tbuckley/cabot-search huggingface dataset:
Philippines joins other developing countries in limiting prices of drugs
Authors: B. Bland
Journal: BMJ (2009)

The Philippines is to impose price controls on some essential drugs, as the government seeks to reduce the cost of drugs that remain beyond the reach of large swathes of the population.

President Gloria Macapagal-Arroyo signed the executive order bringing in maximum retail prices on five key drugs on Monday 27 July. This followed the failure of a number of drug companies, including Pfizer, to cut prices by 50% in line with a new law designed to make them more affordable.

The Philippines, a third of whose population lives on less than $1 a day, is the latest …
NHS payments should focus on value, not single episodes of care, conference hears
Authors: N. Hawkes
Journal: BMJ (2014)

The NHS needs to focus on the value it can deliver to patients and shed its attachment to historical structures and institutions to achieve better outcomes at lower cost, a conference in London heard on 22 January.

Michael Porter, a Harvard Business School expert on healthcare, said that focusing on value to patients was “the only goal that unites all parts of the system,” encouraging cooperation, reducing fragmentation, and making the best use of every pound spent. 

The NHS had been too timid about shaking up the way care was delivered and too reluctant to tell patients that for the best care they might need to travel somewhere other than their local hospital, he said. But to achieve these two objectives the NHS would have to change its payment system so that it covered “bundles” of care rather than single episodes, and it needed to collect robust outcome measures to convince doctors and …
Activation of Hedgehog signalling plays a crucial role in the pathogenesis of systemic sclerosis
Authors: A. Horn, C. Dees, A. Akhmetshina, K. Palumbo, N. Busch, O. Distler, G. Schett, J. H W Distler
Journal: Annals of the Rheumatic Diseases (2010)

The Hedgehog (Hh) pathway plays important roles in embryonic tissue development, in the pathogenesis of various tumours and in hepatic fibrosis. The ligand Sonic Hedgehog (Shh) binds to the transmembrane receptor Patched, which releases the membrane protein Smoothened (Smo) from its repression. As a result, Smo activates the transcription factor GLI-Kruppel family member (Gli2)for further activation of several target genes.

The expression of Shh, Smo and Gli2 in human skin sections was analysed …
Pitted keratolysis: clinical manifestations in 53 cases
Authors: H. TAKAMA, Y. TAMADA, K. YANO, Y NITTA, T. IKEYA
Journal: British Journal of Dermatology (1997)

Pitted keratolysis (PK) has been reported to be more common among bare-footed people living in tropical regions. It is now known that the disease is not limited to the tropics but has a world-wide distribution. However, no study has previously been performed analysing the clinical manifestations of the disease in temperate countries. A survey of 53 patients revealed several distinctive clinical features. Hyperhidrosis is the most frequently observed symptom of this condition. Malodour and sliminess of the skin are also distinctive features, evident in 88.7% and 69.8% of the cases, respectively. The most common sites of onset of PK are the pressure-bearing areas, such as the ventral aspect of the toe, the ball of the foot and the heel. The next most common site is a friction area, the interface of the toes. Lesions are rarely seen on the non-pressure-bearing locations. Some of the primary lesions originate as a small defect along the plantar furrow, which gradually grows into the characteristics crateriform pit. Several clinical features are helpful in diagnosing PK.
INTRAVENOUS INJECTION OF ERGOT.EFFECTS ON THE MAMMALIAN CIRCULATION.
Authors: TORALD SOLLMANN
Journal: JAMA (1905)

Ergot is commonly supposed to produce a powerful and persistent contraction of blood vessels. This belief rests mainly on clinical evidence, which is not conclusive; even when the observations are correct, they generally admit of other explanations. For instance, the hemostatic action of ergot in postpartum hemorrhage is now referred to the contraction of the uterine muscle, rather than to a vasoconstriction. It is also generally assumed that the vasoconstriction has been firmly established by experimental evidence. An inspection of any of the critical text-books of pharmacology, however, will suffice to show that different investigators have obtained variable results on mammals. This caused us to undertake the present investigation, the original object of which was to determine, on dogs, the circulatory effects of the ergot preparations as found on the market, in therapeutic doses, normally and in the pathologic conditions in which the drug is recommended. We intended to use
Topical methyl-aminolevulinate photodynamic therapy using red light-emitting diode light for treatment of multiple actinic keratoses: A randomized, double-blind, placebo-controlled study
Authors: David Pariser, Robert Loss, Michael Jarratt, William Abramovits, James Spencer, Roy Geronemus, Philip Bailin, Suzanne Bruce
Journal: Journal of the American Academy of Dermatology (2008)
Abstract 3445: Targeting Thromboxane A2 receptor (TP) to block breast cancer metastasis
Authors: Xuejing Zhang, Daotai Nie
Journal: Cancer Research (2012)

