tbuckley/cabot-search huggingface dataset:
Celebrating the ACP Centennial: From the <i>Annals</i> Archive—Blood Pressure Variation
Authors: Deborah Cotton
Journal: Annals of Internal Medicine (2015)

Editorials1 September 2015Celebrating the ACP Centennial: From the Annals Archive—Blood Pressure VariationDeborah Cotton, MD, MPHDeborah Cotton, MD, MPHSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M15-1637 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail During the 2015 centennial year of the American College of Physicians, publisher of Annals of Internal Medicine, Annals editors will link an article in each issue with an earlier paper from our archives addressing the same disease or clinical question. We hope our readers find this interesting and we welcome comments, especially from physicians who were practicing at the time of publication of the original paper who might offer insight into the impact of the earlier paper on their knowledge or practice.In this issue, Muntner and colleagues (1) conclude that greater variability of blood pressure across outpatient clinic visits ...References1. Muntner P, Whittle J, Lynch AI, Colantonio LD, Simpson LM, Einhorn PT, et al. Visit-to-visit variability of blood pressure and coronary heart disease, stroke, heart failure, and mortality. A cohort study. Ann Intern Med. 2015;163:329-38. doi:10.7326/M14-2803 LinkGoogle Scholar2. Mueller SC, Brown GE. Hourly rhythms in blood pressure in persons with normal and elevated pressures. Ann Intern Med. 1930;3:1190-200. doi:10.7326/0003-4819-3-12-1190 LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Deborah Cotton, MD, MPHAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoHourly Rhythms in Blood Pressure in Persons With Normal and Elevated Pressures SELMA C. MUELLER and GEORGE E. BROWN Visit-to-Visit Variability of Blood Pressure and Coronary Heart Disease, Stroke, Heart Failure, and Mortality Paul Muntner , Jeff Whittle , Amy I. Lynch , Lisandro D. Colantonio , Lara M. Simpson , Paula T. Einhorn , Emily B. Levitan , Paul K. Whelton , William C. Cushman , Gail T. Louis , Barry R. Davis , and Suzanne Oparil Visit-to-Visit Variability of Blood Pressure and Coronary Heart Disease, Stroke, Heart Failure, and Mortality Paul Muntner , Jeff Whittle , Amy I. Lynch , Lisandro D. Colantonio , Lara M. Simpson , Paula T. Einhorn , Emily B. Levitan , Paul K. Whelton , William C. Cushman , Gail T. Louis , Barry R. Davis , and Suzanne Oparil Metrics 1 September 2015Volume 163, Issue 5Page: 389KeywordsArchivesBlood pressureExerciseFeversHospitalsHypertensionOutpatient clinicsPathogenesisSleepSympathetic nervous system ePublished: 1 September 2015 Issue Published: 1 September 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 16278: Gut Microbiome Metabolic Phenotypes are Biomarkers for Severity of Myocardial Infarction
Authors: John E Baker, Vy Lam, Jidong Su, James S Tweddell, Nita H Salzman, Garrett J Gross
Journal: Circulation (2013)

Intestinal microbiota have been mechanistically linked to myocardial infarction. We assessed the hypothesis that low molecular weight metabolites produced by intestinal microbiota and carried to th...
Mobilisation of PBSC for Allogenic Transplantation By the Use of G-CSF Biosimilar Zarzio® in Healthy Donors
Authors: Javier Anguita, Pascual Balsalobre, Elena González-Arias, Sara Redondo, Ana Pérez-Corral, Cristina Pascual, David Serrano, Mi Kwon, Mariana Bastos, Cristina MuÃ±oz, Jorge Gayoso, Jose Luis Diez-Martin
Journal: Blood (2014)
Abstract 1679: Inhibiting KRAS-reprogrammed glutamine metabolism sensitizes pancreatic cancer to NQO1-bioactivatable drugs
Authors: Gaurab Chakrabarti, David A. Boothman
Journal: Cancer Research (2014)

