tbuckley/cabot-search huggingface dataset:
Platelets in rheumatoid arthritis: exploring the anti-inflammatory and antithrombotic potential of TNF inhibitors
Authors: Armen Yuri Gasparyan, George D Kitas
Journal: Annals of the Rheumatic Diseases (2016)

Manfredi et al 1 explore the relationship between tumour necrosis factor α (TNFα), TNFα inhibition and platelet activation in rheumatoid arthritis (RA). Using elegant systems they demonstrate that TNFα activates platelets and promotes their proinflammatory and procoagulant actions, while TNF inhibition (TNFi) prevents platelet activation. They suggest this is a potential mechanism explaining why TNFi associates with a reduction of cardiovascular (CV) events in patients with RA, as shown in some observational studies. Should we then be(come) interested in platelet biology in RA?

The potential role of platelets in the pathogenesis of RA and related comorbidities has, in fact, received much less attention than it deserves. Platelets are small (1–2 μm) anucleate cells that are intimately involved in thrombosis, angiogenesis, bone remodelling, inflammation and autoimmunity. Their bidirectional, damaging and protective roles across pathophysiological processes have been explored in several clinical and laboratory studies. The discovery of specific platelet markers and agonists, which target a range of membrane-bound receptors, has resulted in better understanding of their role. It is now clear that platelet reactivity throughout their short lifespan (8–10 days) is determined by megakaryopoiesis, which is regulated quantitatively by thrombopoietin; any chemical compound targeting the maturation of platelet precursors in the bone marrow either directly or indirectly can alter the thrombotic, immune and inflammatory potential of circulating platelets.2 ,3

Activated platelets shed highly active membranous structures—microparticles—and transform from disc-shaped to enlarged cells with pseudopods that facilitate their interaction with other platelets, neutrophils, lymphocytes and other immune cells. Circulating neutrophils, in turn, interact with activated platelets to boost their ‘thromboinflammatory’ potential.4 Circulating cellular complexes of platelets are often found in the blood stream of patients with inflammatory conditions, such as RA, and it is suggested that platelet-derived microparticles along with other biological agents play a more important role in the development …
Abstract POSTER-THER-1403: FZD7 drives aggressiveness in stem-A subtype of ovarian cancer via regulation of non-canonical Wnt/PCP pathway
Authors: Mohammad Asad, Wong Meng Kang, Tan Tuan Zea, Mahesh Choolani, Jeffery Low, Seiichi Mori, Jean Paul Thiery, Ruby Yun-Ju Huang
Journal: Clinical Cancer Research (2015)

Abstract Ovarian cancer (OC) can be classified into five biologically distinct molecular subgroups—Epi-A, Epi-B, Mes, Stem-A and Stem-B. Among them, Stem-A expresses genes relating to stemness and is correlated with poor clinical prognosis. In this study, we show that FZD7, a receptor for Wnt signalling, is overexpressed in the Stem-A subgroup. To elucidate the functional roles of FZD7, we used an RNA interference (RNAi) gene knockdown approach in three Stem-A cell lines: CH1, PA1 and OV-17R. Si-FZD7 OC cells showed reduced cell proliferation with an increase in the G0/G1 subpopulation, with no effect on apoptosis. The cells also displayed a distinctive morphological change by colony compaction to become more epithelial-like and polarised with smaller inter-nuclear distances and increased z-axis height. Immunofluorescence (IF) staining patterns of pan-cadherin and β-catenin suggested an increase in cadherin-based cell-cell adhesion in si-FZD7 cells. We also observed a significant rearrangement in the actin cytoskeleton and an increase in tensile contractility in si-FZD7 OC cells, as evident by the loss of stress fibres and the redistribution of phospho-myosin light chain (pMLC) from the sites of cell-cell contacts to the periphery of cell colonies. Furthermore, there was reciprocal regulation of RhoA and Rac1 activities upon FZD7 knockdown, with a significant reduction in RhoA activity and a concomitant up-regulation in Rac1 activity. These changes in pMLC and RhoA as well as the increased TOPFLASH reporter activities in si-FZD7 cells suggested involvement of the non-canonical Wnt/planar cell polarity (PCP) pathway. Selected PCP pathway genes (CELSR3, PRICKLE4, DAAM1, PFN2, PCDH9, PCDHA1, PCDHB17, PCDHB3, SPRY1, and PTK7) were found to be more highly expressed in Stem-A than non Stem-A subgroup of OC. Taken together, our results suggest that FZD7 might drive aggressiveness in Stem-A OC by regulating cell proliferation, cell cycle progression, maintenance of the mesenchymal phenotype, and cell migration via CK1ϵ-mediated non-canonical Wnt/PCP pathway. Citation Format: Mohammad Asad, Wong Meng Kang, Tan Tuan Zea, Mahesh Choolani, Jeffery Low, Seiichi Mori, Jean Paul Thiery, Ruby Yun-Ju Huang. FZD7 drives aggressiveness in stem-A subtype of ovarian cancer via regulation of non-canonical Wnt/PCP pathway [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-THER-1403.
Letter to the editor: HIV-1 outbreak among injecting drug users in Greece, 2011: a preliminary report
Authors: M Salminen
Journal: Eurosurveillance (2011)