Abstract The thromboxane A2 (TXA2) receptor, TP, is a G-protein coupled receptor. Previous studies in our lab have shown that the TP pathway regulates tumor cell cytoskeleton and TP activation induces rapid tumor cell contractions through small GTPase RhoA activation. Conversely, TP depletion reduces the metastatic dissemination of breast cancer cells in vivo by blocking the extravasation of tumor cells. Humans express two TP isoforms, TPγ and TPα. We report here that elevated TPγ expression is associated with metastasis in patients with breast cancer. While TPγ is expressed in all breast cancer cell lines that we examined, TPγ is only expressed in malignant cell lines, indicates that TPγ plays a role in breast cancer progression. Treatment with a selective TPγ inhibitor (CAY10535) blocks TP agonist (U46619) induced cell body contraction and RhoA activation. Additionally, TPγ inhibitor reduces migratory capacity and invasiveness in human breast cancer cell lines. Our previous work has shown that active TP is required for efficient extravasation of tumor cells in vivo; in this study, we further demonstrate that mice treated with SQ29548 (a high affinity TP antagonist) prior to tumor cell injection developed fewer metastatic lesions than the mice treated with SQ29548 after tumor cell injection. In all, our study indicated that TPγ can be targeted to reduce the risk of breast cancer metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3445. doi:1538-7445.AM2012-3445
Plasma Retinol-Binding Protein 4 (RBP4) Levels and Risk of Coronary Heart Disease
Authors: Qi Sun, Urban A. Kiernan, Ling Shi, David A. Phillips, Barbara B. Kahn, Frank B. Hu, JoAnn E. Manson, Christine M. Albert, Kathryn M. Rexrode
Journal: Circulation (2013)

Retinol-binding protein 4 (RBP4) may play an important role in the origin of insulin resistance and metabolic syndrome. Few prospective data are available on the relationship between RBP4 and coronary heart disease (CHD). Furthermore, previous studies did not distinguish among full-length and truncated forms of RBP4 that might have various biological activities.
A neoepitope generated by an FLT3 internal tandem duplication (FLT3-ITD) is recognized by leukemia-reactive autologous CD8+ T cells
Authors: Claudine Graf, Florian Heidel, Stefan Tenzer, Markus P. Radsak, Fian K. Solem, Cedrik M. Britten, Christoph Huber, Thomas Fischer, Thomas Wölfel
Journal: Blood (2006)
Hay-Fever Not a Contraindication to Antitoxin
Authors: Edward M. Colie
Journal: JAMA (1910)

To the Editor:—  The note in the Medicolegal department (June 18, 1910, p. 2094), in regard to the use of tetanus antitoxin on patients who have hay-fever, leads me to say that I have used the antitoxin as a prophylactic measure on several occasions. Many patients have suffered in varying degree from hay-fever, yet in no case have I seen any untoward effect follow its use.  I myself suffer severely from hay-fever during August and September of each year. Last September I received an injury which made it seem wise to use a single large injection of the antitoxin. At the time I was suffering severely from hayfever. I suffered no inconvenience whatsoever following the injection.  There is at times so much at stake as a result of injuries which tetanus may complicate, and prophylactic treatment is so very satisfactory, that I should not in the least hesitate either to
GW25-e2356 Nesiritide fails to reduce the mortality of patients with acute decompensate heart failure: an updated systematic review and cumulative meta-analysis
Authors: Bin Yan, Liyuan Peng, Xiaojing Zhao, Hsingchun Chung, Lijun Li, Lingfang Zeng, None Heanyeeong, Gang Wang
Journal: Journal of the American College of Cardiology (2014)
Organ distribution and fate of human platelets: Studies of asplenic and splenomegalic patients
Authors: Robin L. Hill‐Zobel, Brian McCandless, S. Andrew Kang, Gundabhaktha Chikkappa, Min‐Fu Tsan
Journal: American Journal of Hematology (1986)