Abstract Patients with pancreatic cancers have one of the highest mortality rates of any cancer with 5-year survival rates of 6%. The therapeutic responses of pancreatic cancers are highly variable and there is a desperate need for agents to specifically and efficaciously treat pancreatic cancer patients. We recently discovered that not only were NAD(P)H:quinone oxidoreductase 1 (NQO1) levels elevated 5- to 40-fold in &amp;gt;90% of pancreatic tumors vs associated normal tissue, but that catalase levels were inversely expressed comparatively, elevated in normal vs tumor tissue. NQO1 represents a unique target to exploit for the therapeutic elimination of pancreatic cancers. NQO1 bioactivatable drugs, such as β-lapachone (β-lap) or deoxynyboquinone (DNQ) and derivatives generate hydrogen peroxide as a mechanism to hyperactivate PARP1 and selectively kill tumors. In addition to catalase, reduced glutathione levels are essential for a cell's protection against hydrogen peroxide. Tumors with mutated KRAS, which constitutes &amp;gt;90% of pancreatic cancers, are metabolically reprogrammed to rely on glutamine to maintain the cell's NADPH and glutathione levels, and therefore, anti-oxidant state (Son et.al., Nature, 2013). The present study evaluated the therapeutic potential of inhibiting this KRAS-reprogrammed metabolic pathway with the small molecule GLS1 inhibitor, BPTES, in combination with NQO1-bioactivatable drugs, β-lapachone or IB-DNQ. Synergistic cell lethality was noted using non-lethal doses of BPTES combined with sublethal doses of β-lapachone in KRAS-driven pancreatic or non-small cell lung cancer cells. ROS levels in BPTES and β-lap treated cell lines were dramatically higher than the ROS levels with either agent alone. This was further supported by a dramatic loss of glutathione and NADPH following combination treatment vs either agent alone. Lethality was completely rescued by the addition of the NQO1 inhibitor, dicoumarol, demonstrating that synergy is dependent on the NQO1 activation of β-lap. Partial rescue was seen with the addition of cell permeable glutathione further demonstrating the importance of ROS in synergy. The addition of cell permeable malate and oxaloacetate, downstream metabolites of the KRAS-driven glutamine pathway, also rescued synergy. Our findings indicate that NQO1-bioactivatable drugs may improve the sensitivities of clinical grade GLS1 inhibitors in pancreatic cancer patients. Citation Format: Gaurab Chakrabarti, David A. Boothman. Inhibiting KRAS-reprogrammed glutamine metabolism sensitizes pancreatic cancer to NQO1-bioactivatable drugs. [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 1679. doi:10.1158/1538-7445.AM2014-1679
Anti-inflammatory effect of beclomethasone dipropionate and formoterol on TNF-α-induced human endothelial cell activation
Authors: Silvana Cianchetti, Cristina Cardini, Gabriele Nicolini, Alessandro Celi, Pierluigi Paggiaro
Journal: European Respiratory Journal (2011)

