tbuckley/cabot-search huggingface dataset:
Photodynamic therapy of arteries. A novel approach for treatment of experimental intimal hyperplasia.
Authors: P Ortu, G M LaMuraglia, W G Roberts, T J Flotte, T Hasan
Journal: Circulation (1992)

BACKGROUND Photodynamic therapy (PDT) uses light activation of otherwise nontoxic dyes for the production of reactive oxygen species that cause cell injury and death. METHODS AND RESULTS The inhibition of intimal hyperplasia (IH) by PDT was studied in the balloon injury model of the rat carotid artery. Chloroaluminum-sulfonated phthalocyanine (CASPc) was the drug chosen for PDT because it does not produce skin photosensitivity and has a high absorption peak of light at 675 nm, a wavelength with good tissue penetration. A pilot study indicated that CASPc administration with laser radiant exposure of 100 J/cm2 resulted in a homogeneous, circumferential effect on the whole artery. Male Sprague-Dawley rats received the balloon catheter injury to the left common carotid artery (day 0) and were equally divided into two groups. Nine rats received either CASPc (5 mg/kg i.v., n = 6) or saline (n = 3) at day 2, before IH was present, and nine rats received CASPc or saline in the same manner on day 7, when IH was already present. Twenty minutes after drug injection, the distal left common carotid artery was irradiated under saline with 675-nm laser light at 100 mW/cm2 for 10(3) seconds (100 J/cm2). At this low laser irradiance, there are no thermal effects, but photoactivation of CASPc occurs. The rats were killed at day 14 after balloon injury when IH reaches a maximum. The arteries were harvested after perfusion-fixation for light microscopy, histological and computerized morphometric evaluation, and transmission electron microscopy (TEM) analysis. The cross-sectional areas of the neointima were measured in the PDT-treated arteries and in the laser-only control arteries. There was a significant mean +/- SD decrease of IH in the PDT-irradiated segments of the arteries (0.06 +/- 0.05 mm2) versus the laser-only control ones (0.17 +/- 0.07 mm2) (t test, p less than 0.001), with no statistical difference between the day 2 and day 7 treated rats. Lack of IH was correlated in 90% of cases with histological absence of medial smooth muscle cells or inflammatory cells, but no other structural injury was identified. TEM analysis showed early evidence of PDT-mediated cytotoxic effects at 4 hours and the absence of collagen or elastic tissue structural alterations. CONCLUSIONS These data demonstrated that PDT can effectively inhibit the IH response when it is used before or during induction of cellular proliferation in this acute model. Although the long-term implications of PDT in arteries need to be defined, this technique may offer a new method for understanding and treating IH.
Australian government attacked for tobacco funding
Authors: C. Zinn
Journal: BMJ (2000)

The Australian Medical Association has used freedom of information laws to reveal that the federal government is granting research and development tax concessions to the tobacco industry worth up to $A500000 (£200000;$320000) a year.

The association's federal president, Dr David Brand, called on the government to scrap the concessions and said that, whereas it was generously funding research to develop high tar cigarettes for Africa, spending on tobacco control in Australia was “miserly.”

“It's just incredible that the government is helping improve a product that kills 18000 Australians a year …
Are other companies prepared?
Authors: J. M. Simper, J. N. Curran, A. Mosahebi
Journal: BMJ (2012)

Poly Implant Prosthese (PIP) breast implants were removed from the market after the discovery that non-medical grade silicone had been used; the company declared bankruptcy. The UK government advised the removal of PIP implants in symptomatic women.1 2 The NHS agreed to pay for the removal and replacement of implants for …
Abstract 3681: Mitral Repair for Functional Mitral Regurgitation in Idiopathic Dilated Cardiomyopathy: Improved Outcome With Ablation of Atrial Fibrillation and/or Resynchronization Therapy
Authors: Michele De Bonis, Maurizio Taramasso, Andrea Galanti, Stefano Benussi, Elisabetta Lapenna, Teresa Kieser, Antonio Grimaldi, Ottavio Alfieri
Journal: Circulation (2009)

PURPOSE: To assess if the addition of cardiac resynchronization therapy (CRT) and/or ablation of AF improves the outcome of patients undergoing mitral repair for functional mitral regurgitation (MR...
Aspiration Pneumonitis—Mendelson's Syndrome
Authors: David E. Dines
Journal: JAMA (1961)

