tbuckley/cabot-search huggingface dataset:
962. Treatment of Feline GM1 Gangliosidosis with Mesenchymal Stem Cells and Lentiviral Gene Therapy
Authors: Douglas R. Martin, Karin Haack, Glenn P. Niemeyer, Nancy R. Cox, Tal Kafri, Henry J. Baker
Journal: Molecular Therapy (2005)

Deficiency of lysosomal |[beta]|-galactosidase causes GM1 gangliosidosis, an inherited, progressive neurological disorder in which GM1 ganglioside accumulates in all tissues, including thymus, liver and brain. In addition to abnormal neuronal histology and function, gangliosidosis pathology involves a significant inflammatory component and therefore is similar to other neurodegenerative disorders such as Alzheimer and Parkinson disease. GM1 gangliosidosis occurs in humans, mice and domesticated animals, including cats, and the feline gangliosidosis model has been used previously by our laboratory to test several therapeutic strategies. In this study, stem cell transplantation and gene therapy have been evaluated separately and in combination as therapeutic approaches for feline GM1 gangliosidosis.
Treatment of Gonorrhoea with Single Oral Doses of Rifampicin
Authors: R. J. C. Cobbold, G. D. Morrison, R. R. Willcox
Journal: BMJ (1968)

Of 103 cases of acute uncomplicated gonorrhoea treated with single oral doses of 900 mg. of a new antibiotic rifampicin 89 were followed, and 10 (11.2%) apparent failures were found. Rifampicin gives results which compare favourably with those obtained under like conditions with similar doses of other orally administered antibiotics. It provides an alternative means of single-session therapy for patients in whom penicillin is contraindicated.
The Physician and the Medical History
Authors: Daniel Levinson
Journal: JAMA (1970)

To the Editor.—  The progress reported in Experimentation in Medical History-Taking ( 210: 1443, 1969) encourages one to hope that clinical medicine is beginning to profit from the exciting advances occurring in the area of information technology. I question, however, whether any device, no matter how sophisticated, can substitute for the physician-obtained history. For one thing, the interview is more than an information-gathering activity; it is the means by which the physician and patient establish the quality of their personal relationship. A physician who does no more than look over a computer printout or a checklist may compromise or destroy his identity as an understanding human being capable of responding to the needs of his patient. The major emphasis of new methods of data-gathering, in my opinion, should be to enhance the value of the interview by freeing the physician from the necessity of personally inquiring about every item in a
Measuring Aspirin Allergy
Authors: M. DAVID POSNER
Journal: Annals of Internal Medicine (1970)

Letters and Comments1 January 1970Measuring Aspirin AllergyM. DAVID POSNER, M.D.M. DAVID POSNER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-1-147_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The superb article by Giraldo, Blumenthal, and Spink, "Aspirin Intolerance and Asthma" (Ann Intern Med 71:479, 1969) influences me to ask—are you measuring a possible allergic phenomenon or are you measuring your measurements? More simply, are the tests you used—within their limits—capable of measuring aspirin or other drug allergy? For example, would you obtain a 100% of statistically significant differences if you were to test 100 people with known immediate reactions to, say, penicillin and to a variety of other drugs?This question of whether and to what extent the standard (and the quantitative limits traditionally accepted)...Reference1. RIMMAHLSTROMBROSS ABI: What is objective tumor response? Cancer 20: 1326-1334, 1967. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: M. DAVID POSNER, M.D.Affiliations: 2381 Wendy Way Los Alamitos, Calif. 90720 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 January 1970Volume 72, Issue 1Page: 147-147KeywordsAllergy and immunologyAspirinAsthmaDrugsPenicillin ePublished: 1 December 2008 Issue Published: 1 January 1970 PDF downloadLoading ...
Assessing Cumulative Health Risks from Exposure to Environmental Mixtures—Three Fundamental Questions
Authors: Ken Sexton, Dale Hattis
Journal: Environmental Health Perspectives (2007)

