tbuckley/cabot-search huggingface dataset:
Regulatable gene expression systems for gene therapy applications: progress and future challenges
Authors: S. Goverdhana, M. Puntel, W. Xiong, J.M. Zirger, C. Barcia, J.F. Curtin, E.B. Soffer, S. Mondkar, G.D. King, J. Hu, S.A. Sciascia, M. Candolfi, D.S. Greengold, P.R. Lowenstein, M.G. Castro
Journal: Molecular Therapy (2005)

Gene therapy aims to revert diseased phenotypes by the use of both viral and nonviral gene delivery systems. Substantial progress has been made in making gene transfer vehicles more efficient, less toxic, and nonimmunogenic and in allowing long-term transgene expression. One of the key issues in successfully implementing gene therapies in the clinical setting is to be able to regulate gene expression very tightly and consistently as and when it is needed. The regulation ought to be achievable using a compound that should be nontoxic, be able to penetrate into the desired target tissue or organ, and have a half-life of a few hours (as opposed to minutes or days) so that when withdrawn or added (depending on the regulatable system used) gene expression can be turned "on" or "off" quickly and effectively. Also, the genetic switches employed should ideally be nonimmunogenic in the host. The ability to switch transgenes on and off would be of paramount importance not only when the therapy is no longer needed, but also in the case of the development of adverse side effects to the therapy. Many regulatable systems are currently under development and some, i.e., the tetracycline-dependent transcriptional switch, have been used successfully for in vivo preclinical applications. Despite this, there are no examples of switches that have been employed in a human clinical trial. In this review, we aim to highlight the main regulatable systems currently under development, the gene transfer systems employed for their expression, and also the preclinical models in which they have been used successfully. We also discuss the substantial challenges that still remain before these regulatable switches can be employed in the clinical setting.
Five hematologic tests and treatments to question
Authors: Lisa K. Hicks, Harriet Bering, Kenneth R. Carson, Adam E. Haynes, Judith Kleinerman, Vishal Kukreti, Alice Ma, Brigitta U. Mueller, Sarah H. O'Brien, Julie A. Panepinto, Marcelo C. Pasquini, Anita Rajasekhar, Ravi Sarode, William A. Wood
Journal: Blood (2014)
Report accuses NHS of institutional racism
Authors: Mark Gould
Journal: BMJ (2004)

The Royal College of Psychiatrists has backed calls for the creation of a mental health “tsar” (national clinical director) for people from black and other ethnic minority groups, one of a series of recommendations in a leaked report into the death of David “Rocky” Bennett, a black patient in an NHS psychiatric unit.

The report, by retired judge Sir John Blofeld, took evidence from some of the most senior figures in psychiatry, including the mental health tsar, Louis Appleby, and was published this week after the BMJ …
Human cytomegalovirus immediate-early mRNAemia versus pp65 antigenemia for guiding pre-emptive therapy in children and young adults undergoing hematopoietic stem cell transplantation: a prospective, randomized, open-label trial
Authors: Giuseppe Gerna, Daniele Lilleri, Fausto Baldanti, Maria Torsellini, Giovanna Giorgiani, Marco Zecca, Piero De Stefano, Jaap Middeldorp, Franco Locatelli, M. Grazia Revello
Journal: Blood (2003)
The Treatment of Traumatic Tetanus with Antitoxins
Authors: S. Copley
Journal: BMJ (1899)

ANTITOXINS IN TRAUMATIC TETANUS.[MWIB.LJIRNAL 337 having been tied in the patient was sent back to bed.About four hours later it was found by the house-surgeon that bleeding had recommenced and that the hypogastric swelling was already again in evidence.Second Operation.-Iwas sent for, and on arrival an hour later deter- mined that the right line of treatment would be to open the bladder in the suprapubic region.This revealed a mass of blood clot within the viscus, which was speedily scooped out with the aid of a spoon.Search was then made for a bleeding area, but as the blood welled up from the position of the trigone, and rendered a clear view impossible, pressure was exerted on the abdominal aorta which effectually controlled the loss.Even then no place from which blood had actually flowed could be seen.No papilloma, or remnaants of one, nor any other growth could be dis- covered, though it is possible that in the manipulations employed in the removal of the blood clot some villous mass may have been dragged off.Removal of the fingers from the aorta immediately caused a r9newal of the hnmorrhage, the blood, as has been said, welling up from about the internal meatus.Water at a temperature of 1200 F. was then run through
Incidental Vertebral Lesions Identified During Technetium-99m Sulfur Colloid Liver-Spleen Imaging
Authors: WEI-JEN SHIH, PEGGY A. DOMSTAD, FRANK H. DeLAND, MARGUERITE PURCELL
Journal: Clinical Nuclear Medicine (1986)