MENDELSON'S syndrome, or peptic-aspiration pneumonia, was first described in obstetrical cases by Mendelson1in 1946. Classically, there is a history of vomiting after inhalation anesthesia, either during the operation or in the early postoperative period. Two to five hours after aspiration there is a dramatic onset of cyanosis, dyspnea, tachycardia, and shock.2Examination of the patient shows no localized signs of lung disease but generalized adventitious sounds and bronchospasm. The condition simulates pulmonary edema with rales, wheezes, and rhonchi throughout both lungs. There is a bloody, frothy sputum and marked pulmonary congestion. A very high pulse and respiratory rate are common, and gross pulmonary edema may supervene, with a rapidly deteriorating course resulting in death from cardiac failure. X-ray of the chest shows soft patchy mottling scattered through the lung fields but no evidence of lung collapse. Postmortem examination of the lungs will show gross swelling of
Direct Presentation of a Melanocyte-Associated Antigen in Peripheral Lymph Nodes Induces Cytotoxic CD8+ T Cells
Authors: Prisca Schuler, Emmanuel Contassot, Magali Irla, Stéphanie Hugues, Olivier Preynat-Seauve, Friederich Beermann, Alena Donda, L.E. French, Bertrand Huard
Journal: Cancer Research (2008)

Abstract Encounter of self-antigens in the periphery by mature T cells induces tolerance in the steady-state. Hence, it is not understood why the same peripheral antigens are also promiscuously expressed in the thymus to mediate central tolerance. Here, we analyzed CD8+ T-cell tolerance to such an antigen constituted by ovalbumin under the control of the tyrosinase promoter. As expected, endogenous CD8+ T-cell responses were altered in the periphery of transgenic mice, resulting from promiscuous expression of the self-antigen in mature medullary epithelial cells and deletion of high-affinity T cells in the thymus. In adoptive T-cell transfer experiments, we observed constitutive presentation of the self-antigen in peripheral lymph nodes. Notably, this self-antigen presentation induced persisting cytotoxic cells from high-affinity CD8+ T-cell precursors. Lymph node resident melanoblasts expressing tyrosinase directly presented the self-antigen to CD8+ T cells, independently of bone marrow–derived antigen-presenting cells. This peripheral priming was independent of the subcellular localization of the self-antigen, indicating that this mechanism may apply to other melanocyte-associated antigens. Hence, central tolerance by promiscuous expression of peripheral antigens is a mandatory, rather than a superfluous, mechanism to counteract the peripheral priming, at least for self-antigens that can be directly presented in lymph nodes. The peripheral priming by lymph node melanoblasts identified here may constitute an advantage for immunotherapies based on adoptive T-cell transfer. [Cancer Res 2008;68(20):8410–8]
Differential Response to Treatment as a Function of the Changing Character of a Depression
Authors: JAMES J. CADDEN, FREDERIC F. FALCH
Journal: American Journal of Psychiatry (1970)

The proper choice of an antidepressant in a given clinical situation is often controversial. The case presented points up the necessity for viewing each episode of a recurrent depressive illness in terms of both the psychopathology and the psychodynamics before choosing a therapeutic agent.
The General Medical Council and the future of revalidation
Authors: Brian D Keighley
Journal: BMJ (2005)

The General Medical Council and the future of revalidation GMC member respondsEditor-Esmail and Kmietowicz give an inaccurate account of the General Medical Council's policy development on revalidation, ignoring an iterative process with interested parties since 1998 in an attempt to introduce the most fundamental change to medical regulation since its foundation in 1858. 1 2 The GMC clearly has had regard to the legitimate interests of three principal groups-government and the NHS, patients and the public, and the various tribes that make up the UK medical profession.Despite suggestions to the contrary, an initial exploratory meeting on revalidation convened by Sir Donald Irvine in June 1998 was held in the context of a high profile professional conduct case, but well before the Bristol inquiry report and absolutely nothing to do with Rodney Ledward or, indeed, Harold Shipman.It was recognised then that some doctors were not keeping fully up to date nor were they indulging in reflective practice.Irvine correctly proposed that there was a need to make registration with the GMC more meaningful to the public than a mere recognition that doctors had reached a certain standard of professional knowledge in their early 20s.Both articles promote the idea that the doctors' regulator should be filling the vacuum within the NHS created by its failing to fulfil its public responsibility to monitor doctors' clinical standards.Clinical governance is now, slowly, being developed and eventually will extend from systems and teams to individuals-but is it reasonable, as both authors postulate, that such monitoring should become the financial and moral responsibility of the GMC sitting in London and Manchester rather than local managers at the coalface?Although revalidation is a continuing process, it becomes summative only every five years.The NHS and its local systems must not be allowed to abrogate their responsibility for the safety of patients on a day to day basis.Nor should they demand that the GMC and its prime function of assuring fitness to practise and the meaning of the medical register be inappropriately promoted as the first line of defence for the maintenance of clinical quality and safety.
Efficacy and safety of long-term treatment with lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma
Authors: M A Dimopoulos, A S Swern, J S Li, M Hussein, L Weiss, Y Nagarwala, R Baz
Journal: Blood Cancer Journal (2014)

