73 to interact with and inhibit GR transcriptional activity. Results We show that both p53 and p73 can bind GR, and that p53 and p73-mediated transcriptional activity is inhibited by GR co-expression. Wild-type p53 efficiently inhibited GR transcriptional activity in cells expressing both proteins. Surprisingly, however, p73 was either unable to efficiently inhibit GR, or increased GR activity slightly. To examine the basis for this difference, a series of p53:p73 chimeric proteins were generated in which corresponding regions of either protein have been swapped. Replacing N- and C-terminal sequences in p53 with the corresponding sequences from p73 prevented it from inhibiting GR. In contrast, replacing p73 N- and C-terminal sequences with the corresponding sequences from p53 allowed it to efficiently inhibit GR. Differences in GR inhibition were not related to differences in transcriptional activity of the p53:p73 chimeras or their ability to bind GR. Conclusion Our results indicate that both N- and C-terminal regions of p53 and p73 contribute to their regulation of GR. The differential ability of p53 and p73 to inhibit GR is due, in part, to differences in their N-terminal and C-terminal sequences.
Emotion and empiricism.
Authors: A L Cochrane, A S St Leger, P Sweetnam
Journal: BMJ (1979)

<h3>Introduction</h3> U.S. HIV/AIDS Strategy has prioritized men who have sex with men (MSM) and people in the Southern U.S. as key populations for HIV prevention interventions. We—a community-academic partnership—conducted formative research on the PrEP care continuum with Black same-gender-loving men (BSGLM) in a Southern U.S. city. <h3>Methods</h3> We conducted six focus group discussions (FGDs) with 35 BSGLM; most had never used PrEP. We explored PrEP awareness and acceptability—the continuum’s first stage. We also conducted 18 in-depth interviews (IDIs) with BSGLM who have taken or discussed PrEP with a provider. The IDIs focused on PrEP uptake—the continuum’s second stage—and adherence and retention in care—the final stage. All FGDs/IDIs were recorded, transcribed, and analyzed using applied thematic analysis. <h3>Results</h3> FGD—participants said BSGLM are generally aware of PrEP, but misinformation exists and knowledge of PrEP-related services is limited. Perceived risk influences PrEP interest—participants explained that BSGLM consider their receptive or insertive role when evaluating HIV vulnerability and BSGLM who do not identify as gay are less interested in PrEP. Fears are also common, including fear of facing consequences of past risky behaviors, others learning of one’s PrEP use, and talking to providers about sexual behaviors. Participants also described existing discrimination and stigma toward BSGLM from multiple sources, including the Black community and the broader MSM community, and concerns about PrEP-related stigma. IDI—participants said PrEP provides a ‘peace of mind’ but acknowledged challenges with pill taking. Several also described experiencing PrEP-related stigma as well as stigma from the Black community for being a Black gay man. <h3>Conclusion</h3> We need multi-level interventions that support BSGLM at each stage of the PrEP care continuum. BSGLM need information to make informed decisions about PrEP and supportive community environments to use PrEP for as long as risk persists.
Degradation of bile salts by human intestinal bacteria.
Authors: M J Hill, B S Drasar
Journal: Gut (1968)

<b>1032</b> <h3><b>Learning Objectives</b></h3> Those involved in training and in the daily practice of nuclear medicine need a firm practical knowledge of radiation safety and the concepts of NRC regulations. We illustrate, in a simplified pictorial format, a comprehensive technique for reviewing Nuclear Regulatory Commission (NRC) scenarios required to safely practice as an authorized user for the safe and effective medical use of radionuclides. We discuss how this exercise will emphasize the concepts of ALARA, training to handle radioactive spills, medical events, pregnancy and breast feeding during radioactive diagnostic and nuclear treatment procedures, the handling of common and uncommon situations including the nuclear patient on dialysis, treatment patients who do not adhere to the regulations, etc. <h3></h3> There are many residents in training and physicians who practice nuclear medicine that need hands on familiarity with the "day to day" practice of radiation safety procedures and Nuclear Regulatory Commission regulations as authorized users. To become more familiar with these important regulations, we have implemented a concept which we refer to as "Radiation Safety Officer For The Day". In this role, the individual in this role under the tutelage of the RSO responds to a wide variety of common and uncommon scenarios which include: how to handle spills, concepts of ALARA, handle a medical event, how to handle a pregnant or breastfeeding patient who needs a nuclear medicine examination or treatment, the ordering and receipts of radioactive materials, waste management, maintaining equipment, etc. We will also emphasize the handling of a variety of uncommon situations which may be encountered on a daily basis. Many of these scenarios will be displayed in a pictorial format. Upon completion of this exercise, the authorized user will have a much better understanding of what is required to be a radiation safety officer and better handle a variety of problems as a authorized user
Reporting on Methods in Clinical Trials
Authors: Rebecca DerSimonian, L.Joseph Charette, Bucknam McPeek, Frederick Mosteller
Journal: New England Journal of Medicine (1982)

