tbuckley/cabot-search huggingface dataset:
The Author's reply
Authors: Amnon Sonnenberg
Journal: Gut (2011)

The author's response: I appreciate the comments by Drs Johnson and Fitzsimmons.1 In my opinion, three separate issues need to be emphasised when trying to understand the long-term time trends of gastric cancer, gastric ulcer and duodenal ulcer as evidenced by their mortality data in my recent article in Gut .2 First, the time trends depicted in the article are not a fluke of the birth-cohort analysis or solely related to the use of mortality data, but truly reflective of changes in the underlying epidemiology of these three diseases. The vital statistics serve as a means to accumulate large populations with gastric cancer or peptic ulcer from different countries and group such patients by their age …
Drug points: Immune complex haemolytic anaemia associated with sulfasalazine
Authors: Valery Teplitsky, Irit Virag, Aaron Halabe
Journal: BMJ (2000)

A 79 year old woman was admitted because of a positive Coombs's test result for haemolytic anaemia (haemoglobin concentration 8.2 g/dl). She had been taking sulfasalazine for ulcerative colitis for five years.

The patient's medical history included a cerebrovascular accident and atrial fibrillation, which were treated with digoxin, verapamil, aspirin, and oxazepam. On admission, aspirin, sulfasalazine, and oxazepam were discontinued, and two units of blood were given. After sulfasalazine was reintroduced, the patient showed evidence of haemolysis: her haemoglobin concentration had decreased by 2.5 g/dl, lactate dehydrogenase concentration had increased from 494 to 2620 U/l, and total bilirubin concentration had increased from 0.4 to 1.4 mg/dl. Sulfasalazine was discontinued, and all biochemical parameters returned to normal. Haematological studies were performed according to published methods.1

The possibility of a drug dependent immune complex was assessed. Agglutination occurred when a mixture of sulfasalazine and the patient's serum was added to normal erythrocytes treated with the endopeptidase ficin. No reactivity was noted when control serum was used or when sulfasalazine was omitted. Preincubation of sulfasalazine with normal erythrocytes gave negative results on addition of the patient's serum, excluding the possibility of a penicillin-like reaction.

Sulfasalazine causes Heinz body anaemia in patients with abnormal haemoglobin and haemolysis in patients deficient in glucose-6-phosphate dehydrogenase. Our patient had a normal concentration of glucose-6-phosphate dehydrogenase, and no Heinz bodies were seen on a blood smear. A few patients with ulcerative colitis treated with sulfasalazine and who have immune haemolytic anaemia have been described, but in none was sulfasalazine clearly implicated.2–4 The manufacturer (Pharmacia Upjohn) could provide no additional information about this side effect. Our report is important as 1.7% of patients with ulcerative colitis develop immune haemolytic anaemia even in the absence of treatment with sulfasalazine.5
Prognostic significance of triple-negative phenotype in breast cancer
Authors: M. Y. Choi, K. E. Lee, H. J. Chang, S. H. Sung, B. I. Moon, H. Y. Choi, H. S. Suh, E. M. Nam, Y. C. Mun, C. M. Seong, S. N. Lee
Journal: Journal of Clinical Oncology (2008)

11587 Background: Triple-negative breast cancers(TNBC) are defined as a lack of expression of estrogen, progesterone receptors and HER2. Recently gene expression analysis identified basal-like subgroup and this is compatible with histological TNBC. The aim of this study was to evaluate the clinico-pathological characteristics and prognosis in breast cancer patients who expressed triple-negative phenotype. Methods: Three hundred forty eight patients who underwent curative breast cancer surgery from January 2000 to December 2005 were analyzed retrospectively. The IHC method was used to define ER, PR and HER2 expression status. HER2 was scored positive if 3+ result was found or amplified gene expression on FISH. Results: Sixty seven cases (19.3%) of 348 patients showed triple-negative expression pattern and forty five cases (12.9%) showed HR-/HER2+ expression pattern and the others showed HR+ expression pattern. The TNBC subgroup was associated with a high tumor grade and high relapse rate. Other characteristics such as age, stage, lympho-vascular invasion, relapse site showed no difference between three subgroups. The 5YSR of HR+, HR-/HER2+ and TNBC subgroup were 94.0, 83.2 and 88.7% (p=0.013) and 5 year DFS rate were 87.4, 75.1 and 79.7%(p=0.011). In multivariate analysis, risk group by IHC was the only independent prognostic factor and TNBC phenotype showed the worst outcome(HR 3.85, 95%CI 1.41–10.52, p=0.008). Conclusions: Both TNBC subgroup and HR-/HER2+ subgroup showed significantly worse prognosis than HR+ subgroup and there was no significant difference between these two subgroups. In multivariate analysis, TNBC showed the significant prognostic variable in breast cancer and to overcome these characteristics of TNBC, it is need to find another powerful molecular targeted agents or new cytotoxic drugs. No significant financial relationships to disclose.
Evolution in the treatment of multiple myeloma and impact on dialysis independence: data from a French cohort from 1999 to 2014
Authors: M Laforet, N Jourde-Chiche, F Haddad, M Sallee, A M Stoppa, P Brunet, B Dussol, S Burtey, B Gondouin
Journal: Blood Cancer Journal (2016)

