tbuckley/cabot-search huggingface dataset:
Long‐term outcome of monoclonal (type 1) cryoglobulinemia
Authors: Antoine Néel, François Perrin, Olivier Decaux, Thomas Dejoie, Benoit Tessoulin, Maxime Halliez, Béatrice Mahé, Thierry Lamy, Fadi Fakhouri, Patrick Jego, Christian Agard, Cécile Vigneau, Lucienne Guenet, Bernard Grosbois, Philippe Moreau, Mohamed Hamidou
Journal: American Journal of Hematology (2014)

The aim of this study is to investigate long‐term outcome of symptomatic type 1 cryoglobulinemia (CG) and its determinants. Retrospective cohort study was conducted in two French University Hospitals. Patients with type 1 CG were identified using laboratory databases. Inclusion criterion was the presence of persistent symptoms of CG. Among 227 screened patients, 36 were included. Skin or vasomotor symptoms were the most frequent features (75%). Nephropathy and neuropathy occurred in 30% and 47% of cases, respectively. The underlying B cell disease (BCD) was a nonmalignant monoclonal gammopathy (NMMG) in 13 (36%) and a hematologic malignancy (HM) in 23 (64%; Waldenstrom macroglobulinemia (WM) in 12, low‐grade non‐Hodgkin lymphoma (NHL) in 6, multiple myeloma (MM) in 4, and chronic lymphocytic leukemia in 1 patient. Severe manifestations affected half the patients and were more frequent with IgG (82 vs. 30% ( P = 0.006)). At last follow‐up, 64% of patients had suffered no hematologic manifestation. Potent chemotherapeutic regimens were mainly used in HM. For patients with NMMG, WM, or NHL, fludarabine or rituximab‐based regimens appeared to yield better responses. Five‐year survival rate was 82%. In multivariate analysis, mortality was significantly higher in older patients (HR: 1.17 per year [95% CI: 1.06–1.28], P = 0.001) and those with nephropathy (HR: 8.9 [95% CI: 1.9–43], P = 0.006). Kidney disease, infections, Richter's transformation, and second malignancies were important sources of morbi‐mortality. Despite its limitations, this series provide novel information regarding type 1 CG. Further studies are needed to improve its management. To date, therapeutic strategy should be tailored according to patient's characteristics (age, comorbidities, underlying BCD), and therapeutic target.Am. J. Hematol. 89:156–161, 2014. © 2013 Wiley Periodicals, Inc.
Relevance of hemoglobin A1c and acute exacerbations of chronic obstructive pulmonary disease
Authors: Haruka Aoki, Takeshi Hisada, Masakiyo Yatomi, Hiroaki Tsurumaki, Reiko Yoshino, Kunio Dobashi, Tamotsu Ishizuka, Masatomo Mori
Journal: European Respiratory Journal (2013)

Background and objective 

Hyperglycaemia during hospital admission is associated with poor outcomes in patients admitted with acute myocardial infarction, stroke and pneumonia. Systemic inflammation may represent a possible cause of glycometabolic disorder. We proposed that is associated with an increased risk of acute exacerbation of COPD (AECOPD).

Methods Patients with COPD were prospectively enrolled and followed between 2009 and 2013. Medical records, HbA1c, fasting glucose and metabolic markers were assessed in 56 COPD patients.

Results 

A total of 56 patients (mean age of 75.7years) were recruited, 18 with AECOPD and 38 without. Clinical data were collected from the patients. HbA1c levels of AECOPD patients were significantly higher on entry point compared with other patients (5.78±0.26; 4.98±0.18, respectively p=0.0361). A negative association between total cholesterol and LDL cholesterol were observed. Moreover, HbA1c tended to increase at AECOPD (+0.3±0.07).

