tbuckley/cabot-search huggingface dataset:
Augmented BH4 by gene transfer restores nitric oxide synthase function in hyperglycemic human endothelial cells
Authors: S CAI, J KHOO, K CHANNON
Journal: Cardiovascular Research (2004)

Objective:: Endothelial dysfunction in diabetes is characterized by decreased nitric oxide (NO) bioactivity and increased superoxide (SO) production. Reduced levels of tetrahydrobiopterin (BH4), an essential cofactor of endothelial NO synthase (eNOS), appear to be associated with eNOS enzymatic uncoupling. We sought to investigate whether augmented BH4 biosynthesis in hyperglycemic human aortic endothelial cells (HAEC) by adenovirus-mediated gene transfer of GTP cyclohydrolase I (GTPCH, the rate-limiting enzyme for the de novo BH4 synthesis), would be sufficient to rescue eNOS activity and dimerization. HAEC were cultured in media with low glucose (5 mM) or high glucose (30 mM). Methods: After 5 days, the cells with/without GTPCH gene transfer (AdeGFP as a control) were prepared for assays of (1) NO with electron paramagnetic resonance (EPR); (2) SO with cytochrome c reduction and dihydroethidine (DHE) fluorescence; (3) BH4 with high-performance liquid chromatography (HPLC); (4) eNOS expression and dimerization with immunoblotting. Results: We found that high glucose decreased HAEC NO and increased SO production, in association with reductions in both total biopterin and BH4 levels. High glucose increased total eNOS protein levels in HAEC 1.5-fold, but this was present principally in the monomeric form. GTPCH gene transfer increased cellular biopterin levels and NO production but decreased SO production. Furthermore, augmenting BH4 increased the eNOS dimer:monomer ratio 2.6-fold. Conclusion: This study demonstrates a critical role for BH4 in regulating eNOS function, suggesting that GTPCH is a rational target to augment endothelial BH4 and recover eNOS activity in hyperglycemic endothelial dysfunction states.
Global Risk Scores and Exercise Testing for Predicting All-Cause Mortality in a Preventive Medicine Program
Authors: Mehmet K. Aktas, Volkan Ozduran, Claire E. Pothier, Richard Lang, Michael S. Lauer
Journal: JAMA (2004)

ContextThe usefulness of exercise stress test results and global cardiovascular risk systems for predicting all-cause mortality in asymptomatic individuals seen in clinical settings is unclear.ObjectivesTo determine the validity for prediction of all-cause mortality of the Framingham Risk Score and of a recently described European global scoring system Systematic Coronary Risk Evaluation (SCORE) for cardiovascular mortality among asymptomatic individuals evaluated in a clinical setting and to determine the potential prognostic value of exercise stress testing once these baseline risks are known.Design, Setting, and ParticipantsProspective cohort study of 3554 asymptomatic adults between the ages of 50 and 75 years who underwent exercise stress testing as part of an executive health program between October 1990 and December 2002; participants were followed up for a mean of 8 years.Main Outcome MeasuresGlobal risk based on the Framingham Risk Score and the European SCORE. Prospectively recorded exercise stress test result abnormalities included impaired physical fitness, abnormal heart rate recovery, ventricular ectopy, and ST-segment abnormalities. The primary end point was all-cause mortality.ResultsThere were 114 deaths. The c-index, which corresponds to receiver operating characteristic curve values, and the Akaike Information Criteria found that the European SCORE was superior to the Framingham Risk Score in estimating global mortality risk. In a multivariable model, independent predictors of death were a higher SCORE (for 1% predicted increase in absolute risk, relative risk [RR], 1.07; 95% confidence interval [CI], 1.04-1.09; P<.001), impaired functional capacity (RR, 2.95; 95% CI, 1.98-4.39; P<.001), and an abnormal heart rate recovery (RR, 1.59; 95%, 1.04-2.41; P = .03). ST-segment depression did not predict mortality. Among patients in the highest tertile from the SCORE, an abnormal exercise stress test result, defined as either impaired functional capacity or an abnormal heart rate recovery, identified a mortality risk of more than 1% per year.ConclusionExercise stress testing when combined with the European global risk SCORE may be useful for stratifying risk in asymptomatic individuals in a comprehensive executive health screening program.
Role of nitric oxide synthesis in the regulation of coronary vascular tone in the isolated perfused rabbit heart
Authors: R. E A Smith, R. M J Palmer, C. A Bucknall, S. Moncada
Journal: Cardiovascular Research (1992)

