tbuckley/cabot-search huggingface dataset:
Effect of the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin as Monotherapy on Glycemic Control in Patients With Type 2 Diabetes
Authors: Pablo Aschner, Mark S. Kipnes, Jared K. Lunceford, Matilde Sanchez, Carolyn Mickel, Debora E. Williams-Herman
Journal: Diabetes Care (2006)

To examine the efficacy and safety of once-daily oral sitagliptin as monotherapy in patients with type 2 diabetes.In a randomized, double-blind, placebo-controlled study, 741 patients (baseline HbA(1c) [A1C] 8.0%) were randomized to sitagliptin 100 or 200 mg or placebo for 24 weeks.Sitagliptin 100 and 200 mg produced significant (P < 0.001) placebo-subtracted reductions in A1C (-0.79 and -0.94%, respectively) and fasting plasma glucose (-1.0 mmol/l [-17.1 mg/dl] and -1.2 mmol/l [-21.3 mg/dl], respectively). Patients with baseline A1C >or=9% had greater reductions in placebo-subtracted A1C with sitagliptin 100 and 200 mg (-1.52 and -1.50%, respectively) than those with baseline A1C <8% (-0.57 and -0.65%) or >or=8 to <9.0% (-0.80 and -1.13%, respectively). In a meal tolerance test, sitagliptin 100 and 200 mg significantly decreased 2-h postprandial glucose (PPG) (placebo-subtracted PPG -2.6 mmol/l [-46.7 mg/dl] and -3.0 mmol/l [-54.1 mg/dl], respectively). Results for the above key efficacy parameters were not significantly different between sitagliptin doses. Homeostasis model assessment of beta-cell function and proinsulin-to-insulin ratio improved with sitagliptin. The incidence of hypoglycemia was similar, and overall gastrointestinal adverse experiences were slightly higher with sitagliptin. No meaningful body weight changes from baseline were observed with sitagliptin 100 (-0.2 kg) or 200 mg (-0.1 kg). The body weight change with placebo (-1.1 kg) was significantly (P < 0.01) different from that observed with sitagliptin.In this 24-week study, once-daily sitagliptin monotherapy improved glycemic control in the fasting and postprandial states, improved measures of beta-cell function, and was well tolerated in patients with type 2 diabetes.
[78] COMPARISON BETWEEN HEPATIC VENOUS PRESSURE GRADIENT (HVPG) AND LIVER STIFFNESS MEASUREMENT (LSM) IN PATIENTS WITH HCV-RELATED FIBROSIS/CIRRHOSIS
Authors: F. Vizzutti, U. Arena, R.G. Romanelli, L. Rega, A. Petrarca, S. Moscarella, F. Marra, G. Laffi, M. Pinzani
Journal: Journal of Hepatology (2007)
Scintigraphic Appearance of Primary Skeletal Leiomyosarcoma
Authors: DENNIS W. WULFECK, NOLAN K. SAKOW, TERRY E. WILLIAMS
Journal: Clinical Nuclear Medicine (1994)

Primary leiomyosarcoma of the bone is an extremely rare entity. Few case reports exist in the literature on this aggressive skeletal neoplasm. To our knowledge, threephase bone scan findings have not been reported.
Intestinal assimilation of a proline-containing tetrapeptide. Role of a brush border membrane postproline dipeptidyl aminopeptidase IV.
Authors: A Morita, Y C Chung, H J Freeman, R H Erickson, M H Sleisenger, Y S Kim
Journal: Journal of Clinical Investigation (1983)

The mechanism of hydrolysis and absorption of a proline-containing tetrapeptide, Leu-Pro-Gly-Gly (10 mM) by rat intestine was examined in vivo by using jejunal perfusion methods. The peptide substrate and hydrolysis products were analyzed by use of an automated amino acid analyzer. Leucine, proline, and glycine were absorbed by the intestine at a significantly higher rate from the tetrapeptide than from an equivalent amino acid mixture. The analysis of the hydrolytic products in the lumen during in vivo perfusion of the tetrapeptide showed that two dipeptides, Leu-Pro and Gly-Gly, were the major products. These two dipeptides were also the major hydrolytic products when a purified rat intestinal brush border membrane preparation was incubated with Leu-Pro-Gly-Gly. The rate of hydrolysis of the tetrapeptide was much higher than that for several other proline-containing peptides (Leu-Pro, Pro-Leu, and Pro-Gly-Gly) that were tested. Studies using Gly-Pro-beta-naphthylamide, a specific substrate for postproline dipeptidyl aminopeptidase IV, showed that this enzyme is mainly localized to the brush border membrane and is responsible for the hydrolysis of the tetrapeptide into the two dipeptides Leu-Pro and Gly-Gly. Thus, brush border membrane dipeptidyl aminopeptidase IV very likely plays an important role at the intestinal mucosal cell surface in the final stages of digestion of proline-containing peptides.
Chemicals and cancer in humans: first evidence in experimental animals.
Authors: J Huff
Journal: Environmental Health Perspectives (1993)

