tbuckley/cabot-search huggingface dataset:
Hypoxia-mediated sorafenib resistance can be overcome by EF24 through Von Hippel-Lindau tumor suppressor-dependent HIF-1α inhibition in hepatocellular carcinoma
Authors: Yingjian Liang, Tongsen Zheng, Ruipeng Song, Jiabei Wang, Dalong Yin, Luoluo Wang, Haitao Liu, Lantian Tian, Xiang Fang, Xianzhi Meng, Hongchi Jiang, Jiaren Liu, Lianxin Liu
Journal: Hepatology (2013)

The increasing incidence of hepatocellular carcinoma (HCC) is of great concern not only in the United States but throughout the world. Although sorafenib, a multikinase inhibitor with antiangiogenic and antiproliferative effects, currently sets the new standard for advanced HCC, tumor response rates are usually quite low. An understanding of the underlying mechanisms for sorafenib resistance is critical if outcomes are to be improved. In this study we tested the hypothesis that hypoxia caused by the antiangiogenic effects of sustained sorafenib therapy could induce sorafenib resistance as a cytoprotective adaptive response, thereby limiting sorafenib efficiency. We found that HCCs, clinically resistant to sorafenib, exhibit increased intratumor hypoxia compared with HCCs before treatment or HCCs sensitive to sorafenib. Hypoxia protected HCC cells against sorafenib and hypoxia-inducible factor 1 (HIF-1α) was required for the process. HCC cells acquired increased P-gp expression, enhanced glycolytic metabolism, and increased nuclear factor kappa B (NF-κB) activity under hypoxia. EF24, a molecule having structural similarity to curcumin, could synergistically enhance the antitumor effects of sorafenib and overcome sorafenib resistance through inhibiting HIF-1α by sequestering it in cytoplasm and promoting degradation by way of up-regulating Von Hippel-Lindau tumor suppressor (VHL). Furthermore, we found that sustained sorafenib therapy led to increased intratumor hypoxia, which was associated with sorafenib sensitivity in HCC subcutaneous mice tumor models. The combination of EF24 and sorafenib showed synergistically effects against metastasis both in vivo and in vitro. Synergistic tumor growth inhibition effects were also observed in subcutaneous and orthotopic hepatic tumors.Hypoxia induced by sustained sorafenib treatment confers sorafenib resistance to HCC through HIF-1α and NF-κB activation. EF24 overcomes sorafenib resistance through VHL-dependent HIF-1α degradation and NF-κB inactivation. EF24 in combination with sorafenib represents a promising strategy for HCC.
Age, BMI, and Race Are Less Important Than Random Plasma Glucose in Identifying Risk of Glucose Intolerance
Authors: David C. Ziemer, Paul Kolm, William S. Weintraub, Viola Vaccarino, Mary K. Rhee, Jane M. Caudle, Jade M. Irving, David D. Koch, K.M. Venkat Narayan, Lawrence S. Phillips
Journal: Diabetes Care (2008)

Age, BMI, and race/ethnicity are used in National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and American Diabetes Association (ADA) guidelines to prompt screening for pre-diabetes and diabetes, but cutoffs have not been evaluated rigorously.
The Treatment of Multiple Myeloma and Macroglobulinemia of Waldenstrom with the Continuous Administration of L-Phenylalanine Mustard.
Authors: Spencer Raab
Journal: Annals of Internal Medicine (1965)

s1 November 1965The Treatment of Multiple Myeloma and Macroglobulinemia of Waldenstrom with the Continuous Administration of L-Phenylalanine Mustard.Spencer Raab, M.D., Miriam Dahlke, M.D.Spencer Raab, M.D.Search for more papers by this author, Miriam Dahlke, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-63-5-913_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe treatment of multiple myeloma with agents such as radioactive phosphorus, urethane, corticosteroids, etc., has been most discouraging. Recently, the use of cyclophosphamide has resulted in some prolongation of survival in this disease. In addition, L-phenylalanine mustard (melphalan) has also been shown to be associated with an initial improvement in some patients. This study was undertaken to assess the value of continuous mainentance therapy with this drug for the life of the patient.All patients in whom the diagnosis of multiple myeloma was made in the past 12 months at the Philadelphia General Hospital and on the wards at the... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Philadelphia, Pennsylvania PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 November 1965Volume 63, Issue 5Page: 913-913KeywordsCyclophosphamideDrug therapyMultiple myelomaPhenylalaninePhosphorus Issue Published: 1 November 1965 PDF downloadLoading ...
The interpretation of the T wave of the electrocardiogram
Authors: D. NOBLE, I. COHEN
Journal: Cardiovascular Research (1978)

