tbuckley/cabot-search huggingface dataset:
A2.5 Association study in portuguese patients with ankylosing spondylitis using the immunochip
Authors: F M Pimentel-Santos, Félicie Costantino, Adrian Cortes, Henri-Jean Garchon, Johanna Hadler, Maxime Breban, Matthew A Brown, Jaime C Branco
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Ankylosing spondylitis (AS), a common inflammatory arthritis affecting primarily the spine and pelvis, is a highly heritable disease. In addition to HLA-B*27, 25 loci were associated with AS in populations of European ancestry in a recent international collaborative study, using the "Immunochip". There is, however, well-known heterogeneity of allele frequencies across populations. We therefore re-examined this large dataset (10,619 patients and 15,145 controls) and focused on the Portuguese sample, asking whether alleles might be distinctly associated with AS in Portugal. <h3>Materials and Methods</h3> We extracted the data subset corresponding to 184 AS patients (according to the modified New York criteria) and 161 controls, all from mainland Portugal. Written informed consent was obtained from all subjects. Removal of outliers with Eigenstrat and quality control of genotyping data left 325 subjects (174 cases / 151 controls) genotyped with 119768 SNPs. Association analysis was performed using PLINK (v1.07). <h3>Results</h3> Apart from the MHC, there was no significant association at the genome-wide level (5 x 10<sup>-8</sup>). However, 14 SNPs in 12 loci were associated with a nominal P &lt; 1 x 10<sup>-4</sup>. The top-ranking SNP was in the inducible T-cell co-stimulator ligand (ICOSLG) gene (P = 7.56 x 10<sup>-7</sup>, OR = 5.014), previously associated in the whole consortium dataset. Other listed loci include USP34, an ubiquitin hydrolase that acts as regulator of the Wnt signalling pathway, CLEC16A, a member of the C-lectin type domain family, and several transcription factors or DNA-binding proteins. <h3>Conclusions</h3> Association of ICOSLG points to a potential alteration of the T-cell costimulation pathway in AS pathogenesis and warrants functional studies. Failure to replicate some of the loci associated in the whole consortium dataset likely results from our relatively small sample size. Conversely, new association findings will need confirmation in independent samples and may lead to population-specific genomic variants predisposing to AS.
More Informative Abstracts of Articles Describing Clinical Practice Guidelines
Authors: R. S. A. Hayward, M. C. Wilson, S. R. Tunis, E. B. Bass, H. R. Rubin, R. B. Haynes
Journal: Annals of Internal Medicine (1993)

Recommendations are proposed for preparing more informative abstracts of articles describing clinical practice guidelines. Information about the development and content of guidelines should be summarized with the following structure.a succinct statement of the objective of the guideline, including the targeted health problem, the targeted patients and providers, and the main reason for developing recommendations concerning this problem for this population.principal practice options that were considered in formulating the guideline.significant health and economic outcomes identified as potential consequences of the practice options.Methods used to gather, select, and synthesize evidence, and the date of the most recent evidence obtained.persons and methods used to assign values (relative importance) to potential outcomes of alternative practice options.the type and magnitude of the main benefits, harms, and costs that are expected to result from guideline implementation.a brief and specific list of key recommendations.the results of any external review, comparison with guidelines developed by other groups, or clinical testing of guideline use.key persons or groups that developed, funded, or endorsed the guideline. Abstracts adhering to these recommendations could enhance readers' ability to appraise the applicability, importance, and validity of guidelines for specific providers, patients, and settings. More informative abstracts could also promote the use of more explicit methods of guideline development, more consistent reporting of guideline documents, and the more appropriate use of guidelines by clinicians.
THE AUTOMATIC TISSUE FORCEPS.
Authors: EMANUEL J. SENN
Journal: JAMA (1895)

The automatic tissue forceps which I have devised, will be found to be an instrument of great utility in operative work and also one of precision. It is made of English steel, and consists of two blades which terminate in teeth. Midway between the extremities of the blades is the catch, which locks and unlocks automatically, synchronously with the grasp or release of tissues. The instrument is operated with the thumb and index finger of the left hand with the same ease as in the use of the ordinary tissue forceps. Pressure sufficient simply to pick up the tissues is all the force required to lock the blades. This is at a minimum, as the blades possess great elasticity and consequently accommodate themselves to the "bite" of tissue, whether large or small. To disengage the blades and release the grip, simply give them another gentle squeeze, when the catch unlocks.
Laparoscopic Cholecystectomy in a Patient with Empyema of the Gallbladder and Situs Inversus
Authors: P. Goh, Y. Tekant, N. S. Shang, S. S. Ngoi
Journal: Endoscopy (1992)