Abstract Little is known about the organ distribution and fate of human platelets. We investigated the kinetics, organ distribution, and fate of autologous 111 In‐oxine‐labeled platelets in 12 normal volunteers, four asplenic subjects, and four patients with splenomegaly. The initial recovery of infused 111 In‐platelets from the circulation was 97.8 ± 9.8% (means ± SD) for asplenic subjects and 26.3 ± 5.9% for splenomegalic patients as compared to 59.2 ± 9.3% for normal controls. The mean platelet survival times as derived from the multiple‐hit model were 9.2 ± 1.0 days for asplenics and 6.2 ± 0.6 days for splenomegalic subjects (8.4 ± 0.8 days for normals). At 30 min postinfusion, 79.4 ± 19.2% of the infused 111 In‐platelets pooled in the spleen of splenomegalic subjects and 42.7 ± 12.2% in normal controls. There was 7.1 ± 2.0, 12.6 ± 3.7, and 29.3 ± 8.4% pooling in the liver of splenomegalic, normal, and asplenic subjects, respectively. At 10 days postinfusion, 37 and 24% of the 111 In‐platelets were sequestered in the spleen and liver of normal control subjects, respectively. Similar figures for splenomegalic subjects were 71 and 14%, respectively. In asplenic subjects, 89% was sequestered in the liver. We conclude that spleen and liver are the primary sites of platelet destruction, accounting for 61% of infused 111 In‐platelets in normal volunteers and 85% in splenomegalies, while the liver is the primary site of platelet destruction, accounting for 89% in asplenic subjects.
Induction of heme oxygenase-1 in factor VIII–deficient mice reduces the immune response to therapeutic factor VIII
Authors: Jordan D. Dimitrov, Suryasarathi Dasgupta, Ana-Maria Navarrete, Sandrine Delignat, Yohann Repesse, Yann Meslier, Cyril Planchais, Maud Teyssandier, Roberto Motterlini, Jagadeesh Bayry, Srinivas V. Kaveri, Sébastien Lacroix-Desmazes
Journal: Blood (2009)
Abstract 1779: Selective oncolysis of multiple myeloma cells by reovirus is mediated through apoptosis
Authors: Chandini M. Thirukkumaran, Zhong-Qiao Shi, Joanne Luider, Karen Kopciuk, Don Morris
Journal: Cancer Research (2011)

Abstract Introduction: Multiple myeloma (MM) is an incurable hematologic malignancy that accounts for 10% of hematopoietic neoplasms. Recently we have demonstrated the potential of reovirus as novel therapeutic agent for MM, however, the oncolytic mechanism has not been elucidated yet. Reovirus is known to utilize multiple signalling pathways for cancer cell destruction depending on histological origin. It is currently unknown if the apoptotic signalling pathways are involved in reovirus mediated cell death of multiple myeloma. Methods: The MM cell lines RPMI 8226, U266, NCIH929, HUNS-1, MC/CAR, and OPM2 were incubated with live or UV-inactivated reovirus at a multiplicity of infection of 40 for 24, 48, and 72 hours respectively. Apoptosis was assayed by Annexin V/7-AAD expression and DNA fragmentation using flow cytometry. RPMI 8226 was further investigated at 2, 6 12, 24 and 48 hours for the presence of Phospho -Akt and activated caspase 3 post reovirus infection. Results: RPMI 8226, U266, and NCIH929 demonstrated an apoptotic response to reovirus infection within 24 hours. All 3 cell lines showed statistically significant (all F tests, p&amp;lt;0.00001) increases in DNA fragmentation in response to reovirus and this increase was more pronounced as time progressed. Similarly expression of Annexin V was significantly higher (all F tests, p&amp;lt;0.00001) in all 3 cell lines with live reovirus treatment but the kinetics were cell line dependent where a significant (p&amp;lt; 0.05) time effect was seen for U266 but not for RPMI 8226 and NCIH929. In contrast, the MM cell lines HUNS-1, MC/CAR, and OPM2 appeared resistant to reovirus infection and showed no evidence of apoptosis at 72 h. Supporting the apoptotic mechanism of cell death, RPMI 8226 showed down regulation of the anti-apoptotic signalling protein, Phospho-Akt, at 24 hours of incubation with reovirus. This was accompanied by a simultaneous expression of activated caspase 3. Conclusion: Not all MM cell lines are amenable to reovirus mediated cell death. This has important implications for the future use of reovirus as a therapeutic agent for cancer and highlights the importance of understanding cell signalling mechanisms as Phase 3 clinical trials of solid tumours with reovirus are currently underway. Ongoing research utilizing pharmacologic and molecular inhibitors of Akt and caspase3 will enable us to confirm the importance of these molecules in reovirus oncolysis of haematological malignancies. Understanding these signalling pathways will help develop a more personalized approach of reovirus therapy for cancer patients in the future. 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 1779. doi:10.1158/1538-7445.AM2011-1779
Regulation of Ventricular Contraction
Authors: S. J. SARNOFF, S. K. BROCKMAN, J. P. GILMORE, R. J. LINDEN, J. H. MITCHELL
Journal: Circulation Research (1960)

