tbuckley/cabot-search huggingface dataset:
Warfarin Use and the Risk for Stroke and Bleeding in Patients With Atrial Fibrillation Undergoing Dialysis
Authors: Mitesh Shah, Meytal Avgil Tsadok, Cynthia A. Jackevicius, Vidal Essebag, Mark J. Eisenberg, Elham Rahme, Karin H. Humphries, Jack V. Tu, Hassan Behlouli, Helen Guo, Louise Pilote
Journal: Circulation (2014)

Background— Current observational studies on warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation (AF) undergoing dialysis found conflicting results. Methods and Results— We conducted a population-based retrospective cohort study of patients aged ≥65 years admitted to a hospital with a primary or secondary diagnosis of AF, in Quebec and Ontario, Canada from 1998 to 2007. The AF cohort was grouped into dialysis (hemodialysis and peritoneal dialysis) and nondialysis patients and into warfarin and no-warfarin users according to the first prescription filled for warfarin within 30 days after AF hospital discharge. We determined the association between warfarin use and the risk for stroke and bleeding in dialysis and nondialysis patients. The cohort comprised 1626 dialysis patients and 204 210 nondialysis patients. Among dialysis patients, 46% (756/1626) patients were prescribed warfarin. Among dialysis patients, warfarin users had more congestive heart failure and diabetes mellitus, but fewer prior bleeding events in comparison with the no-warfarin users. Among dialysis patients, warfarin use, in comparison with no-warfarin use, was not associated with a lower risk for stroke (adjusted hazard ratio, 1.14; 95% confidence interval, 0.78–1.67) but was associated with a 44% higher risk for bleeding (adjusted hazard ratio, 1.44; 95% confidence interval, 1.13–1.85) after adjusting for potential confounders. Propensity score–adjusted analyses yielded similar results. Conclusions— Our results suggest that warfarin use is not beneficial in reducing stroke risk, but it is associated with a higher bleeding risk in patients with AF undergoing dialysis.
Nonuraemic calciphylaxis and pancreatic cancer: a previously unreported association
Authors: J.E. Hawkes, M. Karavan, A.R. Bowen, E.M. Summers
Journal: British Journal of Dermatology (2014)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, We report the case of a 77‐year‐old white man with stage IIA (T3, N0, M0) pancreatic adenocarcinoma, who presented for evaluation of painful ulcers of the lower extremities. The development of the patient's leg ulcers preceded the diagnosis of his pancreatic cancer by 4 months. His past medical history was significant for atrial fibrillation, diabetes mellitus, hypertension and hyperlipidaemia. On presentation, the patient had extensive retiform erythema and macular purpura with necrotic eschars and scattered, erythematous shallow ulcerations on the bilateral lower extremities (Fig. 1). Initial laboratory studies revealed an unremarkable urinalysis, normal renal function (creatinine 97·24 μmol L−1), hypoalbuminaemia (27 g L−1), elevated Westergren sedimentation rate (35 mm h−1), elevated corrected calcium (2·79 mmol L−1), normal phosphorus (0·97 mmol L−1) and a normal intact parathyroid hormone (PTH; 54 ng L−1) level. Anticardiolipin, antinuclear antibodies, antiglomerular basement membrane and antineutrophil cytoplasmic antibodies were all negative. Factor V Leiden genetic testing was negative. As the patient was on warfarin, protein C and S testing was not performed. Cancer antigen CA 19‐9 was markedly elevated (1106 U mL−1) and computed tomography of the abdomen/pelvis revealed a mass arising from the head of the pancreas. Biopsy of the lower extremity revealed ischaemic necrosis of the epidermis, prominent fat necrosis, fibrous expansion of the interlobular septae and calcium deposition within the vessel walls of small capillaries, as well as larger, muscular blood vessels. Calcification of small vessels within the lobular fat was verified using von Kossa stain, thus confirming the diagnosis of calcifying panniculitis or calciphylaxis (Fig. 2).
CONGENITAL ATRESIA OF THE ESOPHAGUS: A NEW DIAGNOSTIC TECHNIC
Authors: Gabriel Tucker
Journal: JAMA (1933)