Differential exposure to mixtures of environmental agents, including biological, chemical, physical, and psychosocial stressors, can contribute to increased vulnerability of human populations and ecologic systems. Cumulative risk assessment is a tool for organizing and analyzing information to evaluate the probability and seriousness of harmful effects caused by either simultaneous and/or sequential exposure to multiple environmental stressors. In this article we focus on elucidating key challenges that must be addressed to determine whether and to what degree differential exposure to environmental mixtures contributes to increased vulnerability of exposed populations. In particular, the emphasis is on examining three fundamental and interrelated questions that must be addressed as part of the process to assess cumulative risk: a) Which mixtures are most important from a public health perspective? and b) What is the nature (i.e., duration, frequency, timing) and magnitude (i.e., exposure concentration and dose) of relevant cumulative exposures for the population of interest? c) What is the mechanism (e.g., toxicokinetic or toxicodynamic) and consequence (e.g., additive, less than additive, more than additive) of the mixture's interactive effects on exposed populations? The focus is primarily on human health effects from chemical mixtures, and the goal is to reinforce the need for improved assessment of cumulative exposure and better understanding of the biological mechanisms that determine toxicologic interactions among mixture constituents.
Effects of upper airway anaesthesia on respiratory-related evoked potentials in humans
Authors: S. Redolfi, M. Raux, C. Donzel-Raynaud, C. Morelot-Panzini, M. Zelter, J-P. Derenne, T. Similowski, C. Straus
Journal: European Respiratory Journal (2005)

Cortical potentials evoked by mid-inspiratory occlusion arise from numerous receptors, many of which are probably within the upper airway. Their precise nature is not known. The aim of the current study was to improve knowledge of this by studying the effects of topical upper airway anaesthesia on respiratory-related evoked potentials. Respiratory-related evoked potentials were described through the averaging of electroencephalogram (EEG) epochs following mid-inspiratory occlusions (C 3 –C Z ; C 4 –C Z ). A total of 21 healthy volunteers (13 male, aged 22–52 yrs) were studied during mouth breathing, before and after topical upper airway anaesthesia (lidocaine). Moreover, 15 subjects were studied during nose breathing with and without anaesthesia. Six subjects were studied whilst inhaling L-menthol. Typical potentials were present in all the subjects, their components featuring normal amplitudes and latencies. The route of breathing and upper airway anaesthesia did not modify the EEG responses to inspiratory occlusions, qualitatively or quantitatively, during mouth or nose breathing. L-menthol had no effect. Upper airway receptors sensitive to topical anaesthesia are unlikely to contribute significantly to mid-inspiratory occlusion-evoked potentials. On the contrary, deeper receptors, such as joint and muscle receptors, could contribute dominantly to these potentials.
Cardiovascular Effects of Methylmethacrylate Cement
Authors: D. J. Peebles, R. H. Ellis, S. D. K. Stride, B. R. J. Simpson
Journal: BMJ (1972)

Experiments were carried out on dogs in an attempt to identify the mechanisms underlying the systemic hypotension associated with the application of acrylic cement substances to raw bone surfaces, as in reconstructive hip surgery. Intravenous injection of the liquid component of such cements (monomeric methylmethacrylate) into six dogs produced a significant fall in blood pressure together with an increase in heart rate and cardiac output. This seemed to be due to peripheral vasodilatation caused directly by the monomer and not through the release of histamine. Absorption of free monomer from the mixed cement into the systemic circulation at operation is likely to have the same effect. Precautionary measures can be taken and groups of patients who are especially at risk can be identified, thus reducing the hazards of total hip replacement.
The ubiquitin-proteasome pathway and endothelial (dys)function
Authors: K. Stangl, V. Stangl
Journal: Cardiovascular Research (2009)

The ubiquitin-proteasome system (UPS) has been recognized as a key regulatory pathway in cardiovascular diseases. Although the role of this system in the pathogenesis of endothelial dysfunction remains largely unknown, available data suggest that proteasome activity is modified by mediators and processes—e.g. nitric oxide and oxidative stress—involved in the regulation of endothelial function. In addition, there is some evidence that the UPS itself modulates the activity of endothelial nitric oxide synthase, the key enzyme of vascular homeostasis, interacts with other vasoactive mediators involved in regulation of endothelial function, influences oxidative stress response in the vasculature, and thereby contributes to regulation of endothelial (dys)function. This review discusses the potential implications of the UPS in endothelial dysfunction.
Abstract 2571: ABT-737, a small molecule Bcl-2/Bcl-xL antagonist, increases docetaxel-mediated apoptosis in human prostate cancer cells
Authors: Ricardo Parrondo, Alicia de las Pozas, Teresita Reiner, Carlos Perez-Stable
Journal: Cancer Research (2011)

