tbuckley/cabot-search huggingface dataset:
Mobilizing Patients in the Intensive Care Unit
Authors: Dale M. Needham
Journal: JAMA (2008)

Early mobilization of patients in the hospital and the intensive care unit has a strong historical precedent. However, in more recent times, deep sedation and bed rest have been part of routine medical care for many mechanically ventilated patients. A growing body of literature demonstrates that survivors of severe critical illness commonly have significant and prolonged neuromuscular complications that impair their physical function and quality of life after hospital discharge. Bed rest, and its associated mechanisms, may play an important role in the pathogenesis of neuromuscular weakness in critically ill patients. A new approach for managing mechanically ventilated patients includes reducing deep sedation and increasing rehabilitation therapy and mobilization soon after admission to the intensive care unit. Emerging research in this field provides preliminary evidence supporting the safety, feasibility, and potential benefits of early mobilization in critical care medicine.
Abstract 2950: miR-34 prevents <i>in vivo</i> lung tumor initiation and progression in the therapeutically resistant Kras;p53 mouse model
Authors: Andrea L. Kasinski, Frank J. Slack
Journal: Cancer Research (2012)

Abstract Lung cancer represents the leading cause of cancers deaths in men and women worldwide, and current therapies fail to treat this disease in the overwhelming majority of cases. The RAS and p53 pathways are two of the most frequently genetically modified pathways in lung cancers. Alterations in both result in loss of responsiveness to current therapies leading to decreased overall patient survival. Because the microRNA, mir-34 is a downstream transcriptional target of p53, which is reduced in its expression in p53 null tumors, we hypothesized that targeting Kras;p53 tumors with miR-34 would represent a novel yet powerful therapeutic to suppress lung tumorigenesis. To this end we have made use of the therapeutically resistant KrasLSL-G12D/+;p53LSL-R172H/+ mouse model of lung cancer. In this work we characterized the tumor progression in these mice following transgene activation specifically in the lung through intratracheal administration of adenoviral particles expressing cre recombinase. We note that adenocarcinomas are evident as early as 10 weeks following cre-recombination with severe lung inflammation presenting at 22 weeks. Epithelial cells from these tumors were harvested and cultured in vitro where they remain propagating, currently at passage 45. All three lines generated support growth in soft agar assays and are invasive based on transwell migration assays. Because of the pro-apoptotic effects of miR-34, we transduced the cells with miR-34-expressing lentivirus. Transduced cells responded with reduced proliferation and decreased migration. Based on these promising results we began two series of in vivo experiments. We first assessed the contribution of miR-34 to prevent tumor formation in KrasLSL-G12D/+;p53LSL-R172H/+ mice. Animals that were treated with miR-34 at the same time as cre-induced recombination of transgenes show little to no evidence of tumorigenesis at 19 weeks, while control animals had multiple nodules that represented ∼8% of the total lung area. The second series of in vivo experiments evaluated the ability of miR-34 to act as a treatment in pre-formed tumors. While miR-34 was unable to reduce the preformed tumors in these animals it was able to prevent further tumor growth. These data support the use of miR-34 as a tumor preventive mechanism and suggest that miR-34 may be useful in sensitizing tumors to other conventional therapeutics. 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 2950. doi:1538-7445.AM2012-2950
Clinically Silent Electrocardiographic Abnormalities and Risk of Primary Cardiac Arrest Among Hypertensive Patients
Authors: David S. Siscovick, T.E. Raghunathan, Pentti Rautaharju, Bruce M. Psaty, Leonard A. Cobb, Edward H. Wagner
Journal: Circulation (1996)