Preview this article: Letter to the editor: HIV-1 outbreak among injecting drug users in Greece, 2011: a preliminary report, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/16/41/art19986-en-1.gif
Dietary Fats and the Diabetic Patient
Authors: Laurance W. Kinsell, Geoffrey Walker, George D. Michaels, Florence E. Olson, Marjorie Coelho, Yvonne McBride, George Fukayama, Joyce Conklin
Journal: New England Journal of Medicine (1959)

VASCULAR disease represents the foremost long-term problem in the diabetic patient. It has been abundantly demonstrated that diabetes predisposes to earlier onset and more rapid progression of atherosclerosis as compared to the clinical pattern of the disease in the nondiabetic portion of the population. The reasons for this remain to be precisely defined. In addition to atherosclerosis, the diabetic person is subject to a form of vascular disease involving the eyes and kidneys that to all intents and purposes is not found in any other disease. In the eye this condition goes on to retinitis proliferans, widespread hemorrhage and eventual . . .
P112 CPAP role on the perioperative outcomes of patients with obstructive sleep apnoea
Authors: VM Macavei, D King, J Sumpter, M Berger, OE Mohr, J Mitic, TC O’Shaughnessy
Journal: Thorax (2015)

<h3>Background</h3> Obstructive sleep apnoea (OSA) has been previously reported as an independent risk factor for intra and post operative adverse events.<sup>1</sup> Early diagnosis of sleep disordered breathing and initiation of CPAP treatment was suggestive to improve operative outcomes.<sup>2</sup> <h3>Objectives</h3> To determine the prevalence of sleep apnoea in a surgical population and establish the role of CPAP on peri-operative outcomes in patients with OSA. <h3>Methods</h3> A retrospective study was performed in a university hospital between 1<sup>st</sup> June 2013 and 1<sup>st</sup> June 2015 and included 160 surgical patients investigated for OSA. Sleep apnoea was defined as dip rate &gt;10 events/hour associated with a desaturation of 4% below the baseline. Statistical analysis was performed with STATA v10 software. <h3>Results</h3> From 160 surgical patients included, 33.1% (53) were females and average age was 54 years. Prevalence of OSA was 44.3% (71/160) and 12.5% (20/160) had severe OSA defined as a dip rate &gt;30 events/hour. Following sleep investigations, 68 patients had surgical interventions: 48.5% (33/68) trauma and orthopaedics, 17.6% (12/68) general surgery, 10.2% (7/68) urology, 8.8% (6/68) gynaecology, 7.3% (5/68) colorectal, 4.4% (3/68) ENT. From 68 patients undergoing surgical procedures, 44.1% (30/68) were diagnosed with OSA and started on CPAP prior to surgery. Peri-operative adverse events were not significantly related to OSA when compared to non OSA patients: intra operative desaturations (23.3% vs 26.3%) and prolonged recovery stay (53.3% vs 55.2%). OSA patients had a lower hospital stay compared to non OSA group (1.7 vs 3.1 days). <h3>Conclusions</h3> We have identified a high prevalence of sleep apnoea of 44% in surgical population. CPAP treatment was found effective in improving operative outcomes of patients with OSA, further studies being needed to confirm these results. Routine pre-assessment screening for OSA followed by sleep investigations for initiation of CPAP prior to surgery is recommended. <h3>References</h3> 1 Vasu TS, Grewal R, Doghramji K. Obstructive sleep apnoea syndrome and perioperative complications.<i> J Clin Sleep Med</i>. 2012;<b>8</b>(2):199–207 2 Gross JB, <i>et al</i>. Practice guidelines for the perioperative management of obstructive sleep apnea: ASA task force on perioperative management of OSA. <i>Anesthesiology</i> 2014;<b>120</b>
Case 11-1976
Authors: Ann B. Barnes, William R. Welch
Journal: New England Journal of Medicine (1976)

