tbuckley/cabot-search huggingface dataset:
Increased exercise tolerance after nitroglycerin oral spray: a new and effective therapeutic modality in angina pectoris.
Authors: A Kimchi, G Lee, E Amsterdam, K Fujii, P Krieg, D T Mason
Journal: Circulation (1983)

The prophylactic antianginal efficacy of nitroglycerin (NTG) oral spray was assessed in 20 patients with angiographically documented coronary disease and stable angina pectoris. The evaluation was by a randomized crossover trial involving treadmill exercise testing. On study day 1, a control treadmill exercise test was performed, followed 30 minutes later by a second exercise test 2 minutes after administration of either placebo (group A, 10 patients) or NTG spray 0.8 mg (group B, 10 patients). One week later, on study day 2, the patients again underwent control treadmill exercise testing followed by a second exercise test after either NTG spray (group A) or placebo (group B). NTG spray delayed the onset of anginal pain during exercise by a mean of 100 +/- 64 seconds (p less than 0.001) in 13 patients and prevented pain entirely in seven. Placebo did not significantly delay the appearance of angina and prevented chest pain in only one patient. NTG spray increased treadmill exercise duration by 31% before the onset of angina (p less than 0.001); placebo did not significantly alter the duration of exercise. NTG spray abolished in six patients and delayed in 14 patients the onset of exercise-induced ST-segment depression of 1 mm (p less than 0.001). Patients achieved a higher heart rate at peak exercise with NTG spray, and yet the maximal exercise-induced ST-segment depression of 2.1 +/- 1.0 mm during the control study declined to 1.3 +/- 0.9 mm on NTG spray (p less than 0.001). Placebo had no effect on exercise ST-segment depression. These data indicate that the oral NTG spray is an effective prophylactic for exercise-induced angina.
Incomplete Absorption of the Carbohydrate in All-Purpose Wheat Flour
Authors: Isabel H. Anderson, Allen S. Levine, Michael D. Levitt
Journal: New England Journal of Medicine (1981)

MALABSORPTION of the carbohydrate lactose is a common cause of flatulence, abdominal discomfort, and diarrhea in otherwise healthy persons. The possibility that such symptoms could result from malabsorption of the other major dietary carbohydrates (sucrose or starch) has received little consideration since these carbohydrates are assumed to be completely absorbed in health.We measured breath hydrogen to assess the absorption of the carbohydrate in white, all-purpose wheat flour. These studies demonstrate that nearly all normal subjects fail to absorb an appreciable portion of this form of starch, possibly because of an interaction between the starch and protein moieties of wheat . . .
DIPHTHERIA INFECTION IN MINNESOTA.RECENT EXPERIENCES WITH THE DISEASE IN SCHOOL CHILDREN AND IN INSTITUTIONAL EPIDEMICS.
Authors: F. F. WESBROOK
Journal: JAMA (1905)

It is not the purpose of this communication to enter into the minute consideration of all phases of the prevention and eradication of diphtheria, but to present briefly the general features of some of the methods which have been found practicable in Minnesota and in which the laboratory has been used as the guide to executive action and restrictive measures. In the work of the Minnesota State Board of Health, the problems have naturally arranged themselves into three main groups. I. The routine work of dealing with diphtheria as it occurs in family life. II. Widespread epidemics in which the day schools have to be closed. III. Infection which gains entrance into institutions in which children or other inmates are housed, employed, taught or confined, and where great opportunity for the spread of infection is present. <h3>I. DIPHTHERIA IN FAMILY LIFE.</h3> The routine work of the State Board of
Pathogenesis of polycythemia vera—new concepts
Authors: David W. Golde, Martin J. Cline
Journal: American Journal of Hematology (1976)

Abstract Data presently available suggest that polycythemia vera is an acquired clonal disorder of the pluripotent stem cell resulting in expansion of committed stem cell pools, most prominently in the erythroid line. In vitro and in vivo studies suggest that erythropoiesis in polycythemia vera is at least partially modulated by erythropoietin.
The Additional Value of Chemotherapy to Radiotherapy in Locally Advanced Nasopharyngeal Carcinoma: A Meta-Analysis of the Published Literature
Authors: J.A. Langendijk, Ch.R. Leemans, J. Buter, J. Berkhof, B.J. Slotman
Journal: Journal of Clinical Oncology (2004)

