tbuckley/cabot-search huggingface dataset:
Treatment of Psychoneurosis
Authors: W. L. Milligan
Journal: BMJ (1951)

During the past few years the production of abreaction by drugs or gases has taken a place in recognized psychi- atric therapy.Sargant and Slater (1940) and Sargant (1942) have described the use of intravenous barbit- urates; Palmer (1944) the use of ether; Rogerson (1944) the use of nitrous oxide; and Simon and Taube (1946) intravenous "methedrine" (methylamphetamine hydro- chloride).Meduna (1947) reported successful abre- actions following inhalation of 30% carbon dioxide and 70% oxygen.None of these methods are completely free from danger, and some are decidedly unpleasant for the patient.High concentrations of carbon dioxide can produce an irreversible failure of the respiratory centre, and in this respect Meduna's method would appear to be fraught with danger.It occurred to me
Towards an individualised target concentration of adalimumab in rheumatoid arthritis
Authors: Emilie Ducourau, David Ternant, Thierry Lequerré, Piéra Fuzibet, Xavier Le Loët, Hervé Watier, Philippe Goupille, Gilles Paintaud, Olivier Vittecoq, Denis Mulleman
Journal: Annals of the Rheumatic Diseases (2014)

Adalimumab, an anti-TNF-α monoclonal antibody, is effective in active rheumatoid arthritis (RA), but the response is highly variable between patients. Good responders have significantly higher adalimumab serum concentrations than non-responders.1 In a recent issue of the Annals , Pouw et al 2 have proposed a therapeutic cut-off concentration for adalimumab that is predictive of clinical response at a population level but, as for other TNF-α antagonists, no individualised target concentration has been defined to adjust the dose in RA.3

In a post hoc analysis we measured adalimumab concentrations in 127 samples from 30 patients with RA who received 40 mg adalimumab subcutaneously every other week.4 Concomitantly to blood sampling, disease activity score in 28 joints (DAS28) was recorded at baseline and at 6 weeks, 12 weeks, 24 weeks and 52 weeks after treatment initiation. Then, we studied the relationship between adalimumab concentration and DAS28 with a direct Emax inhibition pharmacokinetic-pharmacodynamic model, using Monolix V.3.1 (INRIA, Saclay, France). Emax models are often used to describe the concentration-response relationship, where the ‘quantity’ of response is monotonically related to drug concentration.5 With such a model, the relationship reaches an asymptote for high adalimumab concentrations when DAS28 reaches its minimal value. Estimated baseline DAS28 and adalimumab IC50, that is, adalimumab concentration leading to 50% decrease of baseline DAS28, were 5.7 (coefficient of variation=10%) and 11.8 mg/L (coefficient of variation=75%), respectively. Therefore, for a patient with a median baseline DAS28=5.7, with an adalimumab concentration of 11.8 mg/L, the baseline DAS28 would be decreased twofold (figure 1). The adalimumab target concentration necessary to achieve a …
Effect of Thiazide Diuretics on Plasma Volume, Body Electrolytes, and Excretion of Aldosterone in Hypertension
Authors: RAY W. GIFFORD, VERNON R. MATTOX, ALAN L. ORVIS, DONALD A. SONES, JOHN W. ROSEVEAR
Journal: Circulation (1961)

A study has been made at the Mayo Clinic of the results of treatment in 28 hypertensive patients receiving thiazide diuretics. The use of these agents produced a significant but very temporary reduction in plasma volume in most patients. The plasma volume reverted to or toward normal after the first week of treatment; therefore, hypovolemia could not explain the prolonged hypotensive effect of these drugs. Administration of thiazide diuretics did not deplete the body of its sodium stores, as measured by isotope studies in five patients on an unrestricted diet. Therapy with thiazides did not produce a persistent increase in urinary aldosterone excretion in the nine patients studied for this possibility.
Pulmonary infiltrates in Costello Syndrome
Authors: N. Waldburg, F. Buehling, M. Evert, O. Burkhardt, T. Welte
Journal: European Respiratory Journal (2004)

This paper reports on a patient with diffuse pulmonary infiltrates directly related to Costello Syndrome. This congenital disorder is characterised by multiple congenital abnormalities, such as psychomotor retardation, short stature, redundant skin, papillomata, curly hair, relative macroencephaly, distinctive face and various defects of internal organs. This study is the first to document the histopathological findings in the lungs. Most conspicuous was the depositing of abnormal collagen and elastic fibres and the development of endogenous lipid pneumonia.
Relationship of small bowel motility to ileoanal reservoir function.
Authors: J S Groom, M A Kamm, R J Nicholls
Journal: Gut (1994)

