tbuckley/cabot-search huggingface dataset:
Modulation of Adrenal Catecholamine Secretion by In Vivo Gene Transfer and Manipulation of G Protein–coupled Receptor Kinase-2 Activity
Authors: Anastasios Lymperopoulos, Giuseppe Rengo, Carmela Zincarelli, Stephen Soltys, Walter J Koch
Journal: Molecular Therapy (2008)

We recently reported that the upregulation of adrenal G protein-coupled receptor kinase-2 (GRK2) causes enhanced catecholamine (CA) secretion by desensitizing sympatho-inhibitory alpha (2)-adrenergic receptors (alpha (2)ARs) of chromaffin cells, and thereby aggravating heart failure (HF). In this study, we sought to develop an efficient and reproducible in vivo adrenal gene transfer method to determine whether manipulation of adrenal GRK2 levels/activity regulates physiological CA secretion in rats. We specifically investigated two different in vivo gene delivery methods: direct injection into the suprarenal glands, and retrograde delivery through the suprarenal veins. We delivered adenoviral (Ad) vectors containing either GRK2 or an inhibitor of GRK2 activity, the beta ARKct. We found both delivery approaches equally effective at supporting robust (>80% of the whole organ) and adrenal-restricted transgene expression, in the cortical region as well as in the medullar region. Additionally, rats with AdGRK2-infected adrenals exhibit enhanced plasma CA levels when compared with control rats (AdGFP-injected adrenals), whereas plasma CA levels after Ad beta ARKct infection were significantly lower. Finally, in isolated chromaffin cells, alpha (2)ARs of AdGRK2-infected cells failed to inhibit CA secretion whereas Ad beta ARKct-infected cells showed normal alpha (2)AR responsiveness. These results not only indicate that in vivo adrenal gene transfer is an effective way of manipulating adrenal gland signalling, but also identify GRK2 as a critically important molecule involved in CA secretion.
Effective Treatment of Early Endobronchial Cancer With Regional Administration of Liposome-p53 Complexes
Authors: Y. Zou, G. Zong, Y.-H. Ling, M. M. Hao, G. Lozano, W. K. Hong, R. Perez-Soler
Journal: JNCI Journal of the National Cancer Institute (1998)

Background : Lung cancer originates in a diffusely damaged bronchial epithelium as a result of sequential and cumulative genetic alterations. We investigated the feasibility of in vivo gene replacement in endobronchial precancerous and cancerous cells by a regionally administered nonviral delivery system. Methods: After evaluating the in vitro transfection efficiency and cytotoxicity of a variety of cationic liposome- p53 formulations, a specific formulation, DP3-p53, was selected for further in vitro and in vivo evaluation. The ability of DP3-p53 to introduce the p53 gene in the normal bronchial epithelium was studied in transgenic mice that lack the p53 gene. The therapeutic effect of DP3-p53 administered intratracheally was studied in two nude mouse models of endobronchial human lung cancer by use of H358 (p53-null) and H322 (p53-mutant) cells. Results : DP3-p53 was able to effectively introduce and express the p53 gene and induce G1 arrest and apoptosis in H358 cells in vitro and to introduce and transcribe the p53 gene in the bronchial epithelium of transgenic mice that lack the p53 gene in vivo . In therapeutic experiments using groups of four or five mice each, administration of five intratracheal doses of DP3-p53 (2 µg or 8 µg DNA per dose) on days 4, 8, 12, 16, and 20 after intratracheal tumor inoculation significantly inhibited lung tumor formation and prolonged by approximately twofold the survival of mice bearing H358 or H322 endobronchial tumor cells in contrast to the survival among untreated mice and mice treated with the DP3-empty vector (P = .007 [two-sided logrank test] for mice bearing H358 cells and P = .008 [twosided logrank test] for those bearing H322 cells). Conclusions/ Implications : Liposome-based p53 delivery through the airways is a potentially effective strategy for the treatment of early endobronchial cancer. These results have important implications for the gene therapy and prevention of human lung cancer. [J Natl Cancer Inst 1998;90:1130-7]
Kistrin, an integrin antagonist, blocks endocytosis of fibrinogen into guinea pig megakaryocyte and platelet alpha-granules.
Authors: P Handagama, D F Bainton, Y Jacques, M T Conn, R A Lazarus, M A Shuman
Journal: Journal of Clinical Investigation (1993)

