tbuckley/cabot-search huggingface dataset:
790. Murine Retroviral but Not Human Cellular Promoters Induce In Vivo Erythroid-Specific Promoter Deregulation That Can Be Prevented by Insulators
Authors: Elodie Robert, Emmanuel Richard, Cecile Ged, Punam Malik, Hubert De Verneuil, Francois Moreau-Gaudry
Journal: Molecular Therapy (2006)

We are interested in the development of lentiviral vectors that co- express a therapeutic gene in an erythroid-specific manner and the MGMT selective gene in a constitutive way for gene therapy of red blood cell (RBC) disorders. We have previously demonstrated that long-term gene expression limited to erythroid progeny was possible in vivo with a chimeric HS40 enhancer and human ankyrin promoter in the area of the constitutive human PGK promoter (PGKp) driving MGMT without loss of tissue-specificity. However, transductions were performed at high multiplicity of infection (MOI) elevating the risk of insertional mutagenesis. In this study, we found that PGKp was not strong enough at low MOI to mediate an in vivo survival advantage in the presence of alkylating agents. To be efficient at one copy per cell, the vector needs to contain strong enhancer- promoter elements. By replacing PGKp with the MND promoter (MNDp), the vector allowed an efficient chemoprotection of transduced hematopoietic stem cells (HSCs) at low MOI (75.1 ± 8.6 % vs 34.8 ± 11 % EGFP+ RBCs for treated (n=3) vs untreated group (n=3)). However, this MNDp interacts with the erythroid one, leading to a partial loss of erythroid-specificity. To avoid this promoter deregulation, the full length cHS4 insulator sequence or its minimal core element were inserted between the two expression units. Murine HSCs were transduced by lentiviral vectors and injected into 12-Gy irradiated BALB/c. Sixteen weeks after transplantation, bone marrow (BM) cells were analyzed by FACS. The core-containing vector combines a similar high chemoprotection efficiency as allowed by MNDp (up to 20-fold in vivo expansion of GFP positive RBCs) and a dramatic decrease of promoter interferences (2, 5 and up to 6-fold decrease of non specific GFP mean fluorescence intensity (MFI) in T-lymphocytes, granulocytes and monocytes respectively, as compared with the MNDp- lentivector). This study demonstrates the interest of insulators for preventing in vivo enhancer activities between 2 promoters. Alternatively, we found that the strong human cellular EF1-α promoter allows similar chemoprotection (86.0 ± 5.0 % vs 34.1 ± 2.5 % EGFP+ RBCs for treated and untreated groups, respectively) but without any deregulation of the erythroid-specific promoter in the absence of insulators. These data suggest that the level of in vivo deregulation induced by a promoter is not correlated with its transcriptional activity but with the presence its strong enhancers. These findings have direct implications for the design of gene therapy vectors.
TECHNIQUE OF INTRA-ABDOMINAL INSERTION OF RADIUM FOR CARCINOMA OF THE CERVIX UTERI
Authors: M. Donaldson
Journal: BMJ (1929)

JNTBAABDOMINAL RADIUM IN CANCER OF CERVIX.been obtainied for hospitals for the putirchase of radiium by these means, scientific and clinical progress has beeni correspoiidingly embarrassed.The mainl hope of advanice in the treatmenit of carcinomna bv iradium lies in the combinied investigations of the clinician, the pathologist, and the physicist, anid it is in .tisway only-, al'd niot by staritlini,g niewspaper headlines, that fu-ture clinical results are likely to improve.
Aortography as an Aid to the Localization of Pheochromocytoma.
Authors: David Z. Morgan
Journal: Annals of Internal Medicine (1965)

s1 November 1965Aortography as an Aid to the Localization of Pheochromocytoma.David Z. Morgan, M.D.David Z. Morgan, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-63-5-902_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThree cases are presented in which pheochromocytomas were precisely localized by retrograde aortography. One patient, a normotensive 23-year-old pharmacy student, was found, during routine screening of his class for experimental purposes, to have persistently elevated 24-hour urinary catecholamine levels ranging from 114 to 337 µg. Aortography established the presence of a right suprarenal tumor. A second case was unique in that aortography permitted the preoperative diagnosis of a pheochromocytoma of the organ of Zuckerkandl. This severely hypertensive woman, age 28, had been thought to have renal artery stenosis because of the presence of a loud abdominal bruit. A retrograde aortogram... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Morgantown, West Virginia PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 November 1965Volume 63, Issue 5Page: 902-902KeywordsCatecholaminesPheochromocytomaRenal arteriesStenosis Issue Published: 1 November 1965 PDF DownloadLoading ...
US health secretary calls on Republicans to move on from Obamacare debate
Authors: M. McCarthy
Journal: BMJ (2015)