Certain human diseases have been traced to exposure to environmental and occupational chemicals. In many instances the first evidence of potential adverse effects came from experimental studies and were subsequently discovered in humans. Associations of human cancers, as a diverse group of diseases, and chemicals have been made since the middle 1700s. Since then, nearly 100 chemicals, mixtures of chemicals, or exposure circumstances are now recognized as being or strongly implicated as being carcinogenic to humans. Of the less than 1000 agents evaluated adequately for carcinogenicity in laboratory animals, a varying spectrum of data from studies on humans are available for only about 20-25%. So far, more than 60 agents are linked unequivocally as causing cancer in humans, and another 50 or so are strongly suspected of being carcinogenic to humans. Not all of these have been or can be evaluated in animals because some are industrial processes or
Bone Marrow Transplantation in Sickle Cell Anemia — The Dilemma of Choice
Authors: Orah S. Platt, Eva C. Guinan
Journal: New England Journal of Medicine (1996)

The clinical complications of sickle cell anemia reflect the vascular damage caused by the abnormal red cells. Filled with hemoglobin S, sickle red cells obstruct and injure vessels when the abnormal hemoglobin polymerizes, is denatured, and releases toxic oxidants. The process insidiously affects vulnerable vascular beds in the spleen, brain, lung, kidney, eye, and heart. Except for the spleen and brain, where the complications may have a developmental component and arise in childhood, the compromise of most organs takes decades to develop. About 20 percent of deaths in sickle cell anemia occur in patients with chronic organ failure. The distressing, . . .
DNA Synthesis in Alveolar Macrophages and Other Changes in Lavaged Cells Following Exposure of CBA/H Mice to Cigarette Smoke
Authors: Simon B. Hornby, Jeremy P. Kellington
Journal: Environmental Health Perspectives (1990)

Traditional methods to determine the proportion of cells in S-phase use radiolabeled precursors of DNA, such as 3H-thymidine, which become incorporated into DNA during its synthesis and are visualized either in tissue sections or in cell preparations by autoradiography. At the Harwell Laboratory the effects of inhaled alpha-emitting actinides on the pulmonary alveolar macrophage population of the rodent lung are being studied. For this research the use of an autoradiographic technique to determine the proportion of cells in S-phase is inappropriate, because of the possible presence of competing sources of radioactivity in the cells under investigation. Consequently, an alternative method has been developed. In this method, 5-bromodeoxyuridine (BrdU), an analogue of thymidine, is incorporated into cells undergoing DNA synthesis. Fluorescein-conjugated monoclonal antibodies, highly specific for BrdU substituted DNA, are available commercially and may be used as a probe for BrdU-labeled cells. This technique for identifying cells in S-phase has been described previously for the flow cytometric analysis of cell suspensions and for cells in tissue sections. An adaptation of this technique for use on cytocentrifuge preparations of cells recovered from mouse lung by bronchoalveolar lavage has been developed and its use is described. Some preliminary results of a short-term experiment with CBA/H mice to determine the effects of exposure to cigarette smoke on the DNA synthesis of alveolar macrophages are also included.
A robust prediction model for all forms of acute coronary syndromes: Estimating the risk of in-hospital death and myocardial infarction in the global registry of acute coronary events registry
Authors: Kim A. Eagle, Michael J. Lim, Andrzej Budaj, Omar H. Dabbous, Karen Pieper, Shaun G. Goodman, Christopher B. Granger, Philippe Gabriel Steg, Joel M. Gore, Keith A. Fox
Journal: Journal of the American College of Cardiology (2003)
Subtractive Transcriptomics: Establishing Polarity Drives <i>In vitro</i> Human Endothelial Morphogenesis
Authors: David A. Glesne, Wen Zhang, Suneeta Mandava, Lyann Ursos, Margaret E. Buell, Lee Makowski, Diane J. Rodi
Journal: Cancer Research (2006)