The mortality rate, so far as I have been able to determine, is 100 per cent in congenital atresia of the esophagus. Death is not due to starvation in most cases, but to pulmonary complications from the aspiration of secretions and from the return of fluids and foods when a gastrostomy has been done through the lower segment of the esophagus. The usual method of diagnosis is the administration of a bismuth preparation or barium sulphate with roentgen study. This outlines the pouch, and if the upper segment of the esophagus communicates with the trachea, the mixture passes into the tracheobronchial tree. If there is no communication between the upper segment of the esophagus and the trachea, unless great care is exercised there will be an overflow and secretions will be aspirated into the trachea, in many cases contributing largely to the pulmonary complication. A female infant 3 days of
Hepatitis B surface antigen genetic elements critical for immune escape correlate with hepatitis B virus reactivation upon immunosuppression
Authors: Romina Salpini, Luna Colagrossi, Maria Concetta Bellocchi, Matteo Surdo, Christina Becker, Claudia Alteri, Marianna Aragri, Alessandra Ricciardi, Daniele Armenia, Michela Pollicita, Fabiola Di Santo, Luca Carioti, Yoram Louzoun, Claudio Maria Mastroianni, Miriam Lichtner, Maurizio Paoloni, Mariarosaria Esposito, Chiara D'Amore, Aldo Marrone, Massimo Marignani, Cesare Sarrecchia, Loredana Sarmati, Massimo Andreoni, Mario Angelico, Jens Verheyen, Carlo‐Federico Perno, Valentina Svicher
Journal: Hepatology (2014)

Hepatitis B virus (HBV) reactivation during immunosuppression can lead to severe acute hepatitis, fulminant liver failure, and death. Here, we investigated hepatitis B surface antigen (HBsAg) genetic features underlying this phenomenon by analyzing 93 patients: 29 developing HBV reactivation and 64 consecutive patients with chronic HBV infection (as control). HBsAg genetic diversity was analyzed by population-based and ultradeep sequencing (UDS). Before HBV reactivation, 51.7% of patients were isolated hepatitis B core antibody (anti-HBc) positive, 31.0% inactive carriers, 6.9% anti-HBc/anti-HBs (hepatitis B surface antibody) positive, 6.9% isolated anti-HBs positive, and 3.4% had an overt HBV infection. Of HBV-reactivated patients, 51.7% were treated with rituximab, 34.5% with different chemotherapeutics, and 13.8% with corticosteroids only for inflammatory diseases. In total, 75.9% of HBV-reactivated patients (vs. 3.1% of control patients; P<0.001) carried HBsAg mutations localized in immune-active HBsAg regions. Of the 13 HBsAg mutations found in these patients, 8 of 13 (M103I-L109I-T118K-P120A-Y134H-S143L-D144E-S171F) reside in a major hydrophilic loop (target of neutralizing antibodies [Abs]); some of them are already known to hamper HBsAg recognition by humoral response. The remaining five (C48G-V96A-L175S-G185E-V190A) are localized in class I/II-restricted T-cell epitopes, suggesting a role in HBV escape from T-cell-mediated responses. By UDS, these mutations occurred in HBV-reactivated patients with a median intrapatient prevalence of 73.3% (range, 27.6%-100%) supporting their fixation in the viral population as a predominant species. In control patients carrying such mutations, their median intrapatient prevalence was 4.6% (range, 2.5%-11.3%; P<0.001). Finally, additional N-linked glycosylation (NLG) sites within the major hydrophilic loop were found in 24.1% of HBV-reactivated patients (vs. 0% of chronic patients; P<0.001); 5 of 7 patients carrying these sites remained HBsAg negative despite HBV reactivation. NLG can mask immunogenic epitopes, abrogating HBsAg recognition by Abs.HBV reactivation occurs in a wide variety of clinical settings requiring immune-suppressive therapy, and correlates with HBsAg mutations endowed with enhanced capability to evade immune response. This highlights the need for careful patient monitoring in all immunosuppressive settings at reactivation risk and of establishing a prompt therapy to prevent HBV-related clinical complications.
Acquired immunodeficiency syndrome presenting as marrow cryptococcosis
Authors: K. F. Wong, S. K. Ma, J. K. C. Chan, K. W. Lam
Journal: American Journal of Hematology (1993)