Recent data indicate that megakaryocyte/platelet alpha-granule fibrinogen is endocytosed from plasma. Because fibrinogen is the major platelet protein present in high concentrations in alpha-granules, fibrinogen uptake into alpha-granules may occur via specific receptors. In that cells of the megakaryocyte/platelet lineage contain two integrins--alpha IIb beta 3 (GP IIb-IIIa) and the vitronectin receptor (alpha v beta 3)--that can bind fibrinogen, one or both of these receptors may mediate the endocytic uptake of fibrinogen. To test this hypothesis, we examined the effect of Kistrin, an RGD-containing protein purified from the venom of Agkistrodon rhodostoma that inhibits fibrinogen binding to human platelet receptors, on endocytosis of fibrinogen by megakaryocytes and platelets. Continuous intravenous infusion of kistrin into guinea pigs (200 micrograms/h) over a 24-h period inhibited collagen-induced platelet aggregation. When biotinylated fibrinogen was injected intravenously into animals receiving Kistrin, megakaryocytes failed to endocytose the labeled fibrinogen. Endocytosis of fibrinogen into platelets was also inhibited in these animals. In contrast, platelets and megakaryocytes obtained from sham-infused control animals contained the injected biotinylated fibrinogen. We conclude that, in addition to the well-known extracellular function of cell adhesion, integrins can also act as receptors that mediate endocytosis of exogenous proteins and incorporate them into regulated secretory granules.
Controversy on drugs affecting ATP sensitive potassium channel in ischaemic heart disease
Authors: G. J Gross
Journal: Cardiovascular Research (1994)

Journal Article Controversy on drugs affecting ATP sensitive potassium channel in ischaemic heart disease Get access Garret J Gross Garret J Gross Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin. USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 1, January 1994, Pages 139–140, https://doi.org/10.1093/cvr/28.1.139 Published: 01 January 1994
Who decides whether the patient is mentally incapacitated?
Authors: W.-C. Leung
Journal: BMJ (1998)

<h3>Background</h3> Skin tests have an important place in the diagnosis of hypersensitivity. Because of a lack of precise skin tests procedures, drug skin tests are often not carried out. However, they could help to determine the cause of hypersensitivity and help in the choice of therapeutic strategy. In our hospital, a dermatologist required us to produce skin tests with cytotoxic and anti-HER2 antibody agents (docetaxel, pertuzumab, trastuzumab) in order to evaluate the hypersensitivity of a patient who developed a photosensitive dermatosis after a second cycle of chemotherapy. <h3>Purpose</h3> The aim of this project was to produce a feasibility study for the production of skin tests with these three molecules. <h3>Material and methods</h3> A literature review was performed to find data about skin tests, and more particularly about safety and non-irritant drug concentrations. Because of a lack of data, we also decided to realise an investigation near the others hospital centres. Chemical tests were carried out such as the measure of the drug pH and the miscibility between the diluant and the medicine. <h3>Results</h3> According to the literature, the pH drug must be between 6 and 9 to avoid skin injuries. By its acidic pH, docetaxel could not be used to produce a patch test (non-diluated drug pH=3, diluated with 0.9 per cent sodium chloride drug pH=4). The pH of the two other agents and of the diluant was acceptable (pH=7). In most of the publications, the excipient used for the preparation of patch tests was petroleum jelly. In cooperation with the doctor, we decided to produce a prick test with docetaxel, prepared by diluting the drug to 5 mg/ml in an aqueous solution of 0.9% sodium chloride. Concerning pertuzumab and trastuzumab, patch tests were obtained by realizing an homogeneous preparation, with a concentration of 30% in petrolatum. <h3>Conclusion</h3> The literature deals mainly with a platinum agent, and more often with skin prick tests and intradermal tests. We were confronted with the difficulty of possessing poor data when facing the request of the dermatologist. Moreover, according to the literature, patch tests commonly reveal false negative results. This activity necessitates the development of a local thesaurus and an economic study. <h3>References and/or acknowledgements</h3> No conflict of interest.
Cholesterol Embolism in Bone Marrow
Authors: ARKADI M. RYWLIN
Journal: Annals of Internal Medicine (1979)