Journal Article The interpretation of the T wave of the electrocardiogram Get access DENIS NOBLE, DENIS NOBLE From the University Laboratory of Physiology, South Parks Road, Oxford Search for other works by this author on: Oxford Academic PubMed Google Scholar IRA COHEN IRA COHEN From the University Laboratory of Physiology, South Parks Road, Oxford Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 12, Issue 1, January 1978, Pages 13–27, https://doi.org/10.1093/cvr/12.1.13 Published: 01 January 1978
Association between edoxaban dose, concentration, anti-Factor Xa activity, and outcomes: an analysis of data from the randomised, double-blind ENGAGE AF-TIMI 48 trial
Authors: Christian T Ruff, Robert P Giugliano, Eugene Braunwald, David A Morrow, Sabina A Murphy, Julia F Kuder, Naveen Deenadayalu, Petr Jarolim, Joshua Betcher, Minggao Shi, Karen Brown, Indravadan Patel, Michele Mercuri, Elliott M Antman
Journal: The Lancet (2015)
Cost Effectiveness of Low-Dose Zidovudine Therapy for Asymptomatic Patients with Human Immunodeficiency Virus (HIV) Infection
Authors: Kevin A. Schulman, Lorna A. Lynn, Henry A. Glick, John M. Eisenberg
Journal: Annals of Internal Medicine (1991)

We did a cost-effectiveness analysis of zidovudine therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection. The incremental direct medical costs of zidovudine therapy were determined, and data on the effects of therapy were derived from the report of the Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Group Protocol 019. Zidovudine therapy has an annual incremental cost of $2653 per person. The cost per year of life saved ranges between $6553 and $70 526, depending on which epidemiologic model of potential long-term zidovudine effect is used (in sensitivity analyses, the cost per year of life saved ranges between $2649 and $250 546). Although expensive, zidovudine therapy has the potential to yield a substantial survival benefit to patients. The cost effectiveness of zidovudine therapy compares favorably with that of other common medical therapies.
Pregnancy and an IUD in Separate Horns of a Bicornate Uterus
Authors: Machelle M. Seibel
Journal: JAMA (1982)

<h3>To the Editor.—</h3> Müllerian abnormalities occur frequently in nature. However, it is thought that they are only clinically important in about one third of cases.<sup>1</sup>For this reason these abnormalities often go undetected. This case represents what we believe is the first report of a simultaneous intrauterine device (IUD) and an intrauterine pregnancy (IUP) in a bicornate uterus diagnosed by ultrasound. It serves to illustrate how a previously undetected uterine anomaly could have led to an unnecessary operative procedure and emphasizes the value of ultrasound in the management of early pregnancy. <h3>Report of a Case.—</h3> A 22-year-old woman, gravida 2 para 2, had regular monthly periods until seven weeks before admission. One week before admission vaginal spotting and left lower abdominal cramping developed, which had gradually increased in intensity during the previous 24 hours. She complained of mild nausea but no other symptoms. Her medical history was unremarkable other
Haemorrhage after Extrapleural Pneumonolysis
Authors: W. P. Cleland
Journal: Thorax (1948)

Moderate or massive haemorrhage into the extrapleural space within a few days of the performance of an extrapleural pneumonolysis occurs in from 5 per cent to 20 per cent of cases.It may give rise to few symptoms, or be severe enough to cause alarming collapse of the patient and justify, if not demand, immediate transfusion.Apart from the immediate and more alarming physiological disturbances, delayed infection or gradulal oblitera- tion of the space may imperil the success of the operation.Hugh Reid (1946), however, in recording his experiences with fifty-four cases, states that only one case had a post-operative haemorrhage which required a blood transfusion.Cases were encoun- tered, however, where the extrapleural space was found to be completely opaque after operation and yet no blood could be aspirated; when the space was explored through an adequate incision blood clot was found and readily removed. BRANCHES OF THE INTERNAL MAMMARY ARTERYRecently when re-operating on an extrapleural pneumothorax which had re-expanded completely soon after operation, I introduced a needle at the site where refills had been given, in order to deter- mine its relationships to the pleural reflection.
Malaria affects children and pregnant women most
Authors: M. Starr
Journal: BMJ (2000)

