tbuckley/cabot-search huggingface dataset:
Abstract 1857: Dichloroacetate (DCA), pyruvate dehydrogenase kinase (PDK) inhibitor, enhances the cytotoxic effect induced by metformin .
Authors: Yong Won Choi, In Kyoung Lim
Journal: Cancer Research (2013)

Abstract It has been recently reported that metformin, widely used as an antidiabetic drug, reduces risk of cancer development in human and animals based on its inhibitory effects observed in the several cancer cells and mouse tumor models. Metformin shows anti-tumor activity indirectly by enhancing insulin sensitivity and decreasing the level of insulin and IGF in serum. And it was also reported that metformin has direct anti-tumor activity through AMPK activation and mTOR inhibition. We also observed that metformin induces cytotoxicity in several different types of cancer cell lines. However when metformin was treated in high glucose condition, cytotoxic effect of metformin was significantly reduced and AMPK activation and mTOR inhibition were not observed. Metformin increased glycolysis by inhibiting mitochondrial respiratory complex I activity weakly and also inhibiting pyruvate dehydrogenase activity more significantly. So cytotoxic effect induced by metformin was dependent on glucose availability. Significant mitochondrial ROS production was observed in metformin treated cancer cells. NADPHs are produced by enhanced glycolysis through the pentose phosphate pathway. Since reducing power of NADPH is important for protection from ROS induced damage, we hypothesized that enhanced glycolysis by inhibition of PDH activity observed in metformin treated cancer cells is a protective role from metformin induced ROS injury. So when PDH activity was enhance by dichloroacetate (DCA), pyruvate dehydrogenase kinase (PDK) inhibitor, ROS production was more increased and resulted in significant cell death. Citation Format: Yong Won Choi, In Kyoung Lim. Dichloroacetate (DCA), pyruvate dehydrogenase kinase (PDK) inhibitor, enhances the cytotoxic effect induced by metformin . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1857. doi:10.1158/1538-7445.AM2013-1857
Bilateral Ex Vivo Renal Artery Reconstruction With Autotransplantation
Authors: Thomas W. Orcutt
Journal: JAMA (1974)

We performed a successful bilateral ex vivo renal artery reconstruction for renovascular hypertension. The technique consists of accurately identifying the lesion, removing the kidney except for its ureteral attachment, and perfusing the kidney with pulsatile oxygenated acellular cryoprecipitated plasma while reconstruction with autogenous saphenous vein is performed. Then the kidney is reimplanted in the ipsilateral iliac fossa. This kind of operation will be useful in some patients with distal segmental renal artery branches or aneurysm. (<i>JAMA</i>228:493-495, 1974)
Ibuprofen and Antihypertensive Drugs
Authors: SANDY A. FUREY
Journal: Annals of Internal Medicine (1988)

Letters and Corrections1 April 1988Ibuprofen and Antihypertensive DrugsSANDY A. FUREY, Ph.D., M.D.SANDY A. FUREY, Ph.D., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-108-4-645 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Radack and colleagues (1) have noted that administration of Ibuprofen, 400 mg three times a day for 21 days, can cause an increase in blood pressure in treated hypertensive patients. A 21-day Ibuprofen regimen in this dosage is useful regimen for chronic treatment of inflammatory conditions, but it exceeds the 10-day maximum recommended duration of use of nonprescription Ibuprofen, making their observations inapplicable to the usual nonprescription use of Ibuprofen (such as for headache or fever). Their conclusion that nonprescription Ibuprofen is unsafe based on this dosage is puzzling, because their data also show that, after 7...References1. RADACKDECKBLOOMFIELD KCS. Ibuprofen interferes with the efficacy of antihypertensive drugs. Ann Intern Med. 1987;107:628-35. LinkGoogle Scholar2. KOOPMANSTHIENGRIBNAU PTF. The influence of Ibuprofen, diclofenac, and sulindac on the blood pressure lowering effect of hydrochlorothiazide. Eur J Clin Pharmacol. 1987;31:553-7. CrossrefMedlineGoogle Scholar3. SACKETT D. The magnitude of compliance and noncompliance. In: SACKETT DL, HAYNES RB, eds. Compliance with Therapeutic Regimens. Baltimore: Johns Hopkins University Press; 1987:1-25. Google Scholar4. VA Cooperative Study Group on Antihypertensive Agents: Comparison of propranolol and hydrochlorothiazide with emphasis on racial differences in response. JAMA. 1982;248:1996-2003. CrossrefMedlineGoogle Scholar5. AMEERGREENBLATT BD. Acetaminophen. Ann Intern Med. 1977;87:202-9. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Whitehall Laboratories New York, NY 10017 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1988Volume 108, Issue 4Page: 645-645KeywordsBlood pressureDrug administrationDrugsFeversHeadachesIbuprofen Issue Published: 1 April 1988 PDF DownloadLoading ...
STUDIES OF THE PLASMIN SYSTEM
Authors: Philip S. Norman
Journal: The Journal of Experimental Medicine (1958)