Three vertebral lesions, two compression fractures, and one metastasis in two patients, were incidentally demonstrated during Tc-99m sulfur colloid liver-spleen studies. Although the scintigraphic photon-deficient area could not be differentiated due to the metastasis and the compression fracture, the abnormal radiocolloid findings of vertebrae may lead to further studies using Tc-99m diphosphonate, Ga-67, radiographic studies, and/or biopsy.
Decreased sodium influx and abnormal red cell membrane lipids in a patient with familial plasma lecithin:Cholesterol acyltransferase deficiency
Authors: Naoki Murayama, Yasushi Asano, Saichi Hosoda, Masaji Maesawa, Masaki Saito, Fumimaro Takaku, Takashi Sugihara, Kosuke Miyashima, Yoshihito Yawata
Journal: American Journal of Hematology (1984)

Abstract Red cell membrane metabolism in familial lecithin:cholesterol acyltransferase (LCAT) deficiency was investigated. The family presented here is the third case discovered in Japan. An increase of free cholesterol was observed in the red cell membranes, concomitant with increased phosphatidyl choline. Osmotic fragility of the patient's red cells was diminished rather than increased. Red cell survival ( 51 Cr T1/2) was shortened (15 days). Sodium influx was markedly decreased, although sodium efflux, both ouabain‐sensitive and ouabain‐insensitive, was normal. The activity of acetyl‐cholinesterase as a marker of the outer leaflet of the red cell membranes was decreased, while the activity of glyceraldehyde‐3‐phosphate dehydrogenase as a marker of the inner leaflet was normal. No abnormalities of adenosine triphosphatases in red cell membranes were observed. These results suggest that the alteration of cholesterol metabolism in the plasma of LCAT deficiency increases the red cell membrane cholesterol and affects the functions of the red cell membranes, especially of the outer leaflet, which may result in decreased sodium influx.
Interaction strategies of lesbian, gay, and bisexual healthcare practitioners in the clinical examination of patients: qualitative study
Authors: Daniel C Riordan
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To explore how lesbian, gay, and bisexual healthcare practitioners manage their identity in the clinical examination of patients. <b>Design</b> Qualitative study using grounded theory. <b>Setting</b> Hospital and primary health care. <b>Participants</b> 16 healthcare professionals who identified themselves as lesbian, gay, or bisexual, and are involved in the clinical examination of patients. <b>Results</b> Healthcare professionals engage in a complex interplay of identity management strategies to avoid homophobic abuse; as a signal of safety from homophobia and understanding for their lesbian, gay, and bisexual patients and as a desexualisation strategy principally for gay men and their women patients. Their training has not helped them deal with ethical and medicolegal anxieties. <b>Conclusion</b> In the light of new legislation, published guidelines will help training and governing bodies understand and help ameliorate the added pressures on their lesbian, gay, and bisexual students and medical staff.
New network hopes to define role of health systems in controlling infectious diseases
Authors: O. Mashta
Journal: BMJ (2011)

A research network has been set up by the London School of Hygiene and Tropical Medicine to share best practices on how health systems can control infectious diseases.

The Research Network for Health Systems and Infection aims to bring together academics, policy makers, and service providers to discuss health systems as they relate to infectious diseases. It is designed to promote collaboration and debate to ensure that vital research in the field is generated and promoted, as well as being accessible to those working within the sector.