Evolution in the treatment of multiple myeloma and impact on dialysis independence: data from a French cohort from 1999 to 2014
Incorporating therapeutic drug monitoring into the World Health Organization hierarchy of tuberculosis diagnostics
Authors: Samiksha Ghimire, Mathieu S. Bolhuis, Marieke G.G. Sturkenboom, Onno W. Akkerman, Wiel C.M. de Lange, Tjip S. van der Werf, Jan-Willem C. Alffenaar
Journal: European Respiratory Journal (2016)

Tuberculosis (TB), once considered as a disease of the past generally afflicting poor people, still claims 1.5 million lives annually [1]. Although 86% of patients with drug susceptible TB are cured with established first-line drugs, treatment is often longer than 6 months due to slow response, compliance problems or adverse drug reactions. In addition, emergence of drug-resistant Mycobacterium tuberculosis strains with an unacceptably low treatment success rate of 50% and TB–HIV co-infection have challenged the goals of global TB control and elimination [1]. Incorporating therapeutic drug monitoring into the WHO hierarchy of tuberculosis diagnostics <http://ow.ly/YcRMw>
GLP-1 Restores Altered Insulin and Glucagon Secretion in Posttransplantation Diabetes
Authors: Thea A.S. Halden, Erlend J. Egeland, Anders Åsberg, Anders Hartmann, Karsten Midtvedt, Hassan Z. Khiabani, Jens J. Holst, Filip K. Knop, Mads Hornum, Bo Feldt-Rasmussen, Trond Jenssen
Journal: Diabetes Care (2016)

OBJECTIVE Development of posttransplantation diabetes (PTDM) is characterized by reduced insulin secretion and sensitivity. We aimed to investigate whether hyperglucagonemia could play a role in PTDM and to examine the insulinotropic and glucagonostatic effects of the incretin hormone glucagon-like peptide 1 (GLP-1) during fasting and hyperglycemic conditions, respectively. RESEARCH DESIGN AND METHODS Renal transplant recipients with (n = 12) and without (n = 12) PTDM underwent two separate experimental days with 3-h intravenous infusions of GLP-1 (0.8 pmol/kg/min) and saline, respectively. After 1 h of infusion, a 2-h hyperglycemic clamp (fasting plasma glucose + 5 mmol/L) was established. Five grams of arginine was given as an intravenous bolus 10 min before termination of the clamp. RESULTS Fasting concentrations of glucagon (P = 0.92) and insulin (P = 0.23) were similar between the groups. In PTDM patients, glucose-induced glucagon suppression was significantly less pronounced (maximal suppression from baseline: 43 ± 12 vs. 65 ± 12%, P &amp;lt; 0.001), while first- and second-phase insulin secretion were significantly lower. The PTDM group also exhibited a significantly lower insulin response to arginine (P = 0.01) but similar glucagon and proinsulin responses compared with control subjects. In the preclamp phase, GLP-1 lowered fasting plasma glucose to the same extent in both groups but reduced glucagon only in PTDM patients. During hyperglycemic clamp, GLP-1 reduced glucagon concentrations and increased first- and second-phase insulin secretion in both groups. CONCLUSIONS PTDM is characterized by reduced glucose-induced insulin secretion and attenuated glucagon suppression during a hyperglycemic clamp. Similar to the case in type 2 diabetes, GLP-1 infusion seems to improve (insulin) or even normalize (glucagon) these pathophysiological defects.
Debriefing after psychological trauma
Authors: D. Summerfield
Journal: BMJ (1995)