Conclusion 

Previous study revealed that comorbid diabetes prolongs length of stay and increases risk of death in patients with AECOPD. However, less evidence exists for relationship of HbA1c with AECOPD. For the first time our study demonstrates that HbA1c is a prognostic factor associated with AECOPD.
Progress of fibrinolysis during tumor necrosis factor infusions in humans. Concomitant increase in tissue-type plasminogen activator, plasminogen activator inhibitor type-1, and fibrin(ogen) degradation products
Authors: VW van Hinsbergh, KA Bauer, T Kooistra, C Kluft, G Dooijewaard, ML Sherman, W Nieuwenhuizen
Journal: Blood (1990)
Combined inhibition of poly (ADP-ribose) polymerase (PARP) and telomerase increases susceptibility of mammalian cells to arsenite-induced DNA damage
Authors: Resham Gurung, Lakshmidevi Balakrishnan, Manoor Prakash Hande
Journal: Clinical Cancer Research (2007)

C15   Telomerase inhibition has been suggested in anti-tumor therapy, as telomerase activity is present in a majority of cancer cells, while it is absent in normal somatic cells. However, the time lag involved for the telomeres to become critically shortened before the onset of cytotoxic effects in cancer cells can lead to drug resistance. Inhibition of DNA repair pathways along with telomerase has been chosen as an alternative strategy to enhance anti-tumor effects and circumvent the possibility of drug resistance. PARP, an important DNA damage sensor, involved in DNA repair has also been shown to have a role in telomere maintenance. Therefore, the effects of combined inhibition of PARP and telomerase in mammalian cells following exposure to sodium arsenite (a carcinogen and a potent DNA damaging agent) were evaluated in this study. Inhibition of PARP by 3-aminobenzamide in telomerase negative mouse embryonic fibroblasts showed an increase in arsenite-induced DNA damage and telomere attrition compared to control cells. Similar effects were observed when PARP and telomerase were inhibited in combination than in those cells treated with either PARP inhibitor or telomerase inhibitor alone. Likewise, DNA damage was found to be higher in PARP inhibited telomerase deficient human fibroblasts as compared to normal human fibroblasts. Cell cycle arrest and apoptosis triggered by increased DNA damage and telomere attrition were also observed to be increased with combined inhibition of PARP and telomerase in mouse embryonic fibroblasts and human fibroblasts. Hence, the results in this study indicate the synergistic effect of combined inhibition of PARP and telomerase and its potential in cancer therapeutics.  *This research is supported by grants from Academic Research Fund, Ministry of Education, Singapore to MPH.
The sticky business of clotting: Riddles to make coagulation stick
Authors: Lisa Senzel
Journal: American Journal of Hematology (2014)

I'm cleaving factor V, So it can't stay alive. Except if it has Leiden, My cleavage site is hidin'. Who am I? When wounds appear, I get in gear, And stick to them like glue. I bind to VIII and collagen, And GPIb too. Who am I? ADAMTS can chop me, But no one else can stop me, On a gel no one can top me, I'm big and strong and ultra long. Who am I? An amino acid mimic, I'm often used in HIT. Make sure you check the PTT And adjust my rate a bit. Who am I? Five sugars I contain, Blocking Xa is my game. I'm short and sweet and indirect, Can you guess my name? In DIC a lot of me Is surely on the make. Fibrin clot will form and break, And that will leave me in its wake. Who am I? Some call me factor I. But substrates I have none. I'm important for the clot. An enzyme I am not. Who am I? I'm a test that helps for VTE, But not for ruling in. I'm only used for ruling out, That's really what I'm all about. Who am I? Head trauma may cause DIC, ‘Cause brain contains a lot of me. A number I have not, But I really start the clot. Who am I? When the liver just begins to fail, I'm the factor that gets low. I have the shortest half life, So the PT starts to go. Who am I? If the liver is completely shot, The coags will prolong a lot. I'm the only factor that's still okay, Endothelium makes me anyway. Who am I? Put tissue factor in a tube, Add patient plasma too. Phospholipid and calcium, That's all you need to do. I'm the time to form the clot I'm a test that's done a lot. Who am I? I've been called a nuisance By those with little taste. Whether I'm important Varies case by case. I prolong the PTT. I can be temporary. But if I stick around, Then clots just may be found. Who am I? I tend to strike the elderly, And I prolong the PTT. I'm a very scary IgG. Check one factor to test for me. Bleeding can be severe, Whenever I am here. Who am I? I'm a factor that goes by just one letter, When I'm around things are better, ‘Cause complement stays in check. If you take me away, Your kidneys will pay, ‘Cause HUS comes on deck. Who am I? I used to be a red cell, But the capillary choked me. In that little tiny vessel, The fibrin strands they broke me. Who am I? In my disease you know The platelet count is low. But if you transfuse platelets, That number will not grow. Who am I? Answers: Activated protein C, von Willebrand factor (vWF), ultra large vWF multimers, argatroban, fondaparinux, D-dimer, fibrinogen, D-dimer, tissue factor, Factor VII, Factor VIII, prothrombin time, lupus anticoagulant, acquired Factor VIII inhibitor, Factor H, schistocyte, ITP. Lisa Senzel1,2,3* 1Hematology Laboratories, Stony Brook University Medical Center, Stony Brook, New York; 2Transfusion Services, Stony Brook University Medical Center, Stony Brook, New York; 3Department of Pathology, Stony Brook University Medical Center, Stony Brook, New York
Irish women graduates shun general practice
Authors: Doug Payne
Journal: BMJ (2001)

