tbuckley/cabot-search huggingface dataset:
Closed-Chest Ablation of Retrograde Conduction in Patients with Atrioventricular Nodal Reentrant Tachycardia
Authors: Michel Haissaguerre, Jean Francois Warin, Philippe Lemetayer, Nadir Saoudi, Jean Pierre Guillem, Pierre Blanchot
Journal: New England Journal of Medicine (1989)

We applied a new technique of catheter ablation to treat atrioventricular nodal reentrant tachycardia and preserve anterograde conduction, performing this procedure in 21 patients with repetitive episodes of tachycardia refractory to antiarrhythmic drugs. Using atrial activation in the His-bundle lead as a reference, we selected the optimal site of ablation by positioning an electrode catheter so that atrial activation occurred simultaneously with or earlier than the reference activation during tachycardia. At this site, the His-bundle deflection was completely absent or was present only at a low amplitude (less than 0.1 mV). In the majority of patients, these criteria could be met by withdrawing the catheter 5 to 10 mm from the site of the His-bundle recording (adjacent to the reference catheter). Shocks of 160 or 240 J were delivered at this site (cumulative energy [mean +/- SD], 689 +/- 442 J). Treatment resulted in preferential abolition or impairment of retrograde nodal conduction. Anterograde conduction, although modified, was preserved in 19 patients; complete heart block persisted in 2 patients. Sixteen patients remained free of arrhythmia, without medication or implantation of a pacemaker, for a mean follow-up period of 14 +/- 8 months (range, 7 to 42). Tachycardia was not inducible in 14 patients in a follow-up electrophysiologic study performed 3.6 +/- 6 months after the procedure. We conclude that catheter ablation is an effective alternative for the treatment of atrioventricular nodal tachycardia in patients with drug-resistant tachycardia.
Successful anti-Id T-cell responses to Id-KLH immunotherapy in B-cell depleted patients with follicular lymphoma (FL) may prolong TTP after rituximab: Phase II trial of FavId
Authors: O. N. Koc, C. Redfern, P. Wiernik, F. Rosenfelt, J. Winter, T. Guthrie, L. Kaplan, P. Holman, J. Densmore, J. Hainsworth
Journal: Journal of Clinical Oncology (2004)

2520 Background: Active immunotherapy of FL is a promising therapeutic strategy. Anti-idiotype (Id) antibody and T-cell responses to Id-KLH have been correlated with responses in patients with FL. In a phase II trial, we evaluated the efficacy of Id-KLH vaccination in patients with FL, after cytoreduction with rituximab and during B-lymphopenia. Anti-Id responses were measured and the TTP was compared to historical data for rituximab alone. Methods: Pts with gr 1,2 FL who were treatment naïve; relapsed/refractory to chemo or relapsed after rituximab were eligible. Rituximab (375mg/m2 weekly x4) was followed by response assessment at wk10. Pts with at least SD (CR/PR/SD) started Id-KLH (1 mg s.q. monthly x 6) 12 wks after the first dose of rituximab. GM-CSF 250 mcg was given s.q. at the Id-KLH injection site on days 1–4. Pts with at least SD after 6 doses of Id-KLH could continue receiving the immunotherapy until progression. 123 pts were biopsied and 95 were eligible. Prior trerapy (in 60 of 95) was chemo and rituximab (31) chemotherapy alone (23) or rituximab alone (6). Id-KLH was successfully manufactured in 100% of eligible pts. All eligible pts have received rituximab and 58 pts have begun Id-KLH. Results: 36 patients (all previously treated) have a minimum of 6 months follow-up from first rituximab dose and are included in this preliminary analysis. 5 pts progressed after rituximab and did not receive Id-KLH. Robust T-cell responses to both Id and KLH were observed (3 of 3 pts). Anti-KLH antibody responses were seen in 2 of 10 pts and were delayed until B-cell recovery. 85% of the Id-KLH treated patients were without disease progression after a median of 9.7 months follow-up, compared with 56% of historical controls treated with rituximab alone (Witzig 2002 JCO 20:2453). Adverse events were infrequent with injection site reaction being most common. Conclusions: Id-KLH induces immune responses even after rituximab mediated B-cell depletion in FL patients. Preliminary data suggest that Id-KLH may prolong TTP after rituximab therapy and this strategy will be tested in a randomized phase III trial. No significant financial relationships to disclose.
Renal Graft Fibrosis and Inflammation Quantification by an Automated Fourier–Transform Infrared Imaging Technique
Authors: Vincent Vuiblet, Michael Fere, Cyril Gobinet, Philippe Birembaut, Olivier Piot, Philippe Rieu
Journal: Journal of the American Society of Nephrology (2015)

