tbuckley/cabot-search huggingface dataset:
Cytokine-mediated regulation of chronic intestinal helminth infection.
Authors: K J Else, F D Finkelman, C R Maliszewski, R K Grencis
Journal: The Journal of Experimental Medicine (1994)

Most inbred strains of mouse infected with the intestinal nematode Trichuris muris are resistant to infection expelling the parasite before adult worms establish. However, a few susceptible strains exist that are incapable of worm expulsion and harbor chronic infections of mature adult worms. Analyses of in vitro cytokine production by cells from the draining lymph node (mesenteric lymph node) have indicated that expulsion phenotype is tightly correlated with the selective expansion of helper T cells (Th) of the Th1 or Th2 cell subset within the mesenteric lymph node, resulting in susceptibility and resistance to T. muris, respectively. We have now confirmed and extended our in vitro observations in a series of experiments involving the in vivo manipulation of host cytokine levels. Depletion of interferon (IFN)-gamma in normally susceptible mice resulted in expulsion of the parasite, representing the first evidence for a role for IFN-gamma in the establishment of chronic helminth infection. Blocking interleukin (IL)-4 function in normally resistant animals prevented the generation of a protective immune response allowing adult stages of the parasite to develop. Conversely the administration of IL-4 to a normally susceptible host facilitated expulsion and indeed enabled established adult worms to be expelled when administered late in infection. In all cases assessment of a variety of in vivo parameters indicative of a Th1- or Th2-type response (parasite-specific immunoglobulin (Ig) G2a and the parasite-specific IgG1, total IgE levels and intestinal mastocytosis, respectively) demonstrated that the in vivo modulation of a Th1- or Th2-specific cytokine allowed the reciprocal Th cell subset to expand and become dominant with dramatic consequences for worm expulsion.
P1-08-22: Treatment Patterns and Clinical Outcomes in Elderly Patients with HER2−Positive Metastatic Breast Cancer from the registHER Observational Study.
Authors: PA Kaufman, AM Brufsky, M Mayer, HS Rugo, D Tripathy, Yood M Ulcickas, S Feng, LI Wang, MG Brammer, DA Yardley
Journal: Cancer Research (2011)

Abstract Background: Data are lacking regarding treatment patterns and outcomes in elderly patients (pts) with HER2−positive (HER2+) metastatic breast cancer (MBC). Methods: registHER is a large, observational cohort of pts with HER2+ MBC diagnosed within 6 months of enrollment. Pts (N=1,001) were followed until death, disenrollment, or June 2009 (median follow-up 27 months). In these analyses, pts were stratified into three groups based on age at MBC diagnosis: younger (&amp;lt;65 years), older (65-74 years), elderly (≥75 years). For Progression Free Survival (PFS) and Overall Survival (OS) analyses of 1st-line trastuzumab (T) vs. no T, older and elderly pts were combined due to small number of events in elderly. Hierarchical multivariate analyses were adjusted for baseline characteristics and treatments. Results: ER/PR status was similar across age groups (Table 1). Elderly pts with HER2+ MBC had higher rates of underlying cardiovascular disease (CVD) than younger or older pts. In pts receiving T-based 1st-line treatment, elderly pts were less likely to receive chemotherapy (C), and more likely to receive T alone or combined with hormone therapy (HT). Central nervous system (CNS) events decreased with increasing age. In T-treated pts, incidence of left ventricular dysfunction (grade ≥3) was higher in elderly pts (3/63 [4.8%]) than in younger (21/746 [2.8%]) or older pts (2/134 [1.5%]). Across age groups, unadjusted median PFS (months) was significantly higher for pts treated with T in 1st-line than those who were not (&amp;lt;65 years T: 11.0; &amp;lt;65 years no T: 3.4; ≥65 years T: 11.7; ≥65 years no T: 4.8). In pts &amp;lt;65 years, unadjusted median OS (months) was significantly higher in T-treated pts; in pts ≥65 years, median OS was similar (&amp;lt;65 years T: 40.4, &amp;lt;65 years no T: 25.9; ≥65 years T: 31.2, ≥65 years no T: 28.5). In multivariate analyses, T in 1st-line was associated with significant improvement in PFS across age (Table 2). In OS, significant improvement was observed for pts &amp;lt;65 years; results were suggestive for pts ≥65 years. Conclusions: Elderly pts (≥75 years) with HER2+ MBC in registHER had higher rates of underlying CVD than younger counterparts and received less aggressive treatment, including less 1st-line T. These population-based, real-world data suggest improved PFS with T as 1st-line therapy across all age groups. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-08-22.
Impact of early perfusion status of the infarct-related artery on short-term mortality after thrombolysis for acute myocardial infarction: Retrospective analysis of four german multicenter studies
Authors: Albrecht Vogt, Rainer von Essen, Ulrich Tebbe, Werner Feuerer, Karl-Friedrich Appel, Karl-Ludwig Neuhaus
Journal: Journal of the American College of Cardiology (1993)
Substance P antagonist inhibits immediate and delayed type cutaneous hypersensitivity reactions
Authors: JOANNA WALLENGREN
Journal: British Journal of Dermatology (1991)

