tbuckley/cabot-search huggingface dataset:
Soluble intercellular adhesion molecule-1 as an early detection marker for radiation pneumonitis
Authors: Y. Ishii, S. Kitamura
Journal: European Respiratory Journal (1999)

To investigate the role of intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of radiation pneumonitis and to determine whether the measurement of soluble ICAM-1 (sICAM-1) levels is useful for predicting the onset of pneumonitis, the levels of sICAM-1 were measured in serum and bronchoalveolar lavage (BAL) fluids from patients with lung malignancy who received radiotherapy. A total of 30 patients were irradiated with a total dose of approximately 60 Gy. Blood samples were taken before, midway and after radiotherapy. BAL was also performed before and after radiotherapy in seven cases. The sICAM-1 concentration was measured using an enzyme-linked immunosorbent assay kit with two different monoclonal antibodies. Twelve out of 30 cases developed radiation pneumonitis (pneumonitis group), and the other cases did not (nonpneumonitis group). Serum levels of sICAM-1 after radiotherapy were significantly elevated in the pneumonitis group, but not in the nonpneumonitis group. In some of the cases in the pneumonitis group, sICAM-1 levels began to increase at an early phase of irradiation. In one case of pneumonitis in which BAL was performed, the total cell count and the number of lymphocytes increased markedly, as did the level of sICAM-1 in BAL fluid. These findings suggest that intercellular adhesion molecule-1 may play an important role in the development of radiation pneumonitis and that soluble intercellular adhesion molecule-1 may be a useful marker for the early detection of radiation pneumonitis.
Hepatitis C and Renal Transplantation in the Era of Modern Immunosuppression
Authors: Kevin C. Abbott, Jay R. Bucci, Cal S. Matsumoto, S. John Swanson, Lawrence Y.C. Agodoa, Kent C. Holtzmuller, David F. Cruess, Thomas G. Peters
Journal: Journal of the American Society of Nephrology (2003)

Kidneys from donors who are positive for hepatitis C virus (DHCV+) have recently been identified as an independent risk factor for mortality after renal transplantation. However, it has not been determined whether risk persists after adjustment for baseline cardiac comorbidity or applies in the era of modern immunosuppression. Therefore, a historical cohort study was conducted of US adult cadaveric renal transplant recipients from January 1, 1996, to May 31, 2001; followed until October 31, 2001. A total of 36,956 patients had valid donor and recipient HCV serology. Cox regression analysis was used to model adjusted hazard ratios for mortality and graft loss, respectively, adjusted for other factors, including comorbid conditions from Center for Medicare and Medicaid Studies Form 2728 and previous dialysis access-related complications. It was found that DHCV+ was independently associated with an increased risk of mortality (adjusted hazard ratio, 2.12, 95% confidence interval, 1.72 to 2.87; P < 0.001), primarily as a result of infection. Mycophenolate mofetil was associated with improved survival in DHCV+ patients, primarily related to fewer infectious deaths. Adjusted analyses limited to recipients who were HCV+, HCV negative, or age 65 and over, or by use of mycophenolate mofetil confirmed that DHCV+ was independently associated with mortality in each subgroup. It is concluded that DHCV+ is independently associated with an increased risk of mortality after renal transplantation adjusted for baseline comorbid conditions in all subgroups. Recipients of DHCV+ organs should be considered at high risk for excessive immunosuppression.
Association of<i>Helicobacter pylori</i>seropositivity with all-cause mortality: fact or fiction?
Authors: Palaniappan Manickam, Prasad Gunasekaran, Rajeev Sudhakar, Vikas Veeranna, Luis Afonso
Journal: Gut (2013)

