tbuckley/cabot-search huggingface dataset:
Abstract 4682: Phase II study of first line chemotherapy with tegafur/uracil and oral leucovorin in elderly patients with advanced or metastatic colorectal cancer.
Authors: Kohei Murata, Hirofumi Yamamoto, Mutsumi Fukunaga, Takeshi Kato, Tadashi Ohnishi, Yoshio Uemura, Hirofumi Ohta, Fumihiko Kimura, Masayuki Ohue, Riichiro Nezu, Mitsugu Sekimoto, Masataka Ikeda, Tsunekazu Mizushima, Yuichiro Doki, Masaki Mori
Journal: Cancer Research (2013)

Abstract Objective: This phase II trial was performed to evaluate the efficacy and tolerability of tegafur/uracil (UFT) and oral leucovorin (LV) in elderly patients with advanced or metastatic colorectal cancer who had not received prior chemotherapy. Methods: Patients aged ≥70 years were eligible. UFT and LV were taken orally on days 1-28 of the cycle at doses of 300 mg/m2/day and 75 mg/body/day, respectively. Treatment was administered on an outpatient basis every 35 days and consisted of at least two cycles until disease progression. Results: A total of 30 patients were enrolled in this study. The median age of the patients was 81.5 years (range: 74-88 years). The observed overall response rate was 17.9%. The estimated median overall survival time was 23.5 months. Two patients (7%) experienced toxicities with a worst grade of 3, and one patient (4%) experienced toxicities with a worst grade of 4. There were no treatment-related deaths. No patients experienced grade 3 or 4 hematological adverse events. Conclusions: Although the response rate to UFT/LV was moderate, a favorable survival time and good tolerability were observed. UFT/LV can be one of the optional treatments for elderly colorectal cancer patients. Citation Format: Kohei Murata, Hirofumi Yamamoto, Mutsumi Fukunaga, Takeshi Kato, Tadashi Ohnishi, Yoshio Uemura, Hirofumi Ohta, Fumihiko Kimura, Masayuki Ohue, Riichiro Nezu, Mitsugu Sekimoto, Masataka Ikeda, Tsunekazu Mizushima, Yuichiro Doki, Masaki Mori, Clinical Study Group of Osaka University (CSGO), Colorectal Group. Phase II study of first line chemotherapy with tegafur/uracil and oral leucovorin in elderly patients with advanced or metastatic colorectal cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4682. doi:10.1158/1538-7445.AM2013-4682
Doctors demand centres for injury prevention
Authors: A. Ferriman
Journal: BMJ (1998)

Injury is the leading cause of death and acquired disability among youngchildren and teenagers, yet far less money is spent on preventing injuries than on disorders that are less destructive, a new report says.

Specialists in child health have produced a strategy document, Action onInjury, which calls for the establishment of four dedicated national agencies–in England, Wales, Scotland, and Northern Ireland–to implement programmes of injury prevention and control, to coordinate the national surveillance of injuries, and to initiate research into the problem.

The document, introduced at a conference in London on Thursday, says …
Inadequate Functional Health Literacy Among Patients at Two Public Hospitals
Authors: Mark V. Williams
Journal: JAMA (1995)

