tbuckley/cabot-search huggingface dataset:
Pleiotropic Beneficial Effects of Sonic Hedgehog Gene Therapy in an Experimental Model of Peripheral Limb Ischemia
Authors: Mariangela Palladino, Ilaria Gatto, Valentina Neri, Stefania Straino, Marcy Silver, Alessandra Tritarelli, Andrea Piccioni, Roy C Smith, Eleonora Gaetani, Douglas W Losordo, Filippo Crea, Maurizio Capogrossi, Roberto Pola
Journal: Molecular Therapy (2011)

We have previously shown that the signaling pathway of the embryonic morphogen Sonic hedgehog (Shh) is recapitulated in the postnatal skeletal muscle in response to ischemia. We have also demonstrated that Shh is an indirect angiogenic agent upregulating various families of angiogenic growth factors and that Shh gene therapy improves angiogenesis and heart function in experimental models of myocardial ischemia. Based on these findings, we hypothesized that Shh gene therapy is beneficial in an experimental model of peripheral ischemia. We found that intramuscular (i.m.) treatment with a plasmid encoding the Shh human gene (phShh) increased blood flow, capillary density, and arteriole density in mice in which peripheral circulation of the hindlimb was disrupted by removal of the common femoral artery. Shh gene therapy also enhanced vasculogenesis, by increasing the number of circulating bone marrow (BM)-derived endothelial precursors and improving the contribution of these cells to the process of neovascularization. Finally, phShh treatment induced upregulation of prototypical angiogenic, arteriogenic, and vasculogenic factors, such as vascular endothelial growth factor (VEGF), angiopoietin 1 (Ang-1), and stromal cell-derived factor-1 (SDF-1α). These data suggest that Shh gene therapy merits further investigation for its ability to trigger the expression of potent trophic factors and stimulate pleiotropic aspects of neovascularization in the setting of ischemia.
WHO on Stroke
Authors: B. LIONEL TRUSCOTT
Journal: Annals of Internal Medicine (1972)

Editorial Notes1 January 1972WHO on StrokeB. LIONEL TRUSCOTT, M.D., PH.D.B. LIONEL TRUSCOTT, M.D., PH.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-76-1-139 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAuthorities from over 30 countries convened in Monaco on 25 to 29 May this year to consider the problem of cerebrovascular disease, promote better rehabilitative procedures, identify necessary resources, and recommend community programs for stroke prevention. The recommendations of the conference have now been published (1) by the World Health Organization, sponsor of the meeting. This slender pamphlet reviews world-wide statistics on stroke incidence and mortality, outlines a suggested schedule of acute treatment, discusses briefly the general goals of a program of prevention, and enumerates problems in future research.Many conferences have considered the problem of cerebrovascular disease. The pattern...References1. Cerebrovascular Diseases: Prevention, Treatment, and Rehabilitation, World Health Organization Technical Report Series, No. 469. Geneva, WHO, 1971, 57 pages Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Department of Neurology Bowman Gray School of Medicine of Wake Forest University Winston-Salem, N.C. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byGenetics of ischemic stroke: where are we now? 1 January 1972Volume 76, Issue 1Page: 139-140KeywordsCerebrovascular diseasesForecastingGlobal healthMortalityStrokeStroke rehabilitation Issue Published: 1 January 1972 PDF downloadLoading ...
NHS watchdog names trusts with outlier death rates
Authors: L. Eaton
Journal: BMJ (2009)

The NHS’s watchdog body has published online the names of hospital trusts in England that were investigated in the past two years because of apparently high death rates. A total of 53 trusts were subjected to 87 investigations over the period.

The data from the Care Quality Commission cover completed investigations it carried out between June 2007 and June 2009. The details include the name of the trust, the medical condition or procedure where deaths rates seemed to be high, what action the commission took, and the reasons why each alert was closed. Alerts could be closed because it was discovered that the data were faulty, because the trust was treating a high number of complex cases, or because the trust had taken …
Exhaled NO Among 7-Year-Old Children Who Attended Head Start in New York City
Authors: M.S. Perzanowski, A. Divjan, R.B. Mellins, S.M. Canfield, M.J. Rosa, G.L. Chew, A.G. Rundle, I.F. Goldstein, J.S. Jacobson
Journal: Journal of Allergy and Clinical Immunology (2009)
Contusion of the Myocardium
Authors: H. Barber
Journal: BMJ (1940)