A clinical trial cannot be adequately interpreted without information about the methods used in the design of the study and the analysis of the results. To determine the frequency of reporting what we consider 11 important aspects of design and analysis, we surveyed all 67 clinical trials published in the New England Journal of Medicine, the Lancet, and the British Medical Journal from July through December 1979 and in the Journal of the American Medical Association from July 1979 through June 1980. Of all 11 items in the 67 trials published in all four journals, 56 per cent were clearly reported, 10 per cent were ambiguously mentioned, and 34 per cent were not reported at all. At least 80 per cent of the 67 trials reported information about statistical analyses, statistical methods used, and random allocation of subjects, yet only 19 per cent reported the method of randomization. Loss to follow-up was discussed in 79 per cent of the articles, treatment complications in 64 per cent, and admission of subjects before allocation in 57 per cent, but eligibility criteria for admission to the trial appeared in only 37 per cent. Although information about whether patients were blind to treatment was given in 55 per cent, information about whether there was blind assessment of outcome was reported in only 30 per cent. The statistical power of the trial to detect treatment effects was discussed in only 12 per cent of the articles. The clinical trials published in The New England Journal of Medicine reported 71 per cent of the 11 items, those in the Journal of the American Medical Association 63 per cent, those in the British Medical Journal 52 per cent, and those in the Lancet 46 per cent. These rates are significantly different (P less than 0.001). We recommend that editors improve the reporting of clinical trials by giving authors a list of the important items to be reported.
Public Health Policy and the AIDS Epidemic
Authors: R Bayer
Journal: New England Journal of Medicine (1991)

In the early and mid-1980s, when democratic nations were forced to confront the public health challenge posed by the epidemic of the acquired immunodeficiency syndrome (AIDS), it was necessary to face a set of fundamental questions: Did the history of responses to lethal infectious diseases provide lessons about how best to contain the spread of human immunodeficiency virus (HIV) infection? Should the policies developed to control sexually transmitted diseases or other communicable conditions be applied to AIDS? If AIDS were not to be so treated, what would justify such differential policies?To understand the importance of these questions, it is . . .
Case of Peculiar and Fatal Haemorrhage from the Mucous Lining of the Vagina: With Remarks
Authors: H. Obre
Journal: BMJ (1857)

THIs case of diseased aortic valves, which was presented to the Pathological Society, is interesting, because it illustrates, as I believe, one of the modes of origin of valvular diseases, not frequently observed.The aortic valves are all incompetent.Two of them are partially destroyed by ulceration; the eroded edges presenting appearances as though the ulceration were still progressing at the time of the patient's death.Two of the valves, again, are fused together at their adjoining angles, and much puckered; a calcareous nodule, the size of a pea, pro- jecting from the upper surface of one of them.The heart is much hypertrophied and dilated on the left side; but the mus- cular tissue is perfectly healthy.The hypertrophy is mani- festly a secondai-y fact, resulting simply from the diseased con- dition of the aortic valves.The aorta itself, the lining mem- brane of the heart, and its mitral and tricuspid valves, are in a perfectly healthy condition.
Sequence diversity within a subgroup of mouse immunoglobulin kappa chains controlled by the IgK-Ef2 locus.
Authors: C Lazure, W T Hum, D M Gibson
Journal: The Journal of Experimental Medicine (1981)