Inappropriate exporting of Western culture may cause additional harm

EDITOR,--Trauma is a growth industry in the West and thus fertile terrain for fashion. Beverley Raphael and colleagues note that debriefing after psychological trauma, which they call a social movement, is being widely instituted in advance of objective evidence of efficacy.1 I wish to highlight one aspect with considerable implications: the export of Western psychological practices of this kind to various peoples affected by war worldwide.2

Rwanda is a good example. The first flows of destitute Tutsi refugees into Tanzania had scarcely …
Some Mechanisms of Formation of Polyploid and Heteroploid Cells in a Murine Ascites Tumor &lt;italic&gt;In Vitro&lt;/italic&gt;
Authors: D. C. Roberts, Glynda E. Cole
Journal: JNCI Journal of the National Cancer Institute (1964)

This paper records the behavior in vitro of cells, at and about the time of their division, in an ascites subline of a naturally occurring murine epithelioma. Under the conditions of these experiments, uninuclear cells of higher ploidy are formed from uninuclear cells of lower ploidy through the intermediate stage of a binuclear cell. The production of the intermediate binuclear cell depends on failure of cytoplasmic cleavage at the time of attempted division of a uninuclear cell. When a binuclear cell divides to produce 2 uninuclear daughters, the chromosomes of both nuclei come together on a single metaphase plate, anaphase and telophase appearing normal. Cytoplasmic cleavage is successful, and two uninuclear daughters are formed. Uninuclear daughters of higher ploidy so produced are viable and capable of further mitoses, which may be normal or may vary in the modes of their division. In a binuclear cell that fails to cleave in successive attempts at division, the chromosomes come together on a single metaphase plate on each occasion, which results in a cell of successively higher ploidy. Rarely, multipolar separation of chromosomes results in reduction of the chromosome complement of a cell. Similar multipolar divisions may give rise to binuclear and trinuclear cells that are usually viable and may undergo further division.
Suffering Before The Cure: Evaluation Of Psychological Morbidities In Adolescents and Young Adults With Hematologic Malignancies In Early Survivorship
Authors: Lori S. Muffly, Fay J Hlubocky, Joseline Gomez, Kate Breitenbach, Mary Lappe, Jennifer McNeer, Wendy Stock, Christopher K Daugherty
Journal: Blood (2013)
Phase I Study of Tremelimumab (Trem) in Combination with Gefitinib (Gef) in Epidermal Growth Factor Receptor Mutant (Egfr-Mut) Non-Small Cell Lung Cancer (Nsclc)
Authors: D. Planchard, N. Chaput-Gras, F. Barlesi, J. Mazieres, N. Byrne, D. Vuillier, L. Lacroix, B. Besse, E. Lanoy, F. Wunder, C. Jannin, K. Malekzadeh, M. Ngocamus, A. Nash, A. Di Pietro, J-C Soria
Journal: Annals of Oncology (2014)
Capacities of Mouse Embryo Cells for Induction of Unscheduled DNA Synthesis by 4-Nitroquinoline 1-Oxide in Primary Culture Systems&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Hidetaka Masuda, Hideya Endo
 4
Journal: JNCI Journal of the National Cancer Institute (1981)

Because 4-nitroquinoline 1-oxide (4-NQO) selectively induces lung tumors in offspring of ICR/Jcl inbred mice, unscheduled DNA synthesis (UDS) induced by 4-NQO was investigated with use of confluent primary cultures of cells from six different organs of ICR/Jcl mouse embryos. The UDS level of lung-derived cells (lung cells), as measured with hydroxyurearesistant incorporation of [3H]thymidine into cellular DNA in the presence of 4-NQO, was at least threefold lower than levels in cells from skin, intestine, kidney, liver, and brain, when compared at equitoxic doses of 4-NQO or equimolar binding of 4-NQO to DNA. Autoradiographic studies also revealed that the percentage of UDS-positive nuclei in lung cells was about one-fifth of other cell types. Cytotoxic examinations showed that the lung cells were the most sensitive to the lethal action of 4-NQO. These results suggest that the capacity of cells from the target organ to repair 4-NQO damage is intrinsically much lower than the capacity of cells from nontarget organs.
Combination Of Indoleamine 2,3-Dioxygenase Inhibitor and Cytotoxic Agents Is a Novel Therapeutic Option For Non-Hodgkin Lymphoma
Authors: Nobuhiko Nakamura, Takeshi Hara, Yuhei Shibata, Takuro Matsumoto, Ryoko Mabuchi, Hiroshi Nakamura, Junichi Kitagawa, Nobuhiro Kanemura, Naoe Goto, Masahito Shimizu, Hisashi Tsurumi, Hisataka Moriwaki
Journal: Blood (2013)
The characterization and dissolution performances of spray dried solid dispersion of ketoprofen in hydrophilic carriers
Authors: Siok-Yee Chan, Yin-Ying Chung, Xin-Zi Cheah, Eryn Yen-Ling Tan, Joan Quah
Journal: Asian Journal of Pharmaceutical Sciences (2015)