BRiTJUNLthe cycle, instead of runninlg to waste.If the flow is adjusted as described, the pressurle within the bladder during expiration should be less than within the face- piece, the valve of which will therefore be kept shut, and consequently no oxygen will pass into the mask. (4)During inspiration the bladder acts as a reservoir of supply.If there were no such reservoir the patient wotuld be depenldent solely on the oxygen flowing through the tubing at the time.Unless the flow was very extravagant he would quickly empty the tubing and feel suffocated.Points of Importance There are three important points in regard to oxygen cylinders which apply to all methods of administration, the-one described above included, but which are not yet universally known; they a-re therefore mentioned.First, effective giving of oxygen by any face apparatus necessi- tates oxygen flows of the order of 5 to 8 litres per minute, and consequently it is desirable to use large cylinders (that is, 100 cu.ft.).The ordinary small 20-cu.ft.cylin- ders, so frequently seen, contain only approximately 570 litres and consequently can last for little more than an hour.Secondly, in order to determine how much oxygen there is within a cylinder it is essential that a pressure gauge be attached, otherwise it is impossible to have any idea.Thirdly, oxygen cylinders should always be fitted with automatic pressure regulators, securing delivery at a constant low pressure (for example, 5 pounds); otherwise-as when an adjustment valve alone is fitted- the delivery pressure falls all the time as the cylinder empties, and must necessitate repeated opening up of the valve unless the flow is correspondingly to fall.Summary A simple method is described of converting the civilian respirator to an oxygen face-piece apparatus.
Intracardiac Injections During Cardiopulmonary Resuscitation
Authors: Richard Davison, Vincent Barresi, Michele Parker, Sheridan N. Meyers, James V. Talano
Journal: JAMA (1980)

Fifty-three patients were observed prospectively for the development of complications resulting from 147 intracardiac injections (ICIs) received during cardiopulmonary resuscitation (CPR). Although pericardial effusion was noted in six of 17 echocardiograms and a hemopericardium found in eight of 28 autopsies, cardiac tamponade was not observed. A pneumothorax developed in one patient. None of the autopsies disclosed coronary artery or ventricular lacerations. Percutaneous puncture of the heart during CPR seldom results in serious complications. When other sites are not readily available, ICIs are safe and valid for the administration of emergency medication. (<i>JAMA</i>244:1110-1111, 1980)
The Interrelationships of Serum Cholesterol, Cholesterol Esters and Phospholipids in Health and in Coronary Artery Disease
Authors: MENARD M. GERTLER, STANLEY MARION GARN, JACOB LERMAN
Journal: Circulation (1950)

Serum cholesterol (free, esters and total) and serum phospholipids were determined in 97 men who had experienced coronary heart disease prior to the age of 40, 146 healthy nonhospitalized men of comparable age and a group of 97 men who were "matched" to the coronary disease group. The mean values for serum cholesterol (total) were 286 mg. per 100 cc., 224 mg. per 100 cc., and 247 mg. per 100 cc. for the coronary disease group, control group and matched control group, respectively. The serum phospholipids were highest in the coronary disease group. It is demonstrated that the interrelationships of the lipids in coronary heart disease are more important than any one of the constituents taken by itself. The theoretic implications of the total cholesterol: phospholipids ratio are considered.
Cardiac Disease Associated With Increased Risk of Nonamnestic Cognitive Impairment
Authors: Rosebud O. Roberts, Yonas E. Geda, David S. Knopman, Ruth H. Cha, V. Shane Pankratz, Bradley F. Boeve, Eric G. Tangalos, Robert J. Ivnik, Michelle M. Mielke, Ronald C. Petersen
Journal: JAMA Neurology (2013)

<h3>Objective</h3>To investigate the association of cardiac disease with amnestic and nonamnestic mild cognitive impairment (aMCI and naMCI, respectively). Nonamnestic mild cognitive impairment, a putative precursor of vascular and other non-Alzheimer dementias, is hypothesized to have a vascular etiology.<h3>Design</h3>A prospective, population-based, cohort study with a median 4.0 years of follow-up.<h3>Setting</h3>Olmsted County, Minnesota.<h3>Participants</h3>A total of 2719 participants were evaluated at baseline and every 15 months using the Clinical Dementia Rating scale, a neurological evaluation, and neuropsychological testing. A diagnosis of normal cognition, MCI, or dementia was made by consensus. Cardiac disease at baseline was assessed from the participant's medical records.<h3>Main Outcome Measures</h3>Incident MCI, aMCI, or naMCI.<h3>Results</h3>Of 1450 participants without MCI or dementia at baseline, 366 developed MCI. Cardiac disease was associated with an increased risk of naMCI (hazard ratio, 1.77 [95% CI, 1.16-2.72]). However, the association varied by sex (P = .02 for interaction). Cardiac disease was associated with an increased risk of naMCI (hazard ratio, 3.07 [95% CI, 1.58-5.99]) for women but not for men (hazard ratio, 1.16 [95% CI, 0.68-1.99]). Cardiac disease was not associated with any type of MCI or with aMCI.<h3>Conclusions</h3>Cardiac disease is an independent risk factor for naMCI; within-sex comparisons showed a stronger association for women. Prevention and management of cardiac disease and vascular risk factors may reduce the risk of naMCI.
Food-poisoning at Sea
Authors: W. S. Parker
Journal: BMJ (1954)

