tbuckley/cabot-search huggingface dataset:
Withdrawing Intensive Life-Sustaining Treatment — Recommendations for Compassionate Clinical Management
Authors: H Brody, M L Campbell, K Faber-Langendoen, K S Ogle
Journal: New England Journal of Medicine (1997)

Despite an ethical and legal consensus regarding the right of patients or their surrogates to refuse life-prolonging therapy, surveys show that dying patients in hospitals in the United States frequently receive unwanted interventions.1,2 One reason for this may be a lack of training among physicians and nurses in the clinical aspects of withdrawing intensive life support. Staff members are highly skilled in aggressive life-extending treatment, and some hospitals now have services specializing in palliative care for patients forgoing life-extending treatment. But there may be no one specifically trained in managing the transition from one style of care to the . . .
Abstract 2643: Inhibition of calpain disrupts the autophagic response initiated by bortezomib resulting in increased death of myeloma cells
Authors: Terry H. Landowski, Aluvia M. Escalante, Ryan McGrath, Matthew R. Karolak, Meredith Henderson, Georgia O. Perrian, Ron Lynch
Journal: Cancer Research (2011)

Abstract The proteasome is a multi-subunit enzyme complex that plays a central role in the regulation of proteins controlling many important cellular functions including cell cycle progression, differentiation, gene transcription and apoptosis. Bortezomib is a potent proteasome inhibitor that has recently been approved for use in refractory multiple myeloma. Our previous work demonstrated that bortezomib induces an endoplasmic reticulum (ER) stress response ultimately leading to Ca2+-dependent apoptotic cell death. Intracellular Ca2+ has also been implicated in the cellular stress response known as autophagy. The biochemical events linking the cellular stress response with the induction of autophagy, and the relationship between autophagy and apoptosis are not well understood. In this study, we investigate the role of the Ca2+ dependent serine protease, calpain, as a mediator of the conversion from autophagic cell survival to accelerated cell death in the ER stress response. Using live cell imaging we demonstrate that bortezomib rapidly initiates autophagy in myeloma cells. Microtubule associated protein 1 light chain 3 beta (LC3) is an autophagic marker that is converted from the inactive form (LC3I) to the autophagosomal membrane-associated (LC3I) form. Simultaneous analysis of the LC3II/I ratio and the polyubiquitin-binding protein, p62/SQSTM1, demonstrates an early elevation in autophagosome formation with an increase in autophagic digestion. Inhibition of the Ca2+-dependent serine protease, calpain, dramatically increases the accumulation of non-functional autophagosomes illustrated by a rise in both the LC3II/I ratio and p62 levels. This effect is accompanied by a significant enhancement or acceleration of cell death. Similarly, elimination of the small catalytic subunit, CAPNS1 using siRNA significantly increased bortezomib-mediated cell death. Our data suggest that inhibition of calpain prevents autophagolysosome maturation, and subverts the survival response thereby enhancing cell death. These data suggest a new therapeutic strategy to enhance the activity of proteasome inhibitors and overcome drug resistance in refractory myeloma and other B cell malignancies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2643. doi:10.1158/1538-7445.AM2011-2643
Case 32-1995
Authors: W.R. Brugge, E.J. Mark
Journal: New England Journal of Medicine (1995)

Presentation of CaseA 78-year-old woman was admitted to the hospital because of worsening dysphagia and odynophagia.For three years, she had had dysphagia, with a sensation of solid food catching in the upper esophagus, which had worsened during the six months before admission. The dysphagia was followed by the coughing up of mucus for as long as an hour and by painful “spasms” in the neck that were provoked by swallowing medication or food. She had lost 4 to 7 kg in weight during the two years before admission. A barium-swallow examination performed elsewhere 26 months before admission showed . . .
Perioperative Chemotherapy of Resectable Gastroesophageal Cancer in Elderly Patients: A Retrospective Analysis
Authors: Cardoso Catarina, Moleiro Joana, Pimenta Ana, Luís Ana Carla, Freire João, Moreira António, Mao Ferro Susana, Serrano Miguel, Ferreira Sara, Dias Pereira António, Casaca Rui, Bettencourt António
Journal: Annals of Oncology (2014)
MYANESIN IN ELECTRIC SHOCK
Authors: W. L. HOLT, M. RINKEL, M. GREENBLATT, R. ANDERSON
Journal: American Journal of Psychiatry (1949)