Presentation of CaseA 24-year-old woman was admitted to the hospital because of abdominal pain.She was well until six weeks previously, when her menstrual period occurred at the normal time but was heavier and more prolonged than usual. One week later she experienced vague abdominal discomfort that progressed to a sensation of pressure and cramps; a physician examined her and found no abnormality. Two weeks before admission the abdominal pain increased with the recurrence of menstrual flow, which again was more profuse than usual and persisted for six days. There was a malodorous, brownish discharge for two days, and . . .
Cancer and Other Causes of Death Among Leprosy Patients&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Shinkan Tokudome, Suminori Kono, Masato Ikeda, Masanori Kuratsune, Shigeru Kumamaru
Journal: JNCI Journal of the National Cancer Institute (1981)

A follow-up study was done on the mortality from 1956 to 1975 among 2,383 Japanese patients with leprosy who were admitted to a leprosarium in Japan. The leprosy was classified into two types: lepromatous and tuberculoid. Irrespective of the type of leprosy or the sex of leprosy patient, mortalities were increased from tuberculosis, pneumonia and bronchitis, nephritis and nephrosis, and from total causes. The suicide rate was high among female patients. Deaths from total malignant neoplasms were higher than expected among patients with lepromatous leprosy for both sexes (49 observed vs. 44.02 expected), whereas they were lower than expected among patients with tuberculoid leprosy (35 observed vs. 36.83 expected); however, the differences were not statistically significant. Mortalities from cancers of the cervix and the esophagus among females with lepromatous leprosy were significantly high. The risk of Iymphoreticular cancers was not increased.
An Analysis of the Lowest Effective Intensity of Prophylactic Anticoagulation for Patients with Nonrheumatic Atrial Fibrillation
Authors: Elaine M. Hylek, Steven J. Skates, Mary A. Sheehan, Daniel E. Singer
Journal: New England Journal of Medicine (1996)

To avert major hemorrhage, physicians need to know the lowest intensity of anticoagulation that is effective in preventing stroke in patients with atrial fibrillation. Since the low rate of stroke has made it difficult to perform prospective studies to resolve this issue, we conducted a case–control study.
Gene Therapy — A Novel Form of Drug Delivery
Authors: Helen M. Blau, Matthew L. Springer
Journal: New England Journal of Medicine (1995)

Gene therapy is a novel form of drug delivery that enlists the synthetic machinery of the patient's cells to produce a therapeutic agent. Using the body to treat its own disease overcomes the need to manufacture highly purified proteins. It also eliminates the need for repeated parenteral administration of proteins (as in hemophilia) or drugs (as in hereditary hypercholesterolemia) and reduces the difficulties of complying with exogenous-drug regimens. Applications of gene therapy are not limited to rare inherited diseases but extend potentially to common acquired disorders, including cancer, heart disease, and the acquired immunodeficiency syndrome. Gene therapy is thus likely . . .
Comparison of Neurocognitive Function After Anthracycline-Based Chemotherapy vs Nonanthracycline-Based Chemotherapy
Authors: Kathleen Van Dyk, Laura Petersen, Patricia A. Ganz
Journal: JAMA Oncology (2016)

This secondary analysis of a prospective longitudinal study investigates whether anthracycline chemotherapy confers greater risk of cognitive decline for breast cancer survivors compared with nonanthracycline-based chemotherapy.
Comfort and patient-centred care without excessive sedation: the eCASH concept
Authors: Jean-Louis Vincent, Yahya Shehabi, Timothy S. Walsh, Pratik P. Pandharipande, Jonathan A. Ball, Peter Spronk, Dan Longrois, Thomas Strøm, Giorgio Conti, Georg-Christian Funk, Rafael Badenes, Jean Mantz, Claudia Spies, Jukka Takala
Journal: Intensive Care Medicine (2016)
Angioscopic Evaluation of Coronary-Artery Thrombi in Acute Coronary Syndromes
Authors: Kyoichi Mizuno, Kimio Satomura, Akira Miyamoto, Ko Arakawa, Toshio Shibuya, Tsunenori Arai, Akira Kurita, Haruo Nakamura, John A. Ambrose
Journal: New England Journal of Medicine (1992)

Disruption of an atherosclerotic plaque in a coronary artery followed by the formation of a thrombus is believed to be the cause of both unstable angina and acute myocardial infarction. Although thrombolytic therapy is efficacious in patients with acute myocardial infarction, for unknown reasons it is far less effective in patients with unstable angina. We postulated that there might be differences in the composition of the coronary-artery thrombi in unstable angina and acute myocardial infarction.
Increasing prescription of drugs for secondary prevention of myocardial infarction
Authors: R. J Sapsford, M. B Robinson, A. S Hall
Journal: BMJ (1996)

such as age and social class) are found to be associated, even after adjustment, it seems sensible to treat such associations with caution until evidence of causality can be obtained-in this case from a prospective randomised controlled trial of the eradication of H pylon infection.We therefore believe that eradication of Hpyloni infection on the grounds of the risk of cardiovascular disease alone, like that of gastric cancer alone,4 is not supported by the current evidence.
Case 28-1998
Authors: Robert W. Simms, Robin E. Kirby
Journal: New England Journal of Medicine (1998)

