tbuckley/cabot-search huggingface dataset:
Haptoglobin or Hemopexin Therapy Prevents Acute Adverse Effects of Resuscitation After Prolonged Storage of Red Cells
Authors: Jan A. Graw, Claire Mayeur, Ivy Rosales, Yumin Liu, Venkata S. Sabbisetti, Frank E. Riley, Osher Rechester, Rajeev Malhotra, H. Shaw Warren, Robert B. Colvin, Joseph V. Bonventre, Donald B. Bloch, Warren M. Zapol
Journal: Circulation (2016)

Extracellular hemoglobin and cell-free heme are toxic breakdown products of hemolyzed erythrocytes. Mammals synthesize the scavenger proteins haptoglobin and hemopexin, which bind extracellular hemoglobin and heme, respectively. Transfusion of packed red blood cells is a lifesaving therapy for patients with hemorrhagic shock. Because erythrocytes undergo progressive deleterious morphological and biochemical changes during storage, transfusion of packed red blood cells that have been stored for prolonged intervals (SRBCs; stored for 35-40 days in humans or 14 days in mice) increases plasma levels of cell-free hemoglobin and heme. Therefore, in patients with hemorrhagic shock, perfusion-sensitive organs such as the kidneys are challenged not only by hypoperfusion but also by the high concentrations of plasma hemoglobin and heme that are associated with the transfusion of SRBCs.To test whether treatment with exogenous human haptoglobin or hemopexin can ameliorate adverse effects of resuscitation with SRBCs after 2 hours of hemorrhagic shock, mice that received SRBCs were given a coinfusion of haptoglobin, hemopexin, or albumin.Treatment with haptoglobin or hemopexin but not albumin improved the survival rate and attenuated SRBC-induced inflammation. Treatment with haptoglobin retained free hemoglobin in the plasma and prevented SRBC-induced hemoglobinuria and kidney injury. In mice resuscitated with fresh packed red blood cells, treatment with haptoglobin, hemopexin, or albumin did not cause harmful effects.In mice, the adverse effects of transfusion with SRBCs after hemorrhagic shock are ameliorated by treatment with either haptoglobin or hemopexin. Haptoglobin infusion prevents kidney injury associated with high plasma hemoglobin concentrations after resuscitation with SRBCs. Treatment with the naturally occurring human plasma proteins haptoglobin or hemopexin may have beneficial effects in conditions of severe hemolysis after prolonged hypotension.
Goodman and Gilman's The Pharmacological Basis of Therapeutics
Authors: Robert C. Hastings, Gillis W. Long
Journal: JAMA (1991)

Being asked to review Goodman and Gilman is a lot like being asked to comment on motherhood. The stature of  G & G , the blue bible of pharmacology, is intimidating. For a reviewer reared in its teachings, it is difficult to find fault. Luckily, in keeping with the textbook's tradition, this new edition is virtually without fault. The book covers an everincreasing body of knowledge in crisp, clear language and its time-honored, familiar format.  The eighth edition marks the 50th anniversary of the textbook. As mentioned in the preface by the senior editor, Alfred Goodman Gilman, the primary objectives of the book have remained the same since his father and Dr Goodman wrote the first edition in 1940: the correlation of pharmacology with related medical sciences, the continual reinterpretation of the actions and uses of drugs in view of medical advances, and the emphasis on applying pharmacodynamics to therapeutics. Dr
Psychiatric Consequences of September 11Bioterrorism and Public Health LawPolice Detainment of a Patient Following Treatment With Radioactive IodineHealth Literacy and Diabetic ControlPreoperative Hand-Rubbing vs Hand-Scrubbing
Authors: Milena J Henzlova
Journal: JAMA (2002)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Multiple Expressed Endogenous Glioma Epitopes as Novel Vaccines for Gliomas
Authors: Pedro R. Lowenstein, Maria G. Castro
Journal: Clinical Cancer Research (2016)