The latest survey of general medical practice in the Republic of Ireland shows a fall in the number of younger doctors in general practice and a smaller percentage of women GPs than expected.

The survey—of 1629 family doctors—was conducted in 2000 by the joint directors of information technology training of the Irish College of General Practitioners. It found that, compared with 1996, the proportion of younger GPs (aged 26-35) had dropped from 17% to 14%, and the proportion of those aged 46–55 …
X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-κB signaling
Authors: Rainer Döffinger, Asma Smahi, Christine Bessia, Frédéric Geissmann, Jacqueline Feinberg, Anne Durandy, Christine Bodemer, Sue Kenwrick, Sophie Dupuis-Girod, Stéphane Blanche, Philip Wood, Smail Hadj Rabia, Denis J. Headon, Paul A. Overbeek, Françoise Le Deist, Steven M. Holland, Kiran Belani, Dinakantha S. Kumararatne, Alain Fischer, Ralph Shapiro, Mary Ellen Conley, Eric Reimund, Hermann Kalhoff, Mario Abinun, Arnold Munnich, Alain Israël, Gilles Courtois, Jean-Laurent Casanova
Journal: Nature Genetics (2001)
Corrigendum to “Biology of AAV Serotype Vectors in Liver-Directed Gene Transfer to Nonhuman Primates”
Authors: Guangping Gao, You Lu, Roberto Calcedo, Rebecca L. Grant, Peter Bell, Lili Wang, Joanita Figueredo, Martin Lock, James M. Wilson
Journal: Molecular Therapy (2006)

The authors regret the following errors: On page 80, the second sentence in the legend to Fig. 2 should read “AST (the right y axes) and rhCG (the left y axes) levels at different time points after vector infusion from each of eight study subjects are presented” instead of “AST (the left y axes) and rhCG (the right y axes) levels at different time points after vector infusion from each of eight study subjects are presented.” On page 80, the right y axes label in Fig. 2 should read “AST (IU/L)” instead of “AST (IU/ml).” On page 85, the second sentence in the legend to Fig. 5 should read “AST (the right y axes) and rhEpo (the left y axes) levels at different time points after vector infusion from each of 10 study subjects are presented “instead of “AST (the left y axes) and rhEpo (the right y axes) levels at different time points after vector infusion from each of 10 study subjects are presented.” On page 85, the left axes label in Fig. 5 should read “Epo (mIU/ml)” instead of “Epo (mU/ml).” Biology of AAV Serotype Vectors in Liver-Directed Gene Transfer to Nonhuman PrimatesGao et al.Molecular TherapyJanuary, 2006In BriefVectors based on adeno-associated viruses (AAVs) show promise for the treatment of genetic diseases. This study evaluates the biology of AAV-mediated gene transfer to liver in nonhuman primates (NHPs) using vectors based on AAV serotypes 2, 7, and 8. Transgenes encoding self-proteins were selected to minimize the confounding development of transgene-specific immune responses. These included the β subunit of choriogonadotropic hormone (bCG) and erythropoietin (Epo), both derived from cDNAs from rhesus macaques. Full-Text PDF Open Archive
Abstract 391: Identification of a novel tumor-suppressor gene through methylome analysis in smoking-associated lung adenocarcinoma
Authors: Issei Imoto
Journal: Cancer Research (2014)