Background:  Among the structural cells, endothelial cells (EC) represent critical elements: they control leukocyte traffic through the adhesion molecule and chemokine expression.   Aim:  To investigate the effect of beclomethasone dipropionate (BDP) and formoterol (F), either alone or in combination, on TNF-α- induced ICAM-1 expression and IL-8 release in human umbilical vein endothelial cells.   Methods:  EC were incubated with BDP (10 -11 -10 -5 M), F (6/100 with respect to BDP concentration) or drug diluent (control cells: CC) and then exposed to TNF-α (200 U/ml; 4 hrs). For BDP/F combination (w/w: 100/6) EC were treated with low doses of BDP (10 -11 and 10 -9 M) and/or FOR (6×10 -13  and 6×10 -11 M). Surface ICAM-1 expression and IL-8 release were measured by ELISA.   Results:  BDP reduced TNF-α-induced IL-8 release (mean±SEM% decrement) with maximal inhibition 23.7±4.2 at 10 -7  M and 22.6±3.7 at 10 -5  M (p vs  CC); F did not significantly affect IL-8 release (9.2±2.8% at the maximal dose tested). In a different experimental set, BDP/F inhibited IL-8 release with respect to BDP alone (10 -9 M/6×10 -11 M: 27.6.2±4.7  vs  10 -9 M: 14.6±3.5%, p -5 M alone; BDP/F, although to a less extent, tended to decrease ICAM-1 expression (10 -9 M/6×10 -11 M: 17.2±0.8  vs  10 -9 M: 9.3±2.1% and F:4.2±2.6, p=0.05, n=5).   Conclusions:  BDP in combination with F is more effective in inhibiting EC activation as compared with BDP alone, thus allowing to use lower BDP doses to reach the maximum inhibitory effect. These results may explain some clinical anti-inflammatory activities of BDP/F combination.
Baseline thymidylate synthase expression according to histological subtypes of non-small cell lung cancer
Authors: G. Scagliotti, V. Monica, P. Ceppi, L. Righi, A. Cambieri, M. Volante, S. Novello, E. Cappelletto, M. Papotti
Journal: Journal of Clinical Oncology (2009)

7521 Background: In non-small cell lung cancer (NSCLC) baseline thymidilate synthase (TS) levels are higher in squamous cell carcinoma (SCC) compared to adenocarcinoma (AC) and randomized clinical trials have shown a selective benefit for patients with non-squamous histology treated with pemetrexed, a TS-inhibiting agent. TS expression in undifferentiated large cell carcinoma (LCC) is unknown. Methods: TS expression at both mRNA (using tissue microdissection and qRT-PCR) and protein (through immunohistochemistry, IHC) levels was tested in 34 surgically resected LCC (stage I=20,II=6,IIIa=8) and compared with TS expression in surgical cases of SCC (n= 31) and AC (n=40). In addition other comparisons were made: a) TS protein expression with Ki-67 index; b) TS mRNA and E2F1 transcription factor mRNA; c) in all histotypes TS protein level with desmocollin-3 (DSC-3) immunostaining, a marker of squamous cell differentiation. TS expression level was assessed in a group of patients (n=22) with cytological diagnosis of NSCLC-NOS (not otherwise specified) and compared with TS data in tissue specimens obtained through subsequent bronchial biopsy or surgical resection. Results: Significantly higher median TS levels in LCC compared to AC (p&lt;0.001 for both mRNA and protein values) and SCC compared to AC (p=0.002 mRNA, p&lt;0.001 protein) were detected. A strong correlation between TS mRNA and protein levels were found (p&lt;0.001) in SCC and AC, but not in LCC. TS and both Ki-67 and E2F1 were significantly correlated in AC and SCC (p=0.003 and p=0.05, respectively), but in LCC no correlation was found. In LCC, significantly higher TS levels were observed in DSC3-positive compared to DSC3-negative tumors (p=0.02). A significant correlation between TS IHC scores in matched cytological and corresponding tissue specimens was observed (p&lt;0.001). Conclusions: This study demonstrates and confirms the: a) differential expression of TS among the NSCLC histotypes; b) lack of DSC-3 immunoreactivity in LCC is associated with lower TS expression; c) assessment of TS by IHC in cytological specimens correlates with the corresponding tissue TS expression. [Table: see text]
Response to pentostatin in hairy-cell leukemia refractory to interferon-alpha. The European Organization for Research and Treatment of Cancer Leukemia Cooperative Group.
Authors: A D Ho, J Thaler, F Mandelli, F Lauria, R Zittoun, R Willemze, G McVie, A M Marmont, O Prümmer, P Stryckmans
Journal: Journal of Clinical Oncology (1989)