Abstract A novel approach to immunization against glioma tumors is described. Immunization against 11 antigens expressed in malignant brain tumors elicits responses to one or more antigens in a large percentage of patients. This novel approach suggests that it could be extended to a phase III trial. Clin Cancer Res; 22(19); 4760–2. ©2016 AACR. See related article by Rampling et al., p. 4776
KRAS and BRAF mutations in colorectal cancer patients in northwest of Iran.
Authors: Roya Dolatkhah, Saeed Dastgiri, Mohammad hossein Somi, Morteza Jabbarpour Bonyadi, Iraj Asvadi Kermani, Faris Farassati
Journal: Journal of Clinical Oncology (2015)

e14508 Background: Several epidemiologic studies have shown that although Iran has a comparatively low rate of colorectal cancer (CRC), its incidence is increasing. Mutations of KRAS and BRAF proto-oncogenes are thought to be key in the progression of CRC. The aim of this study was to examine the epidemiological characteristics of colorectal cancer in the East Azerbaijan province and the prevalence of KRAS and BRAFmutations. Methods: Polymerase chain reactions using the KRAS and BRAF primers, KRAS exon 2 and BRAFexon 15 were performed in 30 colorectal cancer patients (13 colon/7 rectum). The Sanger sequencing method was used to determine the mutation points. After mutation analysis, the clinical and pathological associations of mutant genes were evaluated. Results: The prevalence of the KRAS gene mutation was 20 % (6 out of 30 cases), of which the most prevalent type was in codon 12, related to nucleotide transition of GGT > GAT. None of the patients had the BRAF gene mutation in exon 15. The odds ratio of the KRAS mutation in high grade CRC was 2.1, increasing 1.1 times with metastasis. The incidence of the KRASgene mutation in patients with right-sided tumors was 3.9-times higher than those with left-sided tumors. Smokers had a 1.2-times higher risk of developing this mutation. In this study, colorectal cancer had a higher incidence in men than women, and 17% of patients were under 50 years of age. Twelve patients (40%) had a family history of CRC in at least one first-degree relative, and there was no significant relationship between the mutation and clinical and pathological aspects of the disease. Conclusions: In Iran, the high proportion of middle-age onset CRC, i.e., 40–50 years, demands more attention in both screening and prevention programs. Further genetic studies are needed in larger and broader populations. 95% Confidence Interval Odd’s ratio KRAS Gene Mutation Upper Lower 17.26 .16 1.67 Male Sex Female(Reference) 11.03 0.09 1.00 <50 Age ≥50(Reference) 3.29 1.34 2.10 High Stage(III,IV) Stage Low Stage(0,I,II) (Reference) 1.25 .93 1.08 Yes Metastasis No(Reference) 7.08 .20 1.18 Yes Smoking No(Reference) 6.21 .06 .60 Yes Alcohol No(Reference)
Mass balance, pharmacokinetics, and metabolism of [<sup>14</sup>C] brivanib (BMS-582664), prodrug of BMS-540215, in subjects with advanced or metastatic solid tumors
Authors: R. Ganapathi, T. Mekhail, C. Wu, B. Fischer, J. Gong, R. A. Iyer, J. Gan, J. Pursley, D. Patricia, E. Masson
Journal: Journal of Clinical Oncology (2009)