Journal Article Role of nitric oxide synthesis in the regulation of coronary vascular tone in the isolated perfused rabbit heart Get access Russell E A Smith, Russell E A Smith Department of Pharmacology, Wellcome Research Laboratories, Langley Court, South Eden Park Road, Beckenham, Kent BR3 3BS, United Kingdom: R M J Palmer, S Moncada; Cardiac Department, King's College Hospital, London SE5 9RS, United Kingdom: R E A Smith, C A Bucknall. Correspondence to Dr Smith at the Wellcome Research Laboratories. Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard M J Palmer, Richard M J Palmer Department of Pharmacology, Wellcome Research Laboratories, Langley Court, South Eden Park Road, Beckenham, Kent BR3 3BS, United Kingdom: R M J Palmer, S Moncada; Cardiac Department, King's College Hospital, London SE5 9RS, United Kingdom: R E A Smith, C A Bucknall. Search for other works by this author on: Oxford Academic PubMed Google Scholar Clifford A Bucknall, Clifford A Bucknall Department of Pharmacology, Wellcome Research Laboratories, Langley Court, South Eden Park Road, Beckenham, Kent BR3 3BS, United Kingdom: R M J Palmer, S Moncada; Cardiac Department, King's College Hospital, London SE5 9RS, United Kingdom: R E A Smith, C A Bucknall. Search for other works by this author on: Oxford Academic PubMed Google Scholar Salvador Moncada Salvador Moncada Department of Pharmacology, Wellcome Research Laboratories, Langley Court, South Eden Park Road, Beckenham, Kent BR3 3BS, United Kingdom: R M J Palmer, S Moncada; Cardiac Department, King's College Hospital, London SE5 9RS, United Kingdom: R E A Smith, C A Bucknall. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 26, Issue 5, May 1992, Pages 508–512, https://doi.org/10.1093/cvr/26.5.508 Published: 01 May 1992 Article history Received: 03 October 1991 Accepted: 10 December 1991 Published: 01 May 1992
ENHANCED CLINICAL EFFECTIVENESS OF PURIFIED CORTICOTROPIN
Authors: M. S. Raben
Journal: JAMA (1952)

Earlier clinical experience with partially purified corticotropin indicated that the purified preparation was somewhat more effective therapeutically than a standard preparation in equivalent amounts.<sup>1</sup>The material, which had been purified using cellulose,<sup>2</sup>assayed 20 U. S. P. units per milligram by the Sayers rat test<sup>3</sup>but was judged to have a clinical potency of 30 units per milligram. Subsequent improvement in the method used in this laboratory for purification of corticotropin<sup>4</sup>has permitted clinical use of a considerably more potent preparation. The purified corticotropin that was obtained in good yield using oxycellulose contained 80 units per milligram bybioassay. The clinical effectiveness of an aqueous solution, as judged from the dose requirements in 18 patients (table 1), suggested the therapeutic potency was about 150 units per milligram. The average daily dose was 0.6 mg. (48 units). Purified corticotropin was administered by subcutaneous injection and was given
Health Savings Accounts — The Ownership Society in Health Care
Authors: James C. Robinson
Journal: New England Journal of Medicine (2005)

Interview with James Robinson and Thomas Lee on health savings accounts and high-deductible plans. (09:47)Download When President George W. Bush, in his second inaugural address, described his vision of an "ownership society," he specified not only the ownership of homes, businesses, and retirement savings, but also that of health insurance. Today, the most visible embodiment of this goal in the health care sector is the health savings account (HSA), which reflects a philosophical shift in emphasis from collective to individual responsibility for the management and financing of care. HSAs form the core of the emerging "consumer-directed" insurance plans, imposing greater cost sharing on enrollees but permitting broader choices than the health maintenance organization (HMO) plans . . .
Effect of Mibefradil, a T-Type Calcium Channel Blocker, on Morbidity and Mortality in Moderate to Severe Congestive Heart Failure
Authors: T. Barry Levine, Peter J. L. M. Bernink, Abraham Caspi, Uri Elkayam, Edward M. Geltman, Barry Greenberg, William J. McKenna, Jalal K. Ghali, Thomas D. Giles, Alon Marmor, Leonardo H. Reisin, Susan Ammon, Elisabet Lindberg
Journal: Circulation (2000)

