tbuckley/cabot-search huggingface dataset:
Abstract P001: Plasma Phospholipid Saturated Fatty Acids and Incident Atrial Fibrillation: the Cardiovascular Health Study
Authors: Amanda M Fretts, Dariush Mozaffarian, David S Siscovick, Luc Djousse, Susan R Heckbert, Irena B King, Barbara McKnight, Colleen Sitlani, Frank M Sacks, Xiaoling Song, Nona Sotoodehnia, Donna Spiegelman, Erin R Wallace, Rozenn N Lemaitre
Journal: Circulation (2014)

Background: Prior studies suggest that circulating fatty acids may influence the risk of atrial fibrillation (AF), but little is known about the associations of circulating saturated fatty acids (SFA) with risk of AF. SFAs of different length differ in dietary and metabolic origin, incorporation into membrane lipid species, membrane properties, and biological activities that may influence the pathophysiology of AF. Moreover, both diet and metabolic pathways are determinants of circulating SFAs. Methods: The study population included 2,899 participants from the Cardiovascular Health Study, a community-based longitudinal cohort of adults aged 65 years or older, free of prevalent coronary heart disease and AF. Cox regression was used to assess the association of all the long-chain saturated fatty acids, palmitic acid (16:0), stearic acid (18:0), arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0), with incident AF. Results: During 29,864 person-years of follow-up, 707 cases of incident AF occurred. After adjustment for other AF risk factors, higher levels of circulating 16:0 were associated with a higher risk of AF (hazard ratio comparing highest to lowest quartiles: 1.48. 95% CI: 1.18, 1.86). On the other hand, higher levels of circulating 18:0, 20:0, 22:0 and 24:0 were each associated with a lower risk of AF. The hazard ratios (95% CI) for AF in the top versus bottom quartile were 0.76 (0.61, 0.95) for 18:0; 0.78 (0.63, 0.97) for 20:0; 0.62 (0.50, 0.78) for 22:0; and 0.68 (0.55, 0.85) for 24:0. Conclusions: Results from this prospective cohort study of older adults demonstrate divergent associations of circulating 16:0 versus longer-chain saturated fatty acids with incident AF, highlighting the need to investigate both determinants of these levels and potential pathways of the observed differential risk.
Morphologic heterogeneity of acute promyelocytic leukemia (APL)
Authors: S. Sinha, L. Aish, T. H. Oo
Journal: Journal of Clinical Oncology (2005)