3566 Background: Brivanib alaninate (BMS-582664, B) is an oral prodrug of BMS-540215, a dual tyrosine kinase inhibitor of VEGFR and FGFR signaling pathways which are important for angiogenesis and tumor growth. The recommended phase II/III dose of B is 800 mg daily. Methods: A two-part, open-label, single-dose study was conducted in subjects with advanced or metastatic solid tumors. Part A represented the period for assessment of the pharmacokinetics (PK), metabolism, and elimination of B, In part A, subjects received a single oral dose of 800 mg [ 14 C]-labeled B containing 100 μCi of total radioactivity (0.125 μCi/mg). Blood was collected at selected time points for analyses of PK, biotransformation, and total radioactivity over a 10-day period. Complete urinary and fecal output was collected over the 10-day period or until discharge, and analyzed for total radioactivity and biotransformation. Part B began when subjects completed Part A. Part B subjects received B administered orally at a dose of 800 mg once daily starting on approximately Day 15 to 17 of study. Subjects continued in this study until disease progression or unacceptable toxicity. Results: 4 subjects (2 NSCLC, 1 ovarian, 1 renal cell carcinoma) were treated with B in both parts A &amp; B. B was tolerable with few G3/4 AEs (increased fatigue, 1 event, cognitive disturbance, 1 event). The results revealed that B is completely converted to active moiety, BMS-540215, after oral administration. BMS-540215 is extensively metabolized in humans. Elimination is primarily via the feces. Following a single oral dose of [ 14 C]-labeled B, approximately 12% and 82% of the administered radioactivity was recovered in the urine and feces, respectively, within 10 days. BMS-540215 accounted for 0.00% and 7.4% of the administered dose in urine and feces, respectively, with the remainder of the dose being minor metabolites. The mean terminal t1/2 of BMS-540215 was 14 hours. Conclusions: After oral administration of single 800 mg oral doses of [ 14 C] B, BMS-540215 was found to be the major active circulating moiety in plasma (22.5%). BMS-540215 is primarily eliminated via metabolism. [ 14 C]-labeled B formulation was well tolerated with no AEs leading to the discontinuation of any subject. [Table: see text]
A single-institution (MSKCC) analysis of incidence and clinical outcomes in patients with thromboembolic events and exocrine pancreas cancer.
Authors: A. S. Epstein, C. Crosbie, S. Gardos, G. A. Soff, M. A. Shah, D. P. Kelsen, E. M. O’Reilly
Journal: Journal of Clinical Oncology (2010)

4062 Background: Pancreas adenocarcinoma (PC) is one of the most common malignancies associated with venous thromboembolism (VTE), but reported incidence ranges vary and contain relatively small patient subsets. Little has been described about arterial thrombotic events (ATE) in PC, as well as the correlation between VTE timing and patient outcomes. Methods: We identified a total of 6,870 patients with PC seen at our institution from 1/1/00 to 12/31/09. Using ICD codes, we analyzed subsets of this patient group with VTE or ATE. Demographic data included vital status, age at diagnosis of PC, timing of thrombotic event (TE), and thrombosis treatment. Results: Any thrombosis was identified in 1,322 (19%), of which 1,179 (17%) had VTE, 143 (2%) had ATE, and 64 (0.9%) of patients had both an ATE and VTE. 290 (25%) of the VTE patients had pulmonary embolism (PE). For patients in whom treatment information was available, low molecular weight heparin (LMWH) was prescribed in 95% and fondaparinux in 6%. 0.4% received warfarin and 23% received aspirin. 19% of VTE patients received an IVC filter. Of patients with deep vein thromboses (DVTs), the mean overall survival (OS) from PC diagnosis to death was 12.9 months, compared with 13.4 months for PC patients without thrombosis. 96% of TEs were diagnosed after the diagnosis of PC. Of note, of the 4% of TEs diagnosed at or before the diagnosis of PC, the OS was 6.2 months, compared with 13.7 months for patients with later TEs. Conclusions: This is the largest single-institution cohort to describe the incidence of and clinical outcomes associated with TE in PC. VTE predominated, but arterial events were also observed. This analysis confirms the relatively high incidence of TEs in PC. While study limitations include lack of stage and treatment details as well as possible sampling error, the observation that a VTE is associated with a markedly worse prognosis if the event precedes or coincides with PC diagnosis, but not necessarily if the VTE occurs later (typically during treatment), suggests a difference in biological significance and prognosis of these events. No significant financial relationships to disclose.
The Debt and the Cash Flow of Residents: I. The Grim Present
Authors: Thomas B. Corkery
Journal: JAMA (1990)