Whether continuous ECG indexes that reflect the severity of left ventricular hypertrophy (LVHI), myocardial injury (CIIS), and QT-interval prolongation (QTI) are associated with the risk of primary cardiac arrest among hypertensive patients, independent of conventional binary ECG criteria, remains unknown.We conducted a population-based case-control study among patients who were free of clinically recognized heart disease and who received care at a health maintenance organization. Cases (n = 131) were treated hypertensive patients who had had a primary cardiac arrest between 1977 and 1990. Controls (n = 562) were a stratified random sample of treated hypertensive patients. Resting ECGs were reviewed to estimate the severity of left ventricular hypertrophy, myocardial injury, and QT-interval prolongation on the basis of the algorithms of the Novacode ECG classification system. After adjustment for other risk factors and binary ECG criteria for the abnormalities, the LVHI, CIIS, and QTI scores were directly related to the risk of primary cardiac arrest. In a comparison of the 80th with the 20th percentile score for the LVHI, the risk was increased 40% (odds ratio, 1.4; 95% CI, 1.0 to 2.0); for the CIIS, the risk was increased 70% (odds ratio, 1.7; 95% CI, 1.2 to 2.5); and for the QTI, the risk was increased 80% (odds ratio, 1.8; 95% CI, 1.3 to 2.7).Our findings suggest that continuous ECG indexes that reflect left ventricular hypertrophy, myocardial injury, and QT-interval prolongation are directly related to the risk of primary cardiac arrest among hypertensive patients without clinically recognized heart disease. Binary ECG criteria may underestimate the prognostic importance of these pathophysiological abnormalities.
The Child-Health Nurse (Pediatric Nurse Practitioner) in Private Practice
Authors: Evan Charney, Harriet Kitzman, Esther Berkow, Cenie Cafarelli, Lois Davis, Frank Disney, Carolyn Friedlander, John Green, Nancy Hare, James MacWhinney, Robert Miller
Journal: New England Journal of Medicine (1971)

Abstract Four registered nurses who had been inactive in nursing were recruited for half-time work and were trained in a four-month program to provide well-child care and telephone-call management of general pediatric problems. During 1969, 1220 newborn infants were assigned in alternate fashion either to team care (pediatrician with trained nurse) or to pediatrician's care alone. For team patients, the nurse alone conducted alternate well-child visits. Data accumulated over two years indicated (1) care by a child-health nurse and pediatrician team was of a quality equal to care by the pediatrician alone; (2) team care was acceptable to parents as well as health professionals; and (3) physicians received fewer telephone calls from team patients. On the other hand, the physicians were involved in somewhat more than the expected half of the well-child visits made by the experimental group.
The Role of Hydrogen Ion Concentration in the Regulation of Pulmonary Arterial Pressure
Authors: JOHN H. K. VOGEL, S. GILBERT BLOUNT
Journal: Circulation (1965)

The relative importance of arterial oxygen tension and hydrogen ion concentration in regulating pulmonary arterial pressure was evaluated in a 43-year-old woman with hypoventilation and obesity. It was shown that hydrogen ion concentration played a dominant role in the regulation of her pulmonary circulation.
SURGICAL TREATMENT OF RETROVERSION OF THE UTERUS.
Authors: FRANKLIN H. MARTIN
Journal: JAMA (1901)

Two operations have become established in surgery as procedures of necessity in the successful treatment of persistent retroversion of the uterus. One is the operation of shortening the round ligaments of the uterus in the inguinal canal or the Alexander operation; the other that of fixing the uterus by some means to the abdominal wall through a laparotomy incision, or the operation of ventral fixation of the uterus. <h3>THE ALEXANDER OPERATION.</h3> The names of Alquie, of Montpellier, Alexander and Adams, of England, should be inseparably coupled with the inception of this operation. Alquie,<sup>7</sup>the Frenchman, conceived the idea and presented a memorial to the Academy of Medicine, Nov. 17, 1840. No operation had been performed. Alexander,<sup>2</sup>of Liverpool, performed his first operation, Dec. 14, 1881, but did not publish until January, 1883. Adams,<sup>3</sup>of Glasgow, operated independently two months later than Alexander, but published more than six
Long term spontaneous evolution of left ventricular function after experimental acute coronary occlusion
Authors: I.-K. JANG, F. V. D. WERF, J. VANHAECKE, W. FLAMENG, H. DE GEEST
Journal: Cardiovascular Research (1988)

In a canine model of acute occlusion of the left anterior descending artery (LAD), left ventriculography was performed before and immediately after occlusion and also one and three weeks later. Regional left ventricular function was evaluated by the centreline method. Global and regional left ventricular function were significantly depressed immediately after occlusion and showed no significant recovery after one and three weeks, except for a decrease in the paradoxical motion of the LAD territory, which was probably due to stiffening of the infarct area.
Abstract LB-251: Manipulation of macrophage phenotype enhances the apoptotic response to chemotherapy in mesothelioma
Authors: V. Courtney Broaddus, Sailaja Battula, Dario Barbone, Collin Blakely, David J. Sugarbaker, Raphael Bueno, Lisa M. Coussens
Journal: Cancer Research (2012)