To determine the ability of patients to complete successfully basic reading and numeracy tasks required to function adequately in the health care setting.Cross-sectional survey.Two urban, public hospitals.A total of 2659 predominantly indigent and minority patients, 1892 English-speaking and 767 Spanish-speaking, presenting for acute care.Functional health literacy as measured by the Test of Functional Health Literacy in Adults (TOFHLA), an instrument that measures ability to read and understand medical instructions and health care information presented in prose passages and passages containing numerical information (eg, prescription bottle labels and appointment slips).A high proportion of patients were unable to read and understand written basic medical instructions. Of 2659 patients, 1106 (41.6%) were unable to comprehend directions for taking medication on an empty stomach, 691 (26%) were unable to understand information regarding when a next appointment is scheduled, and 1582 (59.5%) could not understand a standard informed consent document. A total of 665 (35.1%) of 1892 English-speaking patients and 473 (61.7%) of 767 Spanish-speaking patients had inadequate or marginal functional health literacy. The prevalence of inadequate or marginal functional health literacy among the elderly (age > or = 60 years) was 81.3% (187/230) for English-speaking patients and 82.6% (57/69) for Spanish-speaking patients, and was significantly higher (P < .001) than in younger patients.Many patients at our institutions cannot perform the basic reading tasks required to function in the health care environment. Inadequate health literacy may be an important barrier to patients' understanding of their diagnoses and treatments, and to receiving high-quality care.
Lack of specificity of albumin-mRNA-positive cells as a marker of circulating hepatoma cells
Authors: C Muller, D Petermann, F Pfeffel, C Oesterreicher, R Fugger
Journal: Hepatology (1997)

The aim of the study was to assess the specificity of albumin-messenger RNA (mRNA)-positive cells in peripheral blood as an indicator for circulating malignant hepatocytes. Albumin-mRNA-positive cells in the peripheral blood mononuclear cell (PMNC) fraction were detected by reverse-transcription polymerase chain reaction (RT-PCR). Albumin-mRNA-positive cells in PMNC were found in 12 of 19 (63%) patients with hepatocellular carcinoma, but also in 22 of 25 (88%) patients with chronic hepatitis without evidence for hepatoma, and in 18 of 19 (94%) of patients with acute viral hepatitis. In addition, 8 of 28 (28%) of healthy control individuals had also albumin-mRNA-positive cells in peripheral blood. PMNC known to be spontaneously negative for albumin-mRNA could be induced in vitro to transcribe albumin-mRNA after activation with a variety of substances such as interleukin-1 (IL-1) plus concanavalin A (Con A), IL-2, bacterial lipopolysaccharide, platelet derived growth factor, alpha-fibroblast growth factor, or hepatocyte growth factor. These results show that the majority of patients with acute and chronic liver disease without evidence for hepatocellular carcinoma has albumin-mRNA-positive cells in their PMNC fraction indicating the nonspecificity of that parameter for the presence of circulating malignant hepatocytes. In addition, in vitro experiments suggest that PMNC are capable of transcribing mRNA for albumin at a low level after activation. In vivo-activated PMNC are likely to be the source of positivity in healthy controls, patients with nonmalignant acute and chronic liver disease, and patients with hepatocellular carcinoma.
Very early/early relapses of acute lymphoblastic leukemia show unexpected changes of clonal markers and high heterogeneity in response to initial and relapse treatment
Authors: C Eckert, T Flohr, R Koehler, N Hagedorn, A Moericke, M Stanulla, R Kirschner-Schwabe, G Cario, Av Stackelberg, C R Bartram, G Henze, M Schrappe, A Schrauder
Journal: Leukemia (2011)
In vitro anticancer activity of docetaxel-loaded micelles based on poly(ethylene oxide)-poly(epsilon-caprolactone) block copolymers: Do nanocarrier properties have a role?
Authors: Luisanna Ostacolo, Monica Marra, Francesca Ungaro, Silvia Zappavigna, Giovanni Maglio, Fabiana Quaglia, Alberto Abbruzzese, Michele Caraglia
Journal: Journal of Controlled Release (2010)
Tyrosine Phosphatase–Related Islet Antigen 2(256–760) Autoantibodies, the Only Marker of Islet Autoimmunity That Increases by Increasing the Degree of BMI in Obese Subjects With Type 2 Diabetes
Authors: Raffaella Buzzetti, Marialuisa Spoletini, Simona Zampetti, Giuseppe Campagna, Lidia Marandola, Francesca Panimolle, Francesco Dotta, Claudio Tiberti
Journal: Diabetes Care (2015)