SUXAMETHONIUM SENSITIVITY MEDICBOURNALNeither particular diseases nor subnormal levels per se are contraindications to the use of suxamethonium, which is regarded as the drug of choice among the relaxants at present available.In anaesthesia no dose of suxamethonium can be pre- conceived with certainty.The rational use of dilute solutions allows each patient to be assessed empirically at the time of administration.
Anaplastic Lymphoma Kinase Gene Rearrangements in Non-small Cell Lung Cancer are Associated with Prolonged Progression-Free Survival on Pemetrexed
Authors: D. Ross Camidge, Scott A. Kono, Xian Lu, Sonia Okuyama, Anna E. Barón, Ana B. Oton, Angela M. Davies, Marileila Varella-Garcia, Wilbur Franklin, Robert C. Doebele
Journal: Journal of Thoracic Oncology (2011)
Metabolic Effects of Rosiglitazone in HIV Lipodystrophy
Authors: Colleen Hadigan, Sigal Yawetz, Abraham Thomas, Fiona Havers, Paul E. Sax, Steven Grinspoon
Journal: Annals of Internal Medicine (2004)

Background: Patients with HIV infection who are treated with antiretroviral agents often lose subcutaneous fat and have metabolic abnormalities, including insulin resistance and reduced adiponectin levels, which may be related to disrupted subcutaneous adipogenesis and altered peroxisome proliferator–activated receptor-γ signaling. Objective: To investigate the effects of rosiglitazone (4 mg/d), a peroxisome proliferator–activated receptor-γ agonist, in HIV-infected men and women with hyperinsulinemia and lipoatrophy. Design: A randomized, double-blind, placebo-controlled, 3-month study. Setting: University hospital. Patients: 28 HIV-infected men and women with hyperinsulinemia and lipoatrophy. Measurements: Insulin sensitivity measured by euglycemic hyperinsulinemic clamp testing; subcutaneous leg fat area measured by computed tomography; adiponectin, free fatty acid, and lipid levels; and safety variables. Results: Rosiglitazone, when compared with placebo, improved insulin sensitivity (mean [±SD] change, 1.5 ± 2.1 mg of glucose/kg of lean body mass per minute vs. −0.4 ± 1.6 mg/kg per minute; P = 0.02), increased adiponectin levels (mean [±SD], 2.2 ± 2.2 µg/mL vs. 0.1 ± 1.1 µg/mL; P = 0.006), and reduced free fatty acid levels (mean [±SD], −0.09 ± 0.1 mmol/L vs. 0.01 ± 0.1 mmol/L; P = 0.02). Mean percentage (±SD) of body fat (1.38% ± 3.03% vs. −0.83% ± 2.76%; P = 0.03) and subcubaneous leg fat area (2.3 ± 8.4 cm2 vs. −0.9 ± 1.9 cm2; P = 0.02) increased significantly with rosiglitazone compared with placebo. Mean total cholesterol levels (±SD) also increased with rosiglitazone compared with placebo (0.6 ± 1.0 mmol/L [25 ± 37 mg/dL] vs. −0.4 ± 0.6 mmol/L [−15 ± 25 mg/dL]; P = 0.007). Limitations: The study was relatively small and of short duration. Conclusions: The authors demonstrated positive effects of rosiglitazone on lipoatrophy; insulin sensitivity; and metabolic indices, including adiponectin levels, in HIV-infected patients with lipoatrophy and insulin resistance. Peroxisome proliferator–activated receptor-γ agonists may correct the metabolic abnormalities associated with disrupted adipogenesis in this population. Further studies must determine the clinical utility of such agents in HIV-infected patients.
Aortic Pseudocoarctation Causing Refractory Hypertension
Authors: Majo Joseph, Yves Leclerc, Stuart J. Hutchison
Journal: New England Journal of Medicine (2002)