Background —Calcium antagonists have proved disappointing in long-term congestive heart failure (CHF) studies. Mibefradil, a new calcium antagonist that selectively blocks T-type calcium channels, has been shown to be an effective antihypertensive, antianginal, and anti-ischemic agent, and because of its different mechanism of action, it may be beneficial as adjunct therapy in CHF patients. Methods and Results —This multicenter, randomized, double-blind study compared mibefradil with placebo as adjunct to usual therapy in 2590 CHF patients (NYHA class II to IV; left ventricular fraction &lt;35%). The initial 50-mg daily dose of mibefradil was uptitrated to 100 mg after 1 month and continued up to 3 years. Patients were monitored at 1 week; 1, 2, and 3 months; and every 3 months thereafter. All-cause mortality, cardiovascular mortality, and cardiovascular morbidity/mortality were analyzed by use of the log-rank test (α=0.05). Substudies included exercise tolerance, plasma hormone and cytokines, echocardiography, and quality of life. Total mortality was similar between mibefradil- and placebo-treated patients ( P =0.151). The 14% increased risk of mortality with mibefradil in the first 3 months was not statistically significant ( P =0.093). Treatment groups had similar cardiovascular mortality ( P =0.246), cardiovascular morbidity/mortality ( P =0.783), and reasons for death or hospitalization. Patients comedicated with mibefradil and antiarrhythmics (class I or III), including amiodarone, had a significantly increased risk of death. Substudies demonstrated no significant differences between treatments. Conclusions —When used as adjunct therapy, mibefradil did not affect the usual outcome of CHF. The potential interaction with antiarrhythmic drugs, especially amiodarone, and drugs associated with torsade de pointes may have contributed to poor outcomes early in the study.
Quality Assurance for Office Laboratories-Reply
Authors: Daniel Baer
Journal: JAMA (1986)

<h3>In Reply.—</h3> Dr Pitts raises two important issues in his letter concerning quality assurance for office laboratories. The first concerns the professional responsibility of the office practitioner-laboratory director for the reliability of test results produced by that laboratory and used in patient care. We must point out that the practitioner will be professionally responsible for erroneous results used in patient care if these involve injury to a patient. Consequently, taking laboratory test analysis into the office requires that clinicians develop a new range of understanding so they can respond to plaintiffs' questions concerning whether particular analyses were functioning properly at the time the result was produced and whether the result was produced from a specimen that actually came from the patient. This involves more than the dreary trappings of laboratory quality control but, rather, an understanding of the issues and problems underlying the development of such programs. The second important
In vivo effects of monoclonal antibodies to distinct epitopes of Qa-2 antigens.
Authors: Y Sharabi, D H Sachs
Journal: The Journal of Experimental Medicine (1990)

The effects of in vivo treatment with anti-Qa-2 mAbs on in vivo and in vitro parameters of T cell immunity have been examined. Two anti-Qa-2 mAbs of the same isotype and with similar avidities but directed against distinct epitopes of the same Qa-2 molecules were studied. mAb 1-1-2 was found to induce rapid T cell depletion, with maximal effect observed within 2-3 d, while administration of mAb 1-9-9 caused little or no depletion in the first few days, and reached maximal effect only by day 8. Surprisingly, administration of both antibodies resulted in a depletion pattern similar to that of the nondepleting antibody 1-9-9. Consistent with these effects on T cell depletion, treatment with 1-1-2 caused significant prolongation of survival of allogeneic skin grafts placed 1 d after antibody administration, while treatment with 1-9-9 or with the combination of both antibodies caused no prolongation. In an attempt to determine the mechanism of this phenomenon, we examined Qa-2 expression on the cell surface by flow microfluorometry after treatment with each of the two mAbs. Our data indicate that mAb 1-9-9 mediates significantly greater modulation of Qa-2 expression from the surface of peripheral T cells within 1 d than does mAb 1-1-2. Apparently, therefore, modulation occurs more rapidly than cell clearance, and the efficiency of T cell depletion and consequent immune suppression is correlated inversely with the ability of each mAb to cause modulation. The ability of 1-9-9 to cause Qa-2 modulation suggests that it may react with a determinant on this molecule of physiological relevance to the natural ligand interactions of Qa-2 antigens.
Vinyl Ether as an Anaesthetic Agent
Authors: None Goldman
Journal: BMJ (1937)