Abstract Disseminated cryptococcal infection is an uncommon initial manifestation in patients with the acquired immunodeficiency syndrome. The most common sites of involvement by cryptococci are the central nervous system and the lungs, and involvement of the marrow is rare. There are few descriptions in the literature on the cytologic findings of marrow cryptococcosis. We report a patient with disseminated cryptococcosis in which cytologic examination of the marrow provides the first clue to the diagnosis. © 1993 Wiley‐Liss, Inc.
Vascular Endothelial Growth Factor/Vascular Permeability Factor Enhances Vascular Permeability Via Nitric Oxide and Prostacyclin
Authors: Toyoaki Murohara, Jeffrey R. Horowitz, Marcy Silver, Yukio Tsurumi, Dongfen Chen, Alison Sullivan, Jeffrey M. Isner
Journal: Circulation (1998)

Background —Vascular endothelial growth factor (VEGF), an endothelial cell mitogen that promotes angiogenesis, was initially identified as a vascular permeability factor (VPF). Abundant evidence suggests that angiogenesis is preceded and/or accompanied by enhanced microvascular permeability. The mechanism by which VEGF/VPF increases vascular permeability (VP), however, has remained enigmatic. Accordingly, we used an in vivo assay of VP (Miles assay) to study the putative mediators of VEGF/VPF-induced permeability. Methods and Results —VEGF/VPF and positive controls (platelet-activating factor [PAF], histamine, and bradykinin) all increased vascular permeability. Prior administration of the tyrosine kinase inhibitors genistein or herbimycin A prevented VEGF/VPF-induced permeability. Placenta growth factor, which binds to Flt -1/VEGF-R1 but not Flk -1/KDR/VEGF-R2 receptor tyrosine kinase, failed to increase permeability. Other growth factors such as basic fibroblast growth factor (FGF), acidic FGF, platelet-derived growth factor-BB, transforming growth factor-β, scatter factor, and granulocyte macrophage-colony stimulating factor (8 to 128 ng) failed to increase permeability. VEGF/VPF-induced permeability was significantly attenuated by the nitric oxide (NO) synthase inhibitors N ω -nitro- l -arginine (10 mg/kg) or N ω -nitro- l -arginine methyl ester (20 mg/kg) and the cyclooxygenase inhibitor indomethacin (5 mg/kg). The inactive enantiomer N ω -nitro- d -arginine methyl ester (20 mg/kg) did not inhibit VEGF/VPF-induced permeability. In vitro studies confirmed that VEGF/VPF stimulates synthesis of NO and prostaglandin metabolites in microvascular endothelial cells. Finally, NO donors and the prostacyclin analogue taprostene administered together but not alone reproduced the increase in permeability observed with VEGF/VPF. Conclusions —These results implicate NO and prostacyclin produced by the interaction of VEGF/VPF with its Flk -1/KDR/VEGF-R2 receptor as mediators of VEGF/VPF-induced vascular permeability. Moreover, this property appears unique to VEGF/VPF among angiogenic cytokines.
Cigarette, alcohol, and illicit drug use down among US teens but e-cigarette use common, survey finds
Authors: M. McCarthy
Journal: BMJ (2014)