To the Editor: Changes in policy on the use of antimicrobials must be based on a broad perspective reflecting microbial epidemiology, ecology, and resistance.The three reports on specific areas of the overall problem of antimicrobial resistance in the October 18 issue 1-3 are valuable, but the authors reach beyond the scope of their results in the conclusions they draw.Gorbach's editorial 4 includes conclusions and assertions that are unsupported by his citations.A ban on the use of antimicrobials in livestock feed could have unintended consequences and undesirable net effects on the environment, economy, and public health.Such a ban could result in increased morbidity and mortality in livestock, jeopardizing food and byproducts.There could also be a substantial increase in animal manure.The potential negative consequences to public health and the environment go far beyond the potential negative effects on livestock profitability.There are now science-based guidelines and stringent regulations for the judicious use of antimicrobials in food-producing animals. 5,6t is unknown whether banning antimicrobials in livestock feed would reduce the incidence of resistant infections in humans.Premature closure of this important debate now by imposition of a ban would lead us to overlook other approaches that could be more beneficial and less costly to society.It is imperative that we use solid science and examine the expected ramifications when proposing changes in antimicrobial-use policy.
Steroid Hormone Receptors: Interaction with Deoxyribonucleic Acid and Transcription Factors*
Authors: MATHIAS TRUSS, MIGUEL BEATO
Journal: Endocrine Reviews (1993)

Gene regulation by steroid hormones is mediated by binding of the hormone ligand to the corresponding receptor that triggers a complex set of interactions of the hormone receptors with each other, with DNA in chromatin, and with a variety of other proteins. In this review we attempt to summarize what is known about these interactions using as the main example the regulation of mouse mammary tumor virus transcription by glucocorticoids and progestins. We describe in some detail the interaction of monomers and homodimers of the steroid receptors with their recognition sequences, and the molecular mechanism used to discriminate between the responsive elements for glucocorticoids/progestins and estrogens. We then review the interactions between homologous and heterologous hormone receptors on complex hormone regulatory regions, before devoting some attention to the synergistic and inhibitory interactions of hormone receptors with other transcription factors. Finally we briefly summarize some of the possible mechanisms that modulate the molecular interactions of hormone receptors. In addition to ligand binding, these include receptor phosphorylation, changes in DNA topology, and the organization of DNA in nucleosomes. From this overview we draw the tentative conclusion that the specificity of the hormonal response in different cells results from a combination of developmental restrictions both in the accessibility of genomic sequence and in the repertoire of regulatory proteins present in each particular cell. In addition, the array of regulatory sequences in DNA and chromatin determines the precise nature of macromolecular interactions of the receptors that are modulated by their degree of phosphorylation.
Novel immunocompetent murine tumor models for the assessment of replication-competent oncolytic adenovirus efficacy
Authors: Gunnel Halldén, Richard Hill, Yaohe Wang, Arthi Anand, Ta-Chiang Liu, Nick R Lemoine, Jennelle Francis, Lynda Hawkins, David Kirn
Journal: Molecular Therapy (2003)

Oncolytic replication-selective adenoviruses constitute a rapidly expanding experimental approach to the treatment of cancer. However, due to the lack of an immunocompetent and replication-competent efficacy model, the role of the host immune response and viral E3 immunoregulatory genes remained unknown. We screened nine murine carcinoma lines for adenovirus (Ad5) uptake, gene expression, replication, and cytopathic effects. In seven of these murine cell lines the infectability and cytopathic effects were similar to those seen with human carcinoma lines. Surprisingly, productive viral replication was demonstrated in several lines; replication varied from levels similar to those for some human carcinoma lines (e.g., CMT-64) to very low levels. Seven of these lines were grown as subcutaneous xenografts in immunocompetent mice and were subsequently injected directly with Ad5, saline, or a replication-deficient control adenovirus particle to assess intratumoral viral gene expression, replication, and antitumoral effects. E1A, coat protein expression, and cytopathic effects were documented in five xenografts; Ad5 replication was demonstrated in CMT-64 and JC xenografts. Ad5 demonstrated significant efficacy compared to saline and nonreplicating control Ad particles in both replication-permissive xenografts (CMT-64, JC) and poorly permissive tumors (CMT-93); efficacy against CMT-93 tumors was significantly greater in immunocompetent mice compared to athymic mice. These murine tumor xenograft models have potential for elucidating viral and host immune mechanisms involved in oncolytic adenovirus antitumoral effects.
1079-85 Adjunctive treatment with a stent-based ventricle to coronary artery bypass (VSTENT™) in patients with multivessel disease undergoing coronary artery bypass surgery (ADVANTAGE)
Authors: Peter Boekstegers, Philip Raake, Rabea Hinkel, Gerhard Steinbeck, Sandra Eiffert, Bruno Reichart, Calin Vicol
Journal: Journal of the American College of Cardiology (2004)
Encyclopedia of Pediatric Psychology
Authors: A. Herbert Schwartz
Journal: JAMA (1980)