Renal interstitial fibrosis and interstitial active inflammation are the main histologic features of renal allograft biopsy specimens. Fibrosis is currently assessed by semiquantitative subjective analysis, and color image analysis has been developed to improve the reliability and repeatability of this evaluation. However, these techniques fail to distinguish fibrosis from constitutive collagen or active inflammation. We developed an automatic, reproducible Fourier-transform infrared (FTIR) imaging-based technique for simultaneous quantification of fibrosis and inflammation in renal allograft biopsy specimens. We generated and validated a classification model using 49 renal biopsy specimens and subsequently tested the robustness of this classification algorithm on 166 renal grafts. Finally, we explored the clinical relevance of fibrosis quantification using FTIR imaging by comparing results with renal function at 3 months after transplantation (M3) and the variation of renal function between M3 and M12. We showed excellent robustness for fibrosis and inflammation classification, with >90% of renal biopsy specimens adequately classified by FTIR imaging. Finally, fibrosis quantification by FTIR imaging correlated with renal function at M3, and the variation in fibrosis between M3 and M12 correlated well with the variation in renal function over the same period. This study shows that FTIR-based analysis of renal graft biopsy specimens is a reproducible and reliable label-free technique for quantifying fibrosis and active inflammation. This technique seems to be more relevant than digital image analysis and promising for both research studies and routine clinical practice.
Controlled Clinical Trial of Peritoneal Lavage for the Treatment of Severe Acute Pancreatitis
Authors: A. David Mayer, Michael J. McMahon, Andrew P. Corfield, Martin J. Cooper, Robin C.N. Williamson, Alan P. Dickson, Michael G. Shearer, Clement W. Imrie
Journal: New England Journal of Medicine (1985)

We performed a multicenter, randomized, controlled clinical trial of therapeutic peritoneal lavage (2 liters per hour for three days) in 91 patients with severe acute pancreatitis. Patients were entered into the study if severe pancreatitis was indicated by multiple laboratory criteria or diagnostic peritoneal lavage. All patients received full supportive treatment. The median time between the onset of symptoms and randomization was 38 hours. Forty-six patients were assigned to the control group and 45 to the lavage group. There were 13 deaths (28 per cent) and 16 patients with major complications (35 per cent) in the control group, as compared with 12 deaths (27 per cent) and 17 patients with major complications (38 per cent) in the lavage group. Lavage did not appear to modify the length of survival, the incidence of pancreatic collections (pseudocysts or abscesses), or the plasma amylase concentration. Considering the statistical power of the design, we conclude that the outcome of severe pancreatitis was not greatly, if at all, influenced by the regimen of peritoneal lavage used in this study. (N Engl J Med 1985; 312:399–404.)
Does physical activity attenuate, or even eliminate, the detrimental association of sitting time with mortality? A harmonised meta-analysis of data from more than 1 million men and women
Authors: Ulf Ekelund, Jostein Steene-Johannessen, Wendy J Brown, Morten Wang Fagerland, Neville Owen, Kenneth E Powell, Adrian Bauman, I-Min Lee
Journal: The Lancet (2016)
Researchers must share data to ensure publication in top journals
Authors: Anne Gulland
Journal: BMJ (2016)

Doctors wishing to publish in the world’s leading medical journals will have to share their data as a condition of publication, the International Committee of Medical Journal Editors has said.

In a joint editorial published in The BMJ and 13 other journals the editors said that because patients have put themselves at risk by taking part in trials researchers have an “ethical obligation” to share data.1

The editors, from journals in Europe, the …
A Comparison of Three Interferon Alfa-2b Regimens for the Long-Term Treatment of Chronic Non-A, Non-B Hepatitis
Authors: Thierry Poynard, Pierre Bedossa, Michèle Chevallier, Philippe Mathurin, Catherine Lemonnier, Christian Trepo, Patrice Couzigou, Jean Louis Payen, Marc Sajus, Jean Marc Costa, Michel Vidaud, Jean Claude Chaput
Journal: New England Journal of Medicine (1995)

We studied the effects of long-term treatment with interferon on histologic features of the liver and serum alanine aminotransferase concentrations in patients with chronic non-A, non-B hepatitis.
Prevalence of Hepatitis C Virus RNA in Organ Donors Positive for Hepatitis C Antibody and in the Recipients of Their Organs
Authors: Brian J.G. Pereira, Edgar L. Milford, Robert L. Kirkman, Stella Quan, Keith R. Sayre, Pamela J. Johnson, Judith C. Wilber, Andrew S. Levey
Journal: New England Journal of Medicine (1992)