At constant heart rates, efferent stimulation of the vagus nerve and of the left stellate ganglion revealed the following: 1. Vagal stimulation exerts a profound depressant effect on the strength of the atrial contraction and can thereby influence ventricular filling and ventricular stroke work; it elevates mean atrial pressure at any given level of ventricular stroke work. This occurs under experimental conditions wherein the vagal stimulation used does not produce an alteration in the performance characteristics of the ventricle. The effects of vagal stimulation are blocked by atropine. 2. Stellate ganglion stimulation or norepinephrine infusion augments the strength of atrial contraction and thus the atrial contribution to ventricular filling. The augmented atrial contraction takes place in a shorter period of time. 3. Stellate ganglion stimulation or norepinephrine infusion increases the external stroke work and power produced by the ventricle from any given mean atrial pressure and from any given end-diastolic pressure or fiber length.4. There is a family of curves representing the relation between end-diastolic fiber length and stroke work, as well as a family of curves representing the relation between mean atrial or end-diastolic pressure and stroke work.5. When taken together with the well-known sympathetic and parasympathetic effects on heart rate, the above data are believed to comprise a reasonably comprehensive description of the means available to the central nervous system for directly inducing acute changes in the activity of the heart.
Pathogenesis and Etiology of Demyelinating Diseases
Authors: Martin R. Krigman
Journal: JAMA (1970)

This monograph is the product of an international symposium held in 1967 to explore the current ideas and research trends in multiple sclerosis. The participants were active investigators representing a variety of disciplines. Since the book is the outgrowth of a conference based upon a multidiscipline approach, it is not a unified text but a series of related papers. The editors have organized the 51 papers by the 68 participants into four broad sections: morphological aspects, virological aspects, immunological aspects, and aspects of mechanisms of other demyelinating processes caused by viruses. Many of the papers are concerned with the role of allergic reactions and viral agents in demyelinating disorders. The individual papers range from original studies to reviews of specialized areas and are based upon basic and clinical research. Although much of the material presented had in part been previously reported, the studies included in the book were generally expanded
TCT-15 Abluminal biodegradable polymer biolimus-eluting stent versus durable polymer everolimus-eluting stent in patients undergoing primary percutaneous coronary intervention: 3 Year follow-up from the COMPARE II trial
Authors: Georgios J. Vlachojannis, Pieter C. Smits, Sjoerd H. Hofma, Mario Togni, Nicolas Vazquez, Mariano Valdes, V. Voudris, Ton Slagboom, Jean-Jacques Goy, A.G. Vuillomenet, Antonio Serra, Ramiro Trillo, Peter den Heijer, Martin van der Ent
Journal: Journal of the American College of Cardiology (2014)
Abstract 623: The PARP3- and ATM-dependent phosphorylation of APLF facilitates DNA double-strand break repair.
Authors: Christine A. Koch, Amanda L. Fenton, Purnata Shirodkar, Li Meng
Journal: Cancer Research (2013)

Abstract APLF is a forkhead associated (FHA)-containing protein with poly(ADP-ribose)-binding zinc finger (PBZ) domains, which undergoes ionizing radiaiton (IR)-induced and ATM-dependent phosphorylation at serine-116 (Ser116). Here we demonstrate that the phosphorylation of APLF at Ser116 in human U2OS cells by ATM is dependent on PARP3 levels and the APLF PBZ domains. The interaction of APLF at sites of DNA damage was diminished by the single substitution of APLF Ser116 to alanine, and the cellular depletion or chemical inhibition of ATM or PARP3 also altered the retention of APLF at sites of laser-induced DNA damage, and impaired the accumulation of Ser116-phosphorylated APLF at IR-induced γH2AX foci in human cells. The data further suggest that ATM and PARP3 participate in a common signaling pathway to facilitate APLF-Ser116 phosphorylation, which, in turn, appears to be required for efficient DNA double-strand break (DSB) repair kinetics and cell survival following IR. Collectively, these findings provide a more detailed understanding of the molecular pathway that leads to the phosphorylation of APLF following DNA damage, and suggest that Ser116-APLF phosphorylation facilitates APLF-dependent DSB repair. Citation Format: Christine A. Koch, Amanda L. Fenton, Purnata Shirodkar, Li Meng. The PARP3- and ATM-dependent phosphorylation of APLF facilitates DNA double-strand break repair. [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 623. doi:10.1158/1538-7445.AM2013-623
Morphological development of the rat heart growing in oculo in the absence of hemodynamic work load.
Authors: S P Bishop, P G Anderson, D C Tucker
Journal: Circulation Research (1990)