Abstract Although investigations of mature normal and tumor-derived capillaries have resulted in characterization of these structures at the phenotypic level, less is known regarding the initial molecular cues for cellular assembly of endothelial cells into human capillaries. Here, we employ a novel combination of microenvironmental manipulation and microarray data filtration over narrowly delineated temporal data series to identify the morphogenesis component apart from the proliferation component, as pooled human microvascular-derived endothelial cells are induced to form capillary-like structures in vitro in a murine tumor-derived matrix. The 217 morphogenesis-specific genes identified using this subtractive transcriptomics approach are mostly independent of the angiogenic proteins currently used as therapeutic targets for aberrant angiogenesis. Quantitative real-time PCR was used to validate 20% of these transcripts. Immunofluorescent analysis of proliferating and tube-forming cells validates at the protein level the morphogenesis-specific expression pattern of 16 of the 217 gene products identified. The transcripts that are selectively up-regulated in tube-forming endothelial cells reveal a temporal expression pattern of genes primarily associated with intracellular trafficking, guided migration, cytoskeletal reorganization, cellular adhesion, and proliferation inhibition. These data show that a sequential up-regulation of genes that establish and maintain polarity occurs during migration and morphogenesis of in vitro human endothelial cells undergoing tubulogenesis; some of which may well be effective as novel antiangiogenic drug targets. (Cancer Res 2006; 66(8): 4030-40)
Mycophenolate mofetil as a systemic antipsoriatic agent: positive experience in 11 patients
Authors: C.C. Geilen, M. Arnold, C.E. Orfanos
Journal: British Journal of Dermatology (2001)

Journal Article Mycophenolate mofetil as a systemic antipsoriatic agent: positive experience in 11 patients Get access C.C. Geilen, C.C. Geilen Department of Dermatology, University Medical Center Benjamin Franklin, The Free University of Berlin, Fabeckstr. 60–62, D‐14195 Berlin‐Dahlem, Germany Christoph C.Geilen. E‐mail: ccgeilen@zedat.fu‐berlin.de Search for other works by this author on: Oxford Academic Google Scholar M. Arnold, M. Arnold Department of Dermatology, University Medical Center Benjamin Franklin, The Free University of Berlin, Fabeckstr. 60–62, D‐14195 Berlin‐Dahlem, Germany Search for other works by this author on: Oxford Academic Google Scholar C.E. Orfanos C.E. Orfanos Department of Dermatology, University Medical Center Benjamin Franklin, The Free University of Berlin, Fabeckstr. 60–62, D‐14195 Berlin‐Dahlem, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 144, Issue 3, 1 March 2001, Pages 583–586, https://doi.org/10.1046/j.1365-2133.2001.04088.x Published: 01 March 2001
Pyrimethamine in the Treatment of Polycythaemia Rubra Vera
Authors: D. E. Pegg, H. T. Ford
Journal: BMJ (1961)