The US health and human services secretary, Sylvia M Burwell, has urged congressional Republicans to move on from the debate over the 2010 Affordable Care Act and work with the Obama administration on issues where Democrats and Republicans share common interests.

“I count myself among those who do not believe that disagreements in some areas—even significant disagreements—should prevent us from moving forward on others,” Burwell said in a speech on 15 January at the New America Foundation, a non-partisan, public policy think tank in Washington, DC.

Republicans, who now have control of both chambers of Congress, have vowed to repeal the 2010 health act or, failing that, dismantle it piece by piece. President Barack Obama has said that he is willing to …
Discordance of Databases Designed for Claims Payment versus Clinical Information Systems: Implications for Outcomes Research
Authors: James G. Jollis
Journal: Annals of Internal Medicine (1993)

Objective: To determine the suitability of insurance claims information for use in clinical outcomes research in ischemic heart disease. Design: Concordance study of two databases. Setting: Tertiary care referral center. Patients: A total of 12 937 consecutive patients hospitalized for cardiac catheterization for suspected ischemic heart disease between July 1985 and May 1990. Interventions: Two-by-two tables were used to compute overall and measures of agreement comparing clinical versus claims data for 12 important predictors of prognosis in patients with ischemic heart disease. Measurements: Kappa statistics (agreement adjusted for chance agreement) were used to quantify agreement rates. Results: Agreement rates between the clinical and claims databases ranged from 0.83 for the diagnosis of diabetes to 0.09 for the diagnosis of unstable angina ( values). Claims data failed to identify more than one half of the patients with prognostically important conditions, including mitral insufficiency, congestive heart failure, peripheral vascular disease, old myocardial infarction, hyperlipidemia, cerebrovascular disease, tobacco use, angina, and unstable angina, when compared with the clinical information system. Conclusions: Our results suggest that insurance claims data lack important diagnostic and prognostic information when compared with concurrently collected clinical data in the study of ischemic heart disease. Thus, insurance claims data are not as useful as clinical data for identifying clinically relevant patient groups and for adjusting for risk in outcome studies, such as analyses of hospital mortality.
COURSE IN MILITARY NEUROPSYCHIATRY
Authors: ROY D. HALLORAN, PAUL I. YAKOVLEV
Journal: American Journal of Psychiatry (1942)

We have outlined our thoughts and experiences with a special one-month semester in military neuropsychiatry as a section of a general seminar. We feel that this brief experimental course helped to refresh both military and civilian physicians on subjects of special practical importance during war time. We also recognize its failure, because of insufficient time, to provide certain essential clinical experiences. However, we believe that a six-weeks' course comprising both lectures and clinics in general and psychiatric hospitals in active medical centers and organized in close collaboration with governmental authorities would rapidly extend the advantages of special training to a large number of military and civilian physicians. We have proposed such a course. The strategic importance of improved standards of detection and treatment of neuropsychiatric disorders both among selectees and those already in service can hardly be exaggerated. Any practical method which will aid in such improvement, we believe, merits most serious consideration. These courses are short, practical and certainly offer at least one readily available means of broadening professional experience in the interests of greater military efficiency and more effective individual treatment, where the appropriate handling of large numbers living under special conditions of war is essential.
Endotoxic Shock Complicating Trans-hepatic Cholangiography
Authors: B. B. Hickey
Journal: BMJ (1973)

In Scotland similar immunoglobulin is pre- pared at the Protein Fractionation Gentre and can be obtained by contacting the director of the appropxiate regional blood transfusion centre who will also provide information re- garding the local follow-up arrangements for the recipient.-Iam, etc.,
SARS treatment: who will lead the way forward?
Authors: Marilynn Larkin
Journal: The Lancet Infectious Diseases (2003)