The authors provide an exhaustive systematic presentation organized alphabetically into "144 medical/psychological problems," which range from specific medical diagnoses frequently made in a primary health care setting to sections on hospitalization, developmental assessment, and behavior therapy. As a supplement to a comprehensive pediatric text, it could be invaluable, although at times redundant. As a reference work of 933 pages with 18 pages of glossaries, and 128 pages of references in a field first named Pediatric Psychology in 1967, it represents either a sign of a proclivity for writing articles or a lack of specific reference to the contributions of the established medical specialties of child psychiatry, psychiatry, and pediatrics. Fortunately, Kanner, Freud, Nelson, et al are all found in the references. Despite the aforementioned and the imbalance of the presentation (ie, hemophilia, 13 pages, vs dwarfism, 2 1/2 pages, and behavior therapy, 19 pages, vs psychotherapy, zero pages), this text
Hypoxia-inducible factor 1 : a new piece in the preconditioning puzzle
Authors: K. Ytrehus
Journal: Cardiovascular Research (2007)

Ischaemic preconditioning has proved to be a unique tool for revealing the role of intracellular signal transduction in cell survival of ischaemic heart muscle.1 Downey and co-workers proposed the existence of a sequence of events involving a trigger, mediators, and end effect(s) that are able to delay the progression of cell death.2 By using pharmacological preconditioning protocols, a set of cell membrane receptors that stimulate cell survival signalling have been identified, and use of specific kinase inhibitors has enabled further identification of the key signalling pathways.3,4 With the development of transgenic mice models, a new set of tools for investigation of mechanisms controlling the progression of cell death in the heart are available.

True ischaemic preconditioning, or endogenous preconditioning, involves ischaemia or hypoxia as a triggering factor, but it has taken almost 20 years to see a clear coupling to intracellular oxygen sensors.5 Starting with the idea that cells in the heart muscle, when subjected to transient ischaemia, release a factor that is important for cardioprotection, the role of adenosine was revealed. Also, bradykinin and opioid peptides play a role as paracrine or autocrine signals in protection by ischaemic preconditioning. Addition of scavengers of reactive oxygen species (ROS) with access to the intracellular compartment (like the lipid-soluble antioxidant N-(2-mercaptoproprionyl)glycine (MPG)) blocks ischaemic preconditioning when given prior to and during a preconditioning stimulus, indicating that ROS that are released during short cycles of ischaemia-reperfusion are involved … 

*Corresponding author. Tel: +47 77 644 781; fax: +47 77 645 440. E-mail address : Kirsti.ytrehus{at}fagmed.uit.no
Progress in the Treatment of Fractures and Dislocations 1950-1960
Authors: John H. Raach
Journal: JAMA (1961)

This handbook should be a welcome addition to the library of any doctor called to treat fractures, dislocations, or traumatic injuries to the skeleton. It is a concise summary of the most acceptable procedures for treatment of these conditions. The summaries are all the more valuable because of extensive references to articles, monographs, and books that pertain to the specific condition and that have appeared almost exclusively within the past 10 years. This handbook should supply a quick reference work for the orthopedic surgeon. It should also afford an excellent résumé of the best current therapy in this field for the general practitioner.
Hepatic γ-Cystathionase Deficiency in Patients With AIDS
Authors: José Antonio Martin
Journal: JAMA (2001)

To the Editor: Patients infected with the human immunodeficiency virus (HIV) exhibit low plasma cysteine levels at all stages of the disease.1 Glutathione (GSH) levels are also reduced in plasma, T lymphocytes, erythrocytes, and lung epithelial-lining fluid in patients with HIV infection.2,3
Epigenomic analysis of the HOX gene loci reveals mechanisms that may control canonical expression patterns in AML and normal hematopoietic cells
Authors: D H Spencer, M A Young, T L Lamprecht, N M Helton, R Fulton, M O'Laughlin, C Fronick, V Magrini, R T Demeter, C A Miller, J M Klco, R K Wilson, T J Ley
Journal: Leukemia (2015)