We read the article by Chen et al with great interest and would like to congratulate them on their findings. Their analysis of the data from the National Health and Nutrition Examination Survey (NHANES III) have shown a lack of association between Helicobacter pylori seropositivity and all-cause mortality in patients more than 40 years of age.1 As there is an existing controversy2–4 in this area, evaluation of other large databases is clinically relevant, particularly if the analyses provides congruent data as in this instance, replicating findings that help consolidate the evidence base in the literature. The …
The Differentiation and Stress Response Factor XBP-1 Drives Multiple Myeloma Pathogenesis
Authors: Daniel R. Carrasco, Kumar Sukhdeo, Marina Protopopova, Raktim Sinha, Miriam Enos, Daniel E. Carrasco, Mei Zheng, Mala Mani, Joel Henderson, Geraldine S. Pinkus, Nikhil Munshi, James Horner, Elena V. Ivanova, Alexei Protopopov, Kenneth C. Anderson, Giovanni Tonon, Ronald A. DePinho
Journal: Cancer Cell (2007)

Multiple myeloma (MM) evolves from a highly prevalent premalignant condition termed MGUS. The factors underlying the malignant transformation of MGUS are unknown. We report a MGUS/MM phenotype in transgenic mice with Eμ-directed expression of the XBP-1 spliced isoform (XBP-1s), a factor governing unfolded protein/ER stress response and plasma-cell development. Eμ-XBP-1s elicited elevated serum Ig and skin alterations. With age, Eμ-xbp-1s transgenics develop features diagnostic of human MM, including bone lytic lesions and subendothelial Ig deposition. Furthermore, transcriptional profiles of Eμ-xbp-1s lymphoid and MM cells show aberrant expression of known human MM dysregulated genes. The similarities of this model with the human disease, coupled with documented frequent XBP-1s overexpression in human MM, serve to implicate XBP-1s dysregulation in MM pathogenesis.
Metabolites of a Tobacco-Specific Lung Carcinogen in Nonsmoking Women Exposed to Environmental Tobacco Smoke
Authors: K. E. Anderson, S. G. Carmella, M. Ye, R. L. Bliss, C. Le, L. Murphy, S. S. Hecht
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: Environmental tobacco smoke (ETS) is associated with lung cancer in nonsmokers. Most epidemiologic studies find a higher risk for lung cancer in nonsmoking women married to smokers than in those married to nonsmokers. We measured metabolites of a tobacco-specific lung carcinogen in urine from healthy, nonsmoking women exposed to ETS. Methods: We recruited women and their partners through advertisements. Couples completed questionnaires on smoking history and demographics, and both partners provided 100 mL of urine; 23 women had male partners who smoked in the home (i.e., exposed women), and 22 women had male partners who did not smoke (i.e., unexposed women). Urine samples were analyzed for nicotine, for cotinine, for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide (NNAL-Gluc), as well as for creatinine. NNAL and NNAL-Gluc are metabolites of the tobacco-specific lung carcinogen 4-(meth-ylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Unpaired Student's t tests were conducted on log-transformed values. All statistical tests are two-sided. Results: Urinary levels of nicotine, cotinine, NNAL, and NNAL-Gluc were statistically significantly higher in exposed women than in unexposed women. Geometric means for these compounds in exposed versus unexposed women, respectively, were as follows: nicotine, 0.050 nmol/mg of creatinine (95% confidence interval [CI] = 0.033 to 0.076) versus 0.008 nmol/mg of creatinine (95% CI = 0.004 to 0.014); cotinine, 0.037 nmol/mg of creatinine (95% CI = 0.022 to 0.061) versus 0.007 nmol/mg of creatinine (95% CI = 0.004 to 0.011); NNAL, 0.013 pmol/mg of creatinine (95% CI = 0.007 to 0.024) versus 0.004 pmol/mg of creatinine (95% CI = 0.002 to 0.007); and NNAL-Gluc, 0.027 pmol/mg of creatinine (95% CI = 0.016 to 0.045) versus 0.004 pmol/mg of creatinine (95% CI = 0.003 to 0.006). Conclusions: Nonsmoking women exposed to ETS take up and metabolize the tobacco-specific lung carcinogen NNK, which could increase their risk of lung cancer. Within couples, the NNAL plus NNAL-Gluc level in exposed women compared with that of their smoking partners averaged 5.6%. Notably, epidemiologic studies have estimated the excess risk for lung cancer in nonsmoking women exposed to ETS as 1%–2% of that in smokers.
Efficacy and Safety of Tenecteplase in Combination With the Low-Molecular-Weight Heparin Enoxaparin or Unfractionated Heparin in the Prehospital Setting
Authors: L. Wallentin, P. Goldstein, P.W. Armstrong, C.B. Granger, A.A.J. Adgey, H.R. Arntz, K. Bogaerts, T. Danays, B. Lindahl, M. Mäkijärvi, F. Verheugt, F. Van de Werf
Journal: Circulation (2003)