The role of substance P (SP) in allergic reactions of the skin was investigated. Spantide, a competitive inhibitor of SP, was injected intracutaneously into the volar aspect of the forearm prior to the following challenges: benzalkonium chloride (irritant delayed reaction), tuberculin (immunological delayed reaction), UVB irradiation, benzoic acid (non-immunological contact urticaria), different food allergens and latex (in patients with immunological contact urticaria). Only the immunological reactions of contact urticaria and the reaction to tuberculin were suppressed by the SP antagonist, indicating that SP is involved in their pathogenesis.
Ghostwriters: Not Always What They Appear
Authors: Lois DeBakey
Journal: JAMA (1995)

<h3>To the Editor.</h3> —We are concerned that the Editorial "Acknowledging Ghosts" in<i>JAMA</i>may be interpreted as a validation of ghostwriting.<sup>1</sup>A ghostwriter is "a person who writes for and gives credit of authorship to another person, who hires him to do so." By definition, the role of the person whose data the ghostwriter uses cannot be "author": "the original writer of a literary work." We see no place for ghostwriting or rewriting in medical manuscripts.<sup>2,3</sup>There is a clear distinction between minor editing and ghostwriting; the first involves inconsiderable changes, the second composing. The effort of the originator of the concept is largely cerebral, preferably novel and creative; the work of the ghostwriter and manuscript editor, like that of others with prescribed, remunerated duties, is largely derivative and technical. The statement that "<i>ghostwriters</i>and editors<i>who make important contributions but do not qualify for authorship</i>[italics ours]
Is your dosage really necessary? Antibiotic dosage in urinary infection.
Authors: D Greenwood, F O'Grady
Journal: BMJ (1977)

Dense cultures of bacteria were exposed to changing concentrations of beta-lactam antibiotics in an in-vitro model of the urinary bladder. The results suggest that uncomplicated urinary infection may respond to lower doses than are usually given without compromising the success of subsequent treatment in those cases in which such minimal treatment fails.
The Willing of Human Bodies for the Promotion of Anatomic Science —<i>Res Ipsa Loquitur</i>
Authors: Benjamin Spector
Journal: New England Journal of Medicine (1960)

THE purpose of the following remarks is to acquaint physicians with the important matter of the willing of bodies after death for the promotion of anatomic science.In my capacity as co-ordinator of anatomic material for Boston University School of Medicine, Harvard Medical School and Tufts University School of Medicine, I have received an ever increasing number of inquiries for information and for forms to be filled out.The primary source of material for the promotion of anatomic science used by the medical schools has been the unclaimed bodies from the institutions under the jurisdiction of the Massachusetts Department of . . .
ACTINOTHERAPY IN CUTANEOUS MEDICINE —A PRELIMINARY COMMUNICATION.
Authors: WILLIAM S. GOTTHEIL
Journal: JAMA (1901)

The employment of light as a therapeutic agent is no new thing in medicine. The best term to employ for the treatment in general is Phototherapy. The use of that especial form, the discovery of which has immortalized the name of Roentgen, is generally known as Radiotherapy. Actinotherapy seems to be the most suitable designation for the employment of the ordinary sun or arc light, or portions of their rays. It is to this latter that I desire to call attention. To go no further back than the time of General Pleasanton, most of us recollect the "blue glass craze" that swept over the land. Wonderful therapeutic results were attributed to its use; and isolated specimens of the blue glass panes that then appeared in so many windows may still be seen. But Pleasanton and his followers truly saw "as through a glass darkly"; their method was not only empirical,
Abstract 5518: A novel 1,3-bis(3,5-dichlorophenyl) urea compound ‘COH-SR4’ for targeting melanoma.
Authors: Lokesh Prasad Gowda Dalasanur Nagaprashantha, James Figarola, Jyotsana Singhal, David Horne, Richard Jove, Samuel Rahbar, Sanjay Awasthi, Sharad S Singhal
Journal: Cancer Research (2013)