We evaluated cardiac muscle development in the absence of hemodynamic work load but in the presence of host factors including blood vessels, nerves, and circulating neurohumoral agents by transplanting 12-day fetal rat ventricle into the anterior eye chamber of adult host rats. Implants were studied by electron microscopy at intervals from 1 to 14 weeks in oculo. For comparison with myocardium developing in oculo, 12-day fetal tissue and 3-, 8-, and 28-day-old normally growing rats were also studied. At 1 week in oculo, myofibrils were laterally located and more frequent than in the 12-day fetus. Fibrils had clear Z bands and H bands, but no M bands. At 10 days in oculo (comparable to birth in normally growing animals), myocyte mitoses were present and tritiated thymidine autoradiography revealed many labeled myocyte nuclei. By 5 weeks in oculo, cells were filled with mature myofibrils with clear M bands and lateral connections between adjacent Z bands. However, myofibril bundles sometimes coursed at sharp angles to each other within single cells. Except for the relative lack of fibrillar polarization and small cell size, ultrastructure of myocytes developing in oculo for 5 or more weeks appeared very similar to myocytes developing in normally growing rats. By 10 weeks in oculo, when in situ growing hearts are clearly in a hypertrophic phase of growth, no mitoses or tritiated thymidine-labeled nuclei were present in myocytes, although labeled nonmyocyte nuclei were present. Morphometric evaluation revealed no change in myocyte diameter or nuclear-to-cytoplasmic ratio from 1 to 3 weeks in oculo, consistent with continued hyperplastic growth. Binucleated cells were present by 3 weeks in oculo and later, and the cytoplasm per nucleus increased fourfold between 3 and 5 weeks in oculo, suggesting conversion to hypertrophic cell growth. We concluded that cells proliferated and differentiated in the absence of a hemodynamic load, but that polarized alignment of myocytes and myofibrils was incomplete.
Effects of humic acid on the viability and coagulant properties of human umbilical vein endothelial cells
Authors: Hsin-Ling Yang, Hui-Chong Chiu, Fung-Jou Lu
Journal: American Journal of Hematology (1996)

We have previously shown that humic acid (well-water humic acid, HA, and synthetic humic acid, SHA) enhances cell surface expression of tissue factor (TF). Here we report that incubation of human umbilical vein endothelial cells (HUVEC) for 2 hr with HA or SHA cause a rapid rise in TF mRNA levels, as shown by Northern blot analysis. To understand the cytotoxic and fibrinolytic effects of HA and SHA on cultured HUVEC, the cells were treated with varying concentrations of HA and SHA for various periods of time. Both HA and SHA (10–200 μg/ml) inhibited the viability of subconfluent HUVEC, cultured in the presence or absence of 20% FBS (Fetal Bovine serum) in the culture medium, in a dose-dependent manner. Both HA and SHA induced surface changes in the HUVEC as revealed by scanning electron micrography (SEM). However, protocatechuic acid, the monomer of SHA, did not significantly inhibit cell growth, and showed a cytotoxic effect only at 200 μg/ml. Furthermore both HA and SHA stimulated HUVEC to produce plasminogen activator inhibitor (PAI-1) and tissue plasminogen activator (t-PA) in a dose and time dependent fashion; the amount of PAI-1 produced was found to exceed that of t-PA. The monomer of SHA did not have this stimulatory effect. These results distinctly suggest that in addition to the inhibition of viability HA is involved in TF induction and PAI-1 synthesis in HUVEC and these may be some of the plausible mechanisms underlying the thrombotic disorders in Blackfoot disease. © 1996 Wiley-Liss, Inc.
Ethnic misclassifications hamper progress in research
Authors: Charles Agyemang
Journal: BMJ (2006)

EDITOR—McDowell et al review the evidence for ethnic differences in susceptibility to adverse drug reactions to cardiovascular drugs.1 They concluded that patients from different ethnic groups have different risks for adverse reactions to cardiovascular drugs and that ethnic group may be one determinant of harms of a given treatment, either because it acts as a surrogate measure …