The inactivation of purified plasmin by serum or plasma was studied using a caseinolytic assay for determination of plasmin. On the basis of kinetic evidence, the presence of two inhibitors in normal human or guinea pig serum or plasma is suggested. The first reacts immediately at any temperature, but is easily dissociable and does not combine with plasmin in a fixed ratio. The second combines more slowly with plasmin at a rate which depends on temperature and on the concentration of both plasmin and inhibitor. There is a fixed ratio of reaction between plasmin and the second inhibitor and the combination does not readily dissociate. There is sufficient of the "slow" inhibitor in normal plasma to inactivate more than 30 times its own content of potential plasmin. The presence of suitable substrate for plasmin tends to reverse the combination with "immediate" inhibitor and to stop the further action of "slow" inhibitor.
CASE OF IMPACTED GALL STONES IN CYSTIC DUCT: OPERATION: RECOVERY
Authors: C. F. Fothergill
Journal: BMJ (1910)

TEa following case was so atypical, and presented a train of symptoms so unlike one'd expectations, that I think it safficiently interesting to record.A lady aged 24, married three years, no children, one mis- carriage, gave a historv of frequent so-called " bilious attacks,"dating from the age of 12, when she had an attack of jaundice.The attacks consisted of headache, naasea, and some vomit- ing, and usually lasted a day, occurring at intervals of several months.
Apolipoprotein A and B (Sf 100-400) metabolism during bezafibrate therapy in hypertriglyceridemic subjects.
Authors: J Shepherd, C J Packard, J M Stewart, R F Atmeh, R S Clark, D E Boag, K Carr, A R Lorimer, D Ballantyne, H G Morgan
Journal: Journal of Clinical Investigation (1984)

This study describes the effects of bezafibrate, an analogue of clofibrate, on the plasma lipid and lipoprotein profiles of 11 hypertriglyceridemic subjects and on their metabolism of apolipoproteins A-I, A-II, and B. The major action of the drug was to lower plasma triglyceride (by 58%; P less than 0.01). This was accompanied by a reduction in the level of very low density lipoprotein apoprotein B (Svedberg units of flotation [Sf] 60-400), whose mean residence time in the plasma fell threefold (from 3.4 to 1.0 h). Synthesis of the B protein in this fraction was not significantly altered, so the drug acts to accelerate the transit of very low density lipoprotein particles down the delipidation cascade. The metabolism of very low density lipoprotein remnant apoprotein B (Sf 12-100) changed little in response to treatment, although we detected a 30% increment (P less than 0.05) in the plasma concentration of this fraction. The mean residence time of these remnant particles in the plasma did not correlate with that of Sf 100-400 very low density lipoprotein apoprotein B, nor was this parameter altered by the drug. The most consistent and significant perturbation seen in the Sf 0-12 fraction (low density lipoprotein) was a reduction in the fractional catabolism of its apoprotein B moiety (26%; P less than 0.05). In those subjects who were grossly hypertriglyceridemic and who responded well to treatment, the level of this protein rose substantially owing to a combined increase in its synthesis and a reduction in its catabolism. In the group as a whole, high density lipoprotein cholesterol rose 13% (P less than 0.02), and detailed examination showed that this was associated with a small but significant increment in the plasma concentration of the high density lipoprotein subfraction 2. High density lipoprotein subfraction 3 also rose on the average, but this was not a consistent feature in all patients. The plasma concentrations and turnovers of the A proteins (A-I and A-II) were not significantly altered by bezafibrate therapy.
Mortality following blood transfusion for non-variceal upper gastrointestinal bleeding
Authors: A. S. Taha, C. McCloskey, T. Craigen, W. Angerson, A. A. Shah, C. G. Morran
Journal: Gut (2011)