Abstract Castration-resistant prostate cancer (CRPC) express high levels of the anti-apoptotic proteins Bcl-2 and Bcl-xL, resulting in drug resistance and association with poor prognosis. Docetaxel (Doc), an antimitotic drug that is the first-line treatment strategy for CRPC, is known to provide a small survival benefit but patients eventually become resistant to Doc with little hope for survival. It is apparent that Doc chemotherapy alone is not enough to counteract the high levels of Bcl-2/Bcl-xL present in CRPC. ABT-737 is a small molecule that binds to Bcl-2/Bcl-xL with high affinity and disrupts their interaction with pro-apoptotic Bax/Bak, thus enhancing pro-apoptotic signals when combined with other drugs. We investigated whether ABT-737 can increase Doc-mediated apoptosis in CRPC cells. Our results in androgen-dependent LNCaP and CRPC PC3 cell lines indicate that ABT-737 (1 μM) increases Doc (1 nM)-mediated cell death and caspase-dependent apoptosis, as determined by trypan blue exclusion, annexin-FITC/propidium iodide flow cytometry, and Western blot analysis. Our data suggests that Doc's anti-cancer effect results from prolonged cyclin B1/Cdk1 activation and inactivation of Bcl-2/Bcl-xL by phosphorylation, resulting in increased apoptosis. We show a correlation between high phosphorylation (P) of Bcl-2(Ser70)/Bcl-xL(Ser62) and increased apoptosis by Doc and Doc + ABT-737 treatments. Furthermore, the Cdk1 inhibitor purvalanol A blocks Doc + ABT-737-mediated increases in P-Bcl-2/P-Bcl-xL and subsequent apoptotic cell death. Lentivirus pLKO.1 shRNA stable knockdown of Bax but not Bak lowers cell death LNCaP and PC3 cells after treatment with Doc + ABT-737. In contrast to LNCaP and PC3, the CRPC DU145 cell line is null for Bax, expresses high levels of anti-apoptotic Mcl-1, and is more resistant to ABT-737. Retrovirus pBABE stable expression of Bax in DU145 cells restores sensitivity to Doc + ABT-737 compared to the empty vector control cells. We conclude that ABT-737 can sensitize CRPC cells to Doc treatment and may provide an important combination chemotherapy strategy for improving overall survival. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2571. doi:10.1158/1538-7445.AM2011-2571
Atrial Natriuretic Peptide Receptor Signaling Plays a Critical Role in Induction of Tolerogenic Dendritic Cells
Authors: W. Zhang, X. Cao, D. Chen, J. Wang, H. Yang, S. Moahapatra, G. Hellermann, X. Kong, R.F. Lockey, S.S. Moahapatra
Journal: Journal of Allergy and Clinical Immunology (2010)
Anticoagulant Therapy in Idiopathic Occlusion of the Axillary Vein
Authors: J. Marks
Journal: BMJ (1956)

PHENYLPROPYL-HYDROXYCOUMARINMEDITSHNA I 24 to 36 hours after starting treatment is known.On no account should a second dose of phenylpropylhydroxycoumarin be given on the result of a pro- thrombin estimation taken less than 24 hours after the initial dose.In young, robust, and not acutely ill patients, increas- ing the initial dose to 27 or 30 mg. may be justified.Such a large dose, however, should be given only when prothrombin estimations can be done at .a moment's notice at all times.According to the prothrombin time at 24 to 36 hours, the second dose will be as follows: (a) Prothrombin time 15 seconds or below, 12 to 15 mg.; (b) pro- thrombin time between 16 and 20 seconds, 9 mg.; (c) prothrombin time between 21 and 24 seconds, 3 to 6 mg.: (d) prothrombin time 25 seconds and over, nil.The maintenance dose of phenylpropyl-hydroxycoumarin will vary between 0.75 and 6 mg.In 80 out of 99 cases the maintenance dose lay within the range of 3 to 4.5 mg.Great care is necessary in assessing the maintenance dose, for even so small an excess as 0.5 mg.over a period of a few days may lead to a dangerous rise in the prothrombin time.Owing to the prolonged cumulative effect of phenylpropyl-hydroxycoumarin it may take several days before the effect of any change in dosage is apparent.Therefore, if possible, alterations in the maintenance dose should not be made more often than every few days.Important factors in assessing the maintenance dose within the range of 0.75 to 6 mg. are the age (apparent rather than real), general health, weight, and liver and renal function.The young, robust, and less acutely ill patients require the largest doses, whilst the elderly, frail, and seriously ill patients need the smallest doses.Any lowering of renal function-for example, raised blood urea-will materially reduce the amount of the maintenance dose needed.Frequent prothrombin estimations are necessary in controlling phenylpropyl-hydroxycoumarin therapy.Phenylpropyl-hydroxycoumarin.appears to be particularly free from toxic effects, and in this series of 104 cases the only adverse reactions were microscopic haematuria in four cases and frank haematuria in one case.This case of frank haematuria, however, was associated with a urinary infection and was not accom- panied by a very marked rise of the prothrombin time.
"THE INTRACARDIAC INJECTION OF EPINEPHRIN"
Authors: J. R. Bridges
Journal: JAMA (1923)

