tbuckley/cabot-search huggingface dataset:
ANTIBIOTIC SYNERGISM AND ANTAGONISM: AN ASSESSMENT OF THE PROBLEM
Authors: ERNEST JAWETZ, JANET B. GUNNISON
Journal: Pharmacological Reviews (1953)

The outline drawn here of combined antibiotic action is, of necessity, tentative and incomplete. Only a framework of the complex structure is discernible at this time. Far too few facts are available to guide the physician, anxious to use drug combinations quickly and to best advantage.  might agree with the warning expressed about another  remedy almost 60 years ago (63): We are not unaware of how much caution is necessary in judging a new remedy.  must beware of hasty conclusions.  have exposed the facts and doctors may be anxious to use this serum. This has not yet reached the point of efficiency we hope for. At any rate let doctors not forget the necessity of a bacteriological diagnosis without which they expose themselves to serious mistakes.The author of this warning statement was concerned with anti-streptococcus serum, a remedy now long forgotten. His words of caution are a timely warning in the field of combined antibiotic therapy.
Arginine vasopressin stimulates net fluid secretion in a polarized subculture of cyst-forming MDCK cells.
Authors: M E Grant, T K Neufeld, E J Cragoe, L W Welling, J J Grantham
Journal: Journal of the American Society of Nephrology (1991)

Transepithelial fluid secretion is an important process in the progressive enlargement of certain types of renal cysts. Arginine vasopressin (AVP) increases the rate of cyst formation and expansion in an in vitro model of renal cysts that uses Madin-Darby canine kidney (MDCK) cells grown in a gelled matrix of Type 1 collagen. In this study, it was determined if AVP promoted net fluid secretion by MDCK cells. The rate of volumetric fluid secretion was determined from the net movement of water across epithelial layers of MDCK cells grown on permeable, collagen-coated membranes. AVP in the basolateral medium (but not in apical medium) at concentrations exceeding 10(-9) M caused sustained basolateral to apical transepithelial fluid secretion (approximately 0.6 microL/cm2/h). 1-Desamino-8-D-AVP, a V2 receptor agonist, had a similar effect. The secreted fluid was hyperosmotic compared with the bath (5.7 to 9.7 mosM). Chloride was consistently secreted, but the absolute level in the secreted fluid was variable. Intracellular cAMP content was increased 187% by a 2-h exposure to AVP and 10(-4) M methylisobutylxanthine. Net fluid secretion was augmented by methylisobutylxanthine and theophylline and was inhibited by ouabain, bumetanide, and a sodium-dependent Cl-/HCO3- exchange inhibitor (L-645,695) but was not altered by clonidine, guanabenz, or indomethacin. AVP-induced fluid secretion was not accompanied by a change in transepithelial hydraulic conductivity. It is suggested that AVP stimulates fluid secretion of MDCK epithelial monolayers by activating V2 receptor-mediated adenylate cyclase. The regulation of net fluid secretion by AVP would appear to depend on modulation of solute transport, rather than on water permeability.
Bichat guidelines for the clinical management of plague and bioterrorism-related plague
Authors: P Bossi, A Tegnell, A Baka, F van Loock, A Werner, J Hendriks, H Maidhof, G Gouvras
Journal: Eurosurveillance (2004)

Yersinia pestis appears to be a good candidate agent for a bioterrorist attack. The use of an aerosolised form of this agent could cause an explosive outbreak of primary plague pneumonia. The bacteria could be used also to infect the rodent population and then spread to humans. Most of the therapeutic guidelines suggest using gentamicin or streptomycin as first line therapy with ciprofloxacin as optional treatment. Persons who come in contact with patients with pneumonic plague should receive antibiotic prophylaxis with doxycycline or ciprofloxacin for 7 days. Prevention of human-to-human transmission via patients with plague pneumonia can be achieved by implementing standard isolation procedures until at least 4 days of antibiotic treatment have been administered. For the other clinical types of the disease, patients should be isolated for the first 48 hours after the initiation of treatment.
CPAP vs Mandibular Advancement Devices and Blood Pressure in Patients With Obstructive Sleep Apnea
Authors: Daniel J. Bratton, Thomas Gaisl, Annette M. Wons, Malcolm Kohler
Journal: JAMA (2015)