Abstract The current clinical modalities in the management of malignant melanomas are met with limited response. The molecular events that regulate oncogenic transformation, invasive progression and resistance to therapy in melanomas are determined by an interplay between various complex signaling networks. In the context of evident demographic risk, limited response to current clinical interventions and molecular complexity of melanomas, novel candidate molecules capable of effectively inducing tumor inhibition along with targeting critical nodes of melanoma signaling assume translational significance. In this regard, we investigated the anti-cancer effects of a novel dichlorophenyl urea compound called SR4 in melanoma. The SR4 treatment decreased the survival and inhibited the clonogenic potential along with inducing apoptosis in vitro cultures of melanoma. SR4 treatments lead to inhibition of GST activity along with inducing G2/M phase cell cycle arrest. Oral administration of 4 mg/kg b.w. SR4 leads to effective inhibition of tumor burdens in both syngeneic and nude mouse models of melanoma. The SR4 treatment was well tolerated and no overt toxicity was observed. The histopathological examination of resected tumor sections reflected decreased blood vessels, decrease in the levels of angiogenesis marker, CD31, and proliferation marker, Ki67, along with an increase in pAMPK levels. Western blot analyses of resected tumor lysates revealed increased PARP cleavage, Bim, pAMPK along with decreased pAkt, vimentin, fibronectin, CDK4 and cyclin B1. Thus, SR4 represents a highly effective candidate for the further development of single agent and combinatorial therapies to effectively target aggressive and clinically resistant melanomas (Supported by NIH grant CA 77495). Citation Format: Lokesh Prasad Gowda Dalasanur Nagaprashantha, James Figarola, Jyotsana Singhal, David Horne, Richard Jove, Samuel Rahbar, Sanjay Awasthi, Sharad S Singhal. A novel 1,3-bis(3,5-dichlorophenyl) urea compound ‘COH-SR4’ for targeting melanoma. [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 5518. doi:10.1158/1538-7445.AM2013-5518
Scientists want more protection after government adviser is sacked
Authors: C. Dyer
Journal: BMJ (2009)

Scientists are calling on the UK government to agree a new statement of principles to protect the independence of its scientific advisers after the home secretary, Alan Johnson, sacked David Nutt as his chief adviser on drug misuse.

Mr Johnson told parliament that he had “lost confidence” in Professor Nutt, a leading expert on the relative risk of different drugs, after he publicly criticised the government’s decision to reclassify cannabis from class C to the more serious class B.

The sacking, and Mr Johnson’s assertion that Professor Nutt was “campaigning” for a change in government policy, caused a media furore, and the home secretary was forced to explain his actions to …
THE DIETETIC TREATMENT OF DIABETES MELLITUS.
Authors: MAX EINHORN
Journal: JAMA (1906)

In no disease does diet form a more important part of the treatment than in diabetes mellitus. As is well known, the nature of the disease consists in the fact that the organism is unable either entirely or nearly so to utilize the carbohydrate foods. We thus have to deal with a genuine anomaly of metabolism, and the main points of treatment will consist of a rational and appropriate diet so long as there is no specific remedy for this disease. As it is possible to live on meat and fat alone without carbohydrates, it was natural to exclude this latter group of foodstuff from the diabetic diet. This was, indeed, done by the earliest observers who had knowledge of the nature of diabetes (Rollo, 1796), and this diet was adhered to with slight modifications until the present time. The following disadvantages are attached to a purely animal diet: It
Increased Levels of Oxidative Stress Indices and Lack of Antioxidant Respond Because of İschemia-Reperfusion Injury Associated with Occurrence of Atrial Fibrillation after Coronary Artery Bypass Surgery
Authors: Veysel Oktay, Onur Baydar, Ümit Yaşar Sinan, İsmail Polat Canbolat, Gürkan İmre, Okay Abacı, Cüneyt Kocaş, Zerrin Yiğit, Cenk Eray Yıldız, Alican Hatemi, Ayşem Kaya
Journal: Journal of the American College of Cardiology (2013)
Role of nicotinamide adenine dinucleotide and adenosine triphosphate in glucocorticoid-induced cytotoxicity in susceptible lymphoid cells.
Authors: N A Berger, S J Berger, D C Sudar, C W Distelhorst
Journal: Journal of Clinical Investigation (1987)