Abstract Data from two randomized pivotal, phase 3 trials evaluating the combination of lenalidomide and dexamethasone in relapsed/refractory multiple myeloma (RRMM) were pooled to characterize the subset of patients who achieved long-term benefit of therapy (progression-free survival ⩾3 years). Patients with long-term benefit of therapy ( n =45) had a median duration of treatment of 48.1 months and a response rate of 100%. Humoral improvement (uninvolved immunoglobulin A) was more common in patients with long-term benefit of therapy (79% vs 55%; P =0.002). Significant predictors of long-term benefit of therapy in multivariate analysis were age&lt;65 years ( P =0.03), β2-microglobulin &lt;2.5 mg/l ( P =0.002) and fewer prior therapies ( P =0.002). The exposure-adjusted incidence rate (EAIR) of grade 3–4 neutropenia was lower in patients with long-term benefit of therapy (13.9 vs 38.2 per 100 patient-years). The EAIR for invasive second primary malignancy was the same in patients with long-term benefit of therapy and other patients (1.7 per 100 patient-years). These findings indicate that patients with RRMM can experience long-term benefit with lenalidomide and dexamethasone treatment with manageable side effects.
A new three-dimensional culture system for hepatocytes using reticulated polyurethane
Authors: Yasuo Sato, Takahiro Ochiya, Yuko Yasuda, Kenichi Matsubara
Journal: Hepatology (1994)

Poly-N-para-vinylbenzyl-lactonamide (PVLA)-coated reticulated polyurethane (PVLA-RPU) has been employed for the long-term maintenance of primary rat hepatocyte cultures. After 3 days of incubation of 2 x 10(7) hepatocytes/cm3 embedded in PVLA-RPU discs and kept in culture medium, most cells showed typical hepatocyte morphology, with some bile canaliculus-like intercellular spaces among the hepatocytes on examination with scanning and transmission electron microscopy. The cells were attached to the surface of the PVLA-RPU and formed multicellular spheroids in the reticulated pores. The hepatocytes maintained various liver-specific functions such as albumin secretion, ammonium metabolism, urea synthesis and gluconeogenesis, and they were viable. The liver-specific functions could be maintained for more than 1 month when the cells were kept in the rats' peritoneal cavities. This new system may be useful as a bioreactor for an artificial liver.
Lipid metabolites of carbon tetrachloride
Authors: Enoch Gordis
Journal: Journal of Clinical Investigation (1969)

5 min after intravenous injection into rats of (14)C- or (36)Cl-carbon tetrachloride, liver lipids were found labeled. Most of the radioactivity was found in the phospholipid fraction. The metabolites were shown to comprise a heterogeneous group of branched long-chain chlorinated fatty acids, probably containing the trichloromethyl side chain. Surviving liver slices also formed these metabolites. In a simple chemical system which generates trichloromethyl free radicals, carbon tetrachloride added to methyl oleate to form esters which behaved like the metabolites during counter-current distribution and urea adduction. The evidence strongly suggests the formation of these metabolites by free radical attack on unsaturated lipids. The relation of these observations to current theories of carbon tetrachloride intoxication is discussed.
Bone marrow-derived lymphoid cell lines from patients with agammaglobulinemia.
Authors: J Schwaber, H Lazarus, F S Rosen
Journal: Journal of Clinical Investigation (1978)