<h3>Introduction</h3> Blood transfusion is integral to the management of non-variceal upper gastrointestinal bleeding (NV-UGIB), but its safety is being questioned in less severe cases. We, therefore aimed to measure 30-day and 2-year mortality after blood transfusion for NV-UGIB. <h3>Methods</h3> This was an observational analysis using routinely collected data at a single hospital in southwest Scotland affiliated to Glasgow University. Cox proportional hazards models were used to estimate the effect of blood transfusion on mortality while adjusting for age, Charlson comorbidity score, the complete Rockall score for acute upper gastrointestinal bleeding, admission status, drug intake, etc. The main outcome measure was death of any cause at 30 days and 2 years after NV-UGIB. <h3>Results</h3> 1340 patients presented with NV-UGIB, 808 males (60.3%), median age 67 years and 564 (42.1%) were transfused. The overall mortality was 5.3% at 30 days and 25.8% at 2 years regardless of transfusion. Mortality was higher in the transfused versus non-transfused patients (P &lt; 0.001, log rank test), as shown in figure 1. Also, in patients with a haemoglobin level greater than 10.0 g/dl, and comparing subjects who were transfused with those who were not, 30-day mortality (95% confidence intervals) was 11.5% (6.7–18.0) versus 3.6% (2.3–5.3), respectively, P &lt; 0.001; and 2-year mortality (95% confidence intervals) was 40% (32–49) versus 20% (17–23), P &lt; 0.001. Adjusted for age, Charlson score, Rockall score and haemoglobin, the hazard ratios (95% confidence intervals) for death after transfusion was 1.88 (1.00–3.55), P = 0.051, at 30 days; and 1.71 (1.28–2.28), P &lt; 0.001, at 2 years. <h3>Conclusion</h3> In patients with less severe NV-UGIB, mortality is higher following blood transfusion. The need for such intervention should be carefully weighed, and alternative measures should be considered where appropriate, particularly in less severe cases.
New Telecommunications Relay Services, Other Communication Advances, Will Aid Disabled People
Authors: Charles Marwick
Journal: JAMA (1993)

PHYSICIANS can now talk with their deaf patients on the telephone everyday and nearly everywhere in the United States—something previously almost impossible—and at the same time be assured of complete confidentiality.  This useful technological advance became possible this summer when a reliable telecommunications relay service for the estimated 26 million deaf, hardof-hearing, and speech-impaired persons in the country went into operation in 49 states, Washington, DC, and Puerto Rico. The system allows those who are deaf or have other communicative disorders to communicate via a regular telephone through a communications assistant.  The single state where the service was not yet available at press time is Oklahoma. The 40-some licensed telephone carriers in that state were not providing the service at that time, said Linda DuBroof, a Federal Communications Commission attorney in the agency's domestic services branch. Under the Americans With Disabilities Act, the licensed carriers have to provide the service.
Drug Testing in Sport: Bayes Theorem Meets Advanced Technology-Reply
Authors: Don H. Catlin
Journal: JAMA (1996)