The possibility that corticosteroid cytotoxicity could be mediated by activation of poly(ADP-ribose) polymerase and consequent depletion of NAD and ATP was evaluated in steroid-sensitive S49.1 and steroid-resistant S49.143R mouse lymphoma cells and in lymphocytes from a patient with chronic lymphocytic leukemia. All cell types were shown to have the enzyme poly(ADP-ribose) polymerase and to increase activity in response to DNA strand breaks. Incubation of susceptible cells with 1 microM dexamethasone resulted in DNA strand breaks. Susceptible cells also showed a dose-dependent decrease in NAD and ATP that preceded loss of cell viability. These studies suggest that steroid-induced cytotoxicity in susceptible lymphocytes is due to the presence of DNA strand breaks that activate poly(ADP-ribose) polymerase to a sufficient degree to consume cellular pools of NAD with a consequent depletion of ATP and loss of cell viability.
FRI0594-HPR Two Different Sets of Handexercises Improved Grip Strength after Eight Weeks in Patients with Arthritis: Table 1.
Authors: S. Brorsson, C. Thorstensson, A. Nilsdotter, A. Bremander
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Hand function measured as grip force and finger extension force is often impaired in patients with rheumatoid arthritis (RA) and hand osteoarthritis (HOA) affecting performance of daily activities why hand exercises are recommended. A number of hand exercises are often used in the clinic but there is little information about “the effects of a minimal set of hand exercises” and if the choice of exercises is important to improve strength and function in the hand. <h3>Objectives</h3> To study the effect on grip- and finger extension strength and patient reported hand function from two different sets of handexercises performed over 8 weeks using a randomized study design. <h3>Methods</h3> Female patients with arthritis (RA and HOA, n=121) were randomly assigned to two different sets of handexercises (HE) for 8 weeks. The four hand exercises applied in the program were exercises commonly used in traditional hand training programs. The exercises were split into two groups depending on if the muscle activation (measured with EMG) were greater in forearm flexor (HE I, n=62) or in extensor muscles (HE II, n=59) (REF). HE I: isolated finger opposition (digits II-V) and rolling the putty with a flat hand, HE II: squeezing the putty and finger extension with putty resistance. The two HE were performed daily and each set was repeated 15 times, training time per day was maximum 5 minutes 7 days/week. Grip strength was measured with Grippit and finger extension strength with EX-it both validated instruments (unit: N). Pain was measured with a Visual Analogue Scale (VAS), 0-10 (best to worst). Hand functions were evaluated with the patient reported questionnaire Quick Disability Arm Shoulder and Hand (QuickDASH), 0-100 (best to worst). <h3>Results</h3> Mean grip strength (p=0.01) and mean finger extension force (p=0.004) increased after the training period in the group using HE I. In HE II the mean finger extension force increased (p=0.044), table 1. Hand function was stable over the training period. <h3>Conclusions</h3> Five daily minutes with two hand exercises resulted increased grip strength and finger extension force after eight weeks. We suggest that hand exercises should be combined and selected to improve both flexor and extensor muscle strength of the forearm. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4883
Gastrointestinal Stromal Tumor Detected on Tc-99m Red Blood Cell Scintigraphy
Authors: Anna A. Hansen, Ronald J. Rosenberg
Journal: Clinical Nuclear Medicine (2007)

A 72-year-old woman presented with several bouts of gastrointestinal bleeding and a hematocrit of 18. A radionuclide tagged RBC bleeding scan demonstrated active small bowel bleeding as well as a region of hyperemia medial to the right iliac vessels. Hyperemic bowel versus vascular mass was postulated. Mesenteric angiography confirmed a hypervascular mass in the right lower quadrant predominantly fed by an ileal branch of the superior mesenteric artery. The patient underwent laparoscopic small bowel resection and excision of a 5.5-cm tumor mass. The immunohistochemical profile, as well as the histologic features of the tumor, was consistent with gastrointestinal stromal tumor.
A Physicians' Wish List for the Clinical Application of Intestinal Metagenomics
Authors: Ingeborg Klymiuk, Christoph Högenauer, Bettina Halwachs, Gerhard G. Thallinger, W. Florian Fricke, Christoph Steininger
Journal: PLoS Medicine (2014)