Purpose The purpose of this meta-analysis was to determine the additional value of neoadjuvant, concurrent, and/or adjuvant chemotherapy to radiation in the treatment of locally advanced nasopharyngeal carcinoma (NPC) with regard to the overall survival (OS) and the incidence of local-regional recurrences (LRR) and distant metastases (DM). Patients and Methods To be eligible, full published studies had to deal with biopsy-proven NPC and have patients randomly assigned to receive conventional radiotherapy (66 to 70 Gy in 7 weeks) or radiotherapy combined with chemotherapy. Results Ten randomized clinical studies were identified, including 2,450 patients. The pooled hazard ratio (HR) of death for all studies was 0.82 (95% CI, 0.71 to 0.95; P = .01) corresponding to an absolute survival benefit of 4% after 5 years. Three categories of trials were defined according to the sequence of chemotherapy, including neoadjuvant chemotherapy, at least concomitant chemoradiotherapy, and adjuvant chemotherapy. A significant interaction term (P = .02) was found among these three categories. The largest effect was found for concomitant chemotherapy, with a pooled HR of 0.48 (95% CI, 0.32 to 0.72), which corresponds to a survival benefit of 20% after 5 years. Comparable results were found for the incidence of LRR and DM. Conclusion The results of this study indicate that concomitant chemotherapy in addition to radiation is probably the most effective way to improve OS in NPC.
Exploiting non-communicable disease
Authors: Des Spence
Journal: BMJ (2012)

The developed world is ever more cynical about Big Pharma, having suffered decades of marketing spin, drug scandals, and the manipulation of research. So drug companies are now eyeing the developing world, with its huge populations, rapidly increasing wealth, and light touch regulation. This is the new colonial frontier, ripe for a health land grab. Non-communicable diseases are the new commodity to exploit. Because they require lifelong prescriptions, chronic diseases are a profit goldmine for drug companies. The World Health Organization supports and legitimises this activity. Meanwhile, wealth inequality, poverty, and basic public health …
RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY INVESTIGATING CHANGES IN NOCTURNAL BLOOD PRESSURE ELEVATIONS ASSOCIATED WITH PERIODIC LEG MOVEMENTS FOLLOWING TREATMENT WITH ROTIGOTINE IN PATIENTS WITH RESTLESS LEGS SYNDROME (WILLIS-EKBOM DISEASE)
Authors: Domenic A. Sica, Axel Bauer, Werner Cassel, Wolfgang Oertel, David Rye, Arthur Walters, John Winkelman, Lars Bauer, Lars Joeres, Frank Grieger, Kimberly Moran, Erwin Schollmayer, John Whitesides
Journal: Journal of the American College of Cardiology (2014)
On Mammography — More Agreement Than Disagreement
Authors: Ann H. Partridge, Eric P. Winer
Journal: New England Journal of Medicine (2009)

Breast cancer is the most common cancer in women in the United States, with more than 190,000 women receiving a diagnosis of invasive disease annually1 and more than 40,000 dying of breast cancer each year. Worldwide, more than 1 million women are diagnosed with breast cancer and more than 500,000 die from it each year.2 During the past two decades, there have been modest but real decreases in breast-cancer mortality that have been attributed to improvements in early detection and treatment. It is in this context that the recent controversy surrounding the optimal approach to breast-cancer screening should be considered. . . .
Immunological Methods: A Symposium Organized by the Council for International Organizations of Medical Sciences Established Under the Joint Auspices of UNESCO and WHO
Authors: Lester S. King
Journal: JAMA (1964)

The dramatic results of organ transplantation and the increased interest in auto-immune diseases have emphasized in recent years the relation of immunologic concepts to basic medical problems. Yet quite apart from the more publicized aspects, immunology has made fabulous progress, and research has developed highly sophisticated techniques which can yield precise and illuminating data. That many of the world's outstanding immunologists should get together and discuss their technical procedures and the applications thereof is not surprising. On the contrary, in this era when symposia are held at the proverbial drop of a hat, the absence of such a meeting might be surprising. But whereas many published symposia have nothing—and we mean literally nothing —to recommend them, the present volume is an outstanding example of excellence. The individual papers are well written and cover a vast range; the discussions are intelligible, the publication format admirable. Even the price does not seem
Postscript on Excretion Rates in Posttransplant Cystinuric Patient
Authors: S. Kelly, E. P. Nolan
Journal: JAMA (1980)