Pancreatic morphology and amylase release from isolated pancreatic acini in response to caerulein was studied in the course of an experimental bile induced acute pancreatitis without acinar necrosis. The inflammation was induced by retrograde microinfusion of 25 microliters bile into the rat bile pancreatic duct. A dissociation between functional and structural findings was seen. One hour after the bile injury, there was a transient change in acinar cell function. The response to stimulation by caerulein was reduced by 50%, whereas the sensitivity to caerulein was normal. There was oedema and an initial leucocyte infiltration of the gland. Six hours, one day, three days, and seven days after the bile injury, there was an acute interstitial oedematous pancreatitis with a modest polymorphonuclear leucocyte infiltration of the interstitium and widespread acinar vacuolisation. Morphological changes were most pronounced at the third postoperative day. Acinar amylase release, however, was normal both in terms of sensitivity and responsiveness to stimulation. These results show that bile injury may result in an initial disturbance of acinar cell function. Normal acinar amylase release prevailing in the course of the inflammation suggests that disturbance of the acinar amylase secretory response is not a primary stimulant of the inflammation before the development of acinar necrosis.
The John Phillips Memorial Lecture: The Diagnosis of Common Hereditary Hemorrhagic Diseases.
Authors: A. J. Quick
Journal: Annals of Internal Medicine (1961)

s1 May 1961The John Phillips Memorial Lecture: The Diagnosis of Common Hereditary Hemorrhagic Diseases.A. J. Quick, M.D.A. J. Quick, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-54-5-1052_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe diagnostic triad—history, physical, and laboratory—is the key to the study of the hereditary bleeding diseases. From the history, it can usually be determined whether the bleeding is spontaneous (capillary) or traumatic (arteriolar). The prototype of the first is found in thrombocytopenia while the second is characteristic of hemophilia.The three hereditary types and the hemorrhagic diseases belonging to them are: 1. sex-linked recessive- classical hemophilia and hemophilia B (also known as Christmas disease and PTC deficiency); 2. autosomal dominant-telangiectasia and von Willebrand's disease (pseudohemophilia); and 3. autosomal recessive- hypoprothrombinemia vera, afibrinogenemia, hyperheparinemia, and deficiencies of factors V (labile factor),... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Milwaukee, Wis. (CS) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1961Volume 54, Issue 5Page: 1052-1052KeywordsAutosomal dominant diseasesCapillariesGenetic diseasesHemophiliaHemophilia BHemorrhagevon Willebrand disease ePublished: 1 December 2008 Issue Published: 1 May 1961 PDF downloadLoading ...
DNA Damage by Benzo(<i>a</i>)pyrene in Human Cells Is Increased by Cigarette Smoke and Decreased by a Filter Containing Rosemary Extract, Which Lowers Free Radicals
Authors: Kroum Alexandrov, Margarita Rojas, Christian Rolando
Journal: Cancer Research (2006)

Abstract We found previously that the human lung benzo(a)pyrene (BP)-7,8-diol-9,10-epoxide-N2-deoxyguanosine (BPDE-dG) adduct concentrate in the target bronchial cells. This adduct is now considered to be critical event in tumorigenesis by BP. In this study, we investigate the contribution of cigarette smoke on the BPDE-dG formation. In a cell-free system, the amount of (−)-anti-BPDE-dG adduct increased linearly with concentration of cigarette smoke in the presence of (+)-BP-7,8-diol. Catalase and superoxide dismutase inhibited its formation by &amp;gt;80%. When MCF-7 cells were treated for 2 hours with the (+)-BP-7,8-diol, cigarette smoke increased dose dependently the formation of (−)-anti-BPDE-dG and decreased the cytochrome P450 (CYP)–dependent formation of (+)-r-7,t-8-dihydroxy-c-9,10-oxy-7,8,9,10-tetrahydro-BP the adduct. Then, cells were treated for up to 1 day with BP and then exposed for 2 hours with cigarette smoke. During these 2 hours, there are twice the increase in the adduct formation in cells treated with cigarette smoke compared with levels in nontreated cells due to CYP activity. Thus, cigarette smoke containing reactive oxygen species may activate the second step of BP metabolic way, leading to the formation of BPDE-dG adduct. Cigarette smoke thus seems may be in part responsible for the formation of the critical lung tumorigenic adduct. Finally, modified cigarette filter containing rosemary extract decreases by &amp;gt;70% of the BPDE-dG adducts level due to the cigarette smoke in MCF-7 cells. This approach may lead to decreasing lung cancer risk in addicted smokers. (Cancer Res 2006; 66(24): 11938-45)
Abstract 622: Degradation of APE1 by the E3 ubiquitin ligase Parkin.
Authors: Timothy L. Scott, Suganya Rangaswamy, Bithika Dhar, LianTeng Zhi, Hansruedi Bueler, Tadahide Izumi
Journal: Cancer Research (2013)