Some patients with an ileoanal reservoir have a high defecation frequency, despite a good anatomical result and the absence of pouchitis. This study aimed to determine whether variation in function is related to a difference in small bowel motility proximal to the reservoir and if small bowel motility is propagated into the reservoir. Ambulatory small bowel and reservoir motility was studied for 24 hours in five patients with good function (median bowel frequency 4 per day, range 3-6) and seven subjects with poor function (median bowel frequency 12 per day, range 10-20). Five solid state pressure sensors were positioned in the small bowel and one in the reservoir. During the fasting nocturnal period (2300-0800 h), patients with poor function had a median of 10 (range 5-13) migrating motor complexes (MMC), significantly greater (p = 0.03) than the corresponding median number of 3 (range 2-7) in patients with good function. A total of 120 MMCs were observed in the whole series of 12 patients. Of these only two were propagated from the small bowel into the reservoir. Discrete clustered contractions were not propagated into the reservoir, although prolonged propagated contractions did pass into the reservoir in one patient. Patients with poor function had similar 24 hour stool output and radiological reservoir size to those with good function, but the median maximum tolerated volume on reservoir distension was 290 ml (range 160-450) for patients with poor function compared with 475 ml (range 460-550) for patients with good function (p = 0.005). Small bowel motility proximal to the reservoir bears an important relationship to pouch function and defecation frequency. Propagation of coordinated proximal small intestinal motility into the reservoir is rare.
Neutrophil induced oxidative injury of cardiac myocytes. A compartmented system requiring CD11b/CD18-ICAM-1 adherence.
Authors: M L Entman, K Youker, T Shoji, G Kukielka, S B Shappell, A A Taylor, C W Smith
Journal: Journal of Clinical Investigation (1992)

We have previously shown that cytokines and postischemic cardiac lymph induce expression of intercellular adhesion molecule-1 (ICAM-1, CD54) on canine adult cardiac myocytes. ICAM-1 expression allows adherence of activated neutrophils to myocytes that is blocked by anti-CD18 mAb, R15.7, or anti-ICAM-1 mAb, CL18/6. Interleukin 1, tumor necrosis factor-alpha, or interleukin 6-stimulated cardiac myocytes were loaded with 2',7'-dichlorofluorescin, and oxidation to the fluorescent dichlorofluorescein was monitored. Fluorescence and neutrophil/myocyte adherence followed the same time course, and both were blocked by monoclonal antibodies to CD18, CD11b, and ICAM-1, but mAb R7.1, recognizing a functional epitope on CD11a, was not inhibitory. The iron chelator, desferroxamine, and the hydroxyl radical scavenger, dimethylthiourea, did not inhibit neutrophil adherence, but completely inhibited fluorescence. In contrast, the extracellular oxygen radical scavengers superoxide dismutase and catalase, and the extracellular iron chelator, starch-immobilized desferroxamine, did not affect either fluorescence or adherence. Under the experimental conditions used, no superoxide production could be detected in the extracellular medium. Fluorescence microscopy demonstrated that fluorescence began within 5 min after neutrophil adherence to an individual myocyte, and myocyte contracture followed rapidly. Fluorescent intensity was highest initially at the site of myocyte-neutrophil adherence. When only neutrophils were loaded with 2',7'-dichlorofluorescein, fluorescence was observed only in those neutrophils adhering to the cardiac myocytes. Thus, adherence dependent on Mac-1 (CD11b/CD18) and ICAM-1 (CD54) activates the neutrophil respiratory burst resulting in a highly compartmented iron-dependent myocyte oxidative injury.
Hydroxymethyl-Glutaryl Coenzyme A Reductase Inhibition Limits Cytomegalovirus Infection in Human Endothelial Cells
Authors: Luciano Potena, Giada Frascaroli, Francesco Grigioni, Tiziana Lazzarotto, Gaia Magnani, Luciana Tomasi, Fabio Coccolo, Liliana Gabrielli, Carlo Magelli, Maria P. Landini, Angelo Branzi
Journal: Circulation (2004)