<h3>To the Editor.—</h3> The daily rates of amino acid excretion by a cystinuric man with transplanted kidneys, first described in a letter (239:1132, 1978), have been remeasured recently, and, once again, have been found to be within the normal range (Table). Now 29 years old and 3 1/2 years after the transplant, he excretes cystine, lysine, ornithine, and arginine at normal rates, similar to the rates excreted 20 months after the operation. Thus, he remains uncystinuric.
1004. Enhanced Survival Uncovers Liver Toxicity in Mice with Orthotopic Advanced Ovarian Cancer Treated with Gemcitabine and Ad5/3-Δ24, a Serotype 3 Receptor Targeted Oncolytic Adenovirus
Authors: Mari Raki, Anna Kanerva, Ari Ristimaki, Renee A. Desmond, Dung T. Chen, Tuuli Ranki, Merja Sarkioja, Lotta Kangasniemi, Akseli Hemminki
Journal: Molecular Therapy (2005)

Top of pageAbstract
Oncolytic adenoviruses a.k.a. conditionally replicating adenoviruses (CRAds) represent a promising approach for treatment of cancers resistant to conventional therapies. Our hypothesis was that efficacy of CRAds might be further improved by using chemotherapeutic agents in a multimodal antitumor approach. Oncolytic tumor killing differs mechanistically from conventional therapies and therefore an additive or synergistic antitumor effect is possible. The toxicity profiles of the agents may be different and could result in enhanced efficacy without increased side effects. Finally, it may be possible to use lower treatment doses and still achieve a greater efficacy than with single agents.

We evaluated Ad5/3-|[Delta]|24 in combination with deoxycytidine analogue gemcitabine against human ovarian adenocarcinoma. Ad5/3-|[Delta]|24 is a serotype 3 receptor targeted CRAd containing a 24 bp deletion in the E1A gene. As a result the E1A protein is unable to bind the retinoblastoma (Rb) protein for induction of viral replication. Therefore the virus replicates selectively in cells dysfunctional in the Rb/p16 pathway, including most if not all cancer cells. Most CRAds are based on adenovirus serotype 5 (Ad5). However, the expression of the Ad5 primary receptor, coxsackie-adenovirus receptor (CAR), is highly variable on ovarian cancer cells. The lack of CAR can be circumvented by substituting the knob domain of Ad5 with the corresponding domain of serotype 3 (Ad3). Ad3 has a distinct receptor which is expressed to high degree on ovarian cancer cells.

For evaluation of the potential interaction between Ad5/3-|[Delta]|24 and gemcitabine in vitro, the cell killing effect of the combination treatment was compared to single treatments on established ovarian adenocarcinoma cell lines. The combination resulted in synergistic cell killing as determined by Chou and Talalay's synergy analysis. However, the effect was dependent on dose and sequencing of the agents. In an orthotopic murine model of aggressive peritoneally disseminated ovarian cancer, the combination of Ad5/3-|[Delta]|24 and gemcitabine increased the survival of mice over either agent alone, and almost 60 % of treated mice were cured. However, sequencing of the agents was critical for toxicity versus efficacy. Mice remained free from intraperitoneal disease, but some succumbed to treatment related toxicity. Possible reasons for the interaction between Ad5/3-|[Delta]|24 and gemcitabine include the chemosensitizing activity of E1A and/or altered replication kinetics. Our results indicate that gemcitabine reduces the initial rate of Ad5/3-|[Delta]|24 replication without affecting the total amount of virus produced.
Eczema in Infancy and Childhood
Authors: Lewis Webb Hill
Journal: New England Journal of Medicine (1950)

