tbuckley/cabot-search huggingface dataset:
Anthracycline-Induced Clinical Heart Failure in a Cohort of 607 Children: Long-Term Follow-Up Study
Authors: L. C.M. Kremer, E. C. van Dalen, M. Offringa, J. Ottenkamp, P. A. Voûte
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To determine the early and late cumulative incidence of anthracycline-induced clinical heart failure (A-CHF) after anthracycline therapy in childhood and to identify associated risk factors. PATIENTS AND METHODS: The cumulative incidence of A-CHF and the risk factors of A-CHF were assessed in a cohort of 607 children who had been treated with anthracyclines between 1976 and 1996. For 96% of the cohort, we obtained the clinical status up to at least January 1997. The mean follow-up time was 6.3 years. RESULTS: The cumulative incidence of A-CHF was 2.8%, after a mean follow-up time of 6.3 years and a mean cumulative dose of anthracyclines of 301 mg/m 2 . A cumulative dose of anthracycline higher than 300 mg/m 2 was associated with an increased risk of A-CHF (relative risk, 11.8; 95% confidence interval, 1.6 to 59.5) compared with a cumulative dose lower than 300 mg/m 2 . The estimated risk of A-CHF increased with time after the start of anthracycline chemotherapy to 2% after 2 years and 5% after 15 years. CONCLUSION: Up to 5% of patients will develop A-CHF 15 years after treatment, and patients treated with a cumulative dose of anthracyclines higher than 300 mg/m 2 are at highest risk for A-CHF. This is thus a considerable and serious problem among these young patients. The findings reinforce the need for strategies for early detection of patients at risk for A-CHF and for the evaluation of other chemotherapeutic possibilities or cardioprotective agents in relation to the survival.
1272 EFFICACY OF BLX 1002 IN ANIMAL MODELS OF NON-ALCOHOLIC FATTY LIVER DISEASE AND DYSLIPIDEMIA
Authors: S. Narayanan, D. Vijayaraj, N.M. Kulkarni, P. Shetty, K. Jayanarayan, P.L. Vinitha, B.R. Navin, J. Mookkan
Journal: Journal of Hepatology (2011)
The avoidability of head and neck injuries in ice hockey: an historical review
Authors: N Biasca, S Wirth, Y Tegner
Journal: British Journal of Sports Medicine (2002)

The number of minor traumatic brain injury (mTBI), cerebral concussions, is increasing and cannot be eliminated by any kind of equipment. Prevention strategies, such as the introduction of "checking from behind" rules have become effective in decreasing the number of severe spinal injuries. A new "head checking" rule should reduce mTBI in the same way in the following years. Mouthguards should be mandatory as an effective device for the prevention of dental and orofacial injuries, as well as reducing the incidence and severity of mTBI. A new internet database system, the International Sports Injury System (ISIS) should improve epidemiological analysis of head, face, and spinal injuries worldwide. ISIS should provide an internationally compatible system for continuous monitoring of risk factors, protective effects of equipment, and protective effects of equipment and effects of changes in rules through the years.
Selective Aggregation of L1210 Leukemia Cells by the Polycation Chitosan&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: A E Sirica, R J Woodman
Journal: JNCI Journal of the National Cancer Institute (1971)

The polycation chitosan, at concentrations ranging from 0.05–0.006 × 10−3 mEq./ml, selectively aggregated L1210 leukemia cells in vitro when compared to normal murine erythrocytes and bone marrow cells, as well as Sarcoma 37 and Ehrlich ascites cells. Poly-L-lysine and polyethylenimine, however, at these concentrations, did not discriminate between the erythrocytes and L1210 cells. Both chitosan and poly-L-lysine (3.2-0.2 × 10−3 mEq./ml) produced dense aggregation, cytoplasmic swelling, and/or cytolysis of the L1210 cells and increased the permeability of these cells to trypan blue. Poly-L-lysine (0.2 × 10−3 mEq./ml) produced similar morphological alterations of the erythrocytes, whereas chitosan, at this concentration, only minimally aggregated the erythrocytes and did not conspicuously alter their morphology. Incubation of the L1210 cells with chitosan or poly-L-lysine partially inhibited the transplantability of the cells, as measured by survival time, after inoculation into (C57BL × DBA)F1 (BDF1) mice. Immunosuppression with 180 m3/kg cyclophosphamide did not significantly alter this effect. Further, chronic chitosan treatment of BDF1 mice, bearing intraperitoneal implants of the L1210 ascites tumor, retarded the dissemination of the leukemic cells into the peripheral blood.
Epigenetic Regulation of BMP7 in the Regenerative Response to Ischemia
Authors: Takeshi Marumo, Keiichi Hishikawa, Masahiro Yoshikawa, Toshiro Fujita
Journal: Journal of the American Society of Nephrology (2008)