In Reply.  —Testing for performance-enhancing drugs is designed to be 100% specific, and with respect to the laboratory that produced the data in Tables 2 and 3 of our article, there is no evidence to the contrary. No false-positive results have occurred in 12 years of accreditation and proficiency testing, and despite numerous reviews by experts, none of the positive cases have been found to be in error. This 100% accuracy for positive results is achieved primarily by properly using a definitive analytic technique to identify compounds. Technical measures of test validity are important but are only part of the story. In addition, unlike many workplace drug-testing programs, testing of athletes includes collecting the urine under direct observation, splitting the urine into 2 portions, analyzing 1 sample at least twice (screen and confirmation) on separate occasions before reporting the result of that specimen, and requiring the analysis of the second portion of
Determination of <i>Blomia tropicalis</i>‐specific IgE and IgG subclasses in atopic dermatitis patients
Authors: J. C. Mori, M. C. Pires, C. E. S. Galvão, J. Ferreira de Mello, F. M. Golcher, F. Montealegre
Journal: Allergy (2001)

Background: To verify the importance of Blomia tropicalis in atopic dermatitis (AD), we determined the cutaneous reactivity and the serum level of B. tropicalis ‐specific IgE and IgG subclasses in AD patients. Methods: B. tropicalis ‐specific IgE and IgG subclasses were determined in AD patients and compared with bronchial asthma (BA) patients and a control group (CG) of nonatopic subjects. Specific IgE was obtained by skin prick test and RAST. B. tropicalis ‐specific IgG subclasses were determined by ELISA. The data were statistically analyzed by chi‐square test (Mantel‐Haenszel) and odds ratio (OR). Results: We detected positive skin prick tests in 61.76% of AD and 83.33% of BA patients, and in 12.5% of the CG. RAST was positive in 44.12% of AD and in 61.90% of BA patients, but not in the CG. B. tropicalis ‐specific IgG1 and IgG2 subclasses showed no significant differences between the three groups. IgG3 subclass positivity was statistically significant in AD patients (41.17%) when compared to BA patients (14.29%) and the CG (16.67%). The determination of B. tropicalis ‐specific IgG4 was positive in 32.35% of AD patients, 21.43% of BA patients, and 8.33% of the CG. Conclusions: These results confirm that the storage mite B. tropicalis is an important allergen in AD. It is possible that IgG3 activates the complement in AD patients, releasing vasoactive amines that further amplify the allergic reaction. The positive results of the B. tropicalis ‐specific IgG4 found in AD and BA were probably due to chronic exposure to this storage mite in the home environment.
Etiologies and Outcomes of Acute Liver Failure in Germany
Authors: Johannes Hadem, Frank Tacke, Tony Bruns, Julia Langgartner, Pavel Strnad, Gerald U. Denk, Panagiotis Fikatas, Michael P. Manns, Wolf P. Hofmann, Guido Gerken, Frank Grünhage, Andreas Umgelter, Christian Trautwein, Ali Canbay
Journal: Clinical Gastroenterology and Hepatology (2012)
Researchers implant tissue engineered bladders
Authors: J. H. Tanne
Journal: BMJ (1999)

Bladders grown in the laboratory with tissue engineering techniques have been successfully implanted and shown to function in animals, according to a study published in Nature Biotechnology (1999;17:140-55).

Dr Anthony Atala, a surgeon and director of the tissue engineering laboratory, and a team from the Boston Children's Hospital and Harvard Medical School claim that …
Acute Ischaemia in Limb Injuries
Authors: E. G. Hardy, D. J. Tibbs
Journal: BMJ (1960)

During the Korean war many injured limbs in which the main artery was damaged were restored to good function by the use of modern arterial techniques (Jahnke and Howard, 1953; Hughes, 1955).Correspondingly good results might be hoped for in comparable civilian injuries similarly treated.It is disappointing, therefore, that of nine such patients admitted recently to this unit attempts to save the injured limb failed in no fewer than six.
Accelerating the Delivery of Patient-Centered, High-Quality Cancer Care
Authors: Edward Abrahams, Margaret Foti, Marcia A. Kean
Journal: Clinical Cancer Research (2015)