Statins exert anti-inflammatory effects independently of cholesterol-lowering properties. Cytomegalovirus (CMV) infection appears to be implicated in the pathophysiology of atherosclerosis by inducing inflammatory modifications in endothelial cells, especially in immunosuppressed patients. We investigated whether the activity of statins can inhibit replication of CMV in human endothelial cells.Human umbilical vein endothelial cells (HUVECs) were infected with CMV and coincubated with fluvastatin at 0.1 and 0.2 micromol/L. Fluvastatin inhibited (P<0.001) CMV antigen expression, and this effect was dose related (P<0.001). Quantitative polymerase chain reaction showed that CMV DNA concentration was consistently lower in supernatants from fluvastatin-treated cells than in infected controls, and viral particle concentration was up to 30 times lower in 0.2 micromol/L fluvastatin-treated cells than in infected controls (10.5+/-0.9 versus 0.34+/-0.03 per 10(3) pfu/mL, P<0.001). Addition of mevalonate to treated cultures almost completely abolished fluvastatin inhibition of viral growth. Electrophoretic mobility shift assay showed that fluvastatin reduced nuclear factor-kappaB binding activity in CMV-infected cells.HMG-CoA inhibition by fluvastatin restrains CMV replication in HUVECs by inhibiting viral antigen expression, DNA synthesis, and viral particle production, conceivably by involving a reduction of nuclear factor-kappaB binding activity.
Intestinal permeability in Behcet's syndrome
Authors: I Fresko
Journal: Annals of the Rheumatic Diseases (2001)

OBJECTIVE To measure the intestinal permeability in patients with Behçet's syndrome (BS) and to compare the results with those obtained from healthy and diseased controls. METHOD The study group comprised 34 patients with BS without known gastrointestinal disease. Ten patients with ankylosing spondylitis (AS), 6 with inflammatory bowel diseases (IBD), 17 with systemic lupus erythematosus (SLE), and 15 healthy subjects (HC) constituted the controls. All patients received 100 μCi (3.7 MBq) of chromium-51 EDTA (51Cr-EDTA) as a radioactive tracer after a 72 hour abstinence from all drugs. The percentage of the isotope excreted in a 24 hour urinary specimen was the measure of permeability. RESULTS The percentage (SD) rate of excretion of 51Cr-EDTA was 4.6 (2.6) in BS, 6 (2.4) in AS, 5.2 (1.9) in IBD, 5.56 (1.78) in SLE, and 2.3 (1) in healthy controls. (Analysis of variance: f=6.4, p=0.0002. BS v HC, AS v HC, SLE v HC significant.) CONCLUSION The intestinal permeability in BS was significantly more than that seen among the healthy controls. Similar results in all the diseased controls cast doubt on its specificity.
Tackling the methylome: recent methodological advances in genome-wide methylation profiling
Authors: Marcos RH Estécio, Jean-Pierre J Issa
Journal: Genome Medicine (2009)

DNA methylation of promoter CpG islands is strongly associated with gene silencing and is known as a frequent cause of loss of expression of tumor suppressor genes, as well as other genes involved in tumor formation. DNA methylation of driver genes is very likely outnumbered by the number of methylated passenger genes, though these can be useful as tumor markers. Much of what is known about the importance of DNA methylation in cancer was gained through small- and moderate-scale analysis of gene promoters and tumor samples. A much better understanding of the role of DNA methylation in cancer, either as a marker of disease or as an active driver of tumorigenesis, will likely be gained from genome-wide studies of this modification in normal and malignant cells. This goal has become more attainable with the recent introduction of large-scale genome analysis methodologies and these have been modified to allow for investigation of DNA methylation. Several research groups have been formed to coordinate efforts and apply these methodologies to decipher the methylome of healthy and diseased tissues. In this article we review technological advances in genome-wide methylation profiling.
Influence of the thymus on the capacity of female mice to reject male skin grafts.
Authors: E S De Pirro, E H Goldberg
Journal: The Journal of Experimental Medicine (1989)

The ability of female mice to reject H-Y-incompatible, but otherwise histocompatible, male skin grafts differs greatly from strain to strain, as is illustrated particularly by the C57BL strain (B6 and other sublines), termed "H-Y rejector," because females invariably and promptly reject C57BL male skin, in comparison with the C3H strain, termed "H-Y nonrejector," because females characteristically accept male C3H skin. To assess the extent to which the thymus governs this rejector vs. nonrejector status, two studies were made. In the first, lethally irradiated B6 (C57BL) and C3H females were restored with (B6 X C3H)F1 female cells, providing a graft-vs.-host-free milieu for differentiation of the same immunopoietic cell population in B6 vs. C3H hosts. With respect to (B6 X C3H)F1 male skin grafts, B6 hosts responded as rejectors and C3H hosts as nonrejectors, signifying that rejector vs. nonrejector status was determined by the host during immunopoiesis. That the main organ responsible for rejector vs. nonrejector determination is the thymus was shown in a second study. Previously thymectomized (B6 X C3H)F1 females received a histocompatible graft of thymus from either B6 or C3H neonatal females and were restored with donor-marked (B6-Ly-5a X C3H)F1 female cells after lethal irradiation. With respect to (B6 X C3H)F1 male skin grafts, the recipients of B6 thymus grafts responded generally as rejectors and the recipients of C3H thymus grafts responded uniformly as nonrejectors.
Medroxyprogesterone acetate therapy in hirsutism
Authors: J.B. SCHMIDT, J. HUBER, J. SPONA
Journal: British Journal of Dermatology (1985)