Abstract Macrophages within the tumor microenvironment (TME) may contribute to tumor chemoresistance. We have found that macrophages constitute a significant percentage of the infiltrating leukocytes in mesothelioma, a highly chemoresistant tumor. We asked whether reprogramming of macrophage phenotype from a Th2 (pro-tumor) to a Th1 (anti-tumor) phenotype would alter the mesothelioma chemoresponsiveness. To address this, we used 3D organotypic models of mesothelioma growth: 1) multicellular spheroids, with mesothelioma cells grown alone or co-cultured with macrophages derived from peripheral blood monocytes, and 2) primary tumor fragment spheroids derived from small fragments of freshly isolated human mesothelioma. Macrophages were incubated with Th1 (LPS &amp; IFNγ) or Th2 (IL-4 &amp;IL-13) cytokines prior to co-culture with mesothelioma spheroids, followed by exposure to standard-of-care chemotherapy, cisplatin plus pemetrexed. Gene expression was evaluated in macrophages to affirm Th1-type (TNF, IL-12, IFNα) versus Th2-type (CD206, IL10) programming. In both spheroid approaches, Th1-type macrophage programming significantly increased the apoptotic response of mesothelioma cells to chemotherapy. Moreover, when CSF1R signaling in macrophages was inhibited by incubation with a small molecular weight kinase antagonist, GW2850, chemoresponsiveness was significantly increased as evidenced by increased presence of apoptotic tumor cells in spheroids. Enhanced chemoresponsiveness of mesothelioma tumor cells was dependent on presence of macrophages because incubation of tumor cells with Th1-type cytokines or GW2850 in the absence of macrophages was without effect. We conclude that manipulating the TME may be a promising therapeutic approach in mesothelioma. This work was supported by a DOD Mesothelioma Program grant PR80717 to Broaddus and Coussens and a T32 Training Grant to Battula and Blakely. 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 LB-251. doi:1538-7445.AM2012-LB-251
Preclinical activity of combined HDAC and KDM1A inhibition in glioblastoma
Authors: Melissa M. Singh, Blake Johnson, Avinashnarayan Venkatarayan, Elsa R. Flores, Jianping Zhang, Xiaoping Su, Michelle Barton, Frederick Lang, Joya Chandra
Journal: Neuro-Oncology (2015)

Glioblastoma (GBM) is the most common and aggressive form of brain cancer. Our previous studies demonstrated that combined inhibition of HDAC and KDM1A increases apoptotic cell death in vitro. However, whether this combination also increases death of the glioma stem cell (GSC) population or has an effect in vivo is yet to be determined. Therefore, we evaluated the translational potential of combined HDAC and KDM1A inhibition on patient-derived GSCs and xenograft GBM mouse models. We also investigated the changes in transcriptional programing induced by the combination in an effort to understand the induced molecular mechanisms of GBM cell death.Patient-derived GSCs were treated with the combination of vorinostat, a pan-HDAC inhibitor, and tranylcypromine, a KDM1A inhibitor, and viability was measured. To characterize transcriptional profiles associated with cell death, we used RNA-Seq and validated gene changes by RT-qPCR and protein expression via Western blot. Apoptosis was measured using DNA fragmentation assays. Orthotopic xenograft studies were conducted to evaluate the effects of the combination on tumorigenesis and to validate gene changes in vivo.The combination of vorinostat and tranylcypromine reduced GSC viability and displayed efficacy in the U87 xenograft model. Additionally, the combination led to changes in apoptosis-related genes, particularly TP53 and TP73 in vitro and in vivo.These data support targeting HDACs and KDM1A in combination as a strategy for GBM and identifies TP53 and TP73 as being altered in response to treatment.
Endoscopic Laser Surgery versus Serial Amnioreduction for Severe Twin-to-Twin Transfusion Syndrome
Authors: Marie-Victoire Senat, Jan Deprest, Michel Boulvain, Alain Paupe, Norbert Winer, Yves Ville
Journal: New England Journal of Medicine (2004)