Myanesin produces muscle relaxation and reversible paralysis. Small doses of myanesin greatly modify the response to electric stimulation in the rabbit. The convulsive threshold, in rabbits, is raised and the tonic phase eliminated for periods up to an hour. Large doses of electric current are without observed effect if given just as myanesin paralysis sets in. Within 2 minutes after myanesin injection muscular response to strong electric stimulation returns. The margin of safety between a paralyzing dose and a lethal dose is relatively small. In man, myanesin also raises the convulsive threshold to electric shock but moderate doses of myanesin do not prevent a strong, tonic-clonic seizure. Myanesin should be injected intravenously only in l% solution in physiologic saline if hemolysis is to be avoided. Because of its complications, myanesin alone is not recommended for practical use to soften the convulsive rigor in electric shock convulsions in man. Dilantin enhances the ability of myanesin to soften convulsive rigor. The combined use of myanesin and dilantin warrants further trials.
Membrane IL1α Inhibits the Development of Hepatocellular Carcinoma via Promoting T- and NK-cell Activation
Authors: Dandan Lin, Lei Lei, Yonghao Liu, Yinsheng Zhang, Bo Hu, Guangming Bao, Yuan Song, Ziqi Jin, Chunliang Liu, Yu Mei, Dedy Sandikin, Yan Wu, Lixiang Zhao, Xiao Yu, Haiyan Liu
Journal: Cancer Research (2016)

Abstract Hepatocellular carcinoma is a worldwide health problem with limited treatment options and poor prognosis. Inflammation associated with liver injury and hepatocyte regeneration can lead to fibrosis, cirrhosis, and eventually, hepatocellular carcinoma. IL1α is one of the most important inflammatory cytokines involved in inflammation and tumor development. IL1α presents as multiple forms in vivo, including precursor, propiece, membrane, and secreted forms, and their functions have been thought to be different. The role of membrane IL1α in hepatocellular carcinoma tumorigenesis is still not clear. Here, we examined the functions of membrane IL1α in murine hepatocellular carcinoma models. We found that membrane IL1α potently inhibited hepatocellular carcinoma tumor growth. Further studies showed that membrane IL1α promoted T- and natural killer (NK)–cell activation in vivo. IFNγ production by CD8+ T and NK cells was also increased as a result of membrane IL1α expression. Moreover, the cytotoxicity of the CTL and NK cells was also enhanced by membrane IL1α expression. Furthermore, in vitro studies demonstrated that membrane IL1α could directly activate T cells and NK cells in a cell contact–dependent manner. Conversely, depletion of both CD8+ T and NK cells suppressed the antitumor activity of membrane IL1α. Our studies demonstrated that membrane IL1α could promote antitumor immune responses through activation of T and NK cells. Thus, our findings provide new insights of IL1α functions during hepatocellular carcinoma development. Cancer Res; 76(11); 3179–88. ©2016 AACR.
Treatment of varicose veins should not be rationed on the basis of complications alone
Authors: D. Carradice
Journal: BMJ (2012)

Our understanding of superficial venous insufficiency has changed recently, and this has been accompanied by a revolution in management concepts and modalities. The article by Nogaro and colleagues on varicose veins confirms that widely held misperceptions about this disease persist,1 and that this area has become a soft target for rationing and budgetary constraint. …
Abstract 2990: Characterization of a mitotic interaction of ATM with AuroraB
Authors: Rebecca L. Danforth, Xi Tang, Chunying Yang, Bo Xu
Journal: Cancer Research (2011)