<h3>To the Editor.—</h3> I am a new physician in practice who recently completed 4 years of medical school in addition to 4 years of postgraduate training. Like most of my colleagues, I have incurred an extraordinary amount of debt to become a physician. I do not regret my decision, but I am troubled by the recent laws that have made low-interest loans unavailable and, most notably, have made the large amount of interest accruing on highinterest loans no longer tax deductible. I understand the need for increased federal revenues, although I believe that it is unfair to apply these new tax law changes toward the loans that were assumed under the old tax laws. The interest on these previously assumed variable-rate educational loans is excessive. Unfortunately, these loans are necessary because of the high cost of our medical training and the absence of low-interest funding. It is true that
Urinary Glycosaminoglycans Predict Outcomes in Septic Shock and ARDS.
Authors: Schmidt Ep, Overdier Kh, Sun X, Lin L, Liu X, Yang Y, Ammons La, Hiller Td, Suflita Ma, Yu Y, Chen Y, Zhang F, Cothren Burlew C, Edelstein Cl, Douglas Is, Linhardt Rj
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Contributions: EPS designed the study, performed statistical analyses, interpreted the data, and wrote the manuscript. KHO, LAA, TDH, and CCB participated in study design and enrolled study subjects. XS, LL, XL, YY, MAS, YY, YC, and FZ designed and performed analyses of urine glycosaminoglycan content. CLE provided patient samples and assisted in study design. ISD participated in study design, performed statistical analyses, interpreted the data, and assisted in manuscript preparation. RJL supervised all analyses of urine glycosaminoglycan content, assisted in study design, interpreted the data, and assisted in manuscript preparation.
Annexin A5 Resistance Is Associated with Thrombotic Risk in Patients with the Lupus Anticoagulant: The Vienna Lupus Anticoagulant and Thrombosis Study (LATS)
Authors: Florian Posch, Johanna Gebhart, Wu Xiao-Xuan, Silvia Koder, Cihan Ay, Jacob H. Rand, Ingrid Pabinger
Journal: Blood (2015)
Impact of EGFR and ALK mutation on the outcomes of non-small cell lung cancer (NSCLC) patients with brain metastases.
Authors: Suresh Kumar Balasubramanian, Vyshak Alva Venur, Samuel T. Chao, Lilyana Angelov, Alireza Mohammad Mohammadi, Gene H. Barnett, Xuefei Jia, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2016)

2005 Background: Brain metastases (BM) are common serious complication of NSCLC. Activating mutations in EGFR and ALK constitute 10-15% and 5% of NSCLC respectively. Patients with multiple BM (≥4) have inferior outcomes compared to single or limited BM (≤ 3) in wild type NSCLC. There is limited information on impact of number of BM on EGFR and ALK positive NSCLC BM. Methods: With IRB approval, the Cleveland Clinic Neuro-Oncology Center's database was used to identify patients treated between 2000-2014 for Non-Small Cell Lung Cancer (NSCLC) BM with mutational status (EGFR/ALK/wild). Overall survival (OS) from the diagnosis of BM was the primary end point. Cox proportional hazards models were used for data analysis. Results: 1032 NSCLC patients with BM were included in the analysis. Among 322 NSCLC BM with mutational analysis, 88 were positive for mutation (ALK = 21; EGFR = 67) and 234 were wild type. Median age at diagnosis in EGFR, ALK + NSCLC BM was 59.5 (range 29.8, 82.6) and 50.6% (43 patients) had KPS > 80. Median number of BM was 2 (range 1, 90) in this group. The median OS for ALK and EGFR + NSCLC BM was 19.93 months vs. 9.87 months for wild type (p .001). The number of brain metastases in the mutation positive group didn't significantly impact OS (BM 1 with 16.7 months vs. 2-3 with 19.1 months and >3 with 23.7 months, p .26) whereas fewer metastases in wild type had significantly better OS on univariate analysis (BM=1 with 12.95 months, 2-3 with 8.1 months and >3 with 7.02 months, p .004). Conclusions: In our cohort, the number of BM does not impact OS in EGFR and ALK positive Non- NSCLC. Overall survival (values presented as estimated median survival in months and p-values). NSCLC BM = 1 BM = 2-3 BM > 3 P Mutation 16.7 19.1 23.7 0.26 Wild type 12.95 8.10 7.02 0.004
Relation of genes in estrogen and vitamin D signaling to bone mineral density loss in aromatase inhibitors treatment.
Authors: Sonia Servitja, Maria Rodriguez-Sanz, Natalia Garcia-Giralt, Elisabet Torres, Dani Prieto-Alhambra, Leonardo Mellibovsky, Ignacio Tusquets, Adolf Diez-Perez, Xavi Nogues
Journal: Journal of Clinical Oncology (2014)