Abstract The mammalian apurinic/apyrimidinic endonuclease 1 (APE1/Ref1) is a DNA repair/redox regulator protein of which cytoplasmic accumulation has been associated with tumorigenesis and poor survival outcome. APE1 is degraded through the ubiquitin/proteasome pathway and previous studies reported APE1 ubiquitination by the E3 ubiquitin ligases MDM2 and UBR3. Here we report that Parkin efficiently polyubiquitinated and degraded APE1. Parkin, a product of the PARK2 gene, is responsible for a type of early onset Parkinson's disease (PD) and has been identified as a tumor suppressor. Expression of Parkin and Pink1 enhanced APE1 ubiquitination and markedly decreased endogenous APE1 in A549, a lung adenocarcinoma cell line. APE1 degradation was blocked by incubation of the cells with MG132, a potent 26S proteasome inhibitor, and by a PD associated point mutation in the Parkin RING domain. The activity of PTEN induced-kinase 1 (Pink1) was required for APE1 degradation. Co-immunoprecipitation revealed that APE1 interacted with Parkin in the presence of Pink1. These results suggest that APE1 stability is dynamically regulated by Parkin in the cytoplasm through the N-terminal APE1 domain. Citation Format: Timothy L. Scott, Suganya Rangaswamy, Bithika Dhar, LianTeng Zhi, Hansruedi Bueler, Tadahide Izumi. Degradation of APE1 by the E3 ubiquitin ligase Parkin. [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 622. doi:10.1158/1538-7445.AM2013-622
The Critical Care Complex
Authors: Forrest J. Cioppa
Journal: JAMA (1971)

To the Editor.—  With the rapid advances in cardiopulmonary physiology, pharmacology, bioelectronics, and new surgical techniques, we are capable of providing virtually miraculous assistance to patients who are critically ill. Today we have available many new techniques and devices for monitoring cardiac function, assisting ventilation, and measuring the efficiency of vital body organs. Usually this sophisticated and highly technical equipment is scattered throughout the hospital in various departments such as the recovery room, the intensive care unit, the coronary care unit, the respiratory unit, and the emergency department. It seems reasonable to assume that centralization of this equipment and the specially trained personnel who operate it would facilitate the use of the equipment, improve the efficiency of the individual units, and strengthen professional competence. The result would be more effective patient care for the critically ill.  This proposed centralized area might be termed the critical care complex or the CCC.
The effects of heart rate, myocardial ischemia and vagal stimulation on the threshold for ventricular fibrillation.
Authors: R G James, J M Arnold, J D Allen, J F Pantridge, R G Shanks
Journal: Circulation (1977)