<h3>To the Editor:</h3> —The editorial on "The Intracardiac Injection of Epinephrin" (The Journal, May 5) is very timely and of considerable interest. April 4, 1923, I was called to see a woman living 7 miles in the country. About the time I got in the house she died from an attack of angina pectoris; at least, the heart had stopped, and she gasped for the last time. The daughter was notifying the relatives over the telephone that the mother had just died, but in the meantime I gave her an injection of epinephrin, 1 c.c., as described in the editorial, and in a few minutes she rallied and is alive and well today. I had a patient die just the other day in the hospital in just the same way, while the nurse was trying to reach me over the telephone; so it seems to me that it should be
Successful childhood immunisations may endanger adults
Authors: M. Schweiger
Journal: BMJ (1994)

Dendritic cells (DC) in the colon may regulate intestinal immunity but remain poorly characterized. In this study a CD11c<sup>+</sup>HLA-DR<sup>+</sup>lin<sup>−</sup> (CD3<sup>−</sup>CD14<sup>−</sup>CD16<sup>−</sup>CD19<sup>−</sup>CD34<sup>−</sup>) population has been identified by flow cytometry in cells obtained by rapid collagenase digestion of human colonic and rectal biopsies. These day 0 (d0) CD11c<sup>+</sup>HLA-DR<sup>+</sup>lin<sup>−</sup> cells comprised ∼0.6% of the mononuclear cells obtained from the lamina propria, were endocytically active, and had the phenotype of immature DC; they were CD40<sup>+</sup> and expressed low levels of CD83 and CD86, but little or no CD80 or CD25. Similar d0 DC populations were isolated from the colonic mucosa of healthy controls and from both inflamed and noninflamed tissue from patients with Crohn’s disease. The lamina propria also contained a population of cells capable of migrating out of biopsies during an overnight culture and differentiating into mature DC with lower levels of endocytic activity and high cell surface expression of CD40, CD80, CD86, CD83, and CD25. This mature DC population was a potent stimulator of an allogeneic mixed leukocyte (MLR). Overnight culture of cells isolated by enzymatic digestion on d0 yielded DC with a phenotype intermediate between that of the d0 cells and that of the cells migrating out overnight. Overnight culture of colonic cells in which DC and HLA-DR<sup>+</sup>lin<sup>+</sup> cells were differentially labeled with FITC-dextran suggested that some of the maturing DC might differentiate from HLA-DR<sup>+</sup>lin<sup>+</sup> progenitors. This study presents the first analysis of the phenotype, maturational status, and migratory activity of human gut DC.
Prussian blue coated gold nanoparticles for simultaneous photoacoustic/CT bimodal imaging and photothermal ablation of cancer
Authors: Lijia Jing, Xiaolong Liang, Zijian Deng, Shanshan Feng, Xiaoda Li, Maomao Huang, Changhui Li, Zhifei Dai
Journal: Biomaterials (2014)
Increased Mortality With Oral Platelet Glycoprotein IIb/IIIa Antagonists
Authors: Derek P. Chew, Deepak L. Bhatt, Shelly Sapp, Eric J. Topol
Journal: Circulation (2001)