There is a high prevalence of liver disease among the recipients of organs from donors with antibodies to hepatitis C virus (HCV). We undertook a study to determine the frequency of persistent HCV infection, as indicated by the presence of HCV RNA, among both cadaveric organ donors positive for antibodies to HCV (anti-HCV) and the recipients of organs from these donors.
Acromegaly Caused by Secretion of Growth Hormone by a Non-Hodgkin's Lymphoma
Authors: Felix Beuschlein, Christian J. Strasburger, Volker Siegerstetter, Darius Moradpour, Peter Lichter, Martin Bidlingmaier, Hubert E. Blum, Martin Reincke
Journal: New England Journal of Medicine (2000)

Acromegaly is a systemic disorder caused by sustained hypersecretion of growth hormone. The typical features include thickening of the skin, enlargement of the hands, feet, and mandible, and visceromegaly.1,2 Active disease is indicated by the presence of excessive sweating and soft-tissue swelling.1,2 Most patients with acromegaly have a growth hormone–secreting pituitary adenoma,3 but a few (less than 1 percent) have hypothalamic or other tumors that secrete growth hormone–releasing hormone.4 Isolated ectopic secretion of growth hormone has been reported only once, in a patient with a pancreatic islet-cell tumor.5,6 Here we describe a patient with recurrent non-Hodgkin's lymphoma . . .
Human Herpesvirus 8 and Interstitial Pneumonitis in an HIV-Negative Patient
Authors: Mario Luppi, Giuseppe Torelli
Journal: New England Journal of Medicine (1996)

To the Editor: A 67-year-old woman who was negative for the human immunodeficiency virus was seen because of low-grade fever, fatigue, night sweats, and weight loss, which had been present for seve...
Hepatic macrophages in homeostasis and liver diseases: from pathogenesis to novel therapeutic strategies
Authors: Cynthia Ju, Frank Tacke
Journal: Cellular and Molecular Immunology (2016)

Macrophages represent a major cell type of innate immunity and have emerged as a critical player and therapeutic target in many chronic inflammatory diseases. Hepatic macrophages consist of Kupffer cells, which are originated from the fetal yolk-sack, and infiltrated bone marrow-derived monocytes/macrophages. Hepatic macrophages play a central role in maintaining homeostasis of the liver and in the pathogenesis of liver injury, making them an attractive therapeutic target for liver diseases. However, the various populations of hepatic macrophages display different phenotypes and exert distinct functions. Thus, more research is required to better understand these cells to guide the development of macrophage-based therapeutic interventions. This review article will summarize the current knowledge on the origins and composition of hepatic macrophages, their functions in maintaining hepatic homeostasis, and their involvement in both promoting and resolving liver inflammation, injury, and fibrosis. Finally, the current strategies being developed to target hepatic macrophages for the treatment of liver diseases will be reviewed.
Abstract A35: Characterization of the genomic landscape of osteosarcoma metastasis
Authors: Amanda L. Koehne, Leanne C. Sayles, Marcus R. Breese, Dedeepya Vaka, Alejandro Sweet-Cordero
Journal: Cancer Research (2016)

Abstract Early metastasis to the lungs is a cardinal feature of osteosarcoma (OS), and complications from metastatic disease remain the most common cause of cancer-related death. Despite the prevalence of metastasis in OS, the pathogenesis is poorly understood. We have established a collection of 16 patient-derived xenografts (PDX) from human OS tumors, both from the primary site as well as metastasis. Our collection includes 9 diagnostic biopsies from primary site tumors, 2 primary tumor resections, 3 lung metastases, and 1 ascites fluid metastasis. Gene expression analysis of an initial set of 5 PDX models (3 metastases, 2 primaries) has been completed. A more extensive analysis of all 16 models by RNAseq and WGS is currently underway. Preliminary gene expression analysis identified a significant number of genes differentially expressed between metastatic samples and non-metastatic samples. This list included genes associated with cell adhesion and motility such as MEGF10, genes associated with endochondral ossification and bone remodeling such as RANKL, and genes associated with deposition of extracellular matrix (ECM) such as COL21A. Another candidate gene, ENPP1, is responsible for mineralization of the ECM and has been implicated in breast cancer metastasis to bone. We have validated differential expression of a number of these genes in independent samples of metastatic OS. We are currently using small hairpin RNA (shRNA), CRISPR, and overexpression vectors to knockdown, silence, and overexpress ENPP1 and other candidate genes in OS cell lines. Using in vitro migration and invasion assays as well as intravenous injection and orthotopic mouse models, we are characterizing the contribution of candidate genes to the metastatic propensity of OS. Citation Format: Amanda L. Koehne, Leanne C. Sayles, Marcus R. Breese, Dedeepya Vaka, Alejandro Sweet-Cordero. Characterization of the genomic landscape of osteosarcoma metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr A35.
A randomized phase III trial of denosumab versus zoledronic acid in patients with bone metastases from castration-resistant prostate cancer.
Authors: K. Fizazi, M. A. Carducci, M. R. Smith, R. Damião, J. E. Brown, L. Karsh, P. Milecki, H. Wang, R. D. Dansey, C. D. Goessl
Journal: Journal of Clinical Oncology (2010)