Abstract Ataxia-telangiectasia mutated (ATM) is a protein kinase that plays a pivotal role in DNA damage-induced cell cycle checkpoints and DNA repair. Mutation of ATM leads to the autosomal recessive disorder ataxia-telangiectasia, characterized by comprehensive clinical phenotypes such as cancer predisposition and neurodegeneration. One of the cellular phenotypes of ATM-deficiency is the spindle assembly checkpoint (SAC) defect and aneuploidy, indicating that ATM has a functional role in mitosis. We have recently demonstrated that ATM is activated in mitosis and that ATM is required for SAC. The molecular mechanism of mitotic ATM activation has started to emerge. We show here using coimmunoprecipitation that ATM interacts with Aurora B in unsynchronized cells and that this interaction increases during mitosis. Aurora B is a protein kinase and mitotic chromosomal passenger involved in the progression of mitosis. Although regulation of the Aurora B activity in response to DNA damage is dependent on ATM, Aurora B appears to serve as an upstream element of the mitotic ATM activation pathway. Aurora B phosphorylates ATM at Ser1403 and this phosphorylation event is required for activation of the SAC. We also show that Ser1403 is dephosphorylated by Protein Phosphatase 1 (PP1), thus implicating PP1 in the regulation of mitosis and the SAC. We demonstrate that the interaction between ATM and Aurora B is partially dependent on the enzymatic activity of both proteins. We also characterize the protein domains essential for the interaction of ATM with Aurora B and study the functional significance of this interaction. These data expand to our understanding of the roles of ATM outside of DNA damage repair and link ATM to cell cycle control. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2990. doi:10.1158/1538-7445.AM2011-2990
THU0065 Role of retinol binding protein 4 in insulin resistance of rheumatoid arthritis patients
Authors: M. Flores-Rodríguez, I. Ferraz-Amaro, V. Hernández-Hernández, J. Viotti, C. Rodríguez de la Rosa, M. González-Gay, M. Arce-Franco, E. Delgado-Frías, M. Gantes, J. Muñiz, M. Dominguez-Luis, A. Herrera-García, J. García-Dopico, L. Medina-Vega, A. Rodríguez-Vargas, F. Diaz-Gonzalez
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> The retinol binding protein 4 (RBP4) has recently been described as a protein highly related with insulin resistance (IR) states like obesity and diabetes. The chronic inflammatory states, like in rheumatoid arthritis (RA), are linked also to insulin resistance by mechanisms that are unknown. Therefore, RA is considered as an insulin resistance model related with a chronic inflammatory state, where diabetes and obesity, classical factors for IR, are absent. The objective of this study is to estimate RBP4 expression in RA patients. <h3>Methods</h3> 101 RA patients and 115 age and sex-matched controls were included. Pancreatic beta cell function was estimated by classical insulinresistance indexes like HOMA (homeostatic model assessment 2). RBP4, C peptide and insuline levels were measured in patients and controls by a specific enzyme-linked immunosorbent assay (ELISA). Multivariate analysis was performed to compare results between patients and controls and the data were adjusted for glucocorticoids intake and for IR classical risk factors. <h3>Results</h3> RBP4 levels did not show differences between controls and patients, after adjusting for sex, age, body mass index (BMI) and waist circumference (lnRBP4 2,83 mcg/dl in patients vs. 2,70 mcg/dl, p=0,33). On going steroids patients showed higher RBP4 levels (lnRBP4 3,03 vs 2,61 mcg/dl, p=0.00), after adjusting for age, sex, BMI and waist circumference. Similarly, in the univariate analysis, RBP4 levels tended to correlate with steroid average dose (r=0,20, p=0,14). In our serie, RBP4 levels were not related with the classical IR characteristics, like abdominal waist and BMI, both in controls and patients. Nor these levels showed relation with ESR, CRP, insuline levels or disease activity indexes. <h3>Conclusions</h3> The molecular mechanisms that lead to IR in RA patients appear to be different from those that ocurr in obesity and diabetes status. RBP4 does not seem to play a role in IR in patients with RA. <h3>Disclosure of Interest</h3> None Declared
Effects of Maternal Marijuana and Cocaine Use on Fetal Growth
Authors: Barry Zuckerman, Deborah A. Frank, Ralph Hingson, Hortensia Amaro, Suzette M. Levenson, Herbert Kayne, Steven Parker, Robert Vinci, Kwabena Aboagye, Lise E. Fried, Howard Cabral, Ralph Timperi, Howard Bauchner
Journal: New England Journal of Medicine (1989)