Background —Numerous clinical trials have established the benefits of intravenous glycoprotein IIb/IIIa inhibition in the management of coronary artery disease. In contrast, the recent large-scale, placebo-controlled, randomized trials of the oral glycoprotein IIb/IIIa antagonists have failed to provide commensurate reductions in late composite ischemic end points despite potent inhibition of platelet aggregation. Methods and Results —The ORs for death, myocardial infarction, urgent revascularization, and major bleeding from the 4 large-scale, placebo-controlled, randomized trials with oral glycoprotein IIb/IIIa inhibitors were calculated and combined. Stratification by low-dose or high-dose therapy and the use of concurrent aspirin was also undertaken. In 33 326 patients followed for &gt;30 days, a consistent and statistically significant increase in mortality was observed with oral glycoprotein IIb/IIIa therapy (OR, 1.37; 95% CI, 1.13 to 1.66; P =0.001). This effect was evident regardless of aspirin coadministration and treatment with either low-dose or high-dose therapy. Although a reduction in urgent revascularization was observed with oral glycoprotein IIb/IIIa inhibition, pooled analysis favored an increase in myocardial infarction that did not demonstrate statistical significance. Conclusions —Although we found a highly significant excess in mortality consistent across 4 trials with 3 different oral glycoprotein IIb/IIIa inhibitor agents, this was associated with a reduction in the need for urgent revascularization and no increase in myocardial infarction. These findings suggest the potential for a direct toxic effect with these agents and argue against a prothrombotic mechanism. Further investigation to elucidate the cause of this increased fatality risk is warranted.
Staff may be disciplined over “fiddling” waiting lists
Authors: Roger Dobson
Journal: BMJ (2004)

Disciplinary action may be taken against staff at an NHS trust where patients were deliberately left off waiting lists.

An independent inquiry into allegations of waiting list mismanagement at Weston General Hospital, Weston-super-Mare, over three years also found that a culture of heavy handed pressure and bullying of staff had developed at Weston Area NHS Trust.

In the wake of the inquiry report the trust has apologised to patients and has also launched a formal investigation into the conduct and performance of some of its staff.

“We accept the findings and recommendations of the …
Response to Letter Regarding Article, “Role of p90 Ribosomal S6 Kinase-Mediated Prorenin-Converting Enzyme in Ischemia and Diabetic Myocardium”
Authors: Seigo Itoh, Bo Ding, Tetsuro Shishido, Nicole Lerner-Marmarosh, Nadan Wang, Naoya Maekawa, Bradford C. Berk, Chen Yan, Burns C. Blaxall, Jun-ichi Abe, Yasuchika Takeishi
Journal: Circulation (2006)
Patterns of hypothalamic-pituitary-gonadal dysfunction in men with liver disease due to differing etiologies
Authors: David H. van Thiel, Judith S. Gavaler, Joel A. Spero, Kimberley M. Egler, Carl Wight, Ajitkumar T. Sanghvi, Ute Hasiba, Jessica H. Lewis
Journal: Hepatology (1981)

The hypothalamic-pituitary-gonadal axis was evaluated in two groups of age-matched men with documented biochemical and histologic liver disease and compared to that of age-matched normal controls. Basal testosterone levels (p &lt; 0.05), spermatozoa concentrations (p &lt; 0.01), and seminal plasma volume (p &lt; 0.01) were reduced in the alcoholics studied with liver disease, but not the hemophiliacs with liver disease when compared to the normal controls. No difference in estradiol levels was noted between groups. Basal follicle-stimulating hormone and luteinizing hormone (LH) concentrations were increased (both p &lt; 0.01) in the alcoholics while only LH concentrations were increased (p &lt; 0.01) in the hemophiliacs compared to the normal controls. Gonadotropins (folliclestimulating hormone and LH) and testosterone responses to clomiphene and to luteinizing hormone-releasing factor (LH only) in the alcoholic population studied, further distinguished the alcoholics from the hemophiliacs and the normal controls. The basal levels of the other anterior pituitary hormones (growth hormone and thyroid-stimulating hormone) as well as their provocative responses to thyrotropin-releasing hormone also distinguished the alcoholics from the hemophiliac population. Based upon these results, we propose that factors other than the liver disease per se are responsible for the disturbances of hypothalamic-pituitary-gonadal function observed in men with biochemically as well as histologically advanced stable liver disease.