Solid dispersion is one of the most promising strategies to improve oral bioavailability of poorly soluble API. However, there are inconsistent dissolution performances of solid dispersion reported which entails further investigation. In this study, solid dispersions of ketoprofen in three hydrophilic carriers, i.e. PVP K30, PVPVA 6:4 and PVA were prepared and characterized. Physical characterization of the physical mixture of ketoprofen and carriers shows certain extent of amorphization of the API. This result is coinciding to evaluation of drug–polymer interaction using ATR-FTIR whereby higher amorphization was seen in samples with higher drug–polymer interaction. XRPD scanning confirms that fully amorphous solid dispersion was obtained for SD KTP PVP K30 and PVPVA system whereas partially crystalline system was obtained for SD KTP PVA. Interestingly, dissolution profiles of the solid dispersion had shown that degree of amorphization of KTP was not directly proportional to the dissolution rate enhancement of the solid dispersion system. Thus, it is concluded that complete amorphization does not guarantee dissolution enhancement of an amorphous solid dispersion system.
Analysis Of The Lin- CD45- CD34/CD133+ Cell Population In G-CSF-Mobilized Peripheral Blood By Polychromatic Flow Cytometry and Micro RNA Profiling
Authors: Yajuan Jiang, David Mallinson, Daria Olijnyk, Sarah Paterson, Susan Ridha, Lisa Tang, Vincent O'Brien, Timothy C. Fong, David W. O'Neill
Journal: Blood (2013)
Abstract POSTER-BIOL-1344: Epigenetic regulation of SPARC in ovarian cancer
Authors: Dylan P. Matthews, Sherine Taylor, Neveen A. Said
Journal: Clinical Cancer Research (2015)

Abstract Background: We have previously reported the tumor suppressor effect of Secreted protein acidic and rich in cysteine (SPARC) in ovarian cancer in vitro and in vivo. We reported that SPARC suppresses ovarian cancer cells interactions with the surrounding environmental cues within the peritoneal milieu. We also reported that the expression of SPARC was decreased in established ovarian cancer cell lines and micro-dissected ovarian cancer cells from advanced tumors consistent with hypermethylation of its promoter. However, the mechanisms of epigenetic regulation of SPARC in ovarian cancer (and other morbidities) are unraveled. Experimental Procedures: In silico analysis, human ovarian cancer tissue microarrays, a panel of established human ovarian cancer cell lines and in vitro ovarian cancer cell models were used. Genetic and pharmacologic manipulation of NFκB subunits and DNA methyl transferases (DNMTs) were used to investigate their involvement in the transcriptional regulation of SPARC expression and function. Results: In silico mapping of SPARC promoter identified consensus binding sites for subunits (RelA and NFκB1). Pharmacologic inhibition of NFκB as well as knockdown of p65-RelA and p50 subunits restored SPARC expression and function in ovarian cancer cells. Treatment of ovarian cancer cells with demethylating agent 5’-azacytidine and knockdown of DNMTs (DNMT1, DNMT3a and DNMT3b) indicated that NFκB-mediated SPARC repression is due to promoter methylation through DNMT3a. In ovarian cancer tissue microarrays, SPARC expression in cancer cells significantly and progressively decreased in advanced stage. The expression of SPARC in cancer cells inversely correlated with nuclear p65-RelA and DNMT3a expression. Conclusion: Our findings indicate that activated NFκB integrates inflammatory signals to exert epigenetic pressure suppressing tumor-SPARC through promoter methylation. Pharmacologic inhibitors of NFκB as well as anti-inflammatory agents may provide a significant therapeutic opportunity. Citation Format: Dylan P. Matthews, Sherine Taylor, Neveen A. Said. Epigenetic regulation of SPARC in ovarian cancer [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-BIOL-1344.
Abstract 16189: Lineage Tracing of Postnatal Cardiomyogenic Progenitor Cells
Authors: Yuan-Hung Liu, Shih-Yun Huang, Yi-Shuan Lin, Hsing-Yu Huang
Journal: Circulation (2014)