Interferon-alpha (IFN-a) or 2'-deoxycoformycin (pentostatin; DCF) have each been shown to be highly active in hairy-cell leukemia (HCL). In this phase II study of the Leukemia Cooperative Group of the European Organization for Research and Treatment of Cancer (EORTC), the efficacy and toxicity of DCF were investigated in patients who were resistant to IFN-a treatment. Resistance was defined as: (1) progressive disease (PD) under IFN-a therapy for more than 2 months; (2) stable disease (SD) after more than 6 months of IFN-a treatment; (3) relapse within 3 months of discontinuing IFN-a; and (4) intolerance to IFN-a because of World Health Organization (WHO) grade 3 or 4 toxicity. DCF was applied at a dosage of 4 mg/m2 weekly x 3, then 4 mg/m2 every other week x 3. Responders were given a maintenance therapy once per month for a maximum of 6 months. At the time of report, 33 patients with resistant disease were evaluable for response and toxicity. Median duration of IFN-a therapy before DCF administration was 14.7 months (range, 1 to 41 months). Complete remissions (CRs) were achieved in 11 patients and partial remissions (PRs) in 15, resulting in a total response rate of 78.8%. Median interval between beginning of DCF therapy to best response was 3.9 months with a range from 2.0 to 7.0 months. Two patients who achieved PR have relapsed 7 and 14 months after cessation of DCF therapy. The median duration of response was over 11.5 months (range, over 3.0 to over 24.0 months). Three patients died within the first 6 weeks of DCF treatment: one of drug-unrelated cardiomyopathy and two of fungal pneumonia. The patients with early death (n = 3) and nonresponsive disease (n = 4) received IFN-a treatment for a longer period (median, 18.0 months) than did the 26 responsive patients (median, 10.0 months). Major side effects included nausea, skin rash, and infections and were otherwise mild. Thus, DCF is highly active in patients with HCL resistant to IFN-a.
Reversal of Hemodialysis Granulocytopenia and Pulmonary Leukostasis
Authors: Keith M. Skubitz, Philip R. Craddock
Journal: Journal of Clinical Investigation (1981)

The transient granulocytopenia of hemodialysis results indirectly from plasma complement activation by dialyzer cellophane membranes. The C5adesarg so produced can induce reversible granulocyte aggregation in vitro and in vivo, and we hypothesized that the pulmonary leukostasis responsible for the granulocytopenia results from embolization of aggregates formed under the influence of C5adesarg produced in the dialyzer. These studies were designed to measure C5adesarg generation during dialysis by granulocyte aggregometry and to determine the reason for the transience of the leukostasis. C5adesarg generation was equally evident throughout dialysis, persisting well after granulocytopenia had reversed, and dialyzer-induced complement activation was insufficient to produce significant depletion of plasma complement titers. That granulocyte deactivation might be responsible for the transience was suggested by the absence of the usual granulocytopenia in a patient with uniquely high levels of C5adesarg in his predialysis plasma. Granulocytes drawn from seven stable uremic patients after granulocytopenia had reversed exhibited a dose-related, selective and irreversible refractoriness to stimulation with C5adesarg, but their responses to n-formyl-Met-Leu-Phe remained normal. Identical deactivation was produced in normal cells by short- or long-term exposure of C5adesarg in vitro. These studies suggest that C5adesarg is indeed generated by the dialyzer throughout hemodialysis and that the transience of the leukostasis and granulocytopenia is due to selective down-regulation of cellular responses to C5adesarg—a phenomenon that hitherto has been described only in vitro and that may be important in limiting the deleterious effects of adherent granulocytes on the endothelium in patients with intravascular complement activation.
EFFECTS OF BACTERIAL ENDOTOXIN ON METABOLISM
Authors: L. Joe Berry, Dorothy S. Smythe
Journal: The Journal of Experimental Medicine (1959)