Treatment of Secondary InfectionSecondary infection of the skin in eczematous infants and children is common, and treatment is very satisfactory when carried out correctly.Pillsbury,28 in a comprehensive paper, discusses the management of bacterial infections of the skin. Bacteria rapidly gain a foothold in skin that is already diseased, and the problem of their removal is complicated by the fact that such skin reacts more adversely to treatment than skin that was previously normal. It should be especially borne in mind that in chronic eczematous lesions in which infection plays a part in keeping the process active there may . . .
COMPARISON OF 4 YEARS CLINICAL OUTCOME OF STENT IMPLANTATION IN RENAL FAILURE PATIENTS WITH DIALYSIS: COMPARISON WITH BARE METAL, STENTS, FIRST GENERATION DRUG-ELUTING STENT AND SECOND GENERATION DRUG-ELUTING STENTS
Authors: Sunao Nakamura, Shotaro Nakamura, Hisao Ogawa, Jang-Ho Bae, Yeo H. Cahyadi, Wasan Udayachalerm, Damras Tresukosol, Sudaratana Tansuphaswadikul
Journal: Journal of the American College of Cardiology (2011)
Abstract 5049: Cyclopamine modulates ABCG2 activity in glioblastoma side population cells
Authors: Jana Balbuena, Gisela Pachon, Guillermo Lopez-Torrents, Xing Fan, Javier S. Castresana, Jordi Petriz
Journal: Cancer Research (2011)

Abstract The Sonic Hedgehog pathway (HH) has been implicated in the maintenance of stem cells in adult tissues. Abnormal HH activation is also associated with initiation of neoplasia by cancer stem cells. Cyclopamine has been used as an inhibitor of the HH, with potential effectiveness in several xenograft models, including gliomas. Side Population (SP) cells are stem cells with expression of ABCG2, a multidrug ABC transporter, able to extrude dyes as Hoechst 33342 (Ho342). SP cells, then, present low fluorescence after staining with Ho342. ABC transporters have been identified as drug-resistance proteins. HH regulates the expression of ABC transporters, and promotes multi-drug resistance by increasing drug efflux by the ABC transporters. Different research groups have shown that SP cells can be depleted following cyclopamine treatment, an observation that would support that SP cells are HH pathway-dependent. We hypothesized that cyclopamine might interact with ABCG2 and limit the number of SP cells. Therefore, we analyzed the effect of cyclopamine and temozolomide on the MXRA cell line (KB cells transfected with the full-length ABCG2 cDNA), and on five astrocytoma cell lines, both in the parental cell lines and in their SP cells. We first evaluated the modulatory effect of cyclopamine on ABCG2 function by measuring the intracellular accumulation of two substrates of ABCG2, Ho342 and mitoxantrone. Secondly, we analyzed the effect of these drugs in the phenotype of SP cells (the cells were incubated with only Ho342, or a combination of Ho342 and cyclopamine, or a combination of Ho342, cyclopamine and temozolomide; afterwards we analyzed the number of SP cells). We saw that cyclopamine significantly decreased the fraction of SP cells but not through a depletion of the SP compartment, but as a consequence of the molecular mechanisms involved in the affinity of cyclopamine and Ho342 for ABCG2, as cyclopamine modulated the ABCG2 transporter by increasing Ho342 and mitoxantrone uptake. Temozolomide had no effect on the SP cells. Therefore, cyclopamine, although decreases the SP fraction of cancer stem cells in glioblastoma cell lines, does not deplete the SP compartment, but modulates ABCG2 activity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5049. doi:10.1158/1538-7445.AM2011-5049
Health Service Prospects: An International Survey
Authors: Odin W. Anderson
Journal: JAMA (1974)

This book was compiled and published to commemorate the 150th anniversary of the eminent medical journal<i>The Lancet</i>in October 1973. The book contains 15 articles by 17 authors who describe the health service systems in 15 countries, namely, the United Kingdom, Belgium, France, German Federal Republic, Italy, Luxembourg, The Netherlands, Sweden, Ghana, Cuba, India, Japan, the Union of Soviet Socialist Republics, China, and the United States. As with all compilations, the scope, detail, and analytical attempts are uneven. All are, however, informative. Given the occasion—the 150th anniversary of<i>The Lancet</i>—and the request for a short review, it would not seem to be appropriate to make invidious evaluations of the papers. What stands out is the apparent range of "workable" systems in different situations. All authors say their respective systems need improvement, albeit they are doing quite well, given the current state of finances, resources, and administrative personnel. These
Decreased stimulatory guanosine triphosphate binding protein in dogs with pressure-overload left ventricular failure.
Authors: J P Longabaugh, D E Vatner, S F Vatner, C J Homcy
Journal: Journal of Clinical Investigation (1988)