Monochorionic twin pregnancies complicated by severe twin-to-twin transfusion syndrome at midgestation can be treated by either serial amnioreduction (removal of large volumes of amniotic fluid) or selective fetoscopic laser coagulation of the communicating vessels on the chorionic plate. We conducted a randomized trial to compare the efficacy and safety of these two treatments.Pregnant women with severe twin-to-twin transfusion syndrome before 26 weeks of gestation were randomly assigned to laser therapy or amnioreduction. We assessed perinatal survival of at least one twin (a prespecified primary outcome), survival of at least one twin at six months of age, and survival without neurologic complications at six months of age on the basis of the number of pregnancies or the number of fetuses or infants, as appropriate.The study was concluded early, after 72 women had been assigned to the laser group and 70 to the amnioreduction group, because a planned interim analysis demonstrated a significant benefit in the laser group. As compared with the amnioreduction group, the laser group had a higher likelihood of the survival of at least one twin to 28 days of age (76 percent vs. 56 percent; relative risk of the death of both fetuses, 0.63; 95 percent confidence interval, 0.25 to 0.93; P=0.009) and 6 months of age (P=0.002). Infants in the laser group also had a lower incidence of cystic periventricular leukomalacia (6 percent vs. 14 percent, P=0.02) and were more likely to be free of neurologic complications at six months of age (52 percent vs. 31 percent, P=0.003).Endoscopic laser coagulation of anastomoses is a more effective first-line treatment than serial amnioreduction for severe twin-to-twin transfusion syndrome diagnosed before 26 weeks of gestation.
A NOVEL RADIOFREQUENCY SIGNAL ANALYSIS FOR CORONARY PLAQUE CHARACTERIZATION AT CULPRIT LESION USING IMAPTM: HOW CAN WE USE THE NEW PARAMETER: CONFIDENCE LEVEL?
Authors: Amane Kozuki, Junya Shite, Toshiro Shinke, Hiromasa Otake, Daisuke Matsumoto, Hiroyuki Kawamori, Masayuki Nakagawa, Ryoji Nagoshi, Hirotoshi Hariki, Takumi Inoue, Tsuyoshi Osue, Yu Taniguchi, Hirotoshi Hiranuma, Ryo Nishio, Ken-ichi Hirata
Journal: Journal of the American College of Cardiology (2011)
Mondor's Disease (Subcutaneous Phlebitis of the Breast Region)
Authors: G. M. Lunn, J. M. Potter
Journal: BMJ (1954)

During the summer of 1950 an explosive outbreak of infective hepatitis took place in one of the smaller Oxford colleges.The total number of cases was 52- 49 occturred within a period of 20 days and comprised the main wave of the epidemic; and 3, occurring later,
Combined in vivo and in vitro approach for the characterization of penicillin-specific polyclonal lymphocyte reactivity: tolerance tests with safe penicillins instead of challenge with culprit drugs
Authors: B. Sachs, T. Al Masaoudi, H.F. Merk, S. Erdmann
Journal: British Journal of Dermatology (2004)

Background Amino-penicillins are a major cause of delayed-type reactions to penicillins. Objectives The aim of this study was to establish a diagnostic approach for the characterization of the individual penicillin-specific polyclonal lymphocyte reactivity in order to detect side chain-specific sensitization to amino-penicillins. Patients can then be advised to undergo a tolerance test with safe penicillins instead of provocation with culprit penicillins for confirmation of penicillin allergy. Methods We investigated penicillin-specific polyclonal lymphocyte reactivity in nine patients with delayed-type reactions to amino-penicillins by a combined in vivo (patch, prick and intracutaneous tests with delayed readings) and in vitro (lymphocyte transformation test, LTT) approach. Results A combination of LTT and skin tests improved the sensitivity for the characterization of penicillin-specific polyclonal lymphocyte reactivity and allowed the detection of three different patterns of lymphocyte reactivity. Four patients showed a side chain-specific sensitization to amino-penicillins in vivo and in vitro and were advised to undergo tolerance tests with safe penicillins. Two patients agreed and were exposed to parenteral benzyl-penicillin and oral phenoxymethyl-penicillin which they tolerated without complications. Conclusions These data suggest that a combined in vivo and in vitro approach is helpful for the detection of side chain-specific sensitization to amino-penicillins. Patients with such sensitization are very likely to tolerate safe penicillins, thereby expanding their therapeutic options when antibiotic treatment is required.
Helpline for patients to report adverse reactions is piloted in England
Authors: S. Mayor
Journal: BMJ (2003)

The NHS in England has introduced a pilot scheme in which people can telephone a helpline to report suspected adverse reactions to a drug.