The combination of a single-bolus fibrinolytic and a low-molecular-weight heparin may facilitate prehospital reperfusion and further improve clinical outcome in patients with ST-elevation myocardial infarction.In the prehospital setting, 1639 patients with ST-elevation myocardial infarction were randomly assigned to treatment with tenecteplase and either (1) intravenous bolus of 30 mg enoxaparin (ENOX) followed by 1 mg/kg subcutaneously BID for a maximum of 7 days or (2) weight-adjusted unfractionated heparin (UFH) for 48 hours. The median treatment delay was 115 minutes after symptom onset (53% within 2 hours). ENOX tended to reduce the composite of 30-day mortality or in-hospital reinfarction, or in-hospital refractory ischemia to 14.2% versus 17.4% for UFH (P=0.080), although there was no difference for this composite end point plus in-hospital intracranial hemorrhage or major bleeding (18.3% versus 20.3%, P=0.30). Correspondingly, there were reductions in in-hospital reinfarction (3.5% versus 5.8%, P=0.028) and refractory ischemia (4.4% versus 6.5%, P=0.067) but increases in total stroke (2.9% versus 1.3%, P=0.026) and intracranial hemorrhage (2.20% versus 0.97%, P=0.047). The increase in intracranial hemorrhage was seen in patients >75 years of age.Prehospital fibrinolysis allows 53% of patients to receive reperfusion treatment within 2 hours after symptom onset. The combination of tenecteplase with ENOX reduces early ischemic events, but lower doses of ENOX need to be tested in elderly patients. At present, therefore, tenecteplase and UFH are recommended as the routine pharmacological reperfusion treatment in the prehospital setting.
Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO)
Authors: Andrea Bacigalupo, Teresa Lamparelli, Paolo Bruzzi, Stefano Guidi, Paolo Emilio Alessandrino, Paolo di Bartolomeo, Rosa Oneto, Barbara Bruno, Mario Barbanti, Nicoletta Sacchi, Maria Teresa Van Lint, Alberto Bosi
Journal: Blood (2001)
Real-World Therapies and the Problem of Vivax Malaria
Authors: J. Kevin Baird
Journal: New England Journal of Medicine (2008)

Wellems and Miller1 wrote of two worlds of malaria: one, of the residents of rural tropical areas in which the disease is endemic, and the other, of travelers to those areas, who typically have greater resources. The distinction is sharp, valid, and important in considering the development of tools to combat the global burden of malaria. Drugs considered safe and effective in one world may not be so in the other.2 The majority of the hundreds of millions of people in whom malaria will develop over the next year will obtain and consume antimalarial medication without medical supervision. Although the . . .
Prevalence of C-Reactive Protein Elevation and Time Course of Normalization in Acute Pericarditis
Authors: Massimo Imazio, Antonio Brucato, Silvia Maestroni, Davide Cumetti, Antonio Dominelli, Giuseppe Natale, Rita Trinchero
Journal: Circulation (2011)