In a pilot study, 26 hirsute females were treated with medroxyprogesterone acetate (MPA). We used an ointment containing 0.2% MPA in 13 patients, subcutaneous injection of MPA into the hairy areas of the face in five patients and intramuscular injection of low doses of MPA in 13 patients, each for an average duration of 16 weeks. The best clinical result was achieved by subcutaneous injection, the next most successful was the intramuscular injection, and the least successful was the topical application. Hair diameter measurements, carried out in 12 patients, were found to be reduced by 33% on average. Serum androgen levels, measured monthly, remained unaffected by topical treatment, but were decreased by intralesional and intramuscular injection. The clinical improvement with topical therapy despite the lack of effect on serum androgen levels supports the idea that MPA works partly at the cellular level. The intralesional and systemic injection of MPA may exert an effect both by systemic androgen suppression and a local action.
The incidence of HL-A antigens in dermatitis herpetiformis
Authors: A.G. WHITE, R.St C. BARNETSON, J.A.G. COSTA, D.B.L. McCLELLAND
Journal: British Journal of Dermatology (2006)

In dermatitis herpetiformis (DH) there are small intestinal abnormalities similar to those in adult coeliac disease (ACD) and there is evidence of other similarities between the two conditions, including immunological disturbances. Two reports of patients with ACD have shown a distinctive distribution of HL‐A phenotypes, with a high incidence of HL‐Ai and 8. A recent paper has described an increased incidence of HL‐A8 in DH. We report a similar study of patients with DH. Twenty‐one of thirty‐five patients had HL‐A8, an incidence of 60%, as compared to 33% of 175 controls. This difference is significant. The relationship of those patients with HL‐A8 to those with abnormal jejunal biopsies, and also to those with circulating auto‐antibodies, is discussed.
THE RELATION OF THE SPLEEN TO BLOOD DESTRUCTION AND REGENERATION AND TO HEMOLYTIC JAUNDICE
Authors: Richard M. Pearce, J. H. Austin, E. B. Krumbhaar
Journal: The Journal of Experimental Medicine (1912)

This investigation brings out three points. 1. During the first three or four weeks after splenectomy hemoglobinuria due to hemolytic serum was not followed by jaundice. 2. One month and more after splenectomy the red cells had an increased resistance to hemolysis. 3. Three and a half months after splenectomy and even later, jaundice occasionally occurred spontaneously. Attempts to explain these three phenomena have been based on the following possibilities: (1) that some function of the spleen is essential for the degradation of hemoglobin or for the elaboration of its derivatives; (2) that there is some interrelation between the spleen and the blood-forming organs or between the spleen and the blood-disintegrating mechanism, or perhaps both interrelations exist; (3) that there is a disturbance of the hemolyzing or bile-forming function of the liver dependent on the blood changes following splenectomy. This multiplicity of problems and likewise of possible explanations has rendered the presentation of the explanatory work in one communication extremely difficult. In the interests of clearness, therefore, the various phases are dealt with in separate papers.
Distinct types of lung disease caused by functional subsets of antiviral T cells.
Authors: W H Alwan, W J Kozlowska, P J Openshaw
Journal: The Journal of Experimental Medicine (1994)