To investigate the effects on infants of the use of marijuana and cocaine during pregnancy and to compare the importance of urine assays with that of interviews in ascertaining drug use, we prospectively studied 1226 mothers, recruited from a general prenatal clinic, and their infants. On the basis of either interviews or urine assays conducted prenatally or post partum, 27 percent of the subjects had used marijuana during pregnancy and 18 percent had used cocaine. When only positive urine assays were considered, the corresponding values were 16 percent and 9 percent, respectively. When potentially confounding variables were controlled for in the analysis, the infants whose mothers had positive urine assays for marijuana, as compared with the infants whose mothers were negative according to both interviews and urine assays, had a 79-g decrease in birth weight (P = 0.04) and a 0.5-cm decrement in length (P = 0.02). Women who had positive assays for cocaine, as compared with nonusers, had infants with a 93-g decrease in birth weight (P = 0.07), a 0.7-cm decrement in length (P = 0.01), and a 0.43-cm-smaller head circumference (P = 0.01). To compare our findings with those of other investigators who did not use urine assays, we repeated the analyses, considering only self-reported use of marijuana (23 percent) and cocaine (13 percent). There were no significant associations between such use as determined by interviews alone and any of the measures of outcome. We conclude that the use of marijuana or cocaine during pregnancy is associated with impaired fetal growth and that measuring a biologic marker of such use is important to demonstrate the association. (N Engl J Med 1989; 320:762–8.)
Midazolam with meperidine and dexmedetomidine vs. midazolam with meperidine for sedation during ERCP: prospective, randomized, double-blinded trial
Authors: Ban Lee, Junghee Ryu, Sang Lee, Min Lee, Sang Jang, Jin-Hyeok Hwang, Ji Ryu, Sang-Hwan Do, Yong-Tae Kim
Journal: Endoscopy (2014)

<b>Background and study aim:</b> The combination of midazolam and opioid has been widely used as a standard sedative regimen for endoscopic retrograde cholangiopancreatography (ERCP). Following recent evidence that dexmedetomidine may exert a synergistic effect in combination with midazolam, this study compared the sedative effect and adverse events of midazolam – meperidine – dexmedetomidine (MMD) and midazolam – meperidine during ERCP. <b>Patients and methods:</b> A total of 110 patients who were scheduled for ERCP were prospectively enrolled and randomly assigned, in a double-blind manner, to the MMD (n = 53) or midazolam – meperidine (n = 57) groups. Each patient received an intravenous (IV) bolus dose of midazolam and meperidine (0.06 mg/kg and 50 mg, 30 % reduction and 25 mg for patients aged ≥ 65 years, respectively). To this dose, a continuous IV infusion of dexmedetomidine (1 μg/kg/h; MMD group) or the same volume of normal saline (midazolam – meperidine group) was added. The sedation level (Ramsay Sedation Scale [RSS]) as well as hemodynamic and respiratory changes were assessed. <b>Results:</b> Adequate sedation (RSS ≥ 3) was maintained during ERCP in 75.5 % and 36.8 % of the MMD and midazolam – meperidine group, respectively (<i>P</i> < 0.001). RSS scores were significantly higher in the MMD group (<i>P</i> < 0.001). Intraoperative bispectral index scores were significantly lower in the MMD group (<i>P</i> < 0.001) than in the midazolam – meperidine group. Lower additional (<i>P</i> = 0.001) and total (<i>P</i> = 0.003) doses of midazolam were required in the MMD group. Patients in the MMD group showed lower pain scores (<i>P</i> < 0.001) and higher satisfaction scores (<i>P</i> < 0.001). Desaturation occurred more frequently in the midazolam – meperidine group (11 vs. 1; <i>P</i> = 0.003). <b>Conclusions:</b> The addition of dexmedetomidine to the midazolam – meperidine regimen provided better sedative efficacy and a superior safety profile during ERCP compared with a midazolam – meperidine regimen. This trial was registered at ClinicalTrials.gov Identifier (NCT01404689).
Abstract 418: Development and characterization of cancer stem cell model from mouse iPS cells
Authors: Ling Chen, Shuichi Matsuda, Tomonari Kasai, Yuh Sugii, Masashi Okada, Koichi Igarashi, Ayano Satoh, Takayuki Kudoh, Takayuki Kudoh, Li Fu, Masaharu Seno
Journal: Cancer Research (2012)