Significant progress has been made in the past 50 years across the field of oncology, and, as a result, the number of cancer survivors in the United States is more than 14.5 million. In fact, the number of cancer survivors continues to grow on an annual basis, which is due in part to improved treatments that help people with cancer live longer, and improvements in early detection that allow doctors to find cancer earlier when the disease is easier to treat. However, in spite of this progress, innovation in cancer research and care is at risk as the rise in health care spending is leading to significant pressure to contain costs. As the oncology community seeks to ensure that innovation in cancer research and care continues, it is imperative that stakeholders focus their attention on the value that the research and care continuum provides. Over the past several years, the Turning the Tide Against Cancer initiative has worked with the cancer community to accelerate the delivery of patient-centered, high-quality cancer research and care, while addressing value and cost. This article highlights policy recommendations that resulted from the convening of an expert working group comprising leaders from across the oncology field. Of the recommendations, the co-conveners have identified several issue areas that merit particular focus in 2015: Support FDA's efforts to modernize its framework for bringing new medicines to patients, through facilitating and implementing innovative approaches to drug development and regulatory review. Ensure that cancer clinical pathways or similar decision-support tools are transparent; developed through a physician-driven process that includes patient input; and meet minimum standards for clinical appropriateness, timeliness, and patient centeredness. Support oncology decision-support tools that are timely, clinically appropriate, and patient centered. Build on existing efforts to convene a multistakeholder committee and develop a report on ways to define and measure value in oncology care, taking into account many of the complex dynamics associated with measuring value, including the interests and needs of patients, as well as the importance of committed and ongoing support for innovative research.These policy options are intended to further the national dialogue and represent meaningful and actionable steps toward supporting cancer research and care that is innovative, efficient, and focused on the patient.
Genetic variation in the KIF1B locus influences susceptibility to multiple sclerosis
Authors: Yurii S Aulchenko, Ilse A Hoppenbrouwers, Sreeram V Ramagopalan, Linda Broer, Naghmeh Jafari, Jan Hillert, Jenny Link, Wangko Lundström, Eva Greiner, A Dessa Sadovnick, Dirk Goossens, Christine Van Broeckhoven, Jurgen Del-Favero, George C Ebers, Ben A Oostra, Cornelia M van Duijn, Rogier Q Hintzen
Journal: Nature Genetics (2008)
Renal blood flow and its response to angiotensin II. An interaction between oral contraceptive agents, sodium intake, and the renin-angiotensin system in healthy young women.
Authors: N K Hollenberg, G H Williams, B Burger, W Chenitz, I Hoosmand, D F Adams
Journal: Circulation Research (1976)

A variety of estrogen- and progestin-containing oral contraceptive agents reduced renal blood flow (RBF) significantly in 23 healthy, nonhypertensive young women, to a mean of 75 +/- 3.3% of the value expected for their age and dietary sodium intake (P less than 0.001). There was also significant activation of the renin-angiotensin system: renin substrate was increased approximately 3-fold in association with a striking increase in the circulating renin activity and angiotensin II levels in relation to sodium intake and excretion. Two observations suggest that the RBF reduction was directly mediated by angiotensin II. A correlation was demonstrable between circulating angiotensin II and RBF (P less than 0.01), and renal vascular responsiveness to angiotensin II infused into the renal artery was reduced significantly (P less than 0.001). Moreover, the oral contraceptive agents modified the basic relationship between sodium balance and vascular responsiveness to angiotensin II, suggesting that the agents acted through some mechanism other than alteration in the state of sodium balance. These observations provide further evidence for an important role of angiotensin II as a determinant of RBF. Renal vasoconstriction may contribute to the genesis of a number of complications, such as sodium retention and hypertension, associated with oral contraceptive use.