Urinary nitrogen excretion over a 17 hour period without food and water was determined for mice poisoned with endotoxin and for control mice with and without the subcutaneous injection of 5 mg. cortisone acetate. Endotoxin did not alter the quantity of nitrogen excreted, compared with that of control mice, but in both groups of animals cortisone increased urinary nitrogen by the same amount. A balance between the quantity of protein catabolized (as estimated by increased urinary nitrogen excretion) and the total carbohydrate stored as a result of cortisone administration was found in fasted and in fed mice but not in endotoxin-poisoned mice. Endotoxin inhibited the motility of the gastrointestinal tract and blocked the absorption of food. Injections of ACTH in normal mice increased protein degradation and carbohydrate synthesis. In endotoxin-poisoned animals, ACTH failed to alter urinary nitrogen excretion and carbohydrate reserves. ACTH increased susceptibility to endotoxin. The number of heat-killed cells of S. typhimurium required to block the increase in urinary nitrogen caused by an injection of ACTH was found to be 10(8). A partial block was found with 5 x 10(7) cells but not with 10(5) cells. Mice infected with S. typhimurium excreted less than the normal amount of urinary nitrogen in response to ACTH 6 to 23 hours postinfection while normal amounts of nitrogen were eliminated 54 to 71 hours postinfection. The number of viable cells in the mice during the earlier period was less than the number of dead cells required to alter the nitrogen output, while the reverse was true during the later period.
Flow limitation at rest may identify a phenotype of chronic obstructive pulmonary disease (COPD)
Authors: Laura Malagrinò, Francesco Costa, Barbara Vagaggini, Claudia De Simone, Cristina Spanu, Alessandro Celi, Pierluigi Paggiaro
Journal: European Respiratory Journal (2011)

Background:  Expiratory flow limitation at rest (FL) promotes dynamic hyperinflation (DH) during exercise in COPD patients.   Aim:  To evaluate whether a specific FL phenotype can be identified in COPD patients.   Subjects and methods:  48 COPD patients (28 male, FEV1%: 53.4) underwent: pulmonary function tests (PFT), cardiopulmonary exercise test (CPET) with assessment of DH, Saint George9s Respiratory Questionnaire (SGRQ), dyspnea scale (MRC), physical activity by Armband. We measured blood haemoglobin (HB) and inflammatory cells, CRP and Pro-BNP; sputum inflammatory cell count and neutrophil elastase. FL was evaluated according to Hyatt by overlapping the tidal and maximal flow-volume curves and categorized as either absent no overlapping, or present any overlapping.   Results:  FL was observed in 38/48 COPD patients. Baseline difference between two groups are reported (*p  Only in FL group, VO2/kg was correlated (p   Conclusions:  Flow imitation at rest, as assessed by a simple, non invasive, inexpensive technique, identifies patients with clinical and functional characteristics suggestive of a specific “emphysema-like” phenotype.
Lidocaine administration to the laryngopharynx for inducing anesthesia before bronchoscopy: A comparative study of Jackson's spray method and ultrasonic nebulization
Authors: Ken-ichi Takahashi, Emiko Yamakawa, Kouki Tsuji, Yukiko Kaneko, Yoko Uraguchi, Kaori Okubo, Toshie Chiyomori, Emiko Murakami, Taeko Kameyama, Kazuki Shima, Yoko Hamakawa, Shohei Kaneda, Susumu Noguchi, Akari Moriyama, Yojiro Yutaka, Hiromichi Katakura, Naoki Sakai, Akira Yamanaka
Journal: European Respiratory Journal (2012)