Abstract The cancer stem cells in capable of continuous proliferation and self-renewal are proposed to play significant roles in oncogenesis, tumor growth, metastasis and cancer recurrence. Cancer stem cells are considered derived from normal stem cells affected by the tumor microenvironment although the mechanism of development is not clear yet. In 2007, Yamanaka's group succeeded in generating Nanog mouse induced pluripotent stem (iPS) cells, in which green fluorescent protein has been inserted into the 5′ untranslated region of the Nanog gene. Usually, iPS cells are considered to be induced into progenitor cells, which differentiate into various normal phenotypes depending on the normal niche. We hypothesized that cancer stem cells could be derived from Nanog mouse iPS cells in the conditioned culture medium of cancer cell lines, which is a mimic of carcinoma microenvironment. As a result, the cells exhibited a high tumorigenicity in vivo with a capacity of self-renewal and the expression of markers associated with stem cell properties and an undifferentiated state. The cells efficiently formed spheroids expressing green fluorescent protein in suspension culture, vasculogenic tubes in MatriGel in vitro and exhibited extensive angiogenesis in vivo, which was confirmed by magnetic resonance imaging and by histochemical analysis. Thus we concluded that a model of cancer stem cells was originally developed using mouse iPS cells and proposed the conditioned culture medium might perform as niche for producing cancer stem cells. It is worthwhile noticing that the mouse iPS cells co-cultured with cancer-derived cells did not form malignant tumors in vivo. This implies that cell-to-cell contact may have inhibitory effect on the conversion of mouse iPS cells into cancer stem cells. Furthermore, demonstration of the genetic alterations and the secreted factors in the tumor microenvironment which convert mouse iPS cells to cancer stem cells, and identification of potentially bona fide markers of cancer stem cells will help the development of novel anti-cancer therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 418. doi:1538-7445.AM2012-418
Case 78-1962
Authors: Gertrud C. Reyersbach, Benjamin Castleman
Journal: New England Journal of Medicine (1962)

Presentation of CaseA seven-day-old male infant was admitted to the hospital because of vomiting and lethargy.The child was the product of an uncomplicated pregnancy and delivery of a twenty-five-year-old gravida 5, para 4. The mother had glycosuria during the pregnancy and during two other pregnancies, but was otherwise aglycosuric. The patient weighed 3 kg. at birth and breathed spontaneously; because of cyanosis oxygen was administered for twenty-four hours, and suctioning was required for excessive airway secretions. Oral feedings were well tolerated, and the urine and stools appeared normal. Mild jaundice was observed on the fourth day of life, . . .
Abstract 5223: The role of bone-marrow derived cells in the intestinal tumor microenvironment of apcmin/+ mouse on tumor response to inhibitors of thymidylate synthase
Authors: Grishma Acharya, Celestia Davis, Nikeya Tisdale, Yu Zhang, Maria Marjorette O Pena
Journal: Cancer Research (2012)

Abstract The vast majority of chemotherapeutic agents have been developed to specifically target actively dividing neoplastic cells. However, tumors are not exclusively composed of a heterogeneous population of neoplastic cells. They also include a heterogeneous collection of host derived infiltrating non-neoplastic cells that together with the extracellular matrix and secreted molecules compose the tumor stroma or microenvironment. Multiple interactions between stromal and tumor cells play a critical role in tumor growth and progression. Therefore, tumor response to chemotherapy and recurrence post-therapy must also be influenced by these interactions. For many decades, inhibitors of the enzyme thymidylate synthase (TS), such as fluoropyrimidines, have been used in the clinical management of various cancers; however, their clinical efficacy continues to be limited by their toxicity to normal cells and acquired resistance by tumor cells. Therapeutic efficacy is often measured by its impact on tumor burden, however, the impact of TS inhibitors on tumor stromal cells and their role on tumor response to therapy is largely unknown. The goal of this project is to determine the role of bone marrow derived tumor stromal cells (BMDCs) in mediating tumor response to systemic therapy with TS inhibitors. We hypothesize that, in addition to targeting tumor cells, TS inhibitors also directly target stromal cells and that the sensitivity of stromal cells to the therapy determines tumor response. Using the ApcMin/+ mouse as a model of intestinal tumorigenesis, we identified and characterized BMDCs in the intestinal tumor stroma. These included Macrophages, Fibroblasts, Pan T cells, Helper T cells, Leukocytes, Mast cells, T-regulatory cells (T-reg) and Myeloid derived suppressor cells (MDSCs), among others. We generated chimeric mice wherein the chemosensitivity of intestinal tumor cells to TS inhibitors was distinct from that of the BMDCs by transplanting eGFP positive bone marrow cells that were genetically modified to express a drug resistant variant of TS. We examined the effect of 5-FU on MDSCs, mast cells, and T-regs, that have previously been shown to promote intestinal tumor development in ApcMin/+ mice. The results showed that MDSCs were specifically sensitive to 5-FU due to its apoptotic effect on these cells. Current studies are aimed at identifying the combination of stromal cells that mediate tumor response to TS inhibitors in order to identify cellular targets for combined therapy that would enhance reduction of tumor burden or delay tumor recurrence. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5223. doi:1538-7445.AM2012-5223