<h3>Importance</h3> Obstructive sleep apnea is associated with higher levels of blood pressure (BP), which can lead to increased cardiovascular risk. <h3>Objective</h3> To compare the association of continuous positive airway pressure (CPAP), mandibular advancement devices (MADs), and inactive control groups (placebo or no treatment) with changes in systolic BP (SBP) and diastolic BP (DBP) in patients with obstructive sleep apnea. <h3>Data Sources</h3> The databases of MEDLINE, EMBASE, and the Cochrane Library were searched up to the end of August 2015 and study bibliographies were reviewed. <h3>Study Selection</h3> Randomized clinical trials comparing the effect of CPAP or MADs (vs each other or an inactive control) on BP in patients with obstructive sleep apnea were selected by consensus. Of 872 studies initially identified, 51 were selected for analysis. <h3>Data Extraction and Synthesis</h3> Data were extracted by one reviewer and checked by another reviewer. A network meta-analysis using multivariate random-effects meta-regression was used to estimate pooled differences between each intervention. Meta-regression was used to assess the association between trial characteristics and the reported effects of CPAP vs inactive control. <h3>Main Outcomes and Measures</h3> Absolute change in SBP and DBP from baseline to follow-up. <h3>Results</h3> Of the 51 studies included in the analysis (4888 patients), 44 compared CPAP with an inactive control, 3 compared MADs with an inactive control, 1 compared CPAP with an MAD, and 3 compared CPAP, MADs, and an inactive control. Compared with an inactive control, CPAP was associated with a reduction in SBP of 2.5 mm Hg (95% CI, 1.5 to 3.5 mm Hg;<i>P</i> &lt; .001) and in DBP of 2.0 mm Hg (95% CI, 1.3 to 2.7 mm Hg;<i>P</i> &lt; .001). A 1-hour-per-night increase in mean CPAP use was associated with an additional reduction in SBP of 1.5 mm Hg (95% CI, 0.8 to 2.3 mm Hg;<i>P</i> &lt; .001) and an additional reduction in DBP of 0.9 mm Hg (95% CI, 0.3 to 1.4 mm Hg;<i>P</i> = .001). Compared with an inactive control, MADs were associated with a reduction in SBP of 2.1 mm Hg (95% CI, 0.8 to 3.4 mm Hg;<i>P</i> = .002) and in DBP of 1.9 mm Hg (95% CI, 0.5 to 3.2 mm Hg;<i>P</i> = .008). There was no significant difference between CPAP and MADs in their association with change in SBP (−0.5 mm Hg [95% CI, −2.0 to 1.0 mm Hg];<i>P</i> = .55) or in DBP (−0.2 mm Hg [95% CI, −1.6 to 1.3 mm Hg];<i>P</i> = .82). <h3>Conclusions and Relevance</h3> Among patients with obstructive sleep apnea, both CPAP and MADs were associated with reductions in BP. Network meta-analysis did not identify a statistically significant difference between the BP outcomes associated with these therapies.
Chromoendoscopy Is More Effective Than Standard Colonoscopy in Detecting Dysplasia During Long-term Surveillance of Patients With Colitis
Authors: James F. Marion, Jerome D. Waye, Yuriy Israel, Daniel H. Present, Maria Suprun, Carol Bodian, Noam Harpaz, Mark Chapman, Steven Itzkowitz, Maria T. Abreu, Thomas A. Ullman, Russell B. McBride, James Aisenberg, Lloyd Mayer
Journal: Clinical Gastroenterology and Hepatology (2015)
Endothelin-1 in angiotensin II-dependent hypertension Answer to the Letter to the Editor
Authors: G Rossi
Journal: Cardiovascular Research (1999)