Alterations in the level and function of the stimulatory guanyl nucleotide binding protein (Gs) from the cardiac sarcolemma were examined in a canine model of heart failure. The present study is based on our previous investigations that demonstrated both a loss of beta-adrenergic agonist high-affinity binding sites and a decreased adenylate cyclase activity in sarcolemma from failing hearts. Using cholera toxin and [32P]NAD, we labeled the alpha subunit of Gs (Gs alpha) and found a 59% reduction in the level of this protein. Further, a 50% reduction in Gs activity was noted in a reconstitution assay utilizing membranes from the mouse S49 lymphoma cell line cyc-, which is deficient in Gs. These data suggest that, in this model of pressure-overload left ventricular failure, the acquired defect in the beta-adrenergic receptor/adenylate cyclase system involves a deficiency in the coupling protein Gs. Such an abnormality may explain the decreased adrenergic responsiveness of the failing left ventricle.
Abstract 1320: Molecular imaging of EMT reveals crosstalk of multiple pathways and provides novel sites for therapeutic intervention of EMT
Authors: Shyam Nyati, Mahaveer Swaroop Bhojani, Venkat Keshamouni, Katrina Schinske, Brian D. Ross, Alnawaz Rehemtulla
Journal: Cancer Research (2010)

Abstract Ionizing radiation therapy have been also suggested to result in increased incidence of local or distant metastasis which is, at least in part, mediated by TGFß signaling. TGFß is a known potentiator of epithelial to mesenchymal transition (EMT), a complex process by which a tumor cell bolsters its metastatic potential by transmogrifying into a highly motile and invasive cell that is ready to take on the challenge of distant travel and resettlement in a new milieu. Therefore it is important, in order to increase efficacy of ionizing radiation, a combination therapy along with inhibitors of EMT pathway, be utilized in the treatment of cancers. To date there is no clinically relevant EMT inhibitor and therefore to assist in the process of identifying a small molecular weight inhibitor, we developed three distinct non-invasive and quantitative molecular imaging reporters for monitoring EMT. These were based on changes in expression profile of E-cadherin and N-cadherin and complementation of luciferase based TGFβR kinase (BTR) activity. In the lung cancer EMT model studies using TGFβ treated A549 cells we demonstrated a time and dose dependent increase in activity of luciferase reporter driven by N-cadherin promoter and a decrease in the activity of a luciferase reporter driven by E-cadherin promoter. These changes were validated by phenotypic alteration of A549 cells and by western blotting for signaling intermediates of EMT pathway. BTR (bioluminescent TGFβR reporter), was a gain of function sensor of SMAD2/3 phosphorylation wherein inhibition of TGFβR signaling leads to increased reporter activity. Such reporters are extremely useful in high throughput screening (HTS) as cytotoxic agents are eliminated early in the screening process. Treatment of A549 cells stably expressing BTR with SB431542 (TGFβR specific inhibitor) lead to a more than 20 fold increase in BTR activity. All three reporters were adapted for HTS assay and were used to screen a library of known kinase inhibitors. Analyses and validation of hits suggested that the loss of epithelial or gain of mesenchymal phenotypes are independent processes. Further it also highlighted complex cross talks between EMT and different pathways involving mTor, Src, p38 MAPK, Akt, JNK, PI3-K, PKA, PKC, GSK-3β, PDGFRK and EGFR. Efficacy of several lead compounds (Erlotinib, SP600125, SB203580, and SB431542) in combination with radiotherapy is being accessed to increase radiation sensitivity in epithelial cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1320.
201Thallium and 67Gallium Scintigraphy in Hodgkin's and Non-Hodgkin's Lymphoma
Authors: S. Dadparvar, K. M. Kapadia, J. L. Damsker, L. Krishna, M. M. Gillan, W. J. Slizofski
Journal: Clinical Nuclear Medicine (1996)

Dadparvar, S.; Kapadia, K.; Damsker, J. L.; Krishna, L.; Gillan, M. M.; Slizofski, W. J. Author Information
1263 HIGH FAT DIET-INDUCED INSULIN RESISTANT DIPEPTIDYL PEPTIDASE 4-DEFICIENT RATS EXHIBIT ATTENUATED HEPATIC EXPRESSION OF CYP7A1 AND ENHANCED EXPRESSION OF LIPOGENESIS ENZYMES
Authors: S. Ben-Shlomo, I. Zvibel, Z. Halpern, R. Oren, S. Fishman
Journal: Journal of Hepatology (2011)