The successful performance of laparoscopic cholecystectomy in a patient with situs inversus viscerum and empyema of the gallbladder is reported. The 62-year-old man presented with pain in the left upper quadrant associated with fever, chills, nausea and vomiting. The abdomen was tender with guarding and a palpable globular mass in the same region. CT scan demonstrated a distended gallbladder with thick shaggy walls which contained a 2 cm gallstone in the neck and also revealed dextrocardia and situs inversus. The patient's postoperative recovery was uneventful.
SENESCENCE, SENILITY, AND ALZHEIMER'S DISEASE
Authors: NAOMI RASKIN, RUTH EHRENBERG
Journal: American Journal of Psychiatry (1956)

1. Two-hundred-seventy cases of patients, aged 60 to 97 years, were reviewed and observations recorded. 2. The largest number suffered from a chronic brain syndrome with arteriosclerotic brain disease. Typical arteriosclerotic vascular changes in small vessels were found in 57 patients and mixed arteriosclerotic and senile changes in 93 patients in this group. 3. Examination of patients with senile brain disease revealed the presence of brain atrophy not proportionate to the age of the patient or the duration of his illness; small to moderate numbers of senile plaques in all; mild to moderate arteriosclerotic changes of large vessels at the base of the brain in many; and a few Alzheimer's fibrillary changes in 4 patients. 4. Eighteen patients previously diagnosed as having arteriosclerotic or senile brain disease who showed typical clinical and neuropathological findings of Alzheimer's disease were so classified regardless of their advanced age and the late onset of the illness. 5. Of the 51 patients with psychoses of different etiology who grew old and died at the state hospital, 48 showed arteriosclerosis and senile changes of mild to moderate degree. Three with "functional" psychosis had apparently normal brains. 6. The degree of brain atrophy was not always indicative of the patient's mental deterioration. Some patients with greatly atrophied brains showed better compensatory mechanisms than others with less pronounced atrophy. 7. From these considerations it follows that 3 approaches are open now for the prevention and treatment of psychoses of old age: ultimate control of general arteriosclerosis, of which cerebral arteriosclerosis is a part; biochemical studies; and last, but not least, keeping old people motivated to use their remaining mental resources.
U.S. Food and Drug Administration perspective of the inclusion of effects of low-level exposures in safety and risk assessment.
Authors: D W Gaylor, P M Bolger, B A Schwetz
Journal: Environmental Health Perspectives (1998)

A brief overview is provided of some of the general safety and risk assessment procedures used by the different centers of the U.S. Food and Drug Administration (U.S. FDA) to evaluate low-level exposures. The U.S. FDA protects public health by regulating a wide variety of consumer products including foods, human and animal drugs, biologics, and medical devices under the federal Food, Drug, and Cosmetic Act. The diverse legal and regulatory standards in the act allow for the consideration of benefits for some products (e.g., drugs) but preclude them from others (e.g., food additives). When not precluded by statutory mandates (e.g., Delaney prohibition), the U.S. FDA considers both physiologic adaptive responses and beneficial effects. For the basic safety assessment paradigm as presently used, for example in the premarket approval of food additives, the emphasis is on the identification of adverse effects and no observed adverse effect level(s) (NOAEL). Generally, the NOAEL is divided by safety factors to establish an acceptable exposure level. This safety assessment paradigm does not preclude the consideration of effects whether they are biologically adaptive or beneficial at lower dose levels. The flexibility to consider issues such as mechanisms of action and adaptive and beneficial responses depends on the product under consideration. For carcinogenic contaminants and radiation from medical devices, the U.S. FDA considers the potential cancer risk at low exposure levels. This generally involves downward extrapolation from the observed dose-response range. The consideration of adverse effects of other toxicologic end points (e.g., reproductive, immunologic, neurologic, developmental) associated with low exposure levels is also becoming more of a reality (e.g., endocrine disrupters). The evaluation of the biologic effects of low-level exposures to toxic substances must include whether the effect is adverse or a normal physiologic adaptive response and also determine the resiliency of a physiologic system. The public health mandate of the U.S. FDA includes an active research program at the National Center for Toxicological Research and the other U.S. FDA centers to support the regulatory mission of the U.S. FDA. This includes the development of knowledge bases, predictive strategies, and toxicologic studies to investigate effects at the lower end of the dose-response range. Because of the wide diversity of legal and regulatory standards for various products regulated by the U.S. FDA agency-wide safety and risk assessment procedures and policies generally do not exist.
Paracrine signaling by glial cell–derived triiodothyronine activates neuronal gene expression in the rodent brain and human cells
Authors: Beatriz C.G. Freitas, Balázs Gereben, Melany Castillo, Imre Kalló, Anikó Zeöld, Péter Egri, Zsolt Liposits, Ann Marie Zavacki, Rui M.B. Maciel, Sungro Jo, Praful Singru, Edith Sanchez, Ronald M. Lechan, Antonio C. Bianco
Journal: Journal of Clinical Investigation (2010)