We are delighted that our paper [1] succeeded in generating interest and discussion. Gardiner and Bennett raised an important issue concerning the potential role of endothelin-1 (ET-1) in the high blood pressure (BP) of transgenic TGR(mREN-2)27 rats [2], a monogenic renin-dependent model of severe hypertension. As far as we can understand, they found a slow-onset hypotensive effect during an acute 8 hr infusion of a mixed ETA/ETB receptor antagonist (SB 209670) in male heterozygous TGR(mREN-2)27 rats, where they recorded invasively intra-arterial blood pressure [3]. This hypotensive effect was surpassed by that induced by losartan. Interestingly, a synergistic hypotensive effect of the two drugs was also noticed. Based on this evidence Gardiner and Bennett would seem to caution on our statement that ET-1 does not play a major role in this form of hypertension. In a previous study in female heterozygous TGR(mREN-2)27 rats we had also found that the BP in vivo and the aortic contractile responses in vitro followed parallel changes with ageing. We therefore suggested that ET-1 could play a role in this model of hypertension [4].

However, chronic studies with ET antagonists in younger rats have given opposite results. In 25 day-old male heterozygous HanRen2/Edin-rats, derived from crossing homozygous TGR(mREN-2)27 with …
Suicidal ideation and young adults
Authors: E J Lieberman
Journal: American Journal of Psychiatry (1993)

SIR: The article by Patrick J. Meehan, M.D., and associates ( 1 ) brings up an important issue, namely, the high prevalence of suicidal thoughts in a normal population. Of 694 college freshmen/women in the sample, 54% had ever considered suicide, 10% had attempted it, and 3% sought help as a result of such attempts. Data presented but not discussed (table 1 of Dr. Meehan and associates’ article) show that 62% of women, compared with 44% of men, had ever considered suicide. Almost the same proportion of men (43%) and women (49%) had thought of specific ways to take their own lives. Another recent study corroborates these findings among high school students: 33% had thought of suicide, and 4.5% reported an attempt in the previous year (2). When half or more of a sizable, typical cohort exhibits a phenomenon associated with psychiatric morbidity and montality, how are we to view it? Not, I submit, by striving to eradicate suicidal thoughts per se, although a reduction in their prevalence might be a good thing. Instead, we might view the phenomenon as fairly typical of a stressful transition. Although a sign of pain, suicidal ideation may indicate health as much as illness. The refusal of suicide suggests a commitment, an engagement with life which is stronger than passive acquiescence. In the psychiatric history, I have come to regard episodes of suicidal ideation with concern, but not qualms, in most cases. It may be no more, and no less, than a pause at the mirror of philosophy: Is this life worth living? Even Albert Camus, who called it “the one truly serious philosophical problem,” remarked that suicide is rarely committed through reflection (3). The literature of autobiography abounds with instances of suicidal ideation followed by an affirmation oflife. Mark Twain wrote about putting a gun to his head at the age of 30: “Many times I have been sorry I did not succeed, but I was never ashamed of having tried” (4). A generation later in Freud’s Vienna, Otto Rank, at age 20, went through a similar crisis and wrote: “Afterwards there grew in me the greatest lust for life and courage towards death” (5). WilliamJames confronted suicide at 28, and wrote at 54, “I take it that no man is educated who has never dallied with the thought of suicide” (6). Many similar examples could be cited, i.e., Arthur Rubinstein, Graham Greene, Karen Homey . . . . Is the episode a sign or harbinger of pathology? I submit that we do not know and should be slow to assume so. Many young people today-close to half-have suicidal thoughts at least once. Epidemiological study may shed light on the psychiatric and social significance of the phenomenon. Meanwhile, we should be cautious about putting suicidal ideation on a single continuum of disease and death. The phenomenon may have as much on more to do with affirmation of life and immunity to actual suicide. It may be a part of normal, healthy adult development.
On the mechanisms of impaired phagocytosis in phosphate depletion.
Authors: M Kiersztejn, I Chervu, M Smogorzewski, G Z Fadda, J M Alexiewicz, S G Massry
Journal: Journal of the American Society of Nephrology (1992)