OBJECTIVE Since patients with type 2 diabetes and positive for type 1 diabetes–specific antibodies have wide variations in BMI, this study evaluated whether the frequency and pattern of islet autoantibody positivity is related to BMI. RESEARCH DESIGN AND METHODS Clinical and biochemical characteristics and islet autoantibodies including GAD and protein tyrosine phosphatases islet antigen-2 (IA-2)IC and IA-2(256–760) were evaluated in 1,850 patients with type 2 diabetes from the Non–Insulin Requiring Autoimmune Diabetes study cohort. BMI was evaluated in all patients, who were then subdivided in three groups according to BMI (&amp;lt;25, ≥25 to &amp;lt;30, and ≥30 kg/m2). RESULTS Out of 1,850, 120 (6.5%) patients were positive for at least one of the following antibodies: GAD (4.1%), IA-2(256–760) (3.3%), or IA-2IC (1.1%). GAD and IA-2IC antibodies showed decreasing frequencies with increasing BMI (P &amp;lt; 0.0001 and 0.0006, respectively, for trend); in contrast, the frequency of IA-2(256–760) antibodies increased with increasing BMI (P = 0.005 for trend). Patients with type 2 diabetes positive for IA-2(256–760) alone showed a phenotype resembling classical obese type 2 diabetes, with higher BMI, waist circumference, and uric acid (P &amp;lt; 0.005 for all), lower thyroid peroxidase antibodies, and lower progression to insulin requirement than GAD antibody–positive patients (P = 0.04 and P = 0.0005, respectively). CONCLUSIONS The IA-2(256–760) antibody appears to represent an antibody marker that mainly identifies a clinical phenotype very similar to obese type 2 diabetes, suggesting a possible different pathogenetic mechanism.
Microarray and Serial Analysis of Gene Expression Analyses Identify Known and Novel Transcripts Overexpressed in Hematopoietic Stem Cells
Authors: Robert W. Georgantas, Vivek Tanadve, Matthew Malehorn, Shelly Heimfeld, Chen Chen, Laura Carr, Francisco Martinez-Murillo, Greg Riggins, Jeanne Kowalski, Curt I. Civin
Journal: Cancer Research (2004)

The human CD34(+)/CD38(-)/Lin(-) cell subset, comprising approximately 1-10% of the CD34(+) cell population, contains few of the less primitive hematopoietic (lineage-committed) progenitor cells (HPCs) but most of the primitive in vivo engrafting (lympho-)hematopoietic stem cells (HSCs). We analyzed gene expression in CD34(+)/CD38(-)/Lin(-) cell populations isolated from normal human adult donor bone marrow, neonatal placental/umbilical cord blood, and mobilized adult donor peripheral blood stem-progenitor cells. As measured by Affymetrix microarrays, 4746 genes were expressed in CD34(+)/CD38(-)/Lin(-) cells from all three tissues. We also determined the transcriptomes of the stem cell-depleted, HPC-enriched CD34(+)/[CD38/Lin](++) cell population from each tissue. Comparison of CD34(+)/CD38(-)/Lin(-) (HSC-enriched) versus CD34(+)/[CD38/Lin](++) (HPC-enriched, HSC-depleted) cells from each tissue yielded 81 genes overrepresented and 90 genes underrepresented, common to all three of the CD34(+)/CD38(-)/Lin(-) cell populations. These transcripts, which are selectively expressed in HSCs from all three tissues, include a number of known genes (e.g., transcription factors, receptors, and signaling molecules) that might play roles in key functions (e.g., survival, self-renewal, differentiation, and/or migration/adhesion) of human HSCs. Many genes/transcripts of unknown function were also detected by microarray analysis. Serial analysis of gene expression of the bone marrow HSC and HPC populations confirmed expression of most of the overrepresented transcripts for which reliable serial analysis of gene expression tags were detected and additionally suggested that current microarrays do not detect as many as 30% of the transcripts expressed in HSCs, including a number of previously unknown transcripts. This work is a step toward full definition of the transcriptome of normal human HSCs and may identify new genes involved in leukemogenesis and cancer stem cells.
Adult generation of glutamatergic olfactory bulb interneurons
Authors: Monika S Brill, Jovica Ninkovic, Eleanor Winpenny, Rebecca D Hodge, Ilknur Ozen, Roderick Yang, Alexandra Lepier, Sergio Gascón, Ferenc Erdelyi, Gabor Szabo, Carlos Parras, Francois Guillemot, Michael Frotscher, Benedikt Berninger, Robert F Hevner, Olivier Raineteau, Magdalena Götz
Journal: Nature Neuroscience (2009)
VICARIOUS MENSTRUATION FROM THE RETINA.
Authors: J. G. HUIZINGA
Journal: JAMA (1902)