Hypothyroidism in humans is characterized by severe neurological consequences that are often irreversible, highlighting the critical role of thyroid hormone (TH) in the brain. Despite this, not much is known about the signaling pathways that control TH action in the brain. What is known is that the prohormone thyroxine (T4) is converted to the active hormone triiodothyronine (T3) by type 2 deiodinase (D2) and that this occurs in astrocytes, while TH receptors and type 3 deiodinase (D3), which inactivates T3, are found in adjacent neurons. Here, we modeled TH action in the brain using an in vitro coculture system of D2-expressing H4 human glioma cells and D3-expressing SK-N-AS human neuroblastoma cells. We found that glial cell D2 activity resulted in increased T3 production, which acted in a paracrine fashion to induce T3-responsive genes, including ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), in the cocultured neurons. D3 activity in the neurons modulated these effects. Furthermore, this paracrine pathway was regulated by signals such as hypoxia, hedgehog signaling, and LPS-induced inflammation, as evidenced both in the in vitro coculture system and in in vivo rat models of brain ischemia and mouse models of inflammation. This study therefore presents what we believe to be the first direct evidence for a paracrine loop linking glial D2 activity to TH receptors in neurons, thereby identifying deiodinases as potential control points for the regulation of TH signaling in the brain during health and disease.
Newcastle-On-Tyne Infirmary: Pleurisy with Effusion--Death--Absence of a Kidney
Authors: None Taylor
Journal: BMJ (1842)

There naturally arose, from the foregoing details, two topics of inquiry-viz., first, whether the symp- toms which have been described were occasioned by poison, and secondly, assuming poison to have been administered, what was it?These two questions were pretty fully discussed, and the members appeared to be unanimously of opinion that the symptoms were attributable to poison, and that arsenic most probably was the deleterious agent which had been admi- nistered.Mr. H.Jackson afterwards exhibited a singular gorget, which was invented some years ago by a very eccentric surgeon, who declared that by the use of this instrument the operation of lithotomy would be rendered "' safe, easy, and agreeable."It is not need- ful to describe the instrument, as it was never used even by the inventor.Mr. Jackson contrasted with it the ingenious gorget which was invented and always used by the late Mr. Stainforth, of Sheffield.
Abstract 3508: High antitumor activity of cetuximab combined with taxotere-cisplatin-flourouracil (TPF) association on an orthotopic head and neck cancer model
Authors: Alexandre Bozec, Anne Sudaka, Marie-Christine Etienne-Grimaldi, Jean-Louis Fischel, Gérard Alain Milano
Journal: Cancer Research (2011)