Background— The role of inflammatory markers is not well defined for either diagnosis or treatment of pericarditis. The aim of this study is to prospectively evaluate the frequency of high-sensitivity C-reactive protein (hs-CRP) elevation in patients with acute pericarditis, its time course of normalization, and the possible importance for diagnosis, therapy, and prognosis. Methods and Results— Two hundred consecutive patients with viral or idiopathic acute pericarditis (mean age, 53±15.5 years; 103 men) were studied from August 2005 to August 2007 in 2 Italian referral centers. Hs-CRP was determined at presentation and then every week until normalization. Hs-CRP elevation was recorded in 156 of 200 cases (78%) at presentation. Recognized causes of a negative hs-CRP at presentation were early assessment in 15 of 44 cases (34%) and previous anti-inflammatory therapies in 22 of 44 cases (50%). Hs-CRP normalization was achieved with the following time course: 120 of 200 (60%) at week 1, 170 of 200 (85%) at week 2, 190 of 200 (95%) at week 3, and all cases (100%) at week 4. In multivariable analysis, incomplete response to empirical anti-inflammatory therapy at week 1 (hazard ratio, 2.98; 95% confidence interval, 1.80 to 4.94; P &lt;0.001), corticosteroid therapy (hazard ratio, 2.80; 95% confidence interval, 1.59 to 4.95; P &lt;0.001), and the presence of elevated hs-CRP at week 1 (hazard ratio, 2.36; 95% confidence interval, 1.32 to 4.21; P =0.004) were independent risk factors for recurrence. Conclusions— Hs-CRP is elevated at the initial presentation in ≈3 of 4 cases of acute pericarditis, identifies patients at higher risk of recurrence, and could be used to monitor disease activity and select appropriate therapy length.
Sport accidents in childhood.
Authors: Y Sahlin
Journal: British Journal of Sports Medicine (1990)

Injuries among children during sporting activities are common. This study is a one year study including children between five and fourteen years of age who sustained their injuries during sporting activities and were treated at Trondheim Regional and University Hospital. Sport accidents account for 27 per cent of all childhood accidents in this age group. Fifty-three per cent of the injured were boys, and 47 per cent were girls. The boys sustained more severe injuries than the girls. Soccer caused the greatest number of injuries. Horse riding and alpine skiing were the cause of the most severe injuries. A more widespread use of protective guards, better technique and body control, better coaching and not allowing the younger children to take part in technically advanced sporting activities might reduce the number and the severity of the sport injuries in children.
Production rates and metabolic clearance rates of human follicle—stimulating hormone in premenopausal and postmenopausal women
Authors: Yank D. Coble, Peter O. Kohler, Charles M. Cargille, Griff T. Ross
Journal: Journal of Clinical Investigation (1969)

The production rates (PR) and the metabolic clearance rates (MCR) of human follicle-stimulating hormone (HFSH) were determined in six pre- and five postmenopausal women. Human FSH (PER-780) labeled with (131)I to specific activities of 50-150 muc/mug was used as a tracer. Both double antibody and trichloroacetic acid (TCA) precipitation techniques were used to determine HFSH-(131)I levels in infusate and plasma. In four of the subjects MCRs measured by both constant infusion and single injection techniques were the same. By constant infusion, plasma HFSH-(131)I levels reached equilibrium between 4-5 hr.MCRs in six premenopausal women were 14.2+/-1.1 (mean +/-SE) ml/min. MCRs in five postmenopausal women were 12.6 +/-1.1 ml/min. Simultaneous HFSH and human luteinizing hormone (HLH) MCRs were determined in a single patient using HFSH-(125)I and HLH-(131)I as tracers by both constant infusion and single injection methods. These studies showed that the MCR of HFSH was 10.8-11.1 ml/min, and the MCR of HLH was 18.5-19.4 ml/min. From these data and previous MCR and PR studies of HLH from this laboratory, it appears that the MCR of HFSH is about one-half that of HLH. Endogenous HFSH and HLH levels were measured by radioimmunoassay. The PRs of HFSH, calculated by the product of endogenous level and MCR, were 146 +/-27mU/min in the premenopausal women and 2141 +/-264 mM/min in the postmenopausal women. 24-hr PRs, based on these results, compared with reports of 24-hr urinary excretions of biologically active HFSH indicate that 3-5% of production is found in urine in biologically active form. After our single injections of HFSH-(131)I, 8-29% was recovered in urine over 24 hr.
Astrocyte-Derived CO Is a Diffusible Messenger That Mediates Glutamate-Induced Cerebral Arteriolar Dilation by Activating Smooth Muscle Cell K <sub>Ca</sub> Channels
Authors: Anlong Li, Qi Xi, Edward S. Umstot, Lars Bellner, Michal L. Schwartzman, Jonathan H. Jaggar, Charles W. Leffler
Journal: Circulation Research (2007)