Kidneys damaged by ischemia have the potential to regenerate through a mechanism involving intrarenal induction of protective factors, including bone morphogenetic protein-7 (BMP7). Epigenetic changes, such as alterations in histone modifications, have also been shown to play a role in various pathologic conditions, but their involvement in ischemic injury and regeneration remains unknown. This study investigated whether changes in histone acetylation, regulated by histone acetyltransferase and histone deacetylase (HDAC), are induced by renal ischemia and involved in the regenerative response. Ischemia/reperfusion of the mouse kidney induced a transient decrease in histone acetylation in proximal tubular cells, likely as a result of a decrease in histone acetyltransferase activity as suggested by experiments with energy-depleted renal epithelial cells in culture. During recovery after transient energy depletion in epithelial cells, the HDAC isozyme HDAC5 was selectively downregulated in parallel with the return of acetylated histone. Knockdown of HDAC5 by RNAi significantly increased histone acetylation and BMP7 expression. BMP7 induction and HDAC5 downregulation in the recovery phase were also observed in proximal tubular cells in vivo after transient ischemia. These data indicate that ischemia induces dynamic epigenetic changes involving HDAC5 downregulation, which contributes to histone re-acetylation and BMP7 induction in the recovery phase. This highlights HDAC5 as a modulator of the regenerative response after ischemia and suggests HDAC5 inhibition may be a therapeutic strategy to enhance BMP7 expression.
Effect of conjugate pneumococcal vaccine followed by polysaccharide pneumococcal vaccine on recurrent acute otitis media: a randomised study
Authors: Reinier Veenhoven, Debby Bogaert, Cuno Uiterwaal, Carole Brouwer, Herma Kiezebrink, Jacob Bruin, Ed IJzerman, Peter Hermans, Ronald de Groot, Ben Zegers, Wietse Kuis, Ger Rijkers, Anne Schilder, Elisabeth Sanders
Journal: The Lancet (2003)
Molecular mechanisms of nutlin-3 involve acetylation of p53, histones and heat shock proteins in acute myeloid leukemia
Authors: Ingvild Haaland, Jill A Opsahl, Frode S Berven, Håkon Reikvam, Hanne K Fredly, Ragnhild Haugse, Bernd Thiede, Emmet McCormack, Sonia Lain, Øystein Bruserud, Bjørn Tore Gjertsen
Journal: Molecular Cancer (2014)

The small-molecule MDM2 antagonist nutlin-3 has proved to be an effective p53 activating therapeutic compound in several preclinical cancer models, including acute myeloid leukemia (AML). We and others have previously reported a vigorous acetylation of the p53 protein by nutlin-treatment. In this study we aimed to investigate the functional role of this p53 acetylation in nutlin-sensitivity, and further to explore if nutlin-induced protein acetylation in general could indicate novel targets for the enhancement of nutlin-based therapy. Nutlin-3 was found to enhance the acetylation of p53 in the human AML cell line MOLM-13 (wild type TP53) and in TP53 null cells transfected with wild type p53 cDNA. Stable isotope labeling with amino acids in cell culture (SILAC) in combination with immunoprecipitation using an anti-acetyl-lysine antibody and mass spectrometry analysis identified increased levels of acetylated Histone H2B, Hsp27 and Hsp90 in MOLM-13 cells after nutlin-treatment, accompanied by downregulation of total levels of Hsp27 and Hsp90. Intracellular levels of heat shock proteins Hsp27, Hsp40, Hsp60, Hsp70 and Hsp90α were correlated to nutlin-sensitivity for primary AML cells (n = 40), and AML patient samples with low sensitivity to nutlin-3 tended to express higher levels of heat shock proteins than more responsive samples. Combination therapy of nutlin-3 and Hsp90 inhibitor geldanamycin demonstrated synergistic induction of apoptosis in AML cell lines and primary AML cells. Finally, TP53 null cells transfected with a p53 acetylation defective mutant demonstrated decreased heat shock protein acetylation and sensitivity to nutlin-3 compared to wild type p53 expressing cells. Altogether, our results demonstrate that nutlin-3 induces acetylation of p53, histones and heat shock proteins, and indicate that p53 acetylation status and the levels of heat shock proteins may participate in modulation of nutlin-3 sensitivity in AML.
Comparison of Insulin Aspart and Lispro
Authors: Carol Homko, Antonio Deluzio, Carolyn Jimenez, Jerzy W. Kolaczynski, Guenther Boden
Journal: Diabetes Care (2003)