6741 Background: Three morphological forms of APL recognized; hypergranular, hypogranular and hyperbasophilic forms. Other subtypes were rare, however, have been described. Methods: We describe a case of AML with PML-RARα fusion gene without above morphology. A 67-year-old caucasian male was hospitalized with diverticulits. He received radioactive seed-implants for prostate cancer 1.5 years ago. CBC showed WBC 9,000/cmm, Hemoglobin 12.4g/dl, platelet 25,000/cmm, neutrophil 5%, band 3%, lymphocyte 30%, monocyte 20%, metamyelocyte 2%, myelocyte 15%, promyelocyte 15%, myeloblast 10%. Clotting profile was normal except INR 1.6 and elevated D-dimers. Bone marrow biopsy was consistent with AML-M2. Induction chemotherapy was initiated resulting in worsening DIC. This raised the suspicion for morphologic variant of APL. The cytogenetic study revealed no diving cells. FISH and PCR studies were positive for PML-RARα fusion gene. He was then started on all-trans retinoic acid. Currently he has received 2 cycles of consolidation chemotherapy. The literature was reviewed for atypical morphologic presentations of APL on MEDLINE. Results: In a review of the literature of t(15:17) in AML subtypes other than M3, there have been 16 reported cases including our case. Male: Female:Unknown- 5:8:3; Subtypes: M1- 6, M2- 5, M4- 1, acute esosinophilic leukemia- 1, M7- 2, undifferentiated L2/M1- 1; DIC: Yes- 4, No-4, unknown- 8; Treatment with ATRA: Yes- 7, No- 6, unknown- 3; Outcomes: Complete hematologic remission - Yes- 7, Died - 3, unknown- 6. Molecular responses: Yes- 1, No- 6, unknown- 9. Conclusion: Patients with t(15;17) are amenable to treatment with ATRA making this most curable AML. The diagnosis of APL can be made from morphology and flow cytometry, but our case and the literature illustrate there are occasions where APL may present with atypical morphology. All efforts must be made rule out PML-RARα gene rearrangement in AML patients, especially with DIC. Summary of APL cases without typical M3 morphology Reference Age/Sex AML subtypes Disseminated Intravascular Coagulation (DIC) Use of All-trans Retinoic Acid (ATRA) Outcome Neame et al 60/F M1 No No Unknown 73F M1 Yes Yes Died 45M M2 Unknown No Unknown 53F M2 Unknown Yes Remission 54M M2 Unknown No Unknown Foley et al 45M L2/M1 Undifferentiated Yes Yes Remission Allford et al 15/F M1 No Yes Died 36/M M2 unknown No Died Head et al unknown M1 unknown unknown unknown unknown M1 unknown unknown unknown unknown M1 unknown unknown unknown Hast et al 22/F M4 Yes No Remission Aventin et al 22/F M7 No Yes Remission Morgan et al 18/F M7 No No Remission Yu et al 66/F Acute eosinophilic leukemia unknown Yes Remission This case 67/M M2 Yes Yes Remission No significant financial relationships to disclose.
Diagnosis and Monitoring of Residual Disease by Quantitative RT-PCR in Eosinophilia-Associated Myeloproliferative Disorders with Rearrangements of PDGFRA and PDGFRB.
Authors: Philipp Erben, Martin C. Mueller, Georgia Metzgeroth, Helena Popp, Christoph Walz, Thomas Schenk, Stephanie Lauber, Jens Kruth, Nicholas C.P. Cross, Rudiger Hehlmann, Andreas Hochhaus, Andreas Reiter
Journal: Blood (2006)
Abstract 18063: Maternal and Postnatal High-Fat Diet Interaction Leads to Greater Risk of Myocardial Dysfunction in Offspring via Obesity-Induced Lipotoxicity, IRS-1 Serine Phosphorylation and Mitochondrial Defects
Authors: Subat Turdi, Wei Ge, Nan Hu, Katharine M Bradley, Jun Ren
Journal: Circulation (2011)

Introduction: Maternal obesity/overnutrition during gestation and lactation are associated with increased prevalence of obesity and cardiovascular risk in adult offspring. Given the pervasive “obesogenic” environment, long-term consequences of maternal and/or postnatal overnutrition on myocardial function warrant immediate attention. Objective: We examined the impact of maternal and long- term postnatal dietary fat exposure on metabolic, myocardial, intracellular Ca2+, insulin and mitochondrial responses. Methods and Results: Pregnant FVB mice were fed either a low-fat (LF, 10% of calories) or high-fat (HF, 45% of calories) diet during gestation and lactation. Weaning male offspring were randomized and placed on either LF or HF (a food-restricted HF-fed mice served as weight control group) for 4 months prior to assessment of metabolic indexes, myocardial histology, cardiac function, insulin signaling, mitochondrial integrity and ROS generation. Compared with LF-fed and HF-fed weight-control mice, postnatal HF intake resulted in obesity (DIO), exhibited marked dyslipidemia, blunted insulin sensitivity, cardiac hypertrophy, compromised myocardial function, intracellular Ca2+ homeostasis and mitochondrial biogenesis, all of which were significantly accentuated in postnatal HF-fed mice with maternal high fat exposure.Interestingly, LF-fed offspring from HF-fed dams displayed higher body weights, increased adiposity and dampened insulin sensitivity compared to LF-fed controls. Maternal HF exposure upregulated postnatal HF-induced IRS-1 serine phosphorylation, PTP1B, lipogenic enzyme SCD-1 and hypertrophic markers while downregulating cardiac AMPK signaling and PGC-1α. Importantly, myocardial and mitochondrial ultrastructural abnormalities were more pronounced in HF-fed offspring with maternal HF exposure, as shown by loss of mitochondrial density and membrane potential, increased ROS generation and apoptosis. Conclusion: We conclude that prenatal fat exposure may program the offspring at a higher risk for postnatal DIO induced cardiac hypertrophy and dysfunction possibly related to cardiac hypertrophy and lipotoxicity, impaired insulin signaling, mitochondrial dysfunction and oxidative stress.
Brief Report: Methotrexate Prevents Wear Particle-Induced Inflammatory Osteolysis in Mice Via Activation of Adenosine A<sub>2A</sub>Receptor
Authors: Aránzazu Mediero, Miguel Perez‐Aso, Tuere Wilder, Bruce N. Cronstein
Journal: Arthritis & Rheumatology (2014)