In vitro infection with Epstein-Barr virus of bone marrow-derived (B) lymphocytes from blood of patients with X-linked or common varied agammaglobulinemia resulted in the establishment of long-term B-lymphoid cell lines (LCL). LCL were established only with B lymphocytes from patients whose B cells failed to respond to in vitro mitogenic stimulation. In contrast, lymphocytes from patients without small B lymphocytes or with B cells that synthesized but failed to secrete Ig failed uniformly to establish LCL. Analysis of the "nonsecretory" B lymphocytes demonstrated the presence of receptors for C3b and C3d as well as surface Ig, but absence of detectable receptors for Epstein-Barr virus. All of the six cell lines that were established formed rosettes with EAC3 but not with sheep erythrocytes. Four of the six LCL were principally surface IgD bearing and did not synthesize detectable Ig for secretion. Two of the cell lines were indistinguishable from cell lines from normal individuals: they had surface IgG, A, M, and D and synthesized and secreted Ig.
Shoulder Affections in Rheumatoid Arthritis
Authors: V. A. I. Laine, K. J. Vainio, K. Pekanmaki
Journal: Annals of the Rheumatic Diseases (1954)

<h3>Abstract</h3> U.S. veterans are 1.5 times more likely to die by suicide than Americans who never served in the military. Considering such high rates, there is an urgent need to develop innovative approaches for objective and clinically applicable assessments to detect individuals at high risk. We hypothesize that speech in suicidal veterans has a range of distinctive acoustic and linguistic features. The purpose of this work is to build an automated machine learning and natural language processing tool to screen for suicidality. Veterans made 588 narrative audio recordings via a mobile app in a real-life setting. In addition, veterans completed self-report psychiatric scales and questionnaires. Recordings were analyzed to extract voice characteristics including prosodic, phonation, and glottal. The audios were also transcribed to extract textual features for linguistic analysis. We evaluated the acoustic and linguistic features using both statistical significance and ensemble feature selection. We also examined the performance of different machine learning algorithms on multiple combinations of features to classify suicidal and non-suicidal audios. Random Forest classifier correctly identified suicidal ideation in veterans based on the combined set of acoustic and linguistic features of speech with 86% sensitivity, 70% specificity, and an area under the receiver operating characteristic curve (AUC) of 80%. Speech analysis of audios collected from veterans in everyday life settings using smartphones is a promising approach for suicidal ideation detection. A machine learning classifier may eventually help clinicians identify and monitor high-risk veterans.
767. Genetic Engineering of an Immortal Human CD8+ T Cell Line
Authors: Stephanie Jones, Cary Hsu, Richard Morgan, Steven Rosenberg
Journal: Molecular Therapy (2006)

Immunotherapy using adoptively transferred autologous tumor specific T lymphocytes in patients has been shown to be effective in treating EBV-induced post-transplant lymphoproliferative diseases and melanoma. These treatments involve concurrent treatment with high dose interleukin-2 as an adjunct to promote the growth and maintenance of these cells in vivo. Persistence of these tumor-specific T-cells has been correlated with objective response. The requirement for the generation of autologous anti-tumor antigen specific T cells is a major limitation in widespread use of adoptive immunotherapy. A primary human T cell line, designated LC15, was generated by activating peripheral blood lymphocytes with OKT3 and IL-2, followed by transduction with a retroviral vector encoding a codon-optimized IL-15 gene. Long-term culture of these cells demonstrated logarithmic growth for more than 365 days, constitutive expression of IL-15, and the development of a clonal CD8+ T cell line. To test the functionality of the LC15 cell line, the cells were stimulated with OKT3. This line produced interferon gamma, IL-2, IL-12, TNF-alpha, GM-CSF, and IL-10 upon stimulation with OKT3. Only low levels of INF-gamma were secreted in the absence of stimulation. This implied that the cell line might be functional, in response to T cell stimulation. To test if this line could be further genetically modified to demonstrate antigen specificity, different gene transfer methods were explored, including RNA electroporation, retroviral and lentiviral vector systems. LC15 proved refractory to transduction by retroviral vectors pseudotyped by the GaLV envelope and only minimally infectable with VSV-g pseudotyped vectors. GFP-expressing lentiviral vectors, using either a CMV promoter or a composite CAG promoter, transduced 25% to 50% of the cells at a MOI 3–4. RNA electroporation with the P53 TCR was also evaluated in this line. Specific interferon-gamma secretion was demonstrated from these electroporated cells after co-culture with p53 expressing cell lines. The LC15's ability to proliferate based on its intrinsic production of IL-15 makes it an attractive effector for adoptive cell transfer.
Residential Greenness and Birth Outcomes: Evaluating the Influence of Spatially Correlated Built-Environment Factors
Authors: Perry Hystad, Hugh W. Davies, Lawrence Frank, Josh Van Loon, Ulrike Gehring, Lillian Tamburic, Michael Brauer
Journal: Environmental Health Perspectives (2014)