I desire to report a case of vicarious menstruation that occurred in my private practice six years ago. Miss R., aged 17; occupation, house work. Both parents are living and are healthy, hard-working people. There is no history of specific trouble or any other hereditary disease. She has never been sick, is strong, robust and well developed. Her menses appeared when she was 14. They were somewhat irregular at first, but had been fairly regular for the last year and a half. They were usually accompanied by headache, some backache and a feeling of indisposition. These symptoms were never sufficiently severe to confine her to bed. During the first day of her October menstrual period, while stooping forward to fasten her shoe, she suddenly felt dizzy and nearly fainted away. Everything she looked at seemed distorted and her vision became dimmer and dimmer. Apparently the left eye was first affected,
A Randomized Controlled Trial of Nebulized Gentamicin in Non–Cystic Fibrosis Bronchiectasis
Authors: Maeve P. Murray, John R. W. Govan, Catherine J. Doherty, A. John Simpson, Thomas S. Wilkinson, James D. Chalmers, Andrew P. Greening, Christopher Haslett, Adam T. Hill
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Bronchiectasis is a chronic debilitating disease with few evidence-based long-term treatments.A randomized controlled trial assessing the efficacy of nebulized gentamicin therapy over 1 year in patients with non-cystic fibrosis bronchiectasis.Sixty-five patients were randomized to either twice-daily nebulized gentamicin, 80 mg, or nebulized 0.9% saline, for 12 months. All were reviewed at three-monthly intervals during treatment and at 3 months' follow-up.At each review the following were assessed: quantitative and qualitative sputum bacteriology; sputum purulence and 24-hour volume; FEV(1), FVC, and forced expiratory flow, midexpiratory phase; exercise capacity; Leicester Cough Questionnaire and St. George's Respiratory Questionnaire; and exacerbation frequency. Fifty-seven patients completed the study. At the end of 12 months' treatment, compared with the saline group, in the gentamicin group there was reduced sputum bacterial density with 30.8% eradication in those infected with Pseudomonas aeruginosa and 92.8% eradication in those infected with other pathogens; less sputum purulence (8.7% vs. 38.5%; P < 0.0001); greater exercise capacity (510 [350-690] m vs. 415 [267.5-530] m; P = 0.03); and fewer exacerbations (0 [0-1] vs. 1.5 [1-2]; P < 0.0001) with increased time to first exacerbation (120 [87-161.5] d vs. 61.5 [20.7-122.7] d; P = 0.02). The gentamicin group had greater improvements in Leicester Cough Questionnaire (81.4% vs. 20%; P < 0.01) and St. George's Respiratory Questionnaire (87.5% vs. 19.2%; P < 0.004) score. No differences were seen in 24-hour sputum volume, FEV(1), FVC, or forced expiratory flow, midexpiratory phase. No P. aeruginosa isolates developed resistance to gentamicin. At follow-up, all outcome measures were similar to baseline.Regular, long-term nebulized gentamicin is of significant benefit in non-cystic fibrosis bronchiectasis but treatment needs to be continuous for its ongoing efficacy. Clinical trial registered with www.clinicaltrials.gov (NCT 00749866).
Calsequestrin 2 (CASQ2) mutations increase expression of calreticulin and ryanodine receptors, causing catecholaminergic polymorphic ventricular tachycardia
Authors: Lei Song, Ronny Alcalai, Michael Arad, Cordula M. Wolf, Okan Toka, David A. Conner, Charles I. Berul, Michael Eldar, Christine E. Seidman, J.G. Seidman
Journal: Journal of Clinical Investigation (2007)