Letters and Corrections1 March 1979Cholesterol Embolism in Bone MarrowARKADI M. RYWLIN, M.D.ARKADI M. RYWLIN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-90-3-443_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In "Cholesterol Embolism: Diagnosis Antemortem by Bone Marrow Biopsy," in the December 1978 issue (1), Pierce and associates state that cholesterol emboli diagnosed by bone marrow biopsy have not been previously reported.I have seen cholesterol emboli in histologic preparations of aspirated and biopsied marrow on several occasions and have reported it (2). A word of caution is in order. The finding of atheromatous emboli in the bone marrow does not necessarily mean that the patient is suffering from widespread manifestations of this process. It may be an incidental finding of minor clinical significance indicating that the...References1. PIERCEWRENCOUSAR JMJ: Cholesterol embolism: diagnosis antemortem by bone marrow biopsy. Ann Intern Med 89:937-938, 1978 LinkGoogle Scholar2. RYWLIN A: Histopathology of the Bone Marrow. Boston, Little, Brown and Company, 1976, p. 181 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByCholesterol Crystal Embolization: A Review of 221 Cases in the English Literature 1 March 1979Volume 90, Issue 3Page: 443-444KeywordsBiopsyBone marrowCholesterol Issue Published: 1 March 1979 PDF DownloadLoading ...
Linkage of type 2 diabetes to the glucokinase gene
Authors: A.T Hattersley, R.C Turner, P Patel, S O'Rahilly, A.T Hattersley, P Patel, J.S Wainscoat, M.A Permutt, Y Tanazawa, K.C Chin, P Watkins
Journal: The Lancet (1992)
Tetanus Mimicking a Psychophysiologic Reaction
Authors: Edward B. Shaw
Journal: JAMA (1967)

To the Editor:—  You may have had a number of letters about the article by C. R. Treadway, MD, and A. J. Prange, Jr., MD, Tetanus Mimicking Psychophysiologic Reaction: Occurrence After Dental Extraction ( 200 :891, 1967). I am sure many readers will share my reservations.  The patient had a long history of neurotic symptoms and for five years had complained of intermittent stiffness of the muscles of her jaw, neck, back, and legs, for which no organic basis could be demonstrated. She had been treated by several physicians for nerves, tension, and headache. Acute symptoms developed after tooth extraction, with pain and muscular soreness on the same side as the extraction. With the patient's increasing difficulty in swallowing and in opening her mouth, tetanus was diagnosed and treated accordingly. Actual trismus and classical muscle spasm was not described.  It may be improper to challenge the diagnosis of the physician who
Cost-Effectiveness of Antibiotic Use
Authors: William L. Aldis
Journal: JAMA (1984)

<h3>To the Editor.—</h3> Recently, we completed an analysis of cost-effectiveness of antibiotic use in our 80-bed rural hospital. From all admissions in an arbitrarily selected month (381 admissions in September 1982), a high-cost antibiotic usage group was selected. This was defined as all patients for whom the cost of antibiotics was more than 1 SD above the group mean for all patients receiving antibiotics. Of 169 patients receiving antibiotics, 38 patients were in this high-cost group. These patients' records were then reviewed to see whether a less expensive but equally effective antibiotic (or combination of antibiotics) could have been used. Using conservative criteria,<sup>1</sup>16 cases were identified for which a less expensive antibiotic could have been used. In many of these cases, the cheaper antibiotic was distinctly preferable to the one actually used (eg, use of penicillin instead of cefamandole for pneumococcal pneumonia proven by Gram's stain and culture).
Psychological Effects of Diethylstilbestrol Exposure
Authors: Ruth W. Schwartz
Journal: JAMA (1977)

The psychological response of daughters and their mothers to discovery of in utero diethylstilbestrol (DES) exposure was studied. At the DES Colposcopy Clinic, 41 daughters and 20 mothers were extensively interviewed. Twelve patients with abnormal cytology tests were controls. Initial anxiety was usually followed by acceptance of the condition after examination and counseling. Patients responded best when informed of their problem by their mothers and when the relationship between mother and daughter was good. The majority of patients found colposcopy to be unpleasant; they tended to be disturbed in proportion to the degree of being upset about DES exposure. The most common problem among mothers was guilt. A questionnaire survey of physicians showed that they had less concern for psychological problems than patients or mothers did. Sensitivity and good communication on the part of medical personnel are recommended.
EVIDENCES OF THE PROGRESS OF NEUROLOGY AND MEDICAL JURISPRUDENCE.
Authors: WILLIAM J. HERDMAN
Journal: JAMA (1898)