Recent studies report that postnatal mammalian hearts undergo cardiomyocyte refreshment. While the exact origin of the cells involved in postnatal cardiomyogenesis remains unclear. Here, we identified a pool of Nkx2.5 enhancer expressing cells in the postnatal mouse heart with cardiomyogenic differentiation potential in vitro. We tracked the expression of a cardiac-specific enhancer of Nkx2.5 using inducible Nkx2.5 enhancer-Cre mice from embryonic development to adulthood and post-myocardial infarction (MI) and documented the Nkx2.5 enhancer expressing cells directly contribute to postnatal cardiomyogenesis in vivo. Upon genetic ablation of these activated progenitors after myocardial injury, the cardiac function deteriorated. Transcriptomic analysis of Nkx2.5 enhancer expressing cells showed high expression of heart development genes. To trace the developmental origin of the activated Nkx2.5 cardiomyogenic progenitor cells, we created different lineage-Cre/Nkx2.5 enh-eGFP/ROSA26 reporter triple transgenic mice. Post-MI Nkx2.5 cardiomyogenic progenitor cells originated from the embryonic epicardial cells, not from the pre-existing cardiomyocytes, endothelial cells, cardiac neural crest cells, or perinatal/postnatal epicardial cells. Together, this study confirmed that cardiac lineage-specific progenitor cells, which originate from embryonic epicardium-derived cells, contribute to postnatal mammalian cardiomyogenesis.
A New Option for Treating IBS With Diarrhea
Authors: Anita Slomski
Journal: JAMA (2016)

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Prevalence of misuse of prescribed benzodiazepines in patients with primary anxiety disorder or major depression
Authors: M J Garvey, G D Tollefson
Journal: American Journal of Psychiatry (1986)

Seventy-one patients with major depression or an anxiety disorder were treated with benzodiazepines. They were followed prospectively for evidence of misuse or abuse. There was no evidence of benzodiazepine abuse. Five patients (all with major depression) misused their benzodiazepines.
Abstract 11345: Resource Demands and the Incidence of Cardiopulmonary Resuscitation Within a Pediatric Cardiac Intensive Care Unit
Authors: Matthew K Bacon, Stephanie J Conrad, Brittney C Hatch, John D Hughes, Michelle K Terrell, Patrick O Maynord, Andrew H Smith
Journal: Circulation (2014)

Background: Econometric evidence suggests exponential declines in the ability to provide critical care services as variable demands exceed a relatively fixed supply of available critical care resources. We hypothesized that increasing demands upon resources within a pediatric cardiac intensive care unit (CICU) is also associated with increases in the incidence and rate of cardiopulmonary resuscitation. Methods and Results: Records from each twelve-hour nursing shift within an eighteen-bed pediatric CICU from 1 July 2010 through 30 April 2014 were retrospectively reviewed. There were 2716 reports available for review from 2769 shifts (97%). During the study period, there were 1,803 surgical and 1,215 medical admissions, accounting for a median census of 15 (interquartile range [IQR] 13-17) patients per shift, and a total of 20,269 patient days (40,538 patient-shifts) over the 44-month study period. Median bed capacity was 83% (IQR 72-94%), and median patient to nursing assignment ratio was 1.5 (IQR 1.4-1.6 patients per nurse assignment). Cardiac arrest (defined as administration of chest compressions) was identified in 138 occasions in 134 shifts, an arrest rate of 3.4 arrests per 1000 patient-shifts. Arrests were no more frequent during night versus day shifts (3.2 v. 3.6 per 1000 patient shifts, p=0.40), nor were they greater during weekend versus weekday shifts (2.9 v. 3.9 per 100 patient-shifts, p=0.14). There was a trend toward an increase in the incidence of cardiac arrest with patient to nurse assignment ratios of less than 1.5 (2.8 v. 3.9 arrests per 1000 patient shifts, p=0.06). Unit occupancy exceeding 85% was associated with a 45% greater rate of cardiac arrest (2.6 v 4.1 arrests per 1000 patient-shifts, 95%CI 0.3 to 2.6 increase, p=0.01). Conclusions: We report a significant increase in the incidence of cardiopulmonary resuscitation at times of greater resource consumption within a pediatric CICU as defined by unit capacity. Multi-institutional studies are necessary to identify generalizable organizational characteristics that may promote efficient allocation of resources and optimize delivery of care to a population of patients at greater risk for significant hospital morbidity.