Sentinel node biopsy for malignant melanoma Having this biopsy gives psychological benefitsEditor-The editorial by Thomas and Patocskai summarises the current state of sentinel lymph node biopsy for malignant melanoma. 1 What the authors omitted to address was patients' perception of the procedure.Anecdotal evidence suggests that patients with melanoma derive psychological benefit from having the procedure, regardless of the result.To investigate any such benefit our unit carried out a study looking at the acceptability and benefits of the procedure.A specially designed questionnaire was sent to 110 patients who had undergone the procedure between August 1997 and February 1999.Ninety eight patients (89%) replied, including all those in whom the result had been positive (19/110).To study any time dependent trends the respondents were subdivided into three subgroups, depending on length of follow up (table).Most patients (95/98) were glad that they had had the procedure, though the effects decreased with time (table).Overall 89 of the patients believed that they had gained some benefit from the biopsy, and 96 said that they would recommend it to other patients.Most patients with melanoma undoubtedly derive at least short term psychological benefits from having a sentinel lymph node biopsy.This effect seems to be independent of the result of the biopsy itself.The decreased reassurance with time may simply represent a time dependent factor but might be due to the frequent clinic visits and additional biopsies of suspicious lesions, which cause increased anxiety in patients with melanoma. 2 The procedure has high patient acceptability and offers patients a proactive option in addition to regular clinic reviews after initial diagnosis.It does not, however, seem greatly to influence patients' worries about being "cured" or fully enable patients to plan for the future.The small psychological benefit shown in our study cannot be used to justify routine sentinel lymph node biopsy in patients with melanoma.The cost and morbidity of this procedure must be balanced by proved survival benefit.We agree with others that until such benefit is shown, sentinel lymph node biopsy should be offered only in a multidisciplinary setting as part of a clinical trial. 1 3
Infantile Phlebitis arising from Inflammation of the Umbilical Vein
Authors: W. B. Herapath
Journal: BMJ (1852)

CASE OF INFANTILE PHLEBITIS.lungs exist, to replenish or purify, by their mechanism, the stream of life.In beautifully arranged order each part of the body is progres- sively perfected; the Great Designer " sees that it is good", and finaly the last prop is taken away, and the fabric stands completed.
Sri Lanka after the tsunami
Authors: S. Siribaddana
Journal: Journal of the Royal Society of Medicine (2005)

Saruban Pasu's account of events in Sri Lanka after the tsunami (April 2005 JRSM1) has several inaccuracies. The town of Ampara was not affected since it is more than 25 km from the sea; the shoreline of Ampara district was affected but not the town. The help people received was from Special Task Force, JVP (cadre-based political party in the government) and Buddhist priests. The LTTE (a banned terrorist organization in the USA, UK and India) and TRO (an LTTE front organization) were not active. The second author, consultant physician from the general hospital Badulla (an adjacent district of Ampara), was personally involved in relief work in the Ampara and Batticloa districts.
Ablative radioiodine therapy for hyperthyroidism: long term follow up study.
Authors: P Kendall-Taylor, M J Keir, W M Ross
Journal: BMJ (1984)

A total of 225 patients were treated for hyperthyroidism with 555 MBq (15 mCi) radioiodine to ablate the thyroid and induce early hypothyroidism. The efficacy of this treatment in eradicating hyperthyroidism and problems of follow up were assessed one to six years later from case records and questionnaires. Information was received from 197 out of 219 live patients (90%) and from 160 doctors concerning 207 patients (92%). Only three patients were not traced and six had died since treatment. The modal time to hypothyroidism was three months, and 64% of patients were hypothyroid at one year; 5.6% had failed to become euthyroid within one year. Ninety five per cent of patients had been seen by the doctor and 82% had had a thyroid test done within the past two years. Most doctors preferred patients to be returned to their care once thyroxine treatment was stabilised. An ablative dose of 131I is recommended as an effective means of treatment which has clear advantages over conventional methods. Good communications and effective follow up should ensure success.
eIF2α phosphorylation as a biomarker of immunogenic cell death
Authors: Oliver Kepp, Michaela Semeraro, José Manuel Bravo-San Pedro, Norma Bloy, Aitziber Buqué, Xing Huang, Heng Zhou, Laura Senovilla, Guido Kroemer, Lorenzo Galluzzi
Journal: Seminars in Cancer Biology (2015)
An Unusual Complication of Lye Ingestion
Authors: Herbert V. Sperling
Journal: JAMA (1974)