Polycythaemia rubra vera has been treated by vene- section, haemolytic drugs, irradiation, and occasionally by alkylating agents.Irradiation by means of injected radiophosphorus (32p) is probably the most widely used treatment at the moment.The introduction of chemical inhibitors of nucleic-acid synthesis has provided yet another method of suppressing the hyperactive erythron in this disease.This paper describes our experience of one such drug-pyrimethamine.Hitchings et al. (1948) showed that many aminopyrimidines inhibit the growth of Lactobacillus casei by preventing the utilization of folic acid.The discovery of the association between antimalarial action and folic- acid antagonism in the case of proguanil (Falco et al., 1949) led to the investigation of the aminopyrimidines as possible antimalarial agents.The most active amino- pyrimidine was found to be 2-4-diamino-5(4-chlorophenyl)-6-ethylpyrimidine (Falco et al., 1951).This drug was called " daraprim and has received the official narne of pyrimethamine.NHC N Cl O 6: NH2C2H5 NPyrimethamine has proved to be a valuable agent in malarial prophylaxis (Vincke and Lips, 1952), and when combined with sulphadiazine is effective against toxo- plasmosis (Frenkel and Hitchings, 1957).Hamilton et al., (1952) reported that the administration of diaminopyrimidines of this type to rats and dogs produced a megaloblastic anaemia with leucopenia.A detailed study of the pharmacology of pyrimethamine was reported by Schmidt et al. (1953), who found that the compound was extremely toxic in high doses, but their data indicated that erythropoietic depression might be obtained at doses low enough to avoid serious effects on other systems.Isaacs (1954) was the first to report the use of pyrimethamine in the treatment of polycythaemia rubra vera.He produced depression of the red-cell count without leucopenia or thrombocytopenia in six patients receiving 12.5-25 mg.daily.A time lag of two to three weeks in the response of the red-cell count was noted.Subjective and objective improvement was obtained in all cases.Frost and Jones (1954) recorded the treatment of six patients receiving 15-25 mg. a day.Satisfactory clinical and haematological remissions occurred in all cases, and side-effects were not reported.Wasserman (1955), however, condemned the use of pyrimethamine in the management of polycythaemia.He found the response to be slow, unpredictable, and unsatisfactory in at least 80% of cases, while side-effects were prominent and troublesome.Leucopenia, thrombocytopenia, petechial and gastro-intestinal haemorrhage, nausea and vomiting, buccal ulceration, and bone-marrow aplasia were all reported. Materials and MethodsThis series consists of five patients presenting consecutively with polycythaemia rubra vera in relapse.Four had previously been treated with 32p.One patient
Chronic oral ascorbic acid therapy worsens skeletal muscle metabolism in patients with chronic heart failure
Authors: Angus K. Nightingale, Jenifer G. Crilley, Nicholas C. Pegge, Ernie A. Boehm, Catherine Mumford, Doris J. Taylor, Peter Styles, Kieran Clarke, Michael P. Frenneaux
Journal: European Journal of Heart Failure (2006)
Taking the Tick Out
Authors: Walter C. Alvarez
Journal: JAMA (1965)

<h3>To the Editor:—</h3> In the Sept 14, 1964, issue (QUESTIONS AND ANSWERS,<i>JAMA</i><b>189</b>:876) you had a question about the removal of a tick from the ear. Years ago, I practiced in ranch country, and every so often someone who slept with dogs would come into the office with a tick in his ear. I found that the best way of getting it out was to put a drop of chloroform on it. Then the tick either backed right out or it let go, and then could be lifted out with ease. Similarly, I would occasionally see an epileptic boy who, after falling down, would lie unconscious for awhile. A fly would get into his nose and soon he would be in a terrible situation with dozens of screw-like maggots eating into the tissues of his nose. Again I found it easy to lift the maggots out after putting
Characterization of a new subpopulation of mouse CD8α+ B220+ dendritic cells endowed with type 1 interferon production capacity and tolerogenic potential
Authors: Pilar Martı́n, Gloria Martı́nez del Hoyo, Fabienne Anjuère, Cristina Fernández Arias, Héctor Hernández Vargas, Africa Fernández-L, Verónica Parrillas, Carlos Ardavı́n
Journal: Blood (2002)
Increased Plasminogen Activator (Urokinase) in Tissue Culture After Fibrin Deposition
Authors: Maria B. Bernik
Journal: Journal of Clinical Investigation (1973)

Lysis of fibrin in tissue culture has been shown to be due to plasminogen activator identified immunologically as urokinase. The present study examines fibrinolytic events in culture, particularly mechanisms leading to increased urokinase levels and accelerated fibrinolysis. Deposition of fibrin on cells in culture was followed by a two- to six-fold increase in urokinase in the supernates and rapid disappearance of the fibrin. Investigation of factors that might be responsible for these events (including fibrin, fibrinogen, vasoactive stimuli, and the enzymes thrombin and plasmin) indicated that the enhanced urokinase yields were mediated through plasmin and thrombin. Study of the possible modes of action of thrombin and plasmin indicated that these enzymes are capable of acting on the cells themselves as well as on cell-produced material. The effect on cells was manifested by mitotic activity or, occasionally, cell injury and death. Although these effects influenced urokinase levels, enhanced yields were explained best by the action of enzymes on cellproduced material. Studies with plasmin and thrombin, and also trypsin, indicated that proteolytic enzymes may act in various ways-affect the stability of urokinase, interfere with inhibition of urokinase by naturally occurring inhibitor(s), and induce urokinase activity from inactive material. Plasma and thrombin appeared to act primarily through the latter mechanism. Inactive material, which gave rise to urokinase upon exposure to proteolytic enzymes and which may represent urokinase precursor, was found in cultures of kidney, lung, spleen, and thyroid. Urokinase in such inactive state appears to be readily accessible to activation by enzymes, particularly plasmin and thrombin, thus facilitating removal of fibrin and possibly also providing pathways to excessive fibrinolysis.
Component‐resolved diagnosis of vespid venom‐allergic individuals: phospholipases and antigen 5s are necessary to identify <i><scp>V</scp>espula</i> or <i><scp>P</scp>olistes</i> sensitization
Authors: R. I. Monsalve, A. Vega, L. Marqués, A. Miranda, J. Fernández, V. Soriano, S. Cruz, C. Domínguez‐Noche, L. Sánchez‐Morillas, M. Armisen‐Gil, R. Guspí, D. Barber
Journal: Allergy (2012)