At time of press, severe acute respiratory syndrome (SARS) seems to be waning, and so the time is right "for a consensus meeting to review our treatment experiences and decide with industry, public-health officials, academia, and others the best strategy for moving forward", says Scott Hammer (Columbia University, NY, USA), who chaired a May 13 SARS conference at the New York Academy of Sciences (http://www.nyas.columbia.edu/sars; figure). "We don't know yet if SARS will be a cycle, so it will be a couple of years at least before we can relax", he warns, adding that, thus far, no organisation has taken the lead in arranging a meeting that might lead to evidence-based treatments.
Direct, MHC-dependent presentation of the drug sulfamethoxazole to human alphabeta T cell clones.
Authors: B Schnyder, D Mauri-Hellweg, M Zanni, F Bettens, W J Pichler
Journal: Journal of Clinical Investigation (1997)

T cells can recognize small molecular compounds like drugs. It is thought that covalent binding to MHC bound peptides is required for such a hapten stimulation. Sulfamethoxazole, like most drugs, is not chemically reactive per se, but is thought to gain the ability to covalently bind to proteins after intracellular drug metabolism. The purpose of this study was to investigate how sulfamethoxazole is presented in an immunogenic form to sulfamethoxazole-specific T cell clones. The stimulation of four CD4(+) and two CD8(+) sulfamethoxazole-specific T cell clones by different antigen-presenting cells (APC) was measured both by proliferation and cytolytic assays. The MHC restriction was evaluated, first, by inhibition using anti-class I and anti-class II mAb, and second, by the degree of sulfamethoxazole-induced stimulation by partially matched APC. Fixation of APC was performed with glutaraldehyde 0.05%. The clones were specific for sulfamethoxazole without cross-reaction to other sulfonamides. The continuous presence of sulfamethoxazole was required during the assay period since pulsing of the APC was not sufficient to induce proliferation or cytotoxicity. Stimulation of clones required the addition of MHC compatible APC. The APC could be fixed without impairing their ability to present sulfamethoxazole. Sulfamethoxazole can be presented in an unstable, but MHC-restricted fashion, which is independent of processing. These features are best explained by a direct, noncovalent binding of sulfamethoxazole to the MHC-peptide complex.
Coronary sinus pacing clinical follow-up.
Authors: P Greenberg, M Castellanet, J Messenger, M H Ellestad
Journal: Circulation (1978)

Coronary sinus pacing is a safe and effective means of pacing from the atrium. In 66 patients with an average follow-up of 14 months, there was a 14% failure rate. There were transient problems in 14% which were subsequently corrected. There was a 6% death rate which was not pacemaker related. Successful atrial pacing with thresholds up to 6.0 mA is feasible. Atrial pacing was successful in 18 of 19 patients with varying degrees of atrioventricular block. Our experience with a new electrode has been very satisfactory.
Host, heredity and helicobacter
Authors: J G NEDRUD, S J CZINN
Journal: Gut (1999)