OBJECTIVE—To compare insulin levels and actions in patients with type 1 diabetes after subcutaneous injection of the rapid-acting insulin analogs aspart and lispro. RESEARCH DESIGN AND METHODS—Seven C-peptide–negative patients with type 1 diabetes (two men and five women) were studied at the General Clinical Research Center at Temple University Hospital two times, 1 month apart. Their plasma glucose was normalized overnight by intravenous infusion of insulin. The next morning, they received subcutaneous injections of either aspart or lispro (9.4 ± 1.9 U) in random order. For the next 4–5 h, their plasma glucose was clamped at ∼5.5 mmol/l with a variable infusion of 20% glucose. The study was terminated after 8 h. RESULTS—Both insulin analogs produced similar serum insulin levels (250–300 pmol/l) at ∼30 min and disappeared from serum after ∼4 h. Insulin aspart and lispro had similar effects on glucose and fat metabolism. Effects on carbohydrate metabolism (glucose uptake, glucose oxidation, and endogenous glucose production) peaked after ∼2–3 h and disappeared after ∼5–6 h. Effects on lipid metabolism (plasma free fatty acid, ketone body levels, and free fatty acid oxidation) appeared to peak earlier (at ∼2 h) and disappeared earlier (after ∼4 h) than the effects on carbohydrate metabolism. CONCLUSIONS—We conclude that both insulin aspart and lispro are indistinguishable from each other with respect to blood levels and that they are equally effective in correcting abnormalities in carbohydrate and fat metabolism in patients with type 1 diabetes.
Trends in Advance Care Planning in Patients With Cancer
Authors: Amol K. Narang, Alexi A. Wright, Lauren H. Nicholas
Journal: JAMA Oncology (2015)

<h3>Importance</h3> Advance care planning (ACP) may prevent end-of-life (EOL) care that is nonbeneficial and discordant with patient wishes. Despite long-standing recognition of the merits of ACP in oncology, it is unclear whether participation in ACP by patients with cancer has increased over time. <h3>Objectives</h3> To characterize trends in durable power of attorney (DPOA) assignment, living will creation, and participation in discussions of EOL care preferences and to explore associations between ACP subtypes and EOL treatment intensity as reflected in EOL care decisions and terminal hospitalizations. <h3>Design, Setting, and Participants</h3> We analyzed prospectively collected survey data from 1985 next-of-kin surrogates of Health and Retirement Study (HRS) participants with cancer who died between 2000 and 2012, including data from in-depth “exit” interviews conducted with the surrogates after the participant’s death. The HRS is a nationally representative, biennial, longitudinal panel study of US residents older than 50 years. Trends in ACP subtypes were tested, and multivariable logistic regression models examined for associations between ACP subtypes and measures of treatment intensity. <h3>Main Outcomes and Measures</h3> Trends in the surrogate-reported frequency of DPOA assignment, living will creation, and participation in discussions of EOL care preferences; associations between ACP subtypes and both surrogate-reported EOL care decisions and terminal hospitalizations. <h3>Results</h3> From 2000 to 2012, there was an increase in DPOA assignment (52% to 74%,<i>P</i> = .03), without significant change in use of living wills (49% to 40%,<i>P</i> = .63) or EOL discussions (68% to 60%,<i>P</i> = .62). Surrogate reports that patients received “all care possible” at EOL increased during the period (7% to 58%,<i>P</i> = .004), and rates of terminal hospitalizations were unchanged (29% to 27%,<i>P</i> = .70). Limiting or withholding treatment was associated with living wills (adjusted odds ratio [AOR], 2.51; 95% CI, 1.53-4.11;<i>P</i> &lt; .001) and EOL discussions (AOR, 1.93; 95% CI, 1.53-3.14;<i>P</i> = .002) but not with DPOA assignment. <h3>Conclusions and Relevance</h3> Use of DPOA increased significantly between 2000 and 2012 but was not associated with EOL care decisions. Importantly, there was no growth in key ACP domains such as discussions of care preferences. Efforts that bolster communication of EOL care preferences and also incorporate surrogate decision makers are critically needed to ensure receipt of goal-concordant care.
Inclusive versus exclusive approaches to sleep and dream research
Authors: Robert Stickgold
Journal: Behavioral and Brain Sciences (2000)