Abstract Background Cross‐reactivity between hymenoptera species varies according to the different allergenic components of the venom. The true source of sensitization must therefore be established to ensure the efficacy of venom immunotherapy. Objective In the Mediterranean region, P olistes dominulus and V espula spp. are clinically relevant cohabitating wasps. A panel of major vespid venom allergens was used to investigate whether serum‐specific IgE ( sIgE ) could be used to distinguish sensitization to either vespid. Methods Fifty‐nine individuals with allergic reactions to vespid stings and positive I mmuno CAP and/or intradermal tests to vespid venoms were studied. sIgE against recombinant and natural venom components from each wasp species was determined using the ADVIA C entaur ® system. Results sIgE against recombinant antigen 5s sensitization to be detected in 52% of the patients tested (13/25). The sensitivity increased to 80% (20/25), when using natural antigen 5s, and to 100% with the complete panel of purified natural components, because the sIgE was positive to either the antigen 5s ( P ol d 5/ V es v 5) or to the phospholipases ( P ol d 1/ V es v 1) of the two vespids, or to both components at the same time. In 69% of cases, it was possible to define the most probable sensitizing insect, and in the rest, possible double sensitization could not be excluded. V espula hyaluronidase was shown to have no additional value as regards the specificity of the assay. Conclusions The major allergens of P . dominulus ’ and V espula vulgaris ’ venom, namely phoshpholipases and antigen 5s, are required to discriminate the probable sensitizing species in vespid‐allergic patients.
Three in four cancer patients with depression are not getting adequate treatment, studies find
Authors: M. Limb
Journal: BMJ (2014)

Major depression in patients with cancer is often “missed” or “overlooked” such that nearly three quarters are not receiving adequate treatment, research has found. Many of these patients would benefit from a new integrated treatment programme found to be “strikingly” more effective than current care at reducing depression and improving the quality of life, the researchers said.

The research findings were contained in three papers, funded by Cancer Research UK and the Scottish government and published simultaneously across three Lancet journals on 28 August (the Lancet, Lancet Psychiatry, and Lancet Oncology ).

One study analysed data from more than 21 000 patients attending cancer clinics in Scotland who had been screened for depression. The researchers said that it was the first report on the prevalence of depression in patients with cancer that was based on a large scale screening service involving rigorous interviews and expert cancer diagnoses.1 It found that major depression was most commonly diagnosed in patients with …
Van Gogh's Suicide
Authors: Ben A. Finkelstein
Journal: JAMA (1971)

<h3>To the Editor.—</h3> Several LETTERS were printed recently (<b>218</b>:595, 1971) repudiating the speculation by Maire in his article, "Van Gogh's Suicide" (<b>217</b>:938, 1971). Since Van Gogh's main problem has been neglected in these letters, your readers may be interested in the following. According to our present day knowledge, Van Gogh suffered from a particular type of epilepsy, most probably a temporal lobe epilepsy which produced at times schizophrenic-like episodes with hallucinations and depression. It is fair to assume that he cut his ear in order to get rid of the hallucinations which bothered him. All his life he was a person whom other people were watching, and about whom they said, "C'est un fou" ("He is crazy"). This was due to his temper, irritability, and exaggerated religiosity. His choice of the southern part of France was not to facilitate the sight of colors; as a matter of fact,