T cells appear to play a central role in viral bronchiolitis, but the effects of different functional and phenotypic subgroups of T cells have not been defined. To test the activities of T cells recognizing individual proteins of respiratory syncytial (RS) virus, virus-specific T cell lines were produced from mice primed by scarification with recombinant vaccinia viruses expressing the major surface glycoprotein (G), fusion protein (F) or second matrix (22K) protein of RS virus. As previously reported, the in vitro characteristics of these cells are predetermined by the choice of RS virus protein: 22K-specific cells are predominantly class I-restricted cytolytic CD8+ cells; F-specific cells, a mixture of cytolytic CD8+ cells and CD4+ cells with a T helper 1 cell (Th1) cytokine secretion profile, whereas those from G-sensitized mice are almost exclusively CD4+, with Th2 characteristics. Mice infected intranasally with RS virus showed mild illness and recovered fully, but developed respiratory distress after intravenous injections of T cells. Dose-for-dose, infected mice receiving G-specific cells suffered the most severe (sometimes fatal) illness, characterized by lung hemorrhage, pulmonary neutrophil recruitment (shock lung) and intense pulmonary eosinophilia. This disease was further enhanced by coinjection of 22K-specific cells, which alone caused mild shock lung without eosinophilia. F-specific cells caused minimal enhancement of pathology and had little or no effect on the disease caused by G-specific cells. Each cell line reduced lung virus titer and combined injections of G- and 22K-specific cells eliminated infection completely. The in vitro characteristics of these antiviral T cell lines therefore predict the pathological effects in vivo. Moreover, different forms of viral bronchiolitis can be caused by functionally distinct types of activated T cell.
A COMMON FAMILIAL COMPONENT IN LUNG CANCER AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Authors: BerniceH. Cohen, CarolG. Graves, DavidA. Levy, Solbert Permutt, EarlL. Diamond, Paul Kreiss, HaroldA. Menkes, Shirley Quaskey, MelvynS. Tockman
Journal: The Lancet (1977)
Cancer Incidence After Radiotherapy for Skin Hemangioma: A Retrospective Cohort Study in Sweden
Authors: C. J. Furst, M. Lundell, L.-E. Holm, C. Silfversward
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Cancer Incidence After Radiotherapy for Skin Hemangioma: A Retrospective Cohort Study in Sweden Get access Carl Johan Fürst, Carl Johan Fürst 3Department of General Oncology (C.J. Frust) and Department of Cancer Prevention (L-E. Holm), Radiumhemmet, Karolinska HospitalS-104 01 Stockholm, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar Marie Lundell, Marie Lundell 4Department of Radiation Physics (M. Lundell) and Department of Tumor Pathology (C.Silfversward), Karolinska Hospital Search for other works by this author on: Oxford Academic PubMed Google Scholar Lars-Erik Holm, Lars-Erik Holm 3Department of General Oncology (C.J. Frust) and Department of Cancer Prevention (L-E. Holm), Radiumhemmet, Karolinska HospitalS-104 01 Stockholm, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar Claes Silfversward Claes Silfversward 4Department of Radiation Physics (M. Lundell) and Department of Tumor Pathology (C.Silfversward), Karolinska Hospital Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 17, 2 November 1988, Pages 1387–1392, https://doi.org/10.1093/jnci/80.17.1387 Published: 02 November 1988 Article history Received: 31 May 1988 Accepted: 29 August 1988 Published: 02 November 1988
Immunology and Immunotherapy of Head and Neck Cancer
Authors: Robert L. Ferris
Journal: Journal of Clinical Oncology (2015)

The immune system plays a key role in the development, establishment, and progression of head and neck squamous cell carcinoma (HNSCC). A greater understanding of the dysregulation and evasion of the immune system in the evolution and progression of HNSCC provides the basis for improved therapies and outcomes for patients. HNSCC cells evade the host immune system through manipulation of their own immunogenicity, production of immunosuppressive mediators, and promotion of immunomodulatory cell types. Through the tumor's influence on the microenvironment, the immune system can be exploited to promote metastasis, angiogenesis, and growth. This article provides a brief overview of key components of the immune infiltrating cells in the tumor microenvironment, reviewing immunological principles related to head and neck cancer, including the concept of cancer immunosurveillance and immune escape. Current immunotherapeutic strategies and emerging results from ongoing clinical trials are presented.
Reporting Recommendations for Tumor Marker Prognostic Studies
Authors: Lisa M. McShane, Douglas G. Altman, Willi Sauerbrei, Sheila E. Taube, Massimo Gion, Gary M. Clark
Journal: Journal of Clinical Oncology (2005)

Lisa M. McShane, Biometric Research Branch, National Cancer Institute, Bethesda, MD Douglas G. Altman, Medical Statistics Group, Cancer Research UK, Centre for Statistics in Medicine, Wolfson College, Oxford, UK Willi Sauerbrei, Institut fuer Medizinische Biometrie und Medizinische Informatik, Universitaetsklinikum Freiburg, Freiburg, Germany Sheila E. Taube, Cancer Diagonisis Program, National Cancer Institute, Bethesda, MD Massimo Gion, Centro Regionale Indicatori Biochimici di Tumore, Ospedale Civile, Venezia, Italy Gary M. Clark, OSI Pharmaceuticals Inc, Boulder, CO For the Statistics Subcommittee of the NCI-EORTC Working Group on Cancer Diagnostics