LBA4507 Background: Bone metastases from hormone-refractory (castration-resistant) prostate cancer (CRPC) are associated with RANKL-mediated osteoclast activation resulting in bone destruction and skeletal-related events (SRE). Denosumab is a fully human monoclonal antibody against RANKL. This phase III, randomized, double-blind, active-controlled trial compared the efficacy and safety of denosumab vs. zoledronic acid (ZA) in patients with metastatic CRPC. Methods: Patients (n = 1,901) with CRPC and at least 1 bone metastasis, but no prior IV bisphosphonate use, received either SC denosumab 120 mg and IV placebo (n = 950), or SC placebo and IV ZA 4 mg (n = 951) adjusted for creatinine clearance every 4 weeks. All patients were instructed to take supplemental calcium and vitamin D. The primary endpoint was time to first on-study SRE, defined as pathologic fracture, radiation or surgery to bone, or spinal cord compression. Results: Denosumab significantly delayed the time to first on-study SRE compared with ZA, (HR 0.82 ; 95% CI: 0.71, 0.95 ; p = 0.008.) The median time to first on-study SRE was 20.7 mo denosumab vs. 17.1 mo ZA, a difference of 3.6 months. Denosumab also significantly delayed the time to first and subsequent on-study SRE (multiple event analysis) (HR 0.82 ; 95% CI: 0.71, 0.94 ; p = 0.004). Greater suppression of the bone turnover markers uNTx and BSAP occurred in denosumab patients compared with ZA (p &lt; 0.0001 for both). Overall, adverse event (AE) rates (97% each) and serious AEs (63% denosumab, 60% ZA) were similar, irrespective of potential relationship to study drugs. AEs of hypocalcemia were reported in 13% and 6% of denosumab and ZA patients. Osteonecrosis of the jaw occurred in 22 (2.3%) denosumab compared with 12 (1.3%) ZA patients (p = 0.09). Overall survival (HR 1.03 ; 95% CI: 0.91, 1.17 ; p = 0.65) and time to cancer progression (HR 1.06; 95% CI: 0.95, 1.18; p = 0.30) were similar between treatment arms. Conclusions: Denosumab demonstrated superiority over ZA in delaying or preventing SREs in patients with bone metastases from CRPC. Adverse events were consistent in both treatment groups with those previously reported in advanced cancer populations. [Table: see text]
Association Between Sitagliptin Use and Heart Failure Hospitalization and Related Outcomes in Type 2 Diabetes Mellitus
Authors: Darren K. McGuire, Frans Van de Werf, Paul W. Armstrong, Eberhard Standl, Joerg Koglin, Jennifer B. Green, M. Angelyn Bethel, Jan H. Cornel, Renato D. Lopes, Sigrun Halvorsen, Giuseppe Ambrosio, John B. Buse, Robert G. Josse, John M. Lachin, Michael J. Pencina, Jyotsna Garg, Yuliya Lokhnygina, Rury R. Holman, Eric D. Peterson
Journal: JAMA Cardiology (2016)