Christoph Steininger and colleagues explore how multiple infectious, autoimmune, metabolic, and neoplastic diseases have been associated with changes in the intestinal microbiome, although a cause-effect relationship is often difficult to establish. Integration of metagenomics into clinical medicine is a challenge, and the authors highlight clinical approaches that are of high priority for the useful medical application of metagenomics. Please see later in the article for the Editors' Summary.
REPORT OF AN EPIDEMIC OF TYPHOID FEVER AND THE USE OF THE WOODBRIDGE TREATMENT.
Authors: JOHN J. ORTON
Journal: JAMA (1896)

<h3>Gentlemen:</h3> —There is a rule in rhetoric which I think is called Pope's Rule: "In words, as fashion, the same rule will hold, Alike fantastic, if too new or old; Be not the first by whom the new are tried, Nor yet the last to lay the old aside." This is a good rule to follow in the use of medicine as well as words. Nearly every mail brings us one or more circulars, singing the praises of some new remedy and it would be difficult and unwise to test them all. Being naturally conservative, and remembering the teachings of one of the now deceased professors of my Alma Mater to avoid "journal practice," it was with doubt and hesitation that I began to treat typhoid fever by the "Woodbridge treatment." During September and October, our little village of about 250 inhabitants passed through one of the worst epidemics of
Towards treating lupus nephritis without oral steroids: a dream-come-true?
Authors: Frédéric A Houssiau, David Isenberg
Journal: Annals of the Rheumatic Diseases (2013)

The discovery in the late 1940s of the very potent anti-inflammatory and immunosuppressive properties of glucocorticoids (GC)1 has dramatically improved the prognosis of severe systemic lupus erythematosus (SLE), with survival rates increasing markedly from 50% at 3 years in 19532 to 92% at 10 years in recent series.3 In particular, intravenous pulse methylprednisolone (MP) therapy, introduced as treatment for severe lupus manifestations in the 1970s,4 displays remarkable and prompt beneficial effects in acutely ill SLE patients suffering from renal impairment, central nervous system disease, arthritis, pleuropericarditis, fever or severe thrombocytopenia.5 ,6 Unfortunately, many patients, especially those taking >7.5 mg per day for long periods, experience the serious consequences of GC therapy, such as, increased risk of infection, avascular osteonecrosis, osteoporosis, myopathy, diabetes mellitus or Cushingoid features, as well as skin bruising and cataracts. Most of these side effects impact upon a patient's body image, being a huge source of emotional distress in young (sometimes teenaged) female patients, who are the principle victims of SLE.

Several longitudinal studies performed in SLE patients have revealed that GCs are the main cause of damage, as determined by the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) damage index (DI).7 Thus, the mean DI rose from 0.33 at baseline to 1.9 after 15 years of follow-up in an inception cohort, and damage was considered as …
Metabolic Effect of Phenylbutazone in Gouty and Non-Gouty Arthritis
Authors: E. R. Huffman, G. M. Wilson, C. J. Smyth, R. Hill
Journal: Annals of the Rheumatic Diseases (1954)

It is a synthetic pyrazol derivative, with the chemical designation 3,5-dioxo-1,2-diphenyl-4-nbutylpyrazolidine.In this clinic, 21 patients with 29 acute episodes of gouty arthritis have been treated with oral doses of 100 or 200 mg.phenylbutazone 4-hrly.In every instance all joint discomfort was controlled within 24 to 48 hrs and most of the attacks were aborted in 8 to 12 hrs.Although phenylbutazone has been shown to be an effective therapeutic agent in gouty arthritis, and its effectiveness has been associated with a fall in the serum level of urate, there has been disagreement regarding the explanation for this phenomenon.Kuzell and others (1952, 1954) and Kidd and others (1953) have reported that the drug has no effect on the excretion of urate.Johnson and others (1954) studied two patients under therapy for periods of 4 days and noted a fall in the serum urate concen- tration with a reduction in the urine urate.Mason (1954) reported that phenylbutazone had a uricosuric effect in three out of four cases of gout and in one subject with Paget's disease of the bone.In our experience, phenylbutazone causes an increase in urate excretion.The observations which form the basis for this report are in agreement with those of Yu, Sirota, and Gutman (1953), who demonstrated a definite increase in the renal clearance of urate in gouty subjects during short-term infusion experi-