Phosphate depletion (PD) impairs the phagocytic ability of polymorphonuclear leukocytes (PMNL). This derangement has been attributed to the low ATP content of PMNL in PD. The mechanisms responsible for the low ATP content are not well defined. Phosphorus deficiency, per se, and/or other cellular metabolic consequences of PD such as a rise in cytosolic calcium ([Ca2+]i) could be responsible. Indeed, PD is associated with a rise in [Ca2+]i in other cells, and such an event may inhibit mitochondrial ATP production. It is also not evident whether the impaired phagocytosis in PD is due to low ATP content and/or a rise in the [Ca2+]i of PMNL. The study presented here examined levels of [Ca2+]i, ATP content, and the phagocytic ability of PMNL from PD and pair-weighed (PW) rats and evaluated the potential beneficial effect of treatment with verapamil (V), which may prevent a rise in [Ca2+]i and the consequent effects on ATP content and the phagocytosis of PMNL. The resting levels of [Ca2+]i of PMNL from PD rats (148 +/- 3.9 nM) were significantly (P less than 0.01) higher, and the ATP contents (4.8 +/- 0.2 nmol/5 x 10(6) PMNL) were significantly (P less than 0.01) lower than in PW (111 +/- 2.8 nM and 9.3 +/- 0.3 nmol/5 x 10(6) PMNL), PW-V (114 +/- 2.2 nM and 9.3 +/- 0.28 nmol/5 x 10(6) PMNL), and PD-V (112 +/- 1.8 nM and 6.6 +/- 0.19 nmol/5 x 10(6) PMNL) animals. Despite the normal [Ca2+]i in the PMNL of PD-V rats, their ATP contents were still significantly (P less than 0.01) lower than those of PW or PW-V rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Endoscopic submucosal dissection for venous lake in the submucosa of the transverse colon
Authors: Hideaki Harada, Satoshi Suehiro, Takanori Shimizu, Emi Ohta, Yasushi Katsuyama, Kenji Hayasaka
Journal: Endoscopy (2015)

Submucosal tumors of the transverse colon that are found incidentally during screening colonoscopy are rare. It is possible for a tiny hypoechoic mass detected in the submucosa of the colorectum by endoscopic ultrasonography (EUS) to be a neuroendocrine tumor (NET).
Quality of Life (Qol) Results from the Phase 3 Revel Study of Ramucirumab + Docetaxel (Ram + Dtx) Versus Placebo + Docetaxel (Pl + Dtx) in Advanced/Metastatic Nsclc Patients (Pts) with Progression After Platinum Based Chemotherapy
Authors: E.B. Garon, T. Ciuleanu, O. Arrieta, K. Prabhash, K.N. Syrigos, T. Göksel, K. Park, R. Kowalyszyn, J. Pikiel, C. Lewanski, M. Thomas, S. Dakhil, J. Kim, N. Karaseva, S. Yurasov, A. Zimmermann, G. Cuyun Carter, M. Reck, F. Cappuzzo, M. Perol
Journal: Annals of Oncology (2014)
An Official American Thoracic Society/European Respiratory Society Policy Statement: Enhancing Implementation, Use, and Delivery of Pulmonary Rehabilitation
Authors: Carolyn L. Rochester, Ioannis Vogiatzis, Anne E. Holland, Suzanne C. Lareau, Darcy D. Marciniuk, Milo A. Puhan, Martijn A. Spruit, Sarah Masefield, Richard Casaburi, Enrico M. Clini, Rebecca Crouch, Judith Garcia-Aymerich, Chris Garvey, Roger S. Goldstein, Kylie Hill, Michael Morgan, Linda Nici, Fabio Pitta, Andrew L. Ries, Sally J. Singh, Thierry Troosters, Peter J. Wijkstra, Barbara P. Yawn, Richard L. ZuWallack
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Section:ChooseTop of pageAbstract <<ContentsOverviewIntroductionMethodsBackground: PRIncreasing Awareness and ...Increasing Patient Access...Ensuring Quality of PR Pr...Future Research To Advanc...ReferencesCITING ARTICLES
Intra-arterial chemotherapy for unresectable pancreatic cancer
Authors: M. Cantore, P. Pederzoli, G. Cornalba, G. Fiorentini, S. Guadagni, L. Miserocchi, A. Frassoldati, C. Ceravolo, F. Smerieri, J.H. Muchmore
Journal: Annals of Oncology (2000)