Presentation of CaseA 64-year-old man was admitted to the hospital because of a productive cough during treatment for suspected Wegener's granulomatosis.The patient had been well until seven months earlier, when he began to have unsteadiness and right-sided tinnitus, with constant maxillary, nasal, frontal, and temporal pain, which was more prominent on the right side. Treatment with prednisone (40 mg daily) was begun, with considerable improvement of the headache. A biopsy of the left temporal artery showed no evidence of arteritis. Two months before admission, a test for antineutrophil cytoplasmic antibody (ANCA) was positive, with a perinuclear pattern of . . .
Oral Ganciclovir for Patients with Cytomegalovirus Retinitis Treated with a Ganciclovir Implant
Authors: Daniel F. Martin, Baruch D. Kuppermann, Richard A. Wolitz, Alan G. Palestine, Hong Li, Charles A. Robinson
Journal: New England Journal of Medicine (1999)

The intraocular ganciclovir implant is effective for local treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome (AIDS), but it does not treat or prevent other systemic manifestations of cytomegalovirus infection.
ATCT-23MULTICENTER RETROSPECTIVE STUDY TO COMPARE CHEMORADIOTHERAPY WITH TEMOZOLOMIDE OR ACNU IN 535 ANAPLASTIC GLIOMAS
Authors: Yoshihiro Muragaki, Yoshitaka Narita, Toshihiro Kumabe, Hideo Nakamura, Motoo Nagane, Soko Ikuta, Takashi Maruyama, Takeo Uzuka, Tamio Ito, Takaaki Beppu, Shingo Takano, Yoshiki Arakawa, Hiroyuki Kobayashi, Toshihiko Wakabayashi, Kazuhiko Sugiyama, Naoya Hashimoto, Ryuta Saito, Ryo Nishikawa, Takamasa Kayama, Soichiro Shibui
Journal: Neuro-Oncology (2015)

BACKGROUND: Standard therapy for anaplastic gliomas (AG) is controversial. In Japan traditional treatment of patients with AG had been chemoradiotherapy with nimustine hydrochloride (RT/ACNU), but shifted to use of temozolomide (RT/TMZ) soon after its approval. Therefore, a retrospective analysis of the overall survival (OS) of patients with AG treated with RT/ACNU or RT/TMZ was performed. PATIENTS AND METHODS: Between 2001 and 2007, 724 patients with AG were treated by the members of Japan Clinical Oncology Group (JCOG). In this cohort 535 patients (median age, 48 years) received either RT/ACNU (439 cases) or RT/TMZ (96 cases). There were 289 anaplastic astrocytomas (AA), 126 anaplastic oligoastrocytomas (AOA), and 120 anaplastic oligodendrogliomas (AO). Multivariate analysis was performed using the Cox proportional hazard model, where covariates were age, KPS score, histology, extent of resection, and chemotherapy (ACNU vs. TMZ) at initial treatment and at recurrence. RESULTS: Medium survival time (MST) of 535 patients was 72 months and a 5-year survival rate was 54%. Univariate analysis showed that MST in the RT/ACNU subgroup (86 months) was significantly longer compared to RT/TMZ subgroup (46 months) (HR: 0.61; P   0.05). Subgroup analysis demonstrated that patients initially treated with RT/ACNU and second line chemotherapy with TMZ at recurrence, had significantly longer OS compared to those, who initially received RT/TMZ treatment followed by second line chemotherapy with various agents at recurrence (HR: 0.37; 95% CI: 0.25-0.57; P < 0.01). CONCLUSION: A randomized phase III study of chemoradiotherapy for anaplastic glioma using upfront TMZ or ACNU followed by second line TMZ at the time of recurrence is warranted and it has been started since May 2014 (JCOG 1016: SANTA).
Use of Antimicrobial Drugs in General Hospitals
Authors: Mervyn Shapiro, Timothy R. Townsend, Bernard Rosner, Edward H. Kass
Journal: New England Journal of Medicine (1979)