Previous trial results have suggested that dipeptidyl peptidase 4 inhibitor (DPP4i) use might increase heart failure (HF) risk in type 2 diabetes mellitus (T2DM). The DPP4i sitagliptin has been shown to be noninferior to placebo with regard to primary and secondary composite atherosclerotic cardiovascular (CV) outcomes in the Trial Evaluating Cardiovascular Outcomes With Sitagliptin (TECOS).To assess the association of sitagliptin use with hospitalization for HF (hHF) and related outcomes.TECOS was a randomized, double-blind, placebo-controlled study evaluating the CV safety of sitagliptin vs placebo, each added to usual antihyperglycemic therapy and CV care among patients with T2DM and prevalent atherosclerotic vascular disease. The median follow-up was 2.9 years. The setting was 673 sites in 38 countries. Participants included 14 671 patients with T2DM and atherosclerotic vascular disease. The study dates were December 2008 through March 2015.Patients were randomized to sitagliptin vs placebo added to standard care.Prespecified secondary analyses compared the effect on hHF, hHF or CV death, and hHF or all-cause death composite outcomes overall and in prespecified subgroups. Supportive analyses included total hHF events (first plus recurrent) and post-hHF death. Meta-analyses evaluated DPP4i effects on hHF and on hHF or CV death.Of 14 671 patients, 7332 were randomized to sitagliptin and 7339 to placebo. Hospitalization for HF occurred in 3.1% (n = 228) and 3.1% (n = 229) of the sitagliptin and placebo groups, respectively (unadjusted hazard ratio, 1.00; 95% CI, 0.83-1.19). There was also no difference in total hHF events between the sitagliptin (n = 345) and placebo (n = 347) groups (unadjusted hazard ratio, 1.00; 95% CI, 0.80-1.25). Post-hHF all-cause death was similar in the sitagliptin and placebo groups (29.8% vs 28.8%, respectively), as was CV death (22.4% vs 23.1%, respectively). No heterogeneity for the effect of sitagliptin on hHF was observed in subgroup analyses across 21 factors (P > .10 for all interactions). Meta-analysis of the hHF results from the 3 reported DPP4i CV outcomes trials revealed moderate heterogeneity (I2 = 44.9, P = .16).Sitagliptin use does not affect the risk for hHF in T2DM, both overall and among high-risk patient subgroups.clinicaltrials.gov Identifier: NCT00790205.
P0559 : Evaluation of large, middle and small hepatitis B surface (HBS) proteins in HBeAg positive patients
Authors: F. Rinker, C.M. Bremer, B. Bremer, M.P. Manns, H. Wedemeyer, L. Yang, V. Pavlovic, C. Wat, A.R. Kraft, D. Glebe, M. Cornberg
Journal: Journal of Hepatology (2015)
Urinary Calcium Excretion in Human Beings
Authors: Howard L. Bleich, Mary Jean Moore, Jacob Lemann, Nancy D. Adams, Richard W. Gray
Journal: New England Journal of Medicine (1979)

CALCIUM is the most abundant cation in human beings. The total body content averages about 25,000 mmol, or 1 kg, in a 70-kg man — virtually all of it occurring in bone.1 Perhaps the most important biochemical property of calcium is that it forms salts that are barely soluble (Fig. 1).2 The solubility of calcium monohydrogen phosphate (CaHPO4·2H20) appears to determine the precipitation of calcium phosphates from aqueous solutions; this salt then undergoes transformation to apatites [Ca10(PO4)6(OH)2 or Ca10(PO4)6CO3], which are the principal . . .
Case 18-1977
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Bernard R. Aserkoff, James J. Galdabini
Journal: New England Journal of Medicine (1977)

Presentation of CaseA 69-year-old woman was admitted to the hospital because of fever and jaundice.Nine days previously she entered another hospital because of fever and malaise. Laboratory studies disclosed that the urine was normal except that the sediment contained 12 to 15 white cells per high-power field. The hematocrit was 33 per cent; the white-cell count was 19,000, with 76 per cent neutrophils and 21 per cent band forms. An automated biochemical scan of a blood specimen disclosed that the alkaline phosphatase and lactic dehydrogenase (LDH) were highnormal; the protein was slightly low. Blood cultures gave no bacterial . . .
Efficacy of Unusually High Doses of Tranexamic Acid for the Treatment of Epistaxis in Hereditary Hemorrhagic Telangiectasia
Authors: Carlo Sabbà, Mauro Gallitelli, Giuseppe Palasciano
Journal: New England Journal of Medicine (2001)

To the Editor: Hereditary hemorrhagic telangiectasia is an autosomal dominant disease characterized by epistaxis, cutaneous telangiectases, and visceral arteriovenous malformations.1 Aminocaproic a...
Measurements of Serum Müllerian Inhibiting Substance in the Evaluation of Children with Nonpalpable Gonads
Authors: Mary M. Lee, Patricia K. Donahoe, Bernard L. Silverman, Tomonobu Hasegawa, Yukihiro Hasegawa, Michael L. Gustafson, YuChiao Chang, David T. MacLaughlin
Journal: New England Journal of Medicine (1997)

Müllerian inhibiting substance, produced constitutively by the prepubertal testes, promotes involution of the müllerian ducts during normal male sexual differentiation. In children with virilization and nonpalpable gonads, only those with testicular tissue should have detectable serum concentrations of müllerian inhibiting substance.