By assuming that REM sleep either plays a critical role in all memory consolidation or no role in any, Vertes &amp; Eastman have chosen to reject, rather than explain, robust experimental findings of a role for sleep in memory and learning. In contrast, Nielsen has attempted to integrate conflicting findings in the dispute over REM versus NREM mentation. Researchers must trust the data more and the theories less, and build integrative rather than exclusionary models if they hope to resolve these knotty problems effectively. [Nielsen; Vertes &amp; Eastman]
Collagen-acetaldehyde adducts in alcoholic and nonalcoholic liver diseases
Authors: Gianluca Svegliati-Baroni, Enrique Baraona, Alan S. Rosman, Charles S. Lieber
Journal: Hepatology (1994)

ABSTRACT Alcoholic and, to a lesser extent, nonalcoholic patients with liver disease have serum antibodies to acetaldehyde–protein adducts produced in vitro. These antibodies presumably reflect the presence of adducts in the liver, but the protein that triggers this immune response has not been identified. To study this, we measured the reactivity of cytosolic proteins to rabbit IgG developed against a P–450 2E1—acetaldehyde adduct, isolated from alcohol–fed rats, that recognizes acetaldehyde–modified epitopes in proteins. Adducts were determined on Western blots by scanning densitometry of antibody–linked alkaline phosphatase activity in 4 normal livers and in needle biopsy specimens from subjects with liver disease, 17 alcoholic and 14 nonalcoholic. In all livers, except for a normal one, we found a reactive protein of at least 200 kD, similar to the collagen–acetaldehyde adduct we reported to be markedly increased in rats with experimentally induced cirrhosis. The immunostaining intensity in the alcoholic patients with liver disease was eightfold (p&lt;0.01) and that in nonalcoholic patients with liver disease was fourfold, greater (p&lt;0.02) than the weak staining in normal livers; it correlated with the degree of inflammation and serum AST or γ–glutamyl transpeptidase activities. The adduct was reproduced on incubation of normal cytosolic proteins with 2.5 mmol/L acetaldehyde, whereas higher concentrations yielded many additional adducts; the adduct also reacted with IgG antibody to rat collagen type I and disappeared after digestion with collagenase, suggesting that the target protein is a form of collagen. The association of this collagen–acetaldehyde adduct with parameters of liver disease activity suggests that the adduct reflects the liver injury and may even contribute to its development, both in alcoholic and in nonalcoholic subjects. (Hepatology 1994;20:111-118.)
Karyotype Analysis of the B16 Mouse Melanoma With Reassessment of the Normal Mouse Idiogram&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: E. M. Stephenson, N. G. Stephenson
Journal: JNCI Journal of the National Cancer Institute (1970)

Karyotypes of in vitro primary and seventeenth passage cells of the B16 mouse melanoma were analyzed in detail and compared with those of normal adult male C57BL mouse cells. Two large, biarmed, metacentric markers, with individual distinguishing characteristics, were constantly present in the tumor cells. The longest telocentric chromosome was abnormally elongated compared to its counterpart in a normal mouse. A single minute was incorporated in the stemline karyotype of 41. In primary in vitro cultures, a relatively large number of cells contained 40 chromosomes and apparently lacked a free minute. Cells of seventeenth passage cultures, though maintaining the typical stemline number, showed separate trends toward the incorporation of an additional minute and toward polypoidy. Only one regularly identifiable "rabbit ear" (R.E.) chromosome occurred in the tumor cells, but an obvious secondary constriction in each arm of the longest metacentric, a probable isochromosome, suggested that a member of the normal mouse R.E. complement may have been involved in the formation of this marker. In an attempt to explain apparent discrepancies between previously published mouse idiograms, two different methods of calculation were used to prepare idiograms of normal C57BL karyotypes. Methods for preparation of a B16 stemline idiogram are illustrated and compared.
A Randomized and Clinical Effectiveness Trial Comparing Two Pharmacogenetic Algorithms and Standard Care for Individualizing Warfarin Dosing (CoumaGen-II)
Authors: Jeffrey L. Anderson, Benjamin D. Horne, Scott M. Stevens, Scott C. Woller, Kent M. Samuelson, Justin W. Mansfield, Michelle Robinson, Stephanie Barton, Kim Brunisholz, Chrissa P. Mower, John A. Huntinghouse, Jeffrey S. Rollo, Dustin Siler, Tami L. Bair, Stacey Knight, Joseph B. Muhlestein, John F. Carlquist
Journal: Circulation (2012)