Adenosine, acting at the A2A receptor, mediates the antiinflammatory effects of methotrexate (MTX) in models of inflammation. We previously reported that A2A receptor ligation diminishes wear particle-driven osteolysis. The aim of this study was to investigate whether MTX treatment could prevent bone resorption caused by inflammatory osteolysis.C57BL/6 mice (6-8 weeks old) received intraperitoneal injections of 1 mg/kg MTX (n = 20) or 0.9% saline (n = 10), starting 2 weeks prior to surgical implantation of 3 mg of wear particles (ultrahigh molecular weight polyethylene [UHMWPE] particles). The MTX-treated mice received daily injections of vehicle or ZM241385 at the surgical site until they were killed, 14 days later. XenoLight RediJect Bone Probe 680 was injected intravenously, and fluorescence analysis of the calvaria using an IVIS imaging system was performed to assess bone formation. Micro-computed tomography (micro-CT) and immunostaining for osteoclast and osteoblast markers were performed.Implantation of wear particles induced bone pitting and thinning, as shown by micro-CT. MTX treatment markedly reduced osteolysis, and this effect was abrogated by treatment with the A2A receptor antagonist ZM241385. Implantation of UHMWPE reduced new bone formation, and MTX treatment restored new bone formation, an effect that was completely reversed by treatment with ZM241385. Histologic examination of particle-exposed calvariae demonstrated that MTX prevented accumulation of an inflammatory infiltrate at the site of particle implantation, increased the number of osteoblasts, and reduced the number of osteoclasts at the site of inflammation, an effect that was reversed by treatment with ZM241385.MTX reduces inflammatory osteolysis indirectly via stimulation of A2A receptor and may represent a novel approach to enhance orthopedic implant survival, delaying or eliminating the need for revision arthroplasty surgery.
Cutting Edge Debate
Authors: Lynne Lamberg
Journal: JAMA (2002)

NEW ORLEANS—A proposed yearlong postgraduate year (PGY) 5 fellowship in dermatologic surgery for dermatologists has sparked objections from the American College of Surgeons (ACS). The residency review committee for dermatology seeks approval of the fellowship by the Accreditation Council for Graduate Medical Education (ACGME). The ACS maintains that the proposed program lacks the comprehensiveness of training programs in plastic surgery, otolaryngology, and other traditional surgical specialties. Dermatologists note that 64 PGY-5 dermatologic surgery programs currently exist. ACGME accreditation would establish uniform standards to ensure educational quality across programs. “Our concern is the type and length of training that entitles physicians to call themselves ‘surgeons,’” said ACS executive director Thomas Russell, MD. “This is not—and should not be—a turf issue,” Russell said, presenting ACS’s view at a session on controversies in dermatology at the annual meeting of the American Academy of Dermatology (AAD). Ronald Wheeland, MD, AAD immediate past president, provided the dermatologists’ perspective.
Abstract 17744: In Vivo Platelet Activation and Aspirin Responsiveness in Type 1 Diabetes Mellitus
Authors: Francesco Zaccardi, Francesca Pagliaccia, Alessandro Rizzi, Giovanna Petrucci, Aida Habib, Luigi Tanese, Paola Rizzo, Francesca Martini, Dario Pitocco, Bianca Rocca, Carlo Patrono
Journal: Circulation (2014)