The minimum current required to cause ventricular fibrillation was determined by electrical stimulation of the normal or ischemic canine left ventricle. The threshold for ventricular fibrillation in the normal heart decreased when the heart rate was rapid. Strong vagal stimulation did not affect the ventricular fibrillation threshold when the heart rate was fixed. The fall in the ventricular fibrillation threshold in the presence of acute myocardial ischemia was greater and more prolonged when the heart rate was rapid. These findings indicate the importance of the immediate correction of tachycardia in patients suffering from acute myocardial infarction.
Differential human multiple myeloma cell line responsiveness to interferon-alpha. Analysis of transcription factor activation and interleukin 6 receptor expression.
Authors: D F Jelinek, K M Aagaard-Tillery, B K Arendt, T Arora, R C Tschumper, J J Westendorf
Journal: Journal of Clinical Investigation (1997)

Although IFN-alpha is commonly used as maintenance treatment for multiple myeloma patients, its effectiveness is varied. In this study, we have used a panel of IL-6 responsive myeloma cell lines that vary remarkably in responsiveness to IFN-alpha. Three cell lines were growth arrested by IFN-alpha; however, IFN-alpha significantly stimulated growth of the fourth cell line, KAS-6/1. Our studies have focused on elucidating the mechanism of differential IFN-alpha responsiveness. First, we have shown that IFN-alpha-stimulated growth of the KAS-6/1 cells did not result from induction of autocrine IL-6 expression. Second, analysis of Stats 1, 2, and 3 and IFN regulatory factor-1 (IRF-1) and IRF-2 activation failed to reveal differences between the IFN-alpha growth-arrested or growth-stimulated cells. Third, although IFN-alpha treatment of the IFN-alpha growth-inhibited cell lines reduced IL-6 receptor (IL-6R) expression, IFN-alpha also reduced KAS-6/1 IL-6R expression. Finally, although IFN-alpha treatment reduced IL-6R numbers on each cell line, analysis of Stat protein activation revealed that the receptors were still functional. We conclude that myeloma cell responsiveness to IFN-alpha is heterogeneous and that mechanisms of IFN-alpha-mediated growth inhibition other than IL-6R downregulation must exist in myeloma. Identification of these mechanisms may allow development of agents that are more universally effective than IFN-alpha.
Abstract 101: Analysis <i>of GNAQ</i> mutations in subtypes of malignant melanoma
Authors: Hanne E. Puntervoll, Edda Vuhahula, Anders Molven, Lars A. Akslen
Journal: Cancer Research (2012)

Abstract Background: The MAP kinase pathway has been implicated in the pathogenesis of cutaneous melanoma, and mutations in BRAF and NRAS are commonly found in subtypes of melanomas as well as in benign nevi. Recently, several publications have reported frequent mutations in codon 209 of GNAQ in blue nevi and uveal melanoma, revealing an alternative path to MAP kinase activation. Aim of study: We wanted to investigate the prevalence of GNAQ mutations in codon 209 in a broad spectre of cutaneous melanoma, previously screened for mutations in BRAF, NRAS and EGFR. Methods: 75 benign and malignant tumors of different subgroups were collected at the Department of Pathology, the Gade Institute, Haukeland University Hospital, including: Spitz nevi, superficial spreading melanoma, superficial spreading melanoma in situ, lentigo malignant melanoma, nodular melanoma, metastases from nodular melanoma and uveal melanoma. Additionally, 14 acral African melanomas were collected at the Department of Pathology, Muhimbili University college of Health Sciences, Dar Es Salaam, Tanzania. Tumor tissue was manually dissected from formalin fixated paraffin-embedded sections, before GNAQ exon 5 was screened for mutations in codon 209 by direct Sanger sequencing. Further sample collection and analysis are ongoing. Results: The sequence analysis detected mutations in codon 209 in all five uveal melanomas tested (four harbored a Q209L mutation, and one had a Q209P mutation). However no mutations were found in any of the other subtypes of malignant melanoma. Conclusion: Our study shows that there appears to be a general lack of GNAQ mutations in cutaneous melanoma. This confirms that there may be different routes to MAP kinase activation in malignant melanoma as suggested by other studies. 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 101. doi:1538-7445.AM2012-101