THE INGESTION of lye, either as a suicidal measure or accidentally, leads to multiple problems. Lye (sodium hydroxide) is highly destructive and may lead to perforation of the esophagus by liquefaction necrosis.<sup>1</sup>Hypovolemic shock and bacterial invasion are other immediate dangers of lye ingestion. Additional well-known complications are stricture formation, pulmonary insufficiency as the result of repeated aspirations, and perforation of the esophagus or stomach as a result of endoscopic examination. Necrosis of the tissues may extend through the entire esophageal wall, producing periesophagitis, pleurisy, pericarditis, mediastinitis, and bronchoesophageal fistula.<sup>2</sup>Chemical gastritis, peritonitis, pulmonary edema, and laryngeal obstructions are other possible complications. Cardona and Daly<sup>3</sup>reported duodenal ulcerations and strictures as a result of lye ingestion. The effects of alkali ingestion are seen primarily in the upper gastrointestinal tract.<sup>4</sup>In our patient, lye ingestion led to perforations of the small intestine and colon. To our knowledge,
Biologic indicators of cadmium nephrotoxicity in persons with low-level cadmium exposure.
Authors: K Nogawa
Journal: Environmental Health Perspectives (1984)

The relationship between abnormal urinary findings and renal function was investigated for 33 Itai-Itai patients, 17 suspected patients, 235 subjects exposed to Cd and 41 subjects not exposed to Cd pollution. High correlation coefficients were observed between urinary findings and renal function in advanced cases of chronic cadmium poisoning, and multiple correlation coefficients between them are as high as 0.73 to 0.86. beta 2-microglobulin in urine also correlated closely with renal function and age in slight to moderate cases of cadmium poisoning. It is concluded that urinary findings such as proteinuria, glucosuria and low molecular weight proteinuria are good indicators of renal dysfunction in moderate to severe cases of chronic cadmium poisoning. In slight to moderate cases beta 2-microglobulin in urine has a close relation with renal dysfunction.
Bevacizumab in neoadjuvant chemotherapy increases the pathological complete response rate in patients with triple‐negative breast cancer
Authors: Mary Kay Barton
Journal: CA A Cancer Journal for Clinicians (2014)

CA: A Cancer Journal for Clinicians publishes information about the prevention, early detection, and treatment of cancer, as well as nutrition, palliative care, survivorship, and additional topics of interest related to cancer care.
Enuresis in Adolescents
Authors: R. C. Browne, A. Ford-Smith
Journal: BMJ (1941)

One case was hopeless from the start; in the other a cure was effected by a wide excision of the lesion." Wound phagedaena " is suggested as a suitable name for ,the condition.We have to thank our colleagues mentioned in the text for their special examinations and reports; Dr. D.
Modulation of cytokine-induced eosinophil infiltration by phosphodiesterase inhibitors.
Authors: V Lagente, M P Pruniaux, J L Junien, I Moodley
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The effects of selective phosphodiesterase (PDE) isoenzyme inhibitors on eosinophil airway infiltration induced by intratracheal administration of recombinant human cytokines were investigated in the guinea pig. Recombinant human IL-5 and IL-8 elicited a concentration-dependent increase in the number of eosinophils in the bronchoalveolar lavage (BAL) fluid. In contrast, no effect was observed after intratracheal injection of recombinant human IL-3 or recombinant human RANTES. Pretreatment with the PDE IV inhibitors rolipram or Ro 20-1724 or the nonselective PDE inhibitor theophylline 1 h before intratracheal injection of IL-5 significantly reduced the number of eosinophils in the BAL fluid at 48 h. In contrast, the selective PDE III inhibitors milrinone and SK&F 94-836 and the PDE I/V inhibitor zaprinast did not inhibit the airway eosinophil infiltration induced by IL-5. Betamethasone also significantly inhibited the IL-5-induced eosinophil infiltration in BAL fluid. Administration of rolipram or betamethasone 1 h before IL-8 significantly reduced airway eosinophil infiltration. Because the selective PDE IV inhibitors markedly inhibited eosinophil infiltration in guinea pig airways induced by cytokines, it is suggested that PDE IV inhibitors have antiinflammatory effects in the airways and may be useful in the treatment of asthma.
Arteriolar and venular patterning in retinas of mice selectively expressing VEGF isoforms
Authors: Ingeborg Stalmans, Yin-Shan Ng, Richard Rohan, Marcus Fruttiger, Ann Bouché, Ali Ÿuce, Hajime Fujisawa, Bart Hermans, Moshe Shani, Sandra Jansen, Dan Hicklin, David J. Anderson, Tom Gardiner, Hans-Peter Hammes, Lieve Moons, Mieke Dewerchin, Désiré Collen, Peter Carmeliet, Patricia A. D’Amore
Journal: Journal of Clinical Investigation (2002)