Astrocyte signals can modulate arteriolar tone, contributing to regulation of cerebral blood flow, but specific intercellular communication mechanisms are unclear. Here we used isolated cerebral arteriole myocytes, astrocytes, and brain slices to investigate whether carbon monoxide (CO) generated by the enzyme heme oxygenase (HO) acts as an astrocyte-to-myocyte gasotransmitter in the brain. Glutamate stimulated CO production by astrocytes with intact HO-2, but not those genetically deficient in HO-2. Glutamate activated transient K(Ca) currents and single K(Ca) channels in myocytes that were in contact with astrocytes, but did not affect K(Ca) channel activity in myocytes that were alone. Pretreatment of astrocytes with chromium mesoporphyrin (CrMP), a HO inhibitor, or genetic ablation of HO-2 prevented glutamate-induced activation of myocyte transient K(Ca) currents and K(Ca) channels. Glutamate decreased arteriole myocyte intracellular Ca2+ concentration and dilated brain slice arterioles and this decrease and dilation were blocked by CrMP. Brain slice arteriole dilation to glutamate was also blocked by L-2-alpha aminoadipic acid, a selective astrocyte toxin, and paxilline, a K(Ca) channel blocker. These data indicate that an astrocytic signal, notably HO-2-derived CO, is used by glutamate to stimulate arteriole myocyte K(Ca) channels and dilate cerebral arterioles. Our study explains the astrocyte and HO dependence of glutamatergic functional hyperemia observed in the newborn cerebrovascular circulation in vivo.
Biliary excretion of lecithin and cholesterol in the dog
Authors: Henry O. Wheeler, Katherine K. King
Journal: Journal of Clinical Investigation (1972)

The biliary excretion rates of bile acid, lecithin, and cholesterol were measured in unanesthetized dogs after interruption of enterohepatic circulation and during infusions of sodium taurocholate, sodium glycocholate, sodium dehydrocholate, SC2644 (a bicyclic organic acid with high choleretic potency), and secretin. Both lecithin output and cholesterol output were directly related to bile acid excretion rate. The curves describing these relationships were concave downward. Molar concentration ratios of lecithin-to-bile acid declined gradually from approximately 0.4 to 0.2 as bile acid output increased from approximately 1 to 70 μmoles/min. Cholesterol-to-lecithin molar ratios were highest (0.05-0.15) at very low rates of bile acid excretion, but descended rapidly to a plateau (0.03-0.04) which was constant over the entire range of bile acid excretion rates from 10 to 70 μmoles/min.
Epidermal Growth Factor Receptor Inhibitor Gefitinib Added to Chemoradiotherapy in Locally Advanced Head and Neck Cancer
Authors: Ezra E.W. Cohen, Daniel J. Haraf, Rangesh Kunnavakkam, Kerstin M. Stenson, Elizabeth A. Blair, Bruce Brockstein, Eric P. Lester, Joseph K. Salama, Allison Dekker, Rosalyn Williams, Mary Ellyn Witt, Tatyana A. Grushko, James J. Dignam, Mark W. Lingen, Olufunmilayo I. Olopade, Everett E. Vokes
Journal: Journal of Clinical Oncology (2010)