Abstract Background : Cetuximab (cetux), an anti-epidermal growth factor receptor (EGFR) monoclonal antibody is a standard of care in advanced head and neck (HN) cancer when combined with irradiation or cisplatin. The TPF association including taxotere (T), cisplatin (P) and fluorouracil (F) has become a chemotherapy of reference in the management of HN tumors. The aim of the study was to evaluate the antitumor activity of the association of cetux with TPF. In addition the potential benefit to add bevacizumab (beva), an anti-VEGF monoclonal antibody, was also examined. Methods : investigations were performed on CAL33 human head and neck cancer cell line (high content of EGFR) injected as an orthotopic xenograft into the mouth floor of nude mice. The anti-tumor efficacy of cetux 2,5 mg/kg, beva 20 mg/kg and of TPF at the MTD (T : 20 mg/kg, P : 6 mg/kg, and F : 17mg/kg) administered alone or in combination at day 3 and 10 after tumor cell injection was assessed at day 12 (animal sacrifice for ethical reasons, 10 animals per treatment group). Tumor volume, tumor histology, tumor cell proliferation (Ki67 by immunohistochemistry) and apoptosis (Bcl2 by immunohistochemistry) were examined. Statistical analyses were performed according to non-parametric methods. Results : As compared to controls, TPF-cetux and TPF-cetux-beva had a significant impact on tumor volume and histological response. The highest efficacy was observed with the combination TPF-cetux. The effects of the association TPF-cetux-beva were not significantly different than those observed with TPF-cetux. Data were corroborated by a diminution in Ki67 labelling and Bcl2 expression. Conclusion : the association of cetux with TPF could be an interesting clinical option to evaluate in advanced HN cancer patients. 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 3508. doi:10.1158/1538-7445.AM2011-3508
Safe blood? Saving lives costs money
Authors: P J Hamilton
Journal: BMJ (1994)

ation ensures that roughly equal numbers move into arms 1 and 2 and also removes the possible bias introduced by the doctor choosing subsequent treatment.Patients are also less likely to be lost to follow up.Mortality figures will be analysed on an intention to treat basis.'We will also be able to compare survival in patients in arm 1 with that in the subgroup of patients in arm 3 who continue to take bromocriptine or are redrawn to arm 1; this will compare the benefits of starting with levodopa versus starting with bromocriptine.In addition, we can use data for patients redrawn from arm 3 to increase the power of analysis of survival in arms 1 and 2.
Diffuse slow washout of myocardial thallium-201: A new scintigraphic indicator of extensive coronary artery disease
Authors: Timothy M. Bateman, Jamshid Maddahi, Richard J. Gray, Franklin L. Murphy, Ernest V. Garcia, Carolyn M. Conklin, Marjorie J. Raymond, Morgan E. Stewart, H.J.C. Swan, Daniel S. Berman
Journal: Journal of the American College of Cardiology (1984)
The Erythrocyte Sedimentation Rate in Congestive Heart Failure
Authors: Howard L. Haber, Jeffrey A. Leavy, Paul D. Kessler, Marrick L. Kukin, Stephen S. Gottlieb, Milton Packer
Journal: New England Journal of Medicine (1991)

Physicians have long believed that the erythrocyte sedimentation rate is low in patients with congestive heart failure, but this concept is based on a misinterpretation of the results in a single report published in 1936. To reevaluate this concept in the modern era, we measured the sedimentation rate in 242 patients who were referred for treatment of chronic heart failure.
Safety and Efficacy of a Recombinant Hepatitis E Vaccine
Authors: Mrigendra Prasad Shrestha, Robert McNair Scott, Durga Man Joshi, Mammen P. Mammen, Gyan Bahadur Thapa, Narbada Thapa, Khin Saw Aye Myint, Marc Fourneau, Robert A. Kuschner, Sanjaya Kumar Shrestha, Marie Pierre David, Jitvimol Seriwatana, David W. Vaughn, Assad Safary, Timothy P. Endy, Bruce L. Innis
Journal: New England Journal of Medicine (2007)