Background: A phase II trial of a new intra-arterial chemotherapy regimen for unresectable pancreatic cancer (UPC).Patients and methods: Ninety-six patients with UPC were treated with intra-arterial chemotherapy at three-weekly intervals.The schedule used was FLEC: 5-fluorouracil 1000 mg/m 2 , folinic acid 100 mg/m 2 , carboplatin 300 mg/m 2 ; epirubicin 60 mg/m 2 .Results: The overall response rates by CT-scan evaluation were: 15% partial response (PR), 44% stable disease (SD), 17% progressive disease (PD).The overall median survival was 9.9 months, and 10.6 and 6.8 for UICC stage III and IV, respectively.Pain reduction occurred in 42% of patients.A weight gain > 7% from baseline occurred in 8% of patients.A total of 341 courses of FLEC were administered.Grade 3-4 hematological toxicity was seen in 25% of patients; ematemesis in 4%; grade 3 gastrointestinal toxicity in 3%; and grade 3 alopecia in 16%.One sudden death, a pre-infarction angina, and a transitory ischemic attack were observed.The only complication related to the angiographic procedure was an intimal dissection of the iliac artery.Conclusions: The intra-arterial FLEC regimen was well tolerated and active.It requires only one day of hospitalization.Efficacy could only be assessed in a randomized study against a gemcitabine containing regimen.
Modulating immunometabolism of tumor specific mouse and human lymphocytes to enhance T cell based therapy for cancer
Authors: Madhusudhanan Sukumar, Jie Liu, Shashank J Patel, Christopher A Klebanoff, Gautam Mehta, Rahul Roychoudhuri, Joseph Crompton, David Clever, Luca Gattinoni, Pawel Muranski, Toren Finkel, Nicholas Restifo
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Tumor cells and tumor infiltrating lymphocytes (TIL) competes for glucose and other metabolites within the tumor microenvironment for their survival. Glucose consumption by tumors metabolically restricts T cell's ability to produce effector cytokines and therefore approaches to
Hepatitis-Associated Liver Cancer: Gaps and Opportunities to Improve Care: Table 1.
Authors: Brian McMahon, Joan Block, Timothy Block, Chari Cohen, Alison A. Evans, Anu Hosangadi, W. Thomas London, Morris Sherman
Journal: JNCI Journal of the National Cancer Institute (2015)

The global burden of hepatocellular carcinoma (HCC; primary liver cancer) is increasing. HCC is often unaccompanied by clear symptomatology, causing patients to be unaware of their disease. Moreover, effective treatment for those with advanced disease is lacking. As such, effective surveillance and early detection of HCC are essential. However, current screening and surveillance guidelines are not being fully implemented. Some at-risk populations fall outside of the guidelines, and patients who are screened are often not diagnosed at an early enough stage for treatment to be effective. From March 17 to 19, 2015, the Hepatitis B Foundation sponsored a workshop to identify gaps and limitations in current approaches to the detection and treatment of HCC and to define research priorities and opportunities for advocacy. In this Commentary, we summarize areas for further research and action that were discussed throughout the workshop to improve the recognition of liver disease generally, improve the recognition of liver cancer risk, and improve the recognition that screening for HCC makes a life-saving difference. Participants agreed that primary prevention of HCC relies on prevention and treatment of viral hepatitis and other underlying etiologies. Earlier diagnosis (secondary prevention) needs to be substantially improved. Areas for attention include increasing practitioner awareness, better definition of at-risk populations, and improved performance of screening approaches (ultrasound, biomarkers for detection, risk stratification, targeted therapies). The heterogeneous nature of HCC makes it unlikely that a single therapeutic agent will be universally effective. Medical management will benefit from the development of new, targeted treatment approaches.
Racotumomab-Alum Vaccine for Maintenance Treatment of Recurrent Platinum-Sensitive Epithelial Ovarian Cancer Patients
Authors: M. Hernandez, S. Alfonso, E. Santiesteban, A. Linchenat, L. Sanchez, A. Valdes, T. Lahera, A. Calvo, M. Arencibia, M. Cepeda, L. Cabrera, A.M. Vázquez, P. Luaces-Lorenzo, T. Crombet, A. Macías
Journal: Annals of Oncology (2014)
TGFβ Treatment Enhances Glioblastoma Virotherapy by Inhibiting the Innate Immune Response
Authors: Jianfeng Han, Xilin Chen, Jianhong Chu, Bo Xu, Walter H. Meisen, Lichao Chen, Lingling Zhang, Jianying Zhang, Xiaoming He, Qi-En Wang, E. Antonio Chiocca, Balveen Kaur, Michael A. Caligiuri, Jianhua Yu
Journal: Cancer Research (2015)