We previously showed that a chromosome 6 locus, IgK-Ef2, controls a pair of prominent bands in normal mouse light-chain isoelectric focusing profiles. Screening of myeloma light chains derived from BALB/c mice (an IgK-EF2 alpha strain) led to the identification of seven light chains cofocusing with the polymorphic bands controlled by IgK-Ef2. Complete sequencing of the variable (V) regions of four of the light chains indicates that they are all members of the same subgroup (Vk-1A) and they differ from one another by 1--3 substitutions. One of the protein differs from the prototype V-region sequence only in the deletion of a single residue at position 95 immediately preceding of J region. The other two differ from the protype V region by 3 (two framework [fr], one complementarity-determined [cdr]) and one (fr) residues, respectively. Complete V-region sequences of two closely related light chains derived from NZB mice (an IgK-Ef2b strain) indicate the NZB proteins are derived from a distinct Vk gene (Vk-1B), differing by four substitutions from the Vk-1A sequence. The results suggest that the IgK-Ef2 polymorphism may be a result of, at least in part, the loss of the gene(s) coding for the Vk-1A subgroups in IgK-Ef2b strains of mice. The nature of the sequence diversity found in the Vk-1A subgroup indicates that either it is coded by a repeated series of virtually identical genes or that somatic mutation of a single Vk-1A gene may give rise to substitutions in framework as well as cdr regions.
Neurospheres Enriched in Cancer Stem–Like Cells Are Highly Effective in Eliciting a Dendritic Cell–Mediated Immune Response against Malignant Gliomas
Authors: Serena Pellegatta, Pietro Luigi Poliani, Daniela Corno, Francesca Menghi, Francesco Ghielmetti, Blanca Suarez-Merino, Valentina Caldera, Sara Nava, Maria Ravanini, Fabio Facchetti, Maria Grazia Bruzzone, Gaetano Finocchiaro
Journal: Cancer Research (2006)

Abstract Cancer stem–like cells (CSC) could be a novel target for cancer therapy, including dendritic cell (DC) immunotherapy. To address this, we developed experiments aimed at DC targeting of neurospheres (NS) from GL261 glioma cells because neurospheres can be enriched in CSC. We obtained murine neurospheres by growing GL261 cells in epidermal growth factor/basic fibroblast growth factor without serum. GL261-NS recapitulated important features of glioblastoma CSC and expressed higher levels of radial glia stem cell markers than GL261 cells growing under standard conditions (GL261 adherent cells, GL261-AC), as assessed by DNA microarray and real-time PCR. GL261-NS brain gliomas were highly infiltrating and more rapidly lethal than GL261-AC, as evidenced by survival analysis (P &amp;lt; 0.0001), magnetic resonance imaging and histology. DC from the bone marrow of syngeneic mice were then used for immunotherapy of GL261-NS and GL261-AC tumors. Strikingly, DC loaded with GL261-NS (DC-NS) cured 80% and 60% of GL261-AC and GL261-NS tumors, respectively (P &amp;lt; 0.0001), whereas DC-AC cured only 50% of GL261-AC tumors (P = 0.0022) and none of the GL261-NS tumors. GL261-NS expressed higher levels of MHC and costimulatory molecules (CD80 and CD86) than GL261-AC; the JAM assay indicated that DC-NS splenocytes had higher lytic activity than DC-AC splenocytes on both GL261-NS and GL261-AC, and immunohistochemistry showed that DC-NS vaccination was associated with robust tumor infiltration by CD8+ and CD4+ T lymphocytes. These findings suggest that DC targeting of CSC provides a higher level of protection against GL261 gliomas, a finding with potential implications for the design of clinical trials based on DC vaccination. (Cancer Res 2006; 66(21): 10247-52)
Salmeterol: a four week study of a long-acting beta-adrenoceptor agonist for the treatment of reversible airways disease
Authors: R Dahl, JS Earnshaw, JB Palmer
Journal: European Respiratory Journal (1991)

A total of 1,068 patients, aged 18-70 yrs, with mild to moderate reversible airways disease, were recruited into a multicentre, double-blind, parallel group study in 76 European centres. Following a 2 week run-in period, the 692 patients fulfilling the entry criteria were randomized to 4 weeks treatment with either salmeterol 12.5, 50 or 100 micrograms or placebo b.d. all given by pressurized inhaler, with assessments of symptoms and ventilatory lung function prior to dosing. All three doses of salmeterol had significant efficacy, manifested by increased morning and evening peak expiratory flow rate (PEFR) (by 35-59 l.min-1 and 11-38 l.min-1, respectively), by reduced diurnal variation in PEFR, and by reduced requirement for additional bronchodilator for symptomatic relief. These effects were dose-related. Daytime asthma symptoms and nocturnal awakenings were significantly reduced by salmeterol treatment, although these reductions were not dose-related. The incidence of adverse events was low. Pharmacologically predictable events (e.g. tremor) were more frequent after treatment with 100 micrograms b.d. than with placebo. On the basis of the efficacy and side-effect information, 50 micrograms b.d. is considered to be the optimum dose for the treatment of this group of asthmatics.