Assess efficacy and toxicity of gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, added to, and in maintenance after, concurrent chemoradiotherapy (CCRT) in locally advanced head and neck cancer (LA-HNC) and correlate outcomes with EGFR gene copy number alterations.Patients with stage III to IV LA-HNC received two cycles of carboplatin/paclitaxel induction chemotherapy (IC) followed by split-course CCRT with fluorouracil, hydroxyurea, twice daily radiotherapy (FHX), and gefitinib (250 mg daily) followed by continued gefitinib for 2 years total. The primary end point was complete response (CR) rate after CCRT. EGFR gene copy number was assessed by fluorescent in situ hybridization.Sixty-nine patients (66 with stage IV disease, 37 with oropharynx primary tumors, and 67 with performance status 0 to 1) were enrolled with a median age of 55 years. Predominant grade 3 or 4 toxicities during IC and CCRT were neutropenia (n = 20) and in-field mucositis (n = 59) and dermatitis (n = 23), respectively. CR rate after CCRT was 90%. After median follow-up of 3.5 years, 4-year overall, progression-free, and disease-specific survival rates were 74%, 72%, and 89%, respectively. To date, one patient has developed a second primary tumor in the aerodigestive tract. In 31 patients with available tissue, high EGFR gene copy number was associated with worse overall survival (P = .02).Gefitinib can be administered with FHX and as maintenance therapy for at least 2 years, demonstrating CR and survival rates that compare favorably with prior experience. High EGFR gene copy number may be associated with poor outcome in patients with LA-HNC treated with this regimen.
Gr-1+CD11b+ Myeloid Cells Tip the Balance of Immune Protection to Tumor Promotion in the Premetastatic Lung
Authors: Hannah H. Yan, Michael Pickup, Yanli Pang, Agnieszka E. Gorska, Zhaoyang Li, Anna Chytil, Yipeng Geng, Jerome W. Gray, Harold L. Moses, Li Yang
Journal: Cancer Research (2010)

The mechanisms by which a primary tumor affects a selected distant organ before tumor cell arrival remain to be elucidated. This report shows that Gr-1+CD11b+ cells are significantly increased in lungs of mice bearing mammary adenocarcinomas before tumor cell arrival. In the premetastatic lungs, these immature myeloid cells significantly decrease IFN-gamma production and increase proinflammatory cytokines. In addition, they produce large quantities of matrix metalloproteinase 9 (MMP9) and promote vascular remodeling. Deletion of MMP9 normalizes aberrant vasculature in the premetastatic lung and diminishes lung metastasis. The production and activity of MMP9 is selectively restricted to lungs and organs with a large number of Gr-1+CD11b+ cells. Our work reveals a novel protumor mechanism for Gr-1+CD11b+ cells that changes the premetastatic lung into an inflammatory and proliferative environment, diminishes immune protection, and promotes metastasis through aberrant vasculature formation. Thus, inhibition of Gr-1+CD11b+ cells could normalize the premetastatic lung environment, improve host immunosurveillance, and inhibit tumor metastasis.
Metformin and risk of hepatocellular carcinoma: are statins the missing link?
Authors: Siddharth Singh, Preet Paul Singh
Journal: Gut (2012)

We read with great interest, the recent article titled ‘Metformin decreases hepatocellular carcinoma risk in a dose-dependent manner: population-based and in vitro studies’ by Chen and colleagues published online in July in the Journal .1 In this large, population-based, case-control study using the Taiwanese National Health Insurance Research Database, they reported that in patients with diabetes mellitus (DM), metformin use is associated with a decrease in the risk of hepatocellular cancer (HCC) in a dose- and duration-dependent manner. Metformin users had a 21% lower risk of HCC on multivariate stratified analysis, after adjusting for potential confounders (age, gender, hepatitis B, hepatitis C, liver cirrhosis, DM duration and antidiabetic …