The patterns of prophylactic use of antimicrobial drugs were reviewed in 5288 charts drawn by a random method from 20 randomly selected short-stay general hospitals in Pennsylvania. About 10 per cent of hospitalized patients received antimicrobial drugs for prophylaxis in operations or nonsurgical procedures, and prophylaxis accounted for about 30 per cent of all antimicrobial drugs administered in hospitals. The drugs used most often for prophylaxis were cephalosporins, followed by benzyl penicillins, ampicillin and tetracyclines, in that order. Despite indications that prophylaxis, when useful at all, is effective only when given concurrently with and for 24 to 48 hours after operation, it was usually continued throughout hospitalization. Almost 80 per cent of prophylactic antimicrobial drugs were administered at least 48 hours after an operation or procedure -- suggesting that limiting prophylaxis to the first 24 to 48 hours, as currently recommended, would substantially reduce expenditures for antimicrobial drugs in hospitals.
Erythrocyte 2,3-Diphosphoglycerate in Adaptive Red-Cell-Volume Deficiency
Authors: Julio M. Rodriguez, Nasrollah T. Shahidi
Journal: New England Journal of Medicine (1971)

Measurement of red-cell volume, plasma volume and erythrocyte 2,3-diphosphoglycerate (2,3-DPG) in five patients with panhypopituitarism and one patient with isolated growth-hormone deficiency revealed marked decrease in the red-cell volume and plasma volume but no increase in the red-cell 2,3-DPG. The same studies performed in two hypophysectomized monkeys gave similar results. Administration of combined human growth hormone and thyroxine to one of the patients and to hypophysectomized monkeys resulted in increases of 45 to 88 per cent in 2,3-DPG within five weeks. The hormonal therapy also restored red-cell volume to normal. Further studies revealed that these calorigenic hormones acted synergetically to increase the concentration of erythrocyte 2,3-DPG. The findings suggest that the level of erythrocyte 2,3-DPG may be a useful guide to differentiate an "adaptive" from pathologic deficiency in red-cell mass.
The Genesis of Coronary Sclerosis
Authors: Timothy Leary
Journal: New England Journal of Medicine (1951)

WITH the increase in specialism there is a tendency for medical information to be contained in special compartments, so to speak. One of the most watertight compartments is that of pathology. Publication of its studies tends to be sharply limited to special journals. This is partly due to the desirability of concentrating pathologic records in special journals as the natural depositories of such data. It is also partly due to the tendency of clinical journals to look on papers dealing with pathologic questions as possibly too "technical" for their readers. However, there are certain fundamental matters that should be a . . .
Ebola virus persists and may be transmitted in survivors’ semen, studies show
Authors: Susan Mayor
Journal: BMJ (2015)

Ebola virus RNA persists in men’s semen after their recovery from Ebola virus disease, preliminary results from a study in Sierra Leone have shown,1 and a case study has reported a suspected case of sexual transmission of the disease from a male survivor to his female partner earlier this year.2

The Ebola persistence study, published in the New England Journal of Medicine ,1 enrolled a convenience sample of 100 men who had survived Ebola virus disease in Sierra Leone. Researchers followed them at intervals after their recovery and collected semen samples in addition to self reported information on their health status. …
Case 14-1992
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, W.N. Katkov, C.C. Compton
Journal: New England Journal of Medicine (1992)

Presentation of CaseA 37-year-old man was admitted to the hospital because of recurrent hematochezia of six days' duration.The patient was well until six days earlier, when hematochezia occurred. The next day he again passed fresh blood per rectum, with a loss of "several cups" of blood. He experienced orthostatic weakness, dizziness, nausea, and syncope and was taken to another hospital, where physical examination showed that the blood pressure was 100 mm Hg systolic. Fluids were given by vein, and his condition was hemodynamically stable thereafter. The hematocrit, determined after the administration of fluids, was 24 percent. On the . . .
Low Urinary<i>chiro</i>-Inositol Excretion in Non-Insulin-Dependent Diabetes Mellitus
Authors: Allison S. Kennington, Cynthia R. Hill, James Craig, Clifton Bogardus, Itamar Raz, Heidi K. Ortmeyer, Barbara C. Hansen, Guillermo Romero, Joseph Larner
Journal: New England Journal of Medicine (1990)

Inositol is a major component of the intracellular mediators of insulin action. To investigate the possible role of altered inositol metabolism in non-insulin-dependent diabetes mellitus (NIDDM), we used gas chromatography and mass spectrometry to measure the myo-inositol and chiro-inositol content of urine specimens from normal subjects and patients with NIDDM. The study subjects were whites, blacks, and Pima Indians. The type of inositol and its concentration in insulin-mediator preparations from muscle-biopsy specimens from normal subjects and diabetic patients were also determined.