In compliance with the by-law of thisAssociation, which specifies the subject upon which the Chairman of each Section shall address its members, it becomes my pleasant privilege as well as duty to attempt a brief review of the progress made in neurology and medical jurisprudence during the past twelve months, and to hazard a few suggestions as to the conduct of the future work of the Section, which if they shall be adopted would, in my judgment, greatly improve the efficiency of its function. And here it might be well to call to mind what the function of this Section is, and what we, who constitute its membership and attend its sessions from year to year, are attempting to accomplish. No doubt the motives which influence us to attend these meetings annually are many and various. Social, fraternal, recreative, and perhaps at times even less laudable inducements than these
Cytomegalovirus Is Not an Occupational Risk for Nurses in Renal Transplant and Neonatal Units
Authors: Carol L. Balfour
Journal: JAMA (1986)

The risk of inpatient-to-nurse transmission of cytomegalovirus (CMV) was assessed in a five-year prospective seroepidemiologic study. We enrolled 263 renal transplant/hemodialysis nurses, 204 neonatal intensive care nurses, 225 student nurses, and 251 blood donor controls. Prevalence of CMV antibody in these 943 subjects was 33.7% and did not differ significantly among the four study groups. Sixteen subjects experienced primary CMV infections. The yearly seroconversion rate, calculated from age-related seroprevalence data, was 1.9%. The rate of seroconversion during the study, established by observing 519 seronegative subjects for 10 420 person-months, was 1.84% per year and did not differ significantly among the study groups. The proportions of patients with CMV infection (1.1% to 11.9%) and disease (0.5% to 3.4%) on study wards were not related to seroconversion in the nurses. The slow rate of acquisition of CMV in susceptible adults suggests that transmission requires prolonged, intimate contact. Nurses and nursing students who practice good personal hygiene are no more likely to acquire CMV than their peers in the community.
597 Genotype and fibrosis stage are major predictors of sustained virological response to retreatment with pegylated combination in non responders to standard combination therapy
Authors: R. Moukari, M.P. Ripault, T. Asselah, N. Boyer, M. Martinot, A. El Ray, D. Vidaud, D. Cazals-Hatem, D. Valla, P. Marcellin
Journal: Journal of Hepatology (2006)
Nonabandonment: Medical Ethics
Authors: Peter A. Engel
Journal: Annals of Internal Medicine (1995)

Letters15 September 1995Nonabandonment: Medical EthicsPeter A. Engel, MDPeter A. Engel, MDAlbany Veterans Affairs Medical Center; Albany, NY 12208Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-6-199509150-00028 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In their essay on nonabandonment, Quill and Cassel [1] argue that the conventional construct of medical ethics constrains our thinking and flexibility in caring for patients. They then propose that the physician–patient relationship be at the core of a new ethical paradigm.In fact, the core of their discussion is not ethics but the physician–patient relationship. Although the authors devote much attention to “relationship” and nonabandonment as sources of ethical principle, they offer little insight into the phenomenology of relationships or the experiential aspects of being a physician. What about doctoring makes connections with patients rewarding, intriguing, ...References1. Quill TE, Cassel CK. Nonabandonment: a central obligation for physicians. Ann Intern Med. 1995; 122:368-74. Google Scholar Author, Article, and Disclosure InformationAffiliations: Albany Veterans Affairs Medical Center; Albany, NY 12208 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 September 1995Volume 123, Issue 6Page: 474-475KeywordsBehaviorEmotionsEuthanasiaMedical ethicsSuicide Issue Published: 15 September 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
SEMI-AUTOMATED EVALUATION OF RIGHT VENTRICULAR VOLUME USING GRADIENT CINE MR DATA SETS: AN IN VITRO VALIDATION STUDY
Authors: David J. Sahn, Muhammad Ashraf, Matthew Martinez, Kiaran McGee, Nandan Anavekar, Thomas Balbach, Keith DesRochers, Thuan Nguyen, Erik L. Ritman, Rick Nishimura
Journal: Journal of the American College of Cardiology (2011)
When an Ear Nodule Hurts
Authors: Frederick A. J. Kingery
Journal: JAMA (1966)