<h3>Introduction</h3> Extracorporeal shock wave lithotripsy (ESWL) of pancreatic duct stones, followed by endoscopic retrograde cholangio-pancreaticography (ERCP) with mechanical clearance of the pancreatic duct, and subsequent stenting is an established treatment option in patients with chronic calcifying pancreatitis. <h3>Aim</h3> To test the efficacy of a modified transportable minilithotriptor for ESWL of pancreatic duct stones. <h3>Methods</h3> We prospectively studied 32 patients with obstructive chronic calcifying pancreatitis with pain as a dominant symptom who underwent extracorporeal shock wave lithotripsy (ESWL) using the modified transportable minilithotriptor. ESWL was followed by ERCP for stone clearance of the pancreatic duct and mechanical removal of stones or stenting. Pre- and postprocedure pain and quality of life was assessed using a 5-point analog score and a 5-step verbal life satisfication. <h3>Results</h3> In all patients the endoscopic treatmet was successful as we could clear the pancretic duct completely from fragmented stones (40.6%) or were able to insert a pancreatic stent for decompression (59.4%) of the duct. A median of 4 ESWL sessions (range 1–15) with a median of 6800 shockwaves (1000–34.700) were required. Pain relief after ESWL only was noted in 24 patients (75.0%), while no change in the intensity of pain was reported by seven patients (21.9%), pain was worse in one patient. All patients underwent ERCP and stent placement, resulting in complete resolution of pain in 17 patients (84.4%), pain improvement in 27 patients (84.4%). When asked to score their quality of life before and after the two procedures were undertaken, all patients found that their overall quality of life significantly improved after ESWL and endoscopic stenting. <h3>Conclusion</h3> Extracorporal shock wave lithotripsy with the mini-lithotriptor results in fragmentation of pancreatic duct calculi. ESWL in conjunction with endoscopic clearance of the main pancreatic duct and stenting is associated with significant improvement in clinical outcome and quality of life in patients with obstructive calcifying chronic pancreatitis.
Effect of Renal Function on Urinary Recovery of Orally Administered Nitrofurantoin
Authors: Joseph Sachs, Taggart Geer, Phyllis Noell, Calvin M. Kunin
Journal: New England Journal of Medicine (1968)

The urinary recovery of nitrofurantoin after a single 100-mg oral dose was studied in subjects with varying renal function. Almost all uremic patients excreted little or no drug in the urine during a 10-hour collection period. Recovery of drug in the urine appeared to be linearly related to creatinine clearance. The highest concentration of drug recovered during any collection period in uremic patients was inadequate to inhibit organisms commonly found in urinary-tract infections. A small group of subjects with impaired renal function, given 100 mg daily, failed to excrete detectable amounts of drug even after five days of treatment. Three azotemic patients receiving 400 mg per day for several days excreted small amounts of drug in the urine. In view of these and other studies, it is recommended that nitrofurantoin be contraindicated in azotemic patients.
Working Capacity of Women Doctors
Authors: M. F. Pattinson
Journal: BMJ (1966)

attitude to Family Care Service Ltd. (26 March, p. 804).The contention that the British patient is not sufficiently affluent to pay something directly -for medical care just does not stand up to the light of scrutiny.It might be of interest to tell you what outpatient charges are at this 200-bed rural mission hospital.Currently two doctors are
THE PREVALENCE OF TYPHOID CARRIERS IN A GENERAL POPULATION
Authors: S. W. WELCH
Journal: JAMA (1925)

The examination of the general population for typhoid carriers in various localities in the past has disclosed an incidence, where the disease is not unduly prevalent, of from 0.3 to 0.8 per cent.<sup>1</sup>These results are based largely on a single fecal examination. Obviously, the urinary carrier and many intermittent intestinal carriers are missed. The difficulties attendant on the successful demonstration of a typhoid carrier are well known. Not only must fairly large numbers of the bacilli be present in the specimen, but also their numbers diminish very rapidly and any delay in the study of the specimen decreases the chance of a positive result. Repeated examinations of the specimen are therefore useless, and success depends on an immediate single plating of the stool. It is evident, then, that if the rapid diminution of the typhoid organism in the feces could be largely prevented, the laboratory examination would become
Metronidazole in Treating Portosystemic Encephalopathy
Authors: Mark D. Uhl
Journal: Annals of Internal Medicine (1996)