575 Background: Bone mineral density (BMD) loss is a consequence of Aromatase Inhibitors (AI) therapy. This study aims to identify variants of genes in the vitamin D and estrogen signaling pathways associated with AI-related BMD loss in the B-ABLE cohort. Methods: B-ABLE is a prospective cohort of women recruited at the time they initiate AI therapy in a bone metabolism unit. Bisphosphonate users were excluded for these analyses. Selected single nucleotide polymorphisms (SNPs) were genotyped. Multivariate linear regression was used to test their association with relative lumbar spine (LS) and femoral neck (FN) BMD loss after 1 and 2 years of follow-up. All models were adjusted for age, body mass index, previous tamoxifen and chemotherapy. Further, potential confounding for baseline 25(OH)-VITD concentrationsand AI used was assessed. Results: 391 participants were included. For estrogen signaling, two SNPs in CYP11A1 (rs2959008 and rs7174179) for the association with FN BMD loss at both one (P=0.003 and P=0.012) and two years (P=0.004 and P=0.002) of follow-up were significant. For LS BMD lossthree SNPs in HSD3B2 (rs2854964), CYP2C19 (rs12248560) and CYP2C9 (rs28371674) were significantly associated at one year of follow-up (P=0.026, P=0.019 and P=0.011 respectively). Only rs12248560 remained also significant at 2 years of follow-up (P=0.014). Regarding vitamin D signaling genes, rs11907350 in CYP24A1 was associated with FN BMD loss at one year. As for LS BMD loss one SNP in GC (rs11907350) at one year of follow-up and one SNP in VDR (rs2544037) at two years of follow-upreached significant p-values (P =0.020 and P=0.024, respectively). Only the SNP rs7174179 in CYP11A1 for FN BMD loss association at 2 years of follow-up remained significant after Bonferroni correction. Conclusions: Several genes in estrogen and vitamin D signaling appeared involved in BMD loss in AI-treated women, suggesting a complex regulation of this outcome.
The interaction between fibrinogen and zymogen FXIII-A2B2 is mediated by fibrinogen residues γ390-396 and the FXIII-B subunits
Authors: James R. Byrnes, Clare Wilson, Anthony M. Boutelle, Chase B. Brandner, Matthew J. Flick, Helen Philippou, Alisa S. Wolberg
Journal: Blood (2016)
Strict BP control in chronic kidney disease reduces long term risk of death, study shows
Authors: Susan Mayor
Journal: BMJ (2016)

Strict blood pressure (BP) control to a lower target than the currently recommended 140/90 mm Hg is associated with reduced risk of premature death, a long term follow-up of people with chronic kidney disease (CKD) taking part in randomised trials has shown.1