Greg Reilly, who is co-founder of the network and studying …
2015 Theme Issue on Trauma Associated With Violence and Human Rights Abuses
Authors: Annette Flanagin, Thomas B. Cole
Journal: JAMA (2014)

JAMA will publish a theme issue on violence and human rights with an emphasis on the causes, consequences, and management of trauma.Violence is an important cause of physical and emotional trauma, and the scope of trauma care is broad, including care for survivors of unintentional injuries as well as injuries resulting from many forms of violence.Injuries and violence cause 5.8 million deaths each year worldwide, accounting for about 10% of the world's deaths, more than the number of deaths that result from malaria, tuberculosis, and AIDS combined. 1,2The primary causes of these 5.8 million deaths are road traffic crashes, suicide, and homicide, followed by falls, drowning, poisoning, burns, and war. 2 In the United States, data from the Global Burden of Disease 2010 Study indicate the following among the leading diseases and injuries contributing to premature mortality: road injury (fifth leading cause), selfharm (sixth), and interpersonal violence (12th). 3For the 2015 JAMA theme issue, we are soliciting papers on trauma resulting from unintentional and intentional injury, from interpersonal and community-levels of violence, and from mass conflict, war, displacement, and natural disasters.JAMA has a long history of publishing on the health effects of trauma in the broadest of contexts.Indeed, the first issue of JAMA in 1883 included articles on traumatic injuries-displacement of the heart from violent unintentional injury 4 and long-term brain atrophy in a soldier and others following amputation of limbs. 5In the late 19th and early 20th centuries, JAMA published articles about what were then considered new concerns about trauma-railroad injuries, abdominal contusions, head injuries, and trauma as a cause of "nervous diseases." 6-9Among 100 landmark articles republished to commemorate JAMA's centennial were 2 important articles related to trauma: "A Clinical Syndrome Following Exposure to Atomic Bomb Explosions," published in 1946, 10 and "Coronary Disease Among United States Soldiers Killed in Action in Korea," published in 1953. 11 Narrowing the focus in the 1980s, JAMA began to publish annual theme issues dedicated to the trauma and health effects of nuclear radiation and war.Recognizing the wider contexts of the health effects of war and violence of all types, these theme issues were then broadened into what have become the JAMA theme issues on violence and human rights.Recent JAMA theme issues on violence and human rights have addressed the antecedents and complications
Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+ T cells
Authors: G. Gallina, L. Dolcetti, P. Serafini, C. D. Santo, I. Marigo, M. P. Colombo, G. Basso, F. Brombacher, I. Borrello, P. Zanovello, S. Bicciato, V. Bronte
Journal: Journal of Clinical Investigation (2006)

Active suppression of tumor-specific T lymphocytes can limit the efficacy of immune surveillance and immunotherapy. While tumor-recruited CD11b+ myeloid cells are known mediators of tumor-associated immune dysfunction, the true nature of these suppressive cells and the fine biochemical pathways governing their immunosuppressive activity remain elusive. Here we describe a population of circulating CD11b+IL-4 receptor α+ (CD11b+IL-4Rα+), inflammatory-type monocytes that is elicited by growing tumors and activated by IFN-γ released from T lymphocytes. CD11b+IL-4Rα+ cells produced IL-13 and IFN-γ and integrated the downstream signals of these cytokines to trigger the molecular pathways suppressing antigen-activated CD8+ T lymphocytes. Analogous immunosuppressive circuits were active in CD11b+ cells present within the tumor microenvironment. These suppressor cells challenge the current idea that tumor-conditioned immunosuppressive monocytes/macrophages are alternatively activated. Moreover, our data show how the inflammatory response elicited by tumors had detrimental effects on the adaptive immune system and suggest novel approaches for the treatment of tumor-induced immune dysfunctions.
No Question of Denial
Authors: Robert M. Levin
Journal: Annals of Internal Medicine (2011)