Catecholamine-induced polymorphic ventricular tachycardia (CPVT) is a familial disorder caused by cardiac ryanodine receptor type 2 (RyR2) or calsequestrin 2 (CASQ2) gene mutations. To define how CASQ2 mutations cause CPVT, we produced and studied mice carrying a human D307H missense mutation (CASQ307/307) or a CASQ2-null mutation (CASQΔE9/ΔE9). Both CASQ2 mutations caused identical consequences. Young mutant mice had structurally normal hearts but stress-induced ventricular arrhythmias; aging produced cardiac hypertrophy and reduced contractile function. Mutant myocytes had reduced CASQ2 and increased calreticulin and RyR2 (with normal phosphorylated proportions) but unchanged calstabin levels, as well as reduced total sarcoplasmic reticulum (SR) Ca2+, prolonged Ca2+ release, and delayed Ca2+ reuptake. Stress further diminished Ca2+ transients, elevated cytosolic Ca2+, and triggered frequent, spontaneous SR Ca2+ release. Treatment with Mg2+, a RyR2 inhibitor, normalized myocyte Ca2+ cycling and decreased CPVT in mutant mice, indicating RyR2 dysfunction was critical to mutant CASQ2 pathophysiology. We conclude that CPVT-causing CASQ2 missense mutations function as null alleles. In the absence of CASQ2, calreticulin, a fetal Ca2+-binding protein normally downregulated at birth, remains a prominent SR component. Adaptive changes to CASQ2 deficiency (increased posttranscriptional expression of calreticulin and RyR2) maintained electrical-mechanical coupling, but increased RyR2 leakiness, a paradoxical response further exacerbated by stress. The central role of RyR2 dysfunction in CASQ2 deficiency unifies the pathophysiologic mechanism underlying CPVT due to RyR2 or CASQ2 mutations and suggests a therapeutic approach for these inherited cardiac arrhythmias.
Book: Hidden Depths: The Story of Hypnosis
Authors: R. Persaud
Journal: BMJ (2002)

Robin Waterfield Macmillan, £20, pp 464 ISBN 0 333 77949 5 ——————— Rating: ![Graphic][1]</img>![Graphic][2]</img> One of the illustrations in this book is of a newspaper advertisement, which screams, “How to get girls through hypnotism!” The author of this entertaining book, Robin Waterfield, prosaically points out beneath the illustration, “It is impossible to make even a hypnotised subject go against her moral code.” This immediately raises the central conundrum with hypnosis—if you can't make people under hypnosis do what they wouldn't have done otherwise, then what's the point of it? The social psychologists argue that it gives subjects an excuse to behave in ways that they would otherwise find difficult to justify, and is no less powerful for that. Waterfield, writer in residence at Sussex University, starts his historical account of hypnosis by stating that, “As sometimes happens, science is actually behind the times on this. A … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif
Prevention of transcoronary macromolecular leakage after ischemia-reperfusion by the calcium entry blocker nisoldipine. Direct observations in isolated rat hearts.
Authors: P F McDonagh, D J Roberts
Journal: Circulation Research (1986)