A nodule on the ear rarely escapes attention. Discovery is usually made by the patient, who is worried about cancer, or by the physician, who can use the nodule to identify another disease. The chalky urate deposits in the gouty tophus (Figure,<i>left</i>), and the subcutaneous nodule of rheumatic fever (Figure,<i>center</i>) reflect visible evidence of generalized disease well known to all physicians. Microscopic examination will provide a diagnosis in questionable cases, as well as identify carcinoma when suspected. Pain is notably absent from all nodules of the ear, except one.<i>Painful nodule of the ear</i>, formerly called nodular chondrodermatitis (Figure,<i>right</i>), is an uncommon disorder which is characterized by exquisite tenderness far out of proportion to its insignificant appearance. The nodule is located in the skin, and cartilage is only secondarily affected, if at all. A compromised blood supply is probably responsible for the lesion, but the exact nature
A fifth of England's hospitals are likely to be in deficit, says King's Fund
Authors: J. Wise
Journal: BMJ (2014)

One in five NHS trusts in England and one in eight clinical commissioning groups have reported a possible overspend by the end of the financial year, a survey by the health think tank the King’s Fund has indicated.1

The survey results show that 22% of NHS trust finance directors who responded expected to be in deficit by the end of the year and that only 47% expected to meet their productivity targets. The latest quarterly monitoring report indicates that the NHS will struggle to meet its target of delivering £20bn (€24bn; $33bn) efficiency savings by 2015.

Finance leads from clinical commissioning groups were slightly more …
525 PROTEASOME INHIBITION BY BORTEZOMIB DURING ONCOLYTIC VIROTHERAPY OF HCC LEADS TO IMPROVED THERAPEUTIC EFFICACY MEDIATED BY MOLECULAR AND IMMUNOLOGICAL MECHANISMS
Authors: B. Boozari, N. Woller, B. Fleischmann-Mundt, T.C. Wirth, M.P. Manns, S. Kubicka, F. Kühnel
Journal: Journal of Hepatology (2009)
Relation of stenosis morphology and clinical presentation to the procedural results of directional coronary atherectomy.
Authors: S G Ellis, N B De Cesare, C A Pinkerton, P Whitlow, S B King, Z M Ghazzel, D J Kereiakes, J J Popma, K K Menke, E J Topol
Journal: Circulation (1991)

BACKGROUND Directional coronary atherectomy has recently become available to treat coronary stenoses. This study was performed to determine the relation of patient characteristics and stenosis morphology to procedural outcome with directional coronary atherectomy to gain insight into which patients might be best treated with this device. METHODS AND RESULTS Four hundred stenoses from 378 patients consecutively treated at six major referral institutions were analyzed. Angiographic data were assessed at a central angiographic laboratory using standardized morphological criteria and computer-assisted quantitative dimensional analyses. Procedural success was achieved in 87.8% of stenoses, and major ischemic complications (death, myocardial infarction, and emergency bypass surgery) occurred in 6.3% of patients. Lesion success and complications were closely correlated with recognized modified American College of Cardiology/American Heart Association Task Force lesion morphological criteria. Observed for type A stenoses were 93% success and 3% complication rates; for type B1 stenoses, 88% success and 6% complication rates; and for type B2 stenoses, 75% success and 13% complication rates, respectively. There were too few type C stenoses treated to analyze. Furthermore, multivariate testing demonstrated stenosis angulation (multivariate p less than 0.001), proximal tortuosity (p less than 0.001), decreased preatherectomy minimum lumen dimension (p = 0.032), and calcification (p = 0.041) to correlate independently with adverse outcome and complex, probably thrombus-associated stenoses to have a favorable outcome (p = 0.055). Operator experience (p = 0.020) and a history of restenosis (p = 0.022) also favorably influenced outcome. CONCLUSIONS The procedural outcome of directional coronary atherectomy is highly associated with coronary stenosis morphology. Furthermore, after appropriate stratification for morphology and clinical presentation, overall atherectomy procedural outcome may be similar to that achieved with coronary angioplasty. However, specific subsets of patients may have relatively better outcome with either atherectomy or balloon angioplasty.