On Being a Doctor6 September 2011No Question of DenialRobert M. Levin, MDRobert M. Levin, MDFrom Boston University School of Medicine, Milton, MA 02186.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-155-5-201109060-00015 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Now in my mid-70s, I have been on the teaching faculty of a Boston medical center for over 40 years. Like many physicians, I believed that belonging to the profession conferred some sort of immunity to disease—illness only happened to patients.Fifteen years ago, I noticed a sense of heaviness and stiffness in my left leg as I walked across campus. I recall the moment vividly because the clumsiness was in sharp contrast to the harmony of the New England fall day. After a few weeks, I told my wife, a neuropsychologist, about the nagging feeling in my leg. She ... Author, Article, and Disclosure InformationAffiliations: From Boston University School of Medicine, Milton, MA 02186.Corresponding Author: Robert M. Levin, MD, Boston University School of Medicine, 13 Meetinghouse Lane, Milton, MA 02186; e-mail, [email protected]net. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 6 September 2011Volume 155, Issue 5Page: 334KeywordsFallsFearImmunityMovement disordersMusclesNeurologyParkinson diseaseStiffnessSurgeryWalking ePublished: 6 September 2011 Issue Published: 6 September 2011 Copyright & PermissionsCopyright © 2011 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Endocinch therapy for gastro-oesophageal reflux disease: a one year prospective follow up
Authors: Z Mahmood
Journal: Gut (2002)

<b>Background:</b> Gastro-oesophageal reflux disease (GORD) is, in the main, treated with either proton pump inhibitor (PPI) drugs or a Nissen fundoplication operation. Recently, BARD developed Endocinch, a device used to place sutures just below the oesophagogastric junction (OGJ) to treat GORD. <b>Aim:</b> To evaluate the long term benefit of the Endocinch technique in patients seen up to 12 months post procedure. <b>Patients:</b> Twenty six patients with symptoms of GORD were recruited and had the procedure performed. Four patients were lost to follow up. <b>Methods:</b> Twenty two patients completed their one year follow up. Pre procedure and post procedure (up to 12 months) assessments included symptom scoring (DeMeester), upper intestinal endoscopy, oesophageal manometry and 24 hour oesophageal pH, and completion of quality of life (QOL) questionnaires. <b>Results:</b> Mean age was 39 years (range 22–62). Heartburn symptom score was reduced from a mean value of 19.22 at baseline to 7.5 at 12 months (n=22) (p&lt;0.0001). Regurgitation score reduced from a mean of 2.27 at baseline to 0.86 at 12 months (n=22) (p&lt;0.001). Mean (SEM) pH DeMeester acid score was reduced from 44.1 (4.3) to 33.32 (4.73) (p=0.028) at three month post procedure. Percentage upright acid exposure and number of reflux episodes were also reduced significantly. Use of PPIs was reduced by 64% at 12 months post procedure. All QOL assessments showed significant improvement (p=0.01). All transient post procedure complaints resolved within 72 hours. <b>Conclusion:</b> The Endocinch procedure is an effective and safe outpatient procedure that offers GORD patients significant improvement in symptomatology, QOL, and reduced requirements for PPIs over at least a one year period.
Endotracheal Tubes in Tonsillectomy
Authors: Richard L. Vardy
Journal: JAMA (1966)

<h3>To the Editor:—</h3> In the editorial "Tonsillectomy Mortality" (<b>194</b>: 824, 1965) the statement is made, "An adequate airway is essential for proper oxygenation. This can be maintained with or without an endotracheal tube, but cannot be compromised at any time without serious consequences." It is difficult to understand why any author can still advocate a tonsillectomy being done without an endotracheal tube in place. This is the only device that can guarantee a proper airway for this surgical procedure. One seldom has the opportunity to say "never" in medicine, but it is my feeling that a tonsillectomy should never be done without an endotracheal tube in place.
Superior mesenteric artery blood flow and gastric emptying in humans and the differential effects of high fat and high carbohydrate meals.
Authors: M B Sidery, I A Macdonald, P E Blackshaw
Journal: Gut (1994)

This study was designed to determine if the differential effect of high fat and high carbohydrate meals on mesenteric blood flow is a result of changed gastric emptying rate. Eight healthy men were studied twice. Superior mesenteric artery blood flow (Doppler ultrasound) was measured before and after a 2.5 MJ meal (either 74% of the energy as carbohydrate or 71% as fat). Emptying of meals was followed by gamma-scintigraphy. The pattern of the superior mesenteric artery blood flow response was different after the two meals (interaction effect p &lt; 0.001 analysis of variance), with a far more sustained response after fat. The time by which half the meal had emptied (t50) was also significantly greater after fat (p &lt; 0.02). Superior mesenteric artery blood flow corresponding to t50 was 449 ml/min after carbohydrate and 592 ml/min after fat. There was a significant curvilinear relation between the superior mesenteric artery blood flow response and gastric emptying after carbohydrate (r2 = 0.94) and no relation at all after fat. This study confirms the finding that ingestion of meals with a high fat content slows gastric emptying compared with meals with a high carbohydrate content in healthy volunteers. A more sustained mesenteric hyperaemia was also recorded after the fat meal compared with the carbohydrate meal. The relation, however, between the volume of meal remaining in the stomach and the mesenteric response was considerably different after the two meals. Further study is required to elucidate the mechanism behind the vascular responses recorded in the mesenteric bed after food in humans.
Case-control study of whether subfertility in men is familial
Authors: R Lilford, A M Jones, D T Bishop, J Thornton, R Mueller
Journal: BMJ (1994)