Hepatitis E virus (HEV) is an important cause of viral hepatitis. We evaluated the safety and efficacy of an HEV recombinant protein (rHEV) vaccine in a phase 2, randomized, double-blind, placebo-controlled trial.In Nepal, we studied 2000 healthy adults susceptible to HEV infection who were randomly assigned to receive three doses of either the rHEV vaccine or placebo at months 0, 1, and 6. Active (including hospital) surveillance was used to identify acute hepatitis and adverse events. The primary end point was the development of hepatitis E after three vaccine doses.A total of 1794 subjects (898 in the vaccine group and 896 in the placebo group) received three vaccine doses; the total vaccinated cohort was followed for a median of 804 days. After three vaccine doses, hepatitis E developed in 69 subjects, of whom 66 were in the placebo group. The vaccine efficacy was 95.5% (95% confidence interval [CI], 85.6 to 98.6). In an intention-to-treat analysis that included all 87 subjects in whom hepatitis E developed after the first vaccine dose, 9 subjects were in the vaccine group, with a vaccine efficacy of 88.5% (95% CI, 77.1 to 94.2). Among subjects in a subgroup randomly selected for analysis of injection-site findings and general symptoms (reactogenicity subgroup) during the 8-day period after the administration of any dose, the proportion of subjects with adverse events was similar in the two study groups, except that injection-site pain was increased in the vaccine group (P=0.03).In a high-risk population, the rHEV vaccine was effective in the prevention of hepatitis E. (ClinicalTrials.gov number, NCT00287469 [ClinicalTrials.gov].).
Payment for general practitioners in hospitals
Authors: P A Jones
Journal: BMJ (1980)

who continued treatment with tamoxifen alone did not have a response.We agree that tamoxifen-induced hyper- calcaemia probably is not uncommon, but as yet there is no firm evidence to support the suggestion that induced hypercalcaemia is indicative of a good response to tamoxifen or other additive hormones used in the treatment of breast cancer.
SALIVATION DUE TO INTRAVENOUS USE OF MERCUROCHROME
Authors: J. C. Bunten
Journal: JAMA (1924)

In a recent issue ofThe Journalthere was an article,<sup>1</sup>on the intravenous use of mercurochrome-220, soluble in septic cases. The reports were brilliant, but there was nothing said of any unpleasant effects from this form of treatment. I report two cases in which very pronounced salivation developed. <h3>Case 1.</h3> —E., a man, aged 21, entered the hospital in a critical condition, suffering with a bilateral lobar pneumonia. The temperature was 105 and he was delirious. We treated him several days without much change; as the fever remained high, we decided to give him some mercurochrome intravenously. The first dose was 10 c.c. of a 2 per cent. solution. In forty-eight hours this dose was repeated. Two days later the patient had a pronounced salivation, loose teeth, gums bleeding and pain. In about a week this condition cleared up. The patient recovered from the pneumonia, and developed an
Abstract 2245: The role of STAT3α in Pten-dependent hematopoietic malignancy
Authors: Tatsuaki Mizutani, Emilio Casanova, Dagmar Stoiber
Journal: Cancer Research (2012)

Abstract Dysregulation of the Janus kinase (Jak) - signal transducer and activator of transcription (Stat) signaling pathway is often associated with cancer. Persistent Stat3 activation has been described in many hematological malignancies. Two isoforms due to alternative splicing have been described for Stat3: Stat3α and Stat3α. Both isoforms exhibit overlapping but distinct biochemical properties. Interestingly, Stat3α has been found in the bone marrow of patients with acute myeloid leukemia (AML) and in several AML cell lines. The role of Stat3α in leukemia development remained elusive so far. To test for an impact of Stat3α in leukemia formation, transgenic mice overexpressing Stat3α have been generated. The expression of the transgene depends on Cre-recombinase activity therefore the mice were intercrossed with Mx-Cre transgenic animals, which enables activation of Cre recombinase in the hematopoietic compartment. This was verified by detection of the reporter protein eYFP in bone marrow cells upon treatment with poly I/C. The Stat3αtgMx-Cretg compound mice were further bred with Ptenfl/fl mice, since loss of Pten in hematopoietic stem cells of mice was reported to lead to myeloproliferative disorder (MPD) that later on progresses to an AML or ALL like disease. Upon poly I/C treatment Stat3αtgMx-CretgPtenfl/fl compound mice diseased with significantly enhanced latency when compared to Mx-CretgPtenfl/fl mice. Accordingly, 20 days after poly I/C injection Stat3αtgMx-CretgPtenfl/fl animals displayed also far less Mac1+Gr1+ myeloid cells than Mx-CretgPtenfl/fl mice. Taken together, our findings suggest that Stat3α acts as a tumor suppressor to prevent Pten dependent MPD/leukemia. 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 2245. doi:1538-7445.AM2012-2245