In the scheme members of the public are being invited to telephone one call centre in the NHS Direct system—Beckenham, which covers southeast London—to report their experiences of possible adverse drug reactions. The scheme will be publicised in local media.

NHS Direct is a 24 hour telephone and online advice and health information service, launched in 1998 as part of …
Dietary Treatment of Type IV Hyperlipoproteinemia
Authors: Antonio M. Gotto, Michael E. DeBakey, John P. Foreyt, Lynne W. Scott, John I. Thornby
Journal: JAMA (1977)

This communication describes an investigation of the effectiveness of dietary counseling in the treatment of patients classified phenotypically as having type IV hyperlipoproteinemia or endogenous hypertriglyceridemia. Over a period of two years, 103 patients who received instructions for a therapeutic diet and regular dietary counseling by a physician and dietitian had a large decline in the concentration of serum triglycerides, as compared to 175 patients with the same diagnosis who received similar diets but little dietary counseling. Over the period of the study, the median plasma triglyceride concentration decreased from 302 to 210 mg/100 ml, the mean triglyceride value from 381 to 263 mg/100 ml, and the mean weight from 84 to 80 kg in the group receiving dietary counseling. (<i>JAMA</i>237:1212-1215, 1977)
T cells specific for hapten-modified self are precommitted for self major histocompatibility complex antigens before encounter with the hapten.
Authors: C A Janeway, P D Murphy, J Kemp, H Wigzell
Journal: The Journal of Experimental Medicine (1978)

The technique of antigen-driven, 5-bromo-deoxyuridine and light suicide has been adapted to eliminate the precursors of cytotoxic effector cells both for alloantigen and for 2,4,6-trinitrophenyl(TNP)-modified stimulator and target cells. Using this technique, the following observations have been made. Precursors of killer cells specific for alloantigen can be suicided independently of precursors of killer cells specific for TNP-modified self cells. The loss of activity during this procedure is not due to either specific or nonspecific suppressor cells, as judged by mixing experiments. With responder cells from F1 animals, it has been possible to show that precursors specific for TNP-modified cells from one parent are suicided independently of precursors specific for TNP-modified cells of the other parent, but only if the parental strains differ in the K and D regions of the H-2 complex. Cells of F1 mice derived from K and D identical, I region different, parental strains were specifically suicided by TNP-modified stimulator cells from either parent. However, the cross-reactive killing of TNP-self targets induced by stimulation with allogeneic cells is not eliminated by first suiciding with TNP-parental cells, suggesting that the precursors of these two types of TNP-self killer cells are different. This is compatible with reported differences in their specificity, as confirmed in this report. Finally, deletion of alloreactive cells by this technique reveals little or no reactivity specific for TNP-modified allogeneic stimulator cells. In summary, these results strongly suggest that recognition of self MHC antigens is preprogrammed in peripheral T cells of normal animals, and is not acquired during the immunization process. They also suggest that cells specific for modified alloantigen are relatively rare in the strains of mice studied.
Different mRNA and Protein Expression of Matrix Metalloproteinases 2 and 9 and Tissue Inhibitor of Metalloproteinases 1 in Benign and Malignant Prostate Tissue
Authors: Ralf Lichtinghagen, Petra B Musholt, Michael Lein, Andreas Römer, Birgit Rudolph, Glen Kristiansen, Steffen Hauptmann, Dietmar Schnorr, Stefan A Loening, Klaus Jung
Journal: European Urology (2002)
Chlorthalidone-Induced Hypercalcemia
Authors: Abraham Weinberger
Journal: JAMA (1975)

<h3>To the Editor.—</h3> In the July 15 issue ofThe Journal(229:267, 1974), Palmer described a patient with hypercalcemia, presumedly secondary to chlorthalidone (Hygroton) administration. Previous reports have shown that thiazides and chlorthalidone can cause permanent hypercalcemia in patients with hyperparathyroidism.<sup>1,2</sup>Adams et al<sup>3</sup>suggested a provocative test with thiazides for the diagnosis of hyperparathyroidism in patients suffering from nephrolithiasis and hypercalciuria. Since the pharmacological action of chlorthalidone is similar to that of thiazides, we wonder whether the patient described by Palmer has normocalcemic hyperparathyroidism. If that be the case, the observed hypercalcemia may represent a reaction to chlorthalidone in a hyperparathyroid patient.