MIEDICAL JOURNAL- is also no ground for refusing employment in a sana- torium.Since no one is entitled to superannuation benefit until the lapse of ten years the tuberculous staff might be accepted under such schemes without grave risk of bankrupting them, " as a tuberculous man who has suLrvived ten years has an expectation of life not widely different from the normal population" (Dr.Trayer). REFERENCES
Ethyl Alcohol Sniffing in Patients Undergoing Hemodialysis
Authors: Elizabeth Evans-Gresch
Journal: JAMA (1976)

<h3>To the Editor.—</h3> In their article (234:841, 1975), De Santo et al report seven patients who presumably became addicted to sniffing the vapors of ethyl alcohol. However, they note that potable ethanol did not cause the same symptoms and could not be substituted for the denatured ethanol in three of the patients. Two other patients obtained similar but less satisfying results from denatured alcohol obtained from a different source. Since the denatured alcohol contains 10% unknown ingredients, it would seem probable that one of these ingredients, rather than the ethanol, is responsible for these patients' addiction. Perhaps the Italian government would be willing to have these ingredients tested by one of the toxicologic laboratories in the country, and if this were indeed the case, change the formulation of the denaturing agent.
Taking folate in pregnancy and risk of maternal breast cancer
Authors: Deborah Charles, Doris Campbell, Marion H Hall, Andy R Ness, George Davey Smith
Journal: BMJ (2005)

a banner headline on the front page of a popular tabloid newspaper read: "Cancer danger of folic acid" on the basis of a paper by Charles et al on taking folate in pregnancy and risk of maternal breast cancer. 1 2 Although coverage in the broadsheets was more balanced, the overall message would inevitably cause concern to women taking folate to reduce the risk of fetal neural tube defect in a desired pregnancy.Despite the likelihood that the most likely explanation for the reported association is chance, as reported in the commentary to the paper, 2 numerous susceptible women will probably not take folate, and some of these may conceive fetuses with neural tube defects.In addition, what company or government will take responsibility for fortification of wheat and corn flour with folate, now that this question has been raised?The authors themselves point out that the numbers are small and the confidence intervals large.The risk was also associated with a much larger dose of folate than is routinely used to reduce the risk of neural tube defects.Those who write such papers and those who publish them cannot disclaim ethical responsibility for how the data are interpreted and must consider more carefully their ethical responsibilities in such situations.
Functional In Vivo Delivery of Multiplexed Anti-HIV-1 siRNAs via a Chemically Synthesized Aptamer With a Sticky Bridge
Authors: Jiehua Zhou, C Preston Neff, Piotr Swiderski, Haitang Li, David D Smith, Tawfik Aboellail, Leila Remling-Mulder, Ramesh Akkina, John J Rossi
Journal: Molecular Therapy (2012)

One of the most formidable impediments to clinical translation of RNA interference (RNAi) is safe and effective delivery of the siRNAs to the desired target tissue at therapeutic doses. We previously described in vivo cell type-specific delivery of anti-HIV small-interfering RNAs (siRNAs) through covalent conjugation to an anti-gp120 aptamer. In order to improve the utility of aptamers as siRNA delivery vehicles, we chemically synthesized the gp120 aptamer with a 3' 7-carbon linker (7C3), which in turn is attached to a 16-nucleotide 2' OMe/2' Fl GC-rich bridge sequence. This bridge facilitates the noncovalent binding and interchange of various siRNAs with the same aptamer. We show here that this aptamer-bridge-construct complexed with three different Dicer substrate siRNAs (DsiRNAs) results in effective delivery of the cocktail of DsiRNAs in vivo, resulting in knockdown of target mRNAs and potent inhibition of HIV-1 replication. Following cessation of the aptamer-siRNA cocktail treatment, HIV levels rebounded facilitating a follow-up treatment with the aptamer cocktail of DsiRNAs. This follow-up injection resulted in complete suppression of HIV-1 viral loads that extended several weeks beyond the final injection. Collectively, these data demonstrate a facile, targeted approach for combinatorial delivery of antiviral and host DsiRNAs for HIV-1 therapy in vivo.
A Drug That Lowers Blood Urea in Uremic Diabetics.
Authors: Guy Lacy Schless
Journal: Annals of Internal Medicine (1970)