Letters15 February 1996Metronidazole in Treating Portosystemic EncephalopathyMark D. Uhl, MD and Caroline A. Riely, MDMark D. Uhl, MDUniversity of Tennessee; Memphis, TN 38163Search for more papers by this author and Caroline A. Riely, MDUniversity of Tennessee; Memphis, TN 38163Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-124-4-199602150-00015 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The antibiotic metronidazole is now commonly used to treat portosystemic encephalopathy. We describe a patient who became psychotic while receiving this drug.A 65-year-old white woman with Child class B liver disease secondary to homozygous (phenotype ZZ) α 1-antitrypsin deficiency was treated for portosystemic encephalopathy using lactulose and metronidazole. After receiving this regimen for approximately 3 months, the patient began to show agitation, emotional lability, verbal abuse, paranoia, and manic behavior, which were witnessed by both family members and medical staff. A computed tomographic scan of the head; thyroid function tests; an electroencephalogram; and assessments of serum ...References1. Munson PL, Mueller RA, Breese GR, eds. Principles of Pharmacology: Basic Concepts and Clinical Applications. New York: Chapman and Hall; 1995. Google Scholar2. Morgan MH, Read AE, Speller DC. Treatment of hepatic encephalopathy with metronidazole. Gut. 1982; 23:1-7. Google Scholar3. Bradley WG, Carlsson IJ, Rassol CG. Metronidazole neuropathy. Br Med J 1977; 2:610-1. Google Scholar4. Kusumi RK, Plouffe JF, Wyatt RH, Fass RJ. Central nervous system toxicity associated with metronidazole therapy. Ann Intern Med. 1980; 93:59-60. Google Scholar5. Farrell G, Baird-Lambert J, Cvejic M, Buchanan N. Disposition and metabolism in patients with liver failure. Hepatology. 1984; 4:722-6. Google Scholar Author, Article, and Disclosure InformationAuthors: Mark D. Uhl, MD; Caroline A. Riely, MDAffiliations: University of Tennessee; Memphis, TN 38163 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byMetronidazole-induced encephalopathy: a systematic reviewIntravenous and Oral Hyperammonemia ManagementManagement of Hepatic Encephalopathy in the HospitalToolbox: Neuropsychiatric adverse effects of antimicrobial agentsMetronidazole-Induced Central Nervous System ToxicityMetronidazole-induced encephalopathy in a patient with liver cirrhosisCurrent and Emerging Strategies for Treating Hepatic EncephalopathyMetronidazole 15 February 1996Volume 124, Issue 4Page: 455KeywordsBrain diseasesCirrhosisDrugsPeripheral neuropathyPhenotypesPortal hypertensionPsychosesRapid plasma reaginSaltsThyroid ePublished: 15 August 2000 Issue Published: 15 February 1996 Copyright & PermissionsCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Effect of Prolonged Alcohol Administration on Calcium Transport in Heart Muscle of the Dog
Authors: RICHARD J. BING, HARALD TILLMANNS, JEAN-MARIE FAUVEL, KEITH SEELER, JAMES C. MAO
Journal: Circulation Research (1974)

The effect of prolonged administration of alcohol on calcium binding and uptake by sarcoplasmic reticulum and mitochondria and on respiratory function of mitochondria was investigated in heart muscle of dogs. Dogs were paired and maintained with and without alcohol for 6 months; alcohol was administered by adding it to drinking water and food with vitamin supplements. Measurements were made after alcohol had been temporarily withheld for 2 days. Prolonged alcohol ingestion resulted in a decline in calcium binding and uptake by sarcoplasmic reticulum and mitochondria, suggesting a diminished affinity of the reticular and mitochondrial membranes for calcium ions. The endogenous calcium content of mitochondria and sarcoplasmic reticulum decreased. Prolonged alcohol administration failed to alter cardiac contractility, although contraction and relaxation tended to diminish following the administration of angiotensin. The results illustrate that one link in the regulation of the state of contraction or relaxation involving myofibrillar calcium transport is weakened in dogs maintained on alcohol for prolonged periods of time.
Problems With the Irradiation of Children and Pregnant Patients
Authors: Giulio J. D'Angio
Journal: JAMA (1973)

A profound therapeutic dilemma often confronts the physician when a child or a pregnant woman must be irradiated. The beneficial effects of aggressive, curative therapy must be balanced against the deleterious consequences of such treatment. <h3>Irradiation of Children</h3> Adults with early Hodgkin's disease have a good prognosis. Long-term survival can be expected.<sup>29</sup>The same can be said for children. Butler<sup>35</sup>discussed the several factors that appear to influence prognosis, ie, sex, age, histologic type, and stage of disease. All things considered, he found the prognosis for children to be better, stage for stage, than for adults, a conclusion differing from that of Jenkin et al,<sup>36</sup>who found no pronounced difference. Radiation therapy is the mainstay of treatment in these patients. However, treatment policies that are considered suitable for adults may be less appropriate for children, because the immediate and late effects of radiation therapy are more pronounced