Introduction: While reduced responsiveness to low-dose aspirin has been associated with type 2 diabetes mellitus (T2DM), aspirin responsiveness remains unexplored in T1DM. Hypothesis: We investigated in vivo platelet activation, as reflected by the urinary excretion of 11-dehydro-TXB2 (TXM) and platelet COX-1 inhibition, as assessed by serum TXB2 (sTXB2), in uncomplicated, normotensive, normolipidemic T1DM subjects on insulin therapy. Methods: Upon informed consent, we enrolled 40 T1DM patients (26M, age 35±11yr, disease duration 16±11yr, BMI 24±2 kg/m2) and 10 healthy controls (6M, age 33±7yr). In 9 patients we assessed the stability of TXM excretion on 3 different visits. Thirty-one patients and all controls were given 100 mg daily aspirin for 21 days, and urinary TXM and sTXB2 were measured before and 24h after stopping aspirin. To assess the influence of glycemic variability on aspirin response, 26 patients underwent continuous glucose monitoring (CGM) for the first 24h after drug withdrawal. Results: TXM excretion in T1DM was significantly higher than in controls (930 [659-1358] vs 568 [385-619] pg/mg creatinine; p&lt;0.001) and quite stable across repeated sampling (p for linear trend = 0.755). By multivariate analysis, urinary TXM was associated with microalbuminuria (β=0.23; p=0.042) at baseline. The degree of inhibition at 24h after aspirin dosing was similar in T1DM and controls for both sTXB2 (98.2% vs 98.6%, p=0.607) and urinary TXM (68.8% vs 68.4%, p=0.962). CGM-derived mean and standard deviation glucose were not associated with sTXB2 or TXM inhibition at 24h. Conclusions: We conclude that enhanced platelet activation in T1DM is independent of glycemic control and associated with kidney/endothelial damage. Moreover, in contrast to T2DM, the response to aspirin is unchanged, suggesting that the metabolic disturbance per se is not responsible for altered pharmacodynamics.
Hydroxychloroquine is a good second‐line treatment for adults with immune thrombocytopenia and positive antinuclear antibodies
Authors: Mehdi Khellaf, Amèlie Chabrol, Matthieu Mahevas, Françoise Roudot‐Thoraval, Nicolas Limal, Laetitia Languille, Philippe Bierling, Marc Michel, Bertrand Godeau
Journal: American Journal of Hematology (2013)

Treatment of patients with lupus‐associated thrombocytopenia (SLE‐ITP) is not standardized. We report data on efficacy and safety of hydroxychloroquine (HCQ) in this setting and in ITP patients with positive antinuclear antibodies (ANA) without definite SLE. Inclusion criteria were: definite diagnosis of ITP with a platelet count (PLT) &lt;50 × 10 9 /L, ANA ≥ 1/160 on Hep2 cells with or without a definite diagnosis of SLE, and no sustained response to at least one previous treatment‐line and treatment with HCQ. Response criteria were Complete Response (CR) for PLT ≥ 100 × 10 9 /L and Response (R) for PLT ≥30 × 10 9 /L and at least twice the initial value. Forty patients (32 females) with a mean age of 35 ± 17 years and PLT at ITP diagnosis of 14 ± 13 × 10 9 /L were analyzed. Twelve (30%) patients had a SLE‐ITP, 28 patients had only positive ANA. All the patients failed to respond to oral prednisone with a median of two treatment‐lines (1–5) before HCQ which was initially given in combination with another ITP treatment in 36 patients. Overall response rate was 60% (24/40) including 18 lasting CR and six lasting R maintained with a median follow‐up of 64 months (6–146), in ¾ of cases with only HCQ and no concomitant ITP treatment. The response rate (CR+R) was higher in the SLE group vs ANA‐positive group (83% vs 50%, P &lt; 0.05 ). No patient stopped HCQ because of a side‐effect. HCQ appears to be a safe and effective second line treatment for patients with SLE‐ITP or ITP and high titer of ANA. This trial was registered at www.clinicaltrials.gov as # NCT01549184. Am. J. Hematol. 89:194–198, 2014. © 2013 Wiley Periodicals, Inc.
TULAREMIA WITH PULMONARY COMPLICATIONS
Authors: G. Gill Richards
Journal: Annals of Internal Medicine (1942)