Abstract Aberrant methylation of promoter DNA and transcriptional repression of specific tumor suppressor genes (TSGs) play an important role in carcinogenesis. In order to identify novel TSG candidates implicated in smoking-associated lung adenocarcinoma (AC), we performed genome-wide methylation profiling of six smoking-associated lung ACs with paired non-cancerous tissues using the single-CpG resolution Infinium array. After defining differentially methylated candidates including known targets in ACs, we analyzed gene expression using microarray/RT-PCR to identify genes potentially silenced by promoter methylation. Frequent hypermethylation and downregulation of candidates was further validated by pyrosequencing and RT-PCR/immunohistochemistry, respectively, in a larger set of ACs, and methylation dependency of silencing was determined by 5-aza-2-deoxycytidine treatment and promoter assay in AC cell lines. Through this approach, we identified one gene matching all of our selection criteria for a possible TSG (HSLAC1, Lab. name). Additionally, functional analyses supported a tumor-suppressive activity in vitro. Our results implicate HSLAC1 as a novel TSG for smoking-associated lung AC. Citation Format: Issei Imoto. Identification of a novel tumor-suppressor gene through methylome analysis in smoking-associated lung adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 391. doi:10.1158/1538-7445.AM2014-391
CONGENITAL OSTEOSCLEROSIS (MARBLE BONE)
Authors: Carroll M. Pounders
Journal: Annals of Internal Medicine (1935)

Article1 February 1935CONGENITAL OSTEOSCLEROSIS (MARBLE BONE)CARROLL M. POUNDERS, M.D., F.A.C.P.CARROLL M. POUNDERS, M.D., F.A.C.P.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-8-8-966 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSince Albers-Schönberg1first wrote about this rare and interesting condition in 1904, descriptions of it with reports of approximately 30 cases have appeared in the literature. The majority of them originated in Germany with a few from America, Switzerland, France and Italy. Since most of the diagnoses have been made by accident while looking for other conditions, it is probable that it is not so rare as has been believed. Liévre2reminds us that it is not likely that the condition would in reality be so largely limited to the German speaking countries and suggests that the diagnosis has doubtless...References1. ALBERS-SCHÖNBERG HE: Röntgenbilder einer seltenen Knochenerkrankung, München. med. Wchnschr., 1904, li, 365. Google Scholar2. LIÉVRE JA: Les os de marbre, Bull. méd., Paris, 1929, xliii, 1231-1234. Google Scholar3. PÉHUPOLICARDDUFOURT MAA: L'ostéopétrose ou maladie des os marmoréens, Presse méd., 1931, xxxix, 999-1003. Google Scholar4. KUDRJAWTZEWA N: Über Marmorknochenkrankheit, Arch. f. klin. Chir., 1930, clix, 658-687. Google Scholar5. KARSHNER RG: Osteopetrosis, Am. Jr. Roentgenol., 1926, xvi, 405-419. Google Scholar6. STEPHENSBREDECK DJJF: Aleukemic myelosis with osteosclerosis, ANN. INT. MED., 1933, vi, 1087-1096. Google Scholar7. PIRIE AH: Development of marble bones, Am. Jr. Roentgenol., 1930, xxiv, 147-153. Google Scholar8. CLAIRMONTSCHINZ PHR: Case of Albers-Schönberg's marble bones, Arch. f. klin. Chir., 1924, cxxxii, 347-380. (Abstr., Jr. Am. Med. Assoc., 1925, lxxxiv, 405.) Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Oklahoma City, Oklahoma*Received for publication July 27, 1934. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAlbers-Schonberg diseaseKrankheiten der Knochen, Gelenke und MuskelnOsteopetrosis 1 February 1935Volume 8, Issue 8Page: 966-971KeywordsBone ePublished: 1 December 2008 Issue Published: 1 February 1935 PDF downloadLoading ...
Gut microbiota inhibit Asbt-dependent intestinal bile acid reabsorption via Gata4
Authors: Carolien Out, Jay V. Patankar, Marcela Doktorova, Marije Boesjes, Trijnie Bos, Sanna de Boer, Rick Havinga, Henk Wolters, Renze Boverhof, Theo H. van Dijk, Anna Smoczek, André Bleich, Vinay Sachdev, Dagmar Kratky, Folkert Kuipers, Henkjan J. Verkade, Albert K. Groen
Journal: Journal of Hepatology (2015)
Investigation of theLith1 candidate genesABCB11 andLXRA in human gallstone disease
Authors: Clemens Schafmayer, Jürgen Tepel, Andre Franke, Stephan Buch, Sören Lieb, Marcus Seeger, Frank Lammert, Bernd Kremer, Ulrich R. Fölsch, Fred Fändrich, Stefan Schreiber, Jochen Hampe
Journal: Hepatology (2006)