Abstract Oncolytic viruses, including oncolytic herpes simplex virus (oHSV), have produced provocative therapeutic responses in patients with glioblastoma, the most aggressive brain tumor. Paradoxically, innate immune responses mediated by natural killer (NK) cells and macrophages/microglia appear to limit oHSV efficacy. Therefore, we investigated whether pretreatment with an immunosuppressive cytokine, TGFβ, might reverse these effects and thereby potentiate oHSV efficacy. TGFβ treatment of NK cells rendered them less cytolytic against oHSV-infected glioblastoma cells and stem-like cells in vitro. Furthermore, TGFβ treatment of NK cells, macrophages, or microglia increased viral titers of oHSV in cocultures with glioblastoma cells. In a syngeneic mouse model of glioblastoma, administering TGFβ prior to oHSV injection inhibited intracranial infiltration and activation of NK cells and macrophages. Notably, a single administration of TGFβ prior to oHSV therapy was sufficient to phenocopy NK-cell depletion and suppress tumor growth and prolong survival in both xenograft and syngeneic models of glioblastoma. Collectively, our findings show how administering a single dose of TGFβ prior to oncolytic virus treatment of glioblastoma can transiently inhibit innate immune cells that limit efficacy, thereby improving therapeutic responses and survival outcomes. Cancer Res; 75(24); 5273–82. ©2015 AACR.
Pharmacotherapy for Chronic Myelogenous Leukemia: A Case-Based Approach
Authors: Stephen Harnicar
Journal: Journal of the National Comprehensive Cancer Network (2011)

TKIs have become the standard of care for CML. Imatinib was the first to transform the outcomes of this disease. Dasatinib and nilotinib were recently added to the armamentarium for imatinib-resistant disease and, more recently, for first-line therapy. When choosing a TKI for patients, adverse effects, presence of mutations in the BCR-ABL kinase domain, and cost should be considered. Once chosen, drug interactions should be evaluated for all patients. New drugs are being studied to prevent disease progression and for patients with T315I mutations. This article reviews the pharmacotherapy of CML with the aid of a patient case.
Miscellaneous Item
Authors: M Rabinovitch
Journal: Cardiovascular Research (1997)

The patient with pulmonary hypertension still mystifies even the most astute of physicians. Pulmonary hypertension can be the result of multiple and diverse etiologies, and these include congenital heart defects, chronic lung disease, hepatic disorders, especially with portal hypertension, and autoimmune disease, particularly scleroderma. It can also arise as an unexplained condition. In the case of a congenital heart defect, the high flow and pressure are thought to be significant etiologically. If the primary etiolŽ ogy is treated in a timely fashion e.g., repair of a congenital heart defect in early infancy, or improvement in a . pulmonary condition , there is a good chance that pulmonary hypertension will regress, whereas, if the primary etiology is unknown, the disease will usually be rapidly progressive and fatal in outcome. The following mini-review will explore some of what we have learned about the pathophysiology of pulmonary hypertension and how common mechanisms at the cellular level may in fact lend themselves to novel therapeutic strategies directed at patients with secondary, as well as unexplained, pulmonary hypertension.