Meeting Abstracts1 May 1970A Drug That Lowers Blood Urea in Uremic Diabetics.Guy Lacy Schless, M.D., (Associate)Guy Lacy Schless, M.D., (Associate)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-803_5 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAn arginine derivative, gamma-guanidinobutyramide (Augmentin®) was investigated with W. J. H. Butterfield of Guy's Hospital Medical School and Sir Charles Dodds, London. No significant hypoglycemic action was detected in 44 diabetics: in 3 who had uremia the blood urea became normal. Subsequently, 12 uremic diabetics were given 0.6 to 1.2 g of Augmentin daily for 10 to 14 days at Guy's Hospital and the Pennsylvania Hospital. Blood urea and blood urea nitrogen (BUN) values, especially below 100 and 50 mg/100 ml, fell toward normal, the greatest fall being 52 and 45 mg/100 ml, respectively. Elevated uric acid levels were lowered... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Guy Lacy Schless, M.D., (Associate)Affiliations: Philadelphia, Pa. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe circulation in diabetes, from HL523 to the NO era 1 May 1970Volume 72, Issue 5Page: 803-804KeywordsArginineBloodBlood urea nitrogenDrugsFallsHypoglycemicsUreaUric acid ePublished: 1 December 2008 Issue Published: 1 May 1970 PDF downloadLoading ...
Arteriovenography of the Portal System
Authors: L. Kreel, R. Williams
Journal: BMJ (1964)

orf strains failed to grow on passage although cytopathic change was produced initially, and a third strain failed to produce any detectable changes in tissue culture.It should be noted that the minimum times given in Table II for a cultural diagnosis are only the earliest appearance of sufficient cytopathic change to be considered typical enough TABLE II.-Minimum Times Before a Provisional Diagnosis was Possible Tissue Culture Electron Earliest Characteristic C.P
Enhanced attenuation of meningeal inflammation and brain edema by concomitant administration of anti-CD18 monoclonal antibodies and dexamethasone in experimental Haemophilus meningitis.
Authors: X Sáez-Llorens, H S Jafari, C Severien, F Parras, K D Olsen, E J Hansen, I I Singer, G H McCracken
Journal: Journal of Clinical Investigation (1991)

Antiinflammatory therapy has been shown to reduce the adverse pathophysiological consequences that occur in bacterial meningitis and to improve outcome from disease. In the present study, modulation of two principal steps of the meningeal inflammatory cascade was accomplished by concomitant administration of dexamethasone to diminish overproduction of cytokines in response to a bacterial stimulus and of a monoclonal antibody directed against adhesion-promoting receptors on leukocytes to inhibit recruitment of white blood cells into the subarachnoid space. Dexamethasone and antibody therapy produced a marked attenuation of all indices of meningeal inflammation and reduction of brain water accumulation after H. influenzae-induced meningitis in rabbits compared with results of each agent given alone and of untreated animals. In addition, the enhanced host's meningeal inflammatory reaction that follows antibiotic-induced bacterial lysis was profoundly ameliorated when dual therapy was administered without affecting clearance rates of bacteria from cerebrospinal fluid and vascular compartments. The combination of both therapeutic approaches may offer a promising mode of treatment to improve further the outcome from bacterial meningitis.
Obama announces fix for canceled health plans
Authors: M. McCarthy
Journal: BMJ (2013)

President Barack Obama announced Thursday that the US administration would allow people to stay on their existing health plans for one more year even if the plans fail to meet the minimum standards set by the Affordable Care Act.

Obama acted after thousands of individuals and families received notices from their insurance companies that their current plans were being canceled.

In many cases the old plans did not provide the benefits and consumer protections mandated by the new health reform law, such as coverage for doctor visits, prescriptions, and annual caps on out-of-pocket expenses. To provide those benefits, new plans being offered to consumers were typically far more expensive than the canceled plans.

Obama had repeatedly promised that the Affordable Care Act would not force people to give up their …
An integrated home oxygen service saves £130 000 per year on home oxygen tariffs
Authors: C Deeming, L Ward, J Townsend, M Monaghan, S Ansari, G Lingam, A G Davison, D J Powrie
Journal: Thorax (2008)

In February 2006 the Department of Health introduced a new home oxygen service with the aim of improving the assessment of patients on oxygen and allowing access to newer technologies such as ambulatory oxygen. Oxygen is provided following completion of a home oxygen order form and is allocated a predetermined tariff according to the delivery device and usage. In South East Essex there are currently 554 patients receiving home oxygen with an annual cost of £668 546.

In response to …
Morbidity and mortality with nonmyeloablative compared with myeloablative conditioning before hematopoietic cell transplantation from HLA-matched related donors
Authors: Razvan Diaconescu, Christopher R. Flowers, Barry Storer, Mohamed L. Sorror, Michael B. Maris, David G. Maloney, Brenda M. Sandmaier, Rainer Storb
Journal: Blood (2004)