Genetic susceptibility in the causation of gallbladder diseases was recognized as early as 1937. A major gallstone susceptibility locus ( Lith1 ) was identified in 1995 by quantitative trait locus mapping in mice. Two attractive positional and functional candidate genes in LXRA and ABCB11 are located in this interval. ABCB11 is associated with progressive familial cholestasis. This study was undertaken to investigate LXRA and ABCB11 as candidate genes for gallstone disease in humans. Eight hundred and ten patients who underwent cholecystectomy for symptomatic gallstone disease (median age of onset, 50 years) were compared with 718 sex-matched control individuals. Control individuals were sonographically free of gallstones. Haplotype tagging and all known coding single nucleotide polymorphisms (SNPs) were genotyped for ABCB11 (n = 29) and LXRA (n = 10). The investigated high-risk patient sample provides a power of greater than 80% for the detection of odds ratios down to 1.55. No evidence of association of the two genes in the single point tagging markers, coding variants or in the sliding window haplotype analysis was detected (all nominal single-point P values ≥ .08). In conclusion , in the investigated German sample, no evidence of association of ABCB11 and LXRA to gallstone susceptibility was detected. The gallstone trait is not allelic to progressive familial cholestasis at the ABCB11 locus. Systematic fine mapping of the Lith1 region is required to identify the causative genetic variants for gallstone in mice and humans.
Abstract 17350: Multimarker Risk Stratification in Patients with Acute Myocardial Infarction
Authors: Michelle L O’Donoghue, David A Morrow, Nihar Desai, Matthew Sherwood, Sabina A Murphy, Christopher P Cannon, Robert E Gerszten, Marc S Sabatine
Journal: Circulation (2014)

Background: Circulating biomarkers have been evaluated largely individually for risk stratification in the setting of acute myocardial infarction (MI). The optimal multimarker strategy remains undefined. Methods: A total of 11 established and emerging biomarkers representing different pathobiological axes were studied. Specifically, MR-proADM, MR-proANP, copeptin, hsCRP, galectin-3, GDF-15, MPO, NT-proBNP, ST-2, PAPP-A and troponin T (TnT) were measured at presentation in 1258 patients from CLARITY-TIMI 28, a randomized trial of clopidogrel in ST-elevation MI (STEMI). Patients were followed for 30 days. Biomarker analyses were adjusted for age, sex, comorbidities, heart rate, blood pressure, creatinine clearance, Killip class, lytic type and timing, anterior MI and treatment arm. Forward stepwise selection was used to assess a multimarker strategy. Results: When examined individually (Figure, left), 7 biomarkers were each associated with an increased risk of CV death or heart failure through 30 days independent of standard clinical factors. In a multimarker model, 3 biomarkers emerged as independent and complementary predictors of CV death or HF: TnT, ST2, and MPO (Figure, right). A multimarker risk score significantly improved the C-statistic for predicting CV death or HF as compared with the TIMI STEMI Risk Score alone (AUC 0.75 to 0.82, P=0.001) as well as the NRI and IDI (P&lt;0.01 for each). Conclusions: In patients with STEMI, a multimarker strategy that combines biomarkers across pathobiological axes of cardiomyocyte necrosis, hemodynamic stress and inflammation provides incremental prognostic information for risk stratification.
The Consult Guys - Hands Up! Did You Cleanse Your Hands?
Authors: Geno J. Merli, Howard H. Weitz
Journal: Annals of Internal Medicine (2015)

Web Exclusives21 July 2015The Consult Guys - Hands Up! Did You Cleanse Your Hands?FREEGeno J. Merli, MD and Howard H. Weitz, MDGeno J. Merli, MDSearch for more papers by this author and Howard H. Weitz, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G15-3007 SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The Consult Guys bring a new perspective to the art and science of medicine with lively discussion and analysis of real-world cases and situations.For more videos from and information on The Consult Guys, visit www.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Disclosures: Geno J. Merli, MD, reports the following: Research grants/contracts: Bristol-Myers Squibb, Janssen, Portola; Consultancies: Bristol-Myers Squibb, Janssen. Howard H. Weitz, MD, reports that he has no financial relationships or interests to disclose.Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 21 July 2015Volume 163, Issue 2Page: CG1KeywordsDisclosureResearch grantsResearch reporting guidelines ePublished: 21 July 2015 Issue Published: 21 July 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.Loading ...