Researchers followed up 1067 people with CKD who had taken part in the African American Study of Kidney Disease, which had randomly allocated them to strict BP control (mean arterial pressure <92 mm Hg) or usual …
Toward the molecular dissection of peritoneal pseudomyxoma
Authors: F. Pietrantonio, F. Perrone, A. Mennitto, E.M. Gleeson, M. Milione, E. Tamborini, A. Busico, G. Settanni, R. Berenato, M. Caporale, F. Morano, I. Bossi, A. Pellegrinelli, M. Di Bartolomeo, F. de Braud, D. Baratti, W.B. Bowne, S. Kusamura, M. Deraco
Journal: Annals of Oncology (2016)
Increased Expression Levels Of SOX11 Correlates To Overall Survival and Adds Prognostic Value To The MIPI and MIPI-B Index In a Homogenously Treated Cohort
Authors: Lena Nordström, Venera Kuci, Sandra Sernbo, Kirsten Groenbaek, Arne Kolstad, Riika Räty, Marja-Liisa Karjalainen, Christian Geisler, Elisabeth Ralfkiaer, Christer Sundström, Anna Laurell, Jan Delabie, Mats Ehinger, Mats Jerkeman, Sara Ek
Journal: Blood (2013)
Genetic Profile and Novel Thrombospondin-1(THBS1) Mutation of Familial AML Syndrome: A Genomic Analysis By Whole Genome Sequencing and Whole Transcriptome Sequencing
Authors: Daeyoon Kim, Youngil Koh, Jeonghwan Youk, Kwang-Sung Ahn, Hwi-Joong Yoon, Hyun Jung Lee, Hyo Jung Kim, Junglim Lee, Sung-Soo Yoon
Journal: Blood (2015)
Generalized Granuloma Annulare Associated with Diabetes Mellitus
Authors: Menglong Ran, Yang Wang
Journal: New England Journal of Medicine (2016)

A 64-year-old man presented with widespread, erythematous-to-violaceous papules that were distributed symmetrically on his trunk, arms, and legs. Skin biopsy revealed palisading granulomatous inflammation that surrounded degenerating collagen within the dermis.
Reliability of diagnosis from Mohs slides: interpersonal and intrapersonal agreement on basal cell carcinoma presence and histological subtype
Authors: C.B. van Lee, E.E.F. Ip Vai Ching, K. Nasserinejad, H.A.M. Neumann, M.G.W. Bol, P.K. Dikrama, N.W.J. Kelleners-Smeets, S. Koljenović, K. Munte, V. Noordhoek Hegt, H.C. de Vijlder, T. Nijsten, R.R. van den Bos
Journal: British Journal of Dermatology (2016)

The success of Mohs micrographic surgery (MMS) depends partly on the correct diagnosis of slides. To determine reliability of diagnosis from Mohs slides. This was a prospective study evaluating the reliability of diagnosis from Mohs slides of basal cell carcinoma (BCC) presence, BCC location on the slide and BCC subtype among six raters who independently assessed 50 Mohs slides twice with a 2‐month interval. Slides were randomly selected whereby difficult‐to‐diagnose slides were oversampled. For each slide, a reference diagnosis was established by an expert panel. Cohen's kappa (κ) was calculated to determine levels of agreement interpersonally (rater vs. reference diagnosis) and intrapersonally (rater at T1 vs. T2). Multivariable logistic regression was used to determine independent risk factors for slides with interpersonal discordant diagnosis. The variables studied were BCC presence, whether a slide was scored as easy or difficult to diagnose, review duration of the 50 slides, profession and years of experience in diagnosis from Mohs slides. Interpersonal and intrapersonal agreement were substantial on BCC presence (κ = 0·66 and 0·68) and moderate on BCC subtype (κ = 0·45 and 0·55). Slides that were scored as difficult to diagnose were an independent risk factor for interpersonal discordant diagnosis on BCC presence (odds ratio 3·54, 95% confidence interval 1·81–6·84). Reliability of diagnosis from Mohs slides was substantial on BCC presence and moderate on BCC subtype. For slides that are scored difficult to diagnose, a second opinion is recommended to prevent misinterpretation and thereby recurrence of skin cancer.