Article1 July 1942TULAREMIA WITH PULMONARY COMPLICATIONSG. GILL RICHARDS, M.D., F.A.C.P.G. GILL RICHARDS, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-17-1-78 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptCredit for the first clinical description of tularemia is due to R. A. Pearce, a country practitioner of Brigham City, Utah, although only a single reference to his work has been found in subsequent reports of this disease. At the annual meeting of the Utah State Medical Society in Salt Lake City, October 3, 1910, he described six cases which he had observed during 1908, and he stated that he had seen 10 others during 1910. An autopsy on the one fatal case was reported as showing a septic meningitis secondary to a horse fly bite on the face.The...References1. FRANCIS E: Tularemia, Jr. Am. Med. Assoc., 1922, lxxviii, 1017. Google Scholar2. PEARCE RA: Insect bites, Northwest Med., 1911, iii, 81. Google Scholar3. MCCOYCHAPIN GWCW: Further observations on a plague-like disease of rodents with a preliminary note on the causative agent, Bacterium tularense , Jr. Infect. Dis., 1912, x, 61. MCCOY, G. W.: Bacterium tularense, the cause of a plague-like disease of rodents, U. S. Pub. Health Bull., 1911, No. 54, 17-23. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Salt Lake City, Utah*Read at the Cleveland meeting of the American College of Physicians, April 5, 1940. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1942Volume 17, Issue 1Page: 78-82KeywordsAutopsyMeningitisSaltsTularemia ePublished: 1 December 2008 Issue Published: 1 July 1942 PDF downloadLoading ...
Immunotherapy in Spring‐Time Hay Fever
Authors: Nils E. Eriksson, Staffan Ahlstedt, Olle Lövhagen
Journal: Allergy (1979)

In a study of the efficacy of two different treatment schedules for perennial immunotherapy, 47 adult patients with spring‐time hay fever due to allergy against birch and other deciduous trees were randomly assigned to three treatment groups: one group received birch, alder and hazel allergen in Allpyral, another group received the same Allpyral mixture and in addition all relevant tree pollens in aqueous extract and a control group received no injections. For determination of antibody litres the radioallergosorbent test (RAST) and the ammonium sulphate precipitation (ASP) technique were used. Cellular responsiveness was studied by measuring birch pollen (BP) induced leucocyte histamine release in peripheral blood. The clinical and immunological response was similar in the two treated groups. Treated patients had fess symptoms and a lower consumption of antihistamine tablets during the pollen season than the control group. Non‐IgE BP antibodies and IgE antibodies recorded with the ASP technique increased after immunotherapy while RAST values did not change significantly. A decrease of RAST values from postseasonal values during the first year to pre‐seasonal values in the following year was seen in all patient groups but was less pronounced in treated than in untreated patients. The decrease was more pronounced in patients with high RAST values of postseasonal sera than in patients with low RAST values. Cellular reactivity increased slightly during the first phase of therapy but returned to the pre‐treatment level later. Clinical improvement was positively correlated to the percentage increase of non‐IgE antibody titres and to the pre‐treatment non‐IgE/IgE antibody ratio. Patients with high preseasonal RAST titres or high cellular sensitivity tended to have more severe symptoms during the pollen season. It is concluded that a mixture of birch, alder and hazel is sufficient for immunotherapy in spring‐term hay fever. It is obvious that changes of a single immunological variable do not account for the therapeutic results in immunotherapy.
Association Between Hyponatremia and Complicated Appendicitis
Authors: Dennis Y. Kim, Nariman Nassiri, Christian de Virgilio, Michael P. Ferebee, Amy H. Kaji, Camille E. Hamilton, Darin J. Saltzman
Journal: JAMA Surgery (2015)

Association Between Hyponatremia and Complicated AppendicitisComplicated appendicitis is associated with worse outcomes among patients with acute appendicitis. 1Preoperative identification of patients with a perforated or gangrenous appendicitis may have important clinical implications regarding the timing of surgery and the suitability for nonoperative management strategies.The objective of this study was to identify clinical variables associated with the presence of complicated appendicitis.Methods | Following institutional review board approval from the Los Angeles Biomedical Research Institute in Torrance, California, we conducted a retrospective analysis of adult patients (>18 years of age) who underwent an appendectomy for acute appendicitis at Harbor-UCLA and Olive View-UCLA Medical Centers over a 3.5-year period.Exclusion criteria included pregnancy and a pathologic diagnosis of chronic appendicitis or appendiceal neoplasm.Complicated appendicitis was defined as the intraoperative finding of a perfo-rated or gangrenous appendix.Variables analyzed included findings from history taking and a physical examination, admission laboratory values, and operative details.Statistically significant variables were entered into a multiple logistic regression model to identify independent predictors of complicated appendicitis.The study participants did not provide informed consent because all study data were deidentified.
Chemopreventive Agent Resveratrol, a Natural Product Derived From Grapes, Triggers CD95 Signaling-Dependent Apoptosis in Human Tumor Cells
Authors: Marie-Véronique Clément, Jayshreekumari L. Hirpara, Sanaul-Haq Chawdhury, Shazib Pervaiz
Journal: Blood (1998)