Coronary microvascular damage appears to play a role in reperfusion injury after myocardial ischemia. This study was designed to afford direct viewing of the effects of myocardial ischemia-reperfusion on the coronary microcirculation and to determine whether pretreatment with the calcium blocker nisoldipine would attenuate any microvascular damage during reperfusion. Four groups of isolated rat hearts were perfused with a solution that contained red cells and fluorescent albumin, but was essentially free of platelets and leukocytes. Group I served as a nonischemic control. Group II hearts were subjected to 30 minutes of no-flow ischemia followed by reperfusion. Group III hearts were pretreated with nisoldipine (1 microgram/min) for 5 minutes before ischemia, and group IV hearts were treated with nitroglycerin (93 micrograms/min) before and after ischemia to mimic the vasodilation caused by nisoldipine. Perfused coronary capillarity and transcoronary extravasation of plasma albumin were measured by direct visualization techniques before and after ischemia. For group I, there was no significant change in coronary resistance, perfused capillarity, or transcoronary extravasation with time. For both groups II and IV, ischemia-reperfusion caused no increase in coronary resistance, but a significant decrease in perfused capillarity and a marked increase in transcoronary extravasation of fluorescent albumin (P less than 0.05). The nisoldipine group (group III) demonstrated a similar decrease in perfused capillarity but no increase in protein extravasation during reperfusion. These results indicate that, in the heart, platelets and/or leukocytes are not absolutely necessary to induce either the no-reflow phenomenon or the permeability damage observed during reperfusion after ischemia. The protective effect of treatment with nisoldipine appeared to be independent of vasodilation. We speculate that this calcium blocker reduced endothelial uptake of calcium during reperfusion, preventing endothelial deformation and formation of interendothelial gaps.
Coexpression of endothelial markers and CD14 by cytokine mobilized CD34+ cells under angiogenic stimulation
Authors: D Nakul-Aquaronne
Journal: Cardiovascular Research (2003)

Objective: A subset of adult peripheral blood leukocytes functions as endothelial progenitor cells that incorporate into the vasculature in animal models of neovascularization. The basic mechanisms by which differentiation proceeds are still unclear. This study analyses the in vitro differentiation of cytokine mobilized, human CD34+ cells. Methods: Granulocyte-monocyte colony stimulating factor mobilized human CD34+ cells were isolated and grown in culture in the presence of vascular endothelial growth factor (50 ng/ml) and basic fibroblast growth factor (10 ng/ml). Their differentiation was followed using cytological and immunohistochemical techniques. Fibronectin-coated culture dishes or three-dimensional cultures were used. Results: CD34+ cells grown on fibronectin-coated dishes differentiated along the granulocytic and monocytic/macrophage lineages with no evidence for an endothelial cell differentiation. CD14+ macrophages appeared in long-term culture and then acquired endothelial cell markers such as VE-cadherin, the endothelial form of NO synthase and the von Willebrand factor. Yet they were unable to form tubular structures in Matrigel®. Only typical macrophages were observed in Matrigel®. Conclusion: Angiogenic stimulation of CD34+ precursor cells leads to cells that expressed mixed macrophage and endothelial cell properties. They could represent an intermediate phenotype in the pathway that leads to mature endothelial cells.
On Aging, Senescence, and Senility
Authors: CHARLES D. ARING
Journal: Annals of Internal Medicine (1972)

Since senility haunts everyone, it behooves us to become aware that evasive action may be required. When bringing up a child, it is well to think of his old age, was the prescient observation of the French moralist Joubert. The prescription for growing old is to accent growth rather than aging. Currently there is no better answer to the problem of senility.
A Spooky Proposal
Authors: Lois DeBakey
Journal: JAMA (1974)

To the Editor.—  Now that one medical journal1has experimented with the rewriting of a research report by a lay journalist, will the hext step be to have professional public speakers deliver scientists' papers  biomedical meetings?2  In addition to wraithy writers and spectral speakers, we might try phantom physicians, ersatz educators, surrogate scholars, and ethereal editors. The list could be extended indefinitely. After all, jazzing it up is where it's at today, isn't it? So who needs authenticity, literacy, scholarship—or the real thing?