Warfarin is characterized by marked variations in individual dose requirements and a narrow therapeutic window. Pharmacogenetics (PG) could improve dosing efficiency and safety, but clinical trials evidence is meager.A Randomized and Clinical Effectiveness Trial Comparing Two Pharmacogenetic Algorithms and Standard Care for Individualizing Warfarin Dosing (CoumaGen-II) comprised 2 comparisons: (1) a blinded, randomized comparison of a modified 1-step (PG-1) with a 3-step algorithm (PG-2) (N=504), and (2) a clinical effectiveness comparison of PG guidance with use of either algorithm with standard dosing in a parallel control group (N=1866). A rapid method provided same-day CYP2C9 and VKORC1 genotyping. Primary outcomes were percentage of out-of-range international normalized ratios at 1 and 3 months and percentage of time in therapeutic range. Primary analysis was modified intention to treat. In the randomized comparison, PG-2 was noninferior but not superior to PG-1 for percentage of out-of-range international normalized ratios at 1 month and 3 months and for percentage of time in therapeutic range at 3 months. However, the combined PG cohort was superior to the parallel controls (percentage of out-of-range international normalized ratios 31% versus 42% at 1 month; 30% versus 42% at 3 months; percentage of time in therapeutic range 69% versus 58%, 71% versus 59%, respectively, all P<0.001). Differences persisted after adjustment for age, sex, and clinical indication. There were fewer percentage international normalized ratios ≥4 and ≤1.5 and serious adverse events at 3 months (4.5% versus 9.4% of patients, P<0.001) with PG guidance.These findings suggest that PG dosing should be considered for broader clinical application, a proposal that is being tested further in 3 major randomized trials. The simpler 1-step PG algorithm provided equivalent results and may be preferable for clinical application.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00927862.
DILANTIN TREATMENT FOR BEHAVIOR PROBLEM CHILDREN WITH ABNORMAL ELECTROENCEPHALOGRAMS
Authors: CHARLOTTE F. WALKER, BARBARA B. KIRKPATRICK
Journal: American Journal of Psychiatry (1947)

A group of behavior problem children with abnormal electroencephalographic findings were treated with dilantin. None of the children presented clinical evidence of epilepsy or were known relatives of epileptics. The physical and neurological examination of all the children was negative. None of the patients were adequately controlled by their environment previous to treatment. All were treated on an out-patient basis and showed definite clinical improvement under dilantin treatment. The results are considered encouraging and warrant further follow-up and study. The implications and significance of recognition and treatment of these cases in terms of prevention or amelioration of adult neuropsychiatric difficulties are discussed.
Lactate on emergency department arrival as a predictor of mortality and site-of-care in pneumonia patients: a cohort study
Authors: Yun-Xia Chen, Chun-Sheng Li
Journal: Thorax (2015)

To investigate the predictive performance of lactate, CURB-65, and a combination of lactate and CURB-65 (LAC-CURB-65) for mortality, hospitalisation and intensive care unit (ICU) admission in pneumonia patients in the emergency department (ED).Consecutive adult patients with pneumonia presenting from January 2012 to May 2014 were divided into low-, moderate- and high-risk groups according to lactate (<2.0, 2.0-4.0, >4.0 mmol/L), CURB-65 (≤1, 2, ≥3) and LAC-CURB-65 (patients with two low risks, any moderate risk, any high risk) values. Mortality, hospitalisation and ICU admission rates were compared between risk classes.Of 1641 patients, 861 (53%) were hospitalised (38% to a general ward, 15% to the ICU) while the remaining 780 (47%) were treated as outpatients or observed in the ED. 547/1641 (33%) patients died within 28 days. Lactate and CURB-65 were higher in patients who died, were hospitalised or were admitted to the ICU compared with patients who were not (p<0.001). Lactate and CURB-65 independently predicted outcomes. The performance of lactate in predicting 28-day mortality, hospitalisation and ICU admission was higher than that of CURB-65 (p<0.01). For LAC-CURB-65, patients at low or moderate risk had mortality rates of 2% and 14%, respectively, and hospitalisation rates of 15% and 40%, respectively, while none were admitted to ICU. Patients at high risk had the highest mortality (52%), hospitalisation (70%) and ICU admission rates (27%).Lactate is superior to CURB-65 in predicting mortality, hospitalisation and ICU admission in pneumonia patients in the ED. LAC-CURB-65 significantly improved the predictive value of CURB-65.