To test the hypothesis that subfertility in men is familial and to examine the distribution of subfertility within families for consistency with a genetic cause.Case-control study and segregation analysis.Two teaching hospitals in Leeds.Cases (probands) were men with an abnormal sperm count who attended a subfertility clinic and whose partners had no major factor contravening fertility. Controls were fathers of two or more children recruited through vasectomy clinics or a maternity department.The incidence of involuntary childlessness among brothers with partners and among sisters and second and third degree male relatives. When possible clinical and laboratory details were obtained from involuntarily childless brothers.Seventeen of the 148 (11.5%) brothers of probands but none of the 169 brothers of controls had sought medical advice for childlessness (P < 0.0005). Four probands had more than one involuntarily childless brother. There were six further brothers whose childlessness was thought to be involuntary bringing the total prevalence of subfertility among brothers of probands to 16%. Segregation analysis was consistent with an autosomal recessive mode of inheritance accounting for 60% of subfertility in men. Seventeen of the 346 (4.9%) uncles of probands and 10 of 420 (2.8%) uncles of controls were reported to be involuntarily childless (P = 0.09), but there was no difference in childlessness among sisters. In three families sperm counts from "affected" brothers confirmed the diagnosis and showed considerable similarities within but not between families.Subfertility in men has a familial component, and the observations are consistent with an autosomal recessive mode of inheritance in over half the cases. Several different genes are probably involved.
The Pemmican B.M.J
Authors: A. P. Bertwistle
Journal: BMJ (1947)

<h3>Objective.</h3> Few if any prevention strategies are available for knee osteoarthritis (OA). In those with symptomatic medial OA, the contralateral knee may be at high risk of disease, and a reduction in medial loading in that knee might prevent disease or its progression there. Our aim was to determine how often persons with medial OA on 1 side had either concurrent or later medial OA on the contralateral side, and whether an intervention known to reduce medial loading in affected knees with medial OA might reduce medial loading in the contralateral knee. Lateral wedge insoles reduce loading across an affected medial knee but their effect on the contralateral knee is unknown. <h3>Methods.</h3> To determine the proportion of persons with medial knee OA who had concurrent medial contralateral OA or developed contralateral medial OA later, we examined knee radiographs from the longitudinal Framingham Osteoarthritis Study. Then, to examine an approach to reducing medial load in the contralateral knee, 51 people from a separate study with painful medial tibiofemoral OA underwent gait analysis wearing bilateral controlled shoes with no insoles, and then with 2 types of wedge insoles laterally posted by 5°. Primary outcome was the external knee adduction moment (EKAM) in the contralateral knee. Nonparametric CI were constructed around the median differences in percentage change in the affected and contralateral sides. <h3>Results.</h3> Of Framingham subjects with medial radiograph knee OA, 137/152 (90%) either had concurrent contralateral medial OA or developed it within 10 years. Of those with medial symptomatic knee OA, 43/67 (64%) had or developed the same disease state in the contralateral knee. Compared to a control shoe, medial loading was reduced substantially on both the affected (median percentage EKAM change −4.84%; 95% CI −11.33% to −0.65%) and contralateral sides (median percentage EKAM change −9.34%; 95% CI −10.57% to −6.45%). <h3>Conclusion.</h3> In persons with medial OA, the contralateral knee is also at high risk of medial OA. Bilateral reduction in medial loading in knees by use of strategies such as lateral wedge insoles might not only reduce medial load in affected knees but prevent knee OA or its progression on the contralateral side.