[Objective] To compare the degrees of pain experienced by patients and additional intraoperative amounts of lidocaine required when lidocaine is administered using Jackson9s spray and an ultrasonic nebulization.  [Methods] Forty patients who were given laryngopharyngeal anesthesia before bronchoscopy were divided into 2 groups of 20 patients each: group A, which was given 4% lidocaine 5 mL by using Jackson9s spray, and group B, which was given 2% lidocaine 10 mL by using an ultrasonic nebulizer. The degrees of pain in patients evaluated on the basis of examination times, amounts of lidocaine administered during bronchoscopy, rates of lidocaine use (obtained by dividing amounts of lidocaine administered during bronchoscopy by examination times), and results of a questionnaire survey consisting of a 5-point evaluation scale for 7 items were compared between the 2 groups.  [Results] There were no significant differences in examination times, amounts of lidocaine administered during bronchoscopy, and degrees of pain between the groups. However, the rates of lidocaine use in group B were significantly lower than those in group A (0.55 ± 0.3 mL/min versus 0.38 ± 0.2 mL/min; p = 0.03). An analysis based on patient age and smoking history showed that the rate of lidocaine use in group A was not significantly high in elderly persons (less than 70 years of age) and smokers (p = 0.05).  [Conclusion] In laryngopharyngeal anesthesia before bronchoscopy, the Jackson spray required a large amount of lidocaine at the time of bronchoscopic examination for bronchoscopy time, compared with the ultrasonic nebulizer.
Multimodal therapy for the management of primary, nonmetastatic Ewing's sarcoma of bone: a long-term follow-up of the First Intergroup study.
Authors: M E Nesbit, E A Gehan, E O Burgert, T J Vietti, A Cangir, M Tefft, R Evans, P Thomas, F B Askin, J M Kissane
Journal: Journal of Clinical Oncology (1990)

A total of 342 previously untreated eligible children were entered into the first Intergroup Ewing's Sarcoma Study (IESS) between May 1973 and November 1978. In group I institutions, patients were randomized between treatment 1 (radiotherapy to primary lesion plus cyclophosphamide, vincristine, dactinomycin, and Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH] [VAC plus ADR]) or treatment 2 (same as treatment 1 without ADR), and group II institutions randomized patients between treatment 2 or treatment 3 (same as treatment 2 plus bilateral pulmonary radiotherapy [VAC plus BPR]). The percentages of patients relapse-free and surviving (RFS) at 5 years for treatments 1, 2, and 3 were 60%, 24%, and 44%, respectively. There was strong statistical evidence of a significant advantage in RFS for treatment 1 (VAC plus ADR) versus 2 (VAC alone) (P less than .001) and 3 (P less than .05) and also of treatment 3 versus 2 (P less than .001). Similar significant results were observed with respect to overall survival. Patients with disease at pelvic sites have significantly poorer survival at 5 years than those with disease at nonpelvic sites (34% v 57%; P less than .001). Among pelvic cases, there was no evidence of differing survival by treatment (P = .81), but among nonpelvic cases, there was strong evidence of differing survival by treatment (P less than .001). The overall percentage of patients developing metastatic disease was 44%; the percentages by treatments 1, 2, and 3 were 30%, 72%, and 42%, respectively. The overall incidence of local recurrence was 15%, and there was no evidence that local recurrence rate differed by treatment. Patient characteristics related to prognosis, both with respect to RFS and overall survival experience, were primary site (nonpelvic patients were most favorable) and patient age (younger patients were more favorable).
The Role of Surgical Pathology in Guiding Cancer Immunotherapy
Authors: Scott B. Lovitch, Scott J. Rodig
Journal: Annual Review of Pathology Mechanisms of Disease (2016)

The recognition that the immune system can identify and destroy tumor cells has driven a paradigm shift in our understanding of human cancer. Therapies designed to enhance this capacity, including cancer vaccines and coinhibitory receptor blockade, have demonstrated clinical efficacy in treating tumors refractory to conventional therapy. In this review, we discuss how the analysis of the immune microenvironment in primary tissue biopsy samples can be used to stratify patients according to clinical outcome, identify patients likely to benefit from specific immunotherapies, and tailor combination immunotherapy to individual patients and tumor types. As immunotherapy gains in complexity and is used in combination with agents that target oncogenic, intracellular signaling pathways, diagnostic pathologists will play an increasingly important part in identifying and quantifying cellular and molecular biomarkers in tissue samples that reflect the nature and magnitude of the antitumor immune response.