Half the world's population lives in urban areas. It is therefore important to identify characteristics of the built environment that are beneficial to human health. Urban greenness has been associated with improvements in a diverse range of health conditions, including birth outcomes; however, few studies have attempted to distinguish potential effects of greenness from those of other spatially correlated exposures related to the built environment.We aimed to investigate associations between residential greenness and birth outcomes and evaluate the influence of spatially correlated built environment factors on these associations.We examined associations between residential greenness [measured using satellite-derived Normalized Difference Vegetation Index (NDVI) within 100 m of study participants' homes] and birth outcomes in a cohort of 64,705 singleton births (from 1999-2002) in Vancouver, British Columbia, Canada. We also evaluated associations after adjusting for spatially correlated built environmental factors that may influence birth outcomes, including exposure to air pollution and noise, neighborhood walkability, and distance to the nearest park.An interquartile increase in greenness (0.1 in residential NDVI) was associated with higher term birth weight (20.6 g; 95% CI: 16.5, 24.7) and decreases in the likelihood of small for gestational age, very preterm (< 30 weeks), and moderately preterm (30-36 weeks) birth. Associations were robust to adjustment for air pollution and noise exposures, neighborhood walkability, and park proximity.Increased residential greenness was associated with beneficial birth outcomes in this population-based cohort. These associations did not change after adjusting for other spatially correlated built environment factors, suggesting that alternative pathways (e.g., psychosocial and psychological mechanisms) may underlie associations between residential greenness and birth outcomes.
Patricia Mary Qura'n (née Gilligan)
Authors: Alex Magee, Bronagh Bunting, Fiona Gibson
Journal: BMJ (2007)

Pioneered the first successful bone marrow transplants in children with primary immunodeficiency and became a fearless university administratorThe dreadful death of Roland Levinsky has shocked the world of paediatric oncology and genetics.He was an immunologist of international renown who performed the UK's first successful bone marrow transplant in children with primary immunodeficiency in 1979 at Great Ormond Street children's hospital.He went on to perform the UK's first successful attempts at gene therapy in children with fatal inherited diseases.He transformed the Institute of Child Health in London into a topclass research institution.Later, he did a similar makeover at Plymouth University, sending it soaring up the league tables.Levinsky was born in South Africa to a British-born mother and Polish/Lithuanian father.His father, died when Roland was 13.Two years later his mother returned to England with her three children.
Treat patients, not communities
Authors: Andrew J Ashworth
Journal: BMJ (2008)

Prescribing heroin to those who use it other than for analgesia simply redefines “offenders” as “patients.”1 2 The term “misuser” implies a lack of social acceptance. Prescription removes the “mis” but, in so doing, allows the “user” to re-enter the social group and solves crime at a stroke by legitimising previously criminal behaviour.

People with drug problems …
Walking. A method for rapid improvement of physical fitness
Authors: Y. Shoenfeld
Journal: JAMA (1980)

This study examined the efficiency of walking with a backpack load as a method for improving physical fitness. Forty-four subjects (average age, 18.8 years) marched at a speed of 5 km/hr for 30 minutes a day, five days a week. Thirty-two subjects walked for 3 weeks with a 3-kg backpack load; 6 subjects marched for 4 weeks with the same load; 6 subjects marched for 3 weeks with a 3-kg load, and with a 6-kg load during the fourth week. A statistically significant increase in aerobic work capacity (VO2max) was observed in all three groups, but was most pronounced in the last group.
The viral oncogene Np9 acts as a critical molecular switch for co-activating β-catenin, ERK, Akt and Notch1 and promoting the growth of human leukemia stem/progenitor cells
Authors: T Chen, Z Meng, Y Gan, X Wang, F Xu, Y Gu, X Xu, J Tang, H Zhou, X Zhang, X Gan, C Van Ness, G Xu, L Huang, X Zhang, Y Fang, J Wu, S Zheng, J Jin, W Huang, R Xu
Journal: Leukemia (2013)
Book Review Taking Our Pulse: The health of America's women By Iris F. Litt. 349 pp. Stanford, Calif., Stanford University Press, 1997. $45 (cloth); $19.95 (paper). 0-8047-2828-3 (cloth); 0-8047-3137-3 (paper).
Authors: Lori A. Bastian
Journal: New England Journal of Medicine (1998)