The murine VEGF gene is alternatively transcribed to yield the VEGF120, VEGF164, and VEGF188 isoforms, which differ in their potential to bind to heparan sulfate and neuropilin-1 and to stimulate endothelial growth. Here, their role in retinal vascular development was studied in mice selectively expressing single isoforms. VEGF164/164 mice were normal, healthy, and had normal retinal angiogenesis. In contrast, VEGF120/120 mice exhibited severe defects in vascular outgrowth and patterning, whereas VEGF188/188 mice displayed normal venular outgrowth but impaired arterial development. It is noteworthy that neuropilin-1, a receptor for VEGF164, was predominantly expressed in retinal arterioles. These findings reveal distinct roles of the various VEGF isoforms in vascular patterning and arterial development in the retina.
TGF-β type II receptor in rat renal vascular development: Localization to juxtaglomerular cells
Authors: Ailian Liu, Barbara J. Ballermann
Journal: Kidney International (1998)

To further define the role of transforming growth factor-beta (TGF-beta) receptors in renal vascular development, detailed immunohistochemical studies of TGF-beta receptor expression were performed from gestational day 15 through adulthood. On gestational day 15, TGF-beta type II receptor immunoreactivity was restricted to perirenal stromal and vascular cells. On gestational day 17 TGF-beta type II receptor immunoreactive stromal cells were observed within the kidney, with the same distribution as stromal alpha-smooth muscle actin and renin immunoreactive cells, and intense stromal TGF-beta type II receptor immunoreactivity continued through postnatal day 5. As vascular development progressed, TGF-beta type II receptor, alpha-smooth muscle actin and renin immunoreactivity became progressively restricted to small renal arteries and arterioles. Expression of TGF-beta type II receptors and renin was very intense in afferent glomerular arterioles during postnatal days 5 to 15, and then became progressively restricted only to juxtaglomerular cells in the mature kidney. TGF-beta type I receptor (ALK-5, ALK-1 and ALK-2) immunoreactivity was not detected in stromal or vascular elements during development or in the mature kidney. Intense TGF-beta type II receptor expression in renal stromal vascular smooth muscle cell precursors and developing blood vessels suggests a role for the TGF-beta type II receptors in the formation of the renal vascular smooth muscle compartment. The continued intense expression in juxtaglomerular cells argues for a role in renin synthesis and/or release. The absence of ALK-5, ALK-1, and ALK-2 in developing vascular smooth muscle and mature juxtaglomerular cells indicates that the canonical view of TGF-beta signaling may not hold in these locations.
Access to Essential Drugs in Poor Countries&lt;SUBTITLE&gt;A Lost Battle?&lt;/SUBTITLE&gt;
Authors: Bernard Pécoul
Journal: JAMA (1999)

Drugs offer a simple, cost-effective solution to many health problems, provided they are available, affordable, and properly used. However, effective treatment is lacking in poor countries for many diseases, including African trypanosomiasis, Shigella dysentery, leishmaniasis, tuberculosis, and bacterial meningitis. Treatment may be precluded because no effective drug exists, it is too expensive, or it has been withdrawn from the market. Moreover, research and development in tropical diseases have come to a near standstill. This article focuses on the problems of access to quality drugs for the treatment of diseases that predominantly affect the developing world: (1) poor-quality and counterfeit drugs; (2) lack of availability of essential drugs due to fluctuating production or prohibitive cost; (3) need to develop field-based drug research to determine optimum utilization and remotivate research and development for new drugs for the developing world; and (4) potential consequences of recent World Trade Organization agreements on the availability of old and new drugs. These problems are not independent and unrelated but are a result of the fundamental nature of the pharmaceutical market and the way it is regulated.