tbuckley/cabot-search huggingface dataset:
Cancer as a Risk Factor for Long-Term Cognitive Deficits and Dementia
Authors: Lara H. Heflin, Beth E. Meyerowitz, Per Hall, Paul Lichtenstein, Boo Johansson, Nancy L. Pedersen, Margaret Gatz
Journal: JNCI Journal of the National Cancer Institute (2005)

Previous studies have shown that cancer survivors frequently experience short-term cognitive deficits, but it is unknown how long these deficits last or whether they worsen over time. Using a co-twin control design, the cognitive function of 702 cancer survivors aged 65 years and older was compared with that of their cancer-free twins. Dementia rates were also compared in 486 of the twin pairs discordant for cancer. Cancer survivors overall, as well as individuals who had survived cancer for 5 or more years before cognitive testing, were more likely than their co-twins to have cognitive dysfunction (odds ratio [OR] = 2.10, 95% confidence interval [CI] = 1.36 to 3.24; P<.001; and OR = 2.71, 95% CI = 1.47 to 5.01; P<.001, respectively). Cancer survivors were also twice as likely to be diagnosed with dementia as their co-twins, but this odds ratio did not reach statistical significance (OR = 2.0, 95% CI = 0.86 to 4.67; P = .10). These results suggest that cancer patients are at increased risk for long-term cognitive dysfunction compared with individuals who have never had cancer, even after controlling for the influence of genetic factors and rearing environment.
Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials
Authors: Michael V Holmes, Paul Newcombe, Jaroslav A Hubacek, Reecha Sofat, Sally L Ricketts, Jackie Cooper, Monique MB Breteler, Leonelo E Bautista, Pankaj Sharma, John C Whittaker, Liam Smeeth, F Gerald R Fowkes, Ale Algra, Veronika Shmeleva, Zoltan Szolnoki, Mark Roest, Michael Linnebank, Jeppe Zacho, Michael A Nalls, Andrew B Singleton, Luigi Ferrucci, John Hardy, Bradford B Worrall, Stephen S Rich, Mar Matarin, Paul E Norman, Leon Flicker, Osvaldo P Almeida, Frank M van Bockxmeer, Hiroshi Shimokata, Kay-Tee Khaw, Nicholas J Wareham, Martin Bobak, Jonathan AC Sterne, George Davey Smith, Philippa J Talmud, Cornelia van Duijn, Steve E Humphries, Jackie F Price, Shah Ebrahim, Debbie A Lawlor, Graeme J Hankey, James F Meschia, Manjinder S Sandhu, Aroon D Hingorani, Juan P Casas
Journal: The Lancet (2011)
Effects of 0.2 ppm ozone on biomarkers of inflammation in bronchoalveolar lavage fluid and bronchial mucosa of healthy subjects
Authors: MT Krishna, J Madden, LM Teran, GL Biscione, LC Lau, NJ Withers, T Sandstrom, I Mudway, FJ Kelly, A Walls, AJ Frew, ST Holgate
Journal: European Respiratory Journal (1998)

Short-term exposure to ozone at peak ambient levels induces neutrophil influx and impairs lung function in healthy humans. In order to investigate the mechanisms contributing to neutrophil recruitment and to examine the role of T-cells in the acute inflammatory response, we exposed 12 healthy humans to 0.2 parts per million (ppm) of ozone and filtered air on two separate occasions for 2 h with intermittent periods of rest and exercise (minute ventilation = 30 L x min(-1)). Fibreoptic bronchoscopy was performed 6 h after the end of exposures. Total protein, tryptase, histamine, myeloperoxidase, interleukin (IL)-8 and growth-related oncogene-alpha (Gro-alpha) were measured and total and differential cell counts were performed in bronchoalveolar lavage (BAL) fluid. Flow cytometry was performed on BAL cells to study total T-cells, T-cell receptors (alphabeta and gammadelta), T-cell subsets (CD4+ and CD8+ cells) and activated T-cell subsets (CD25+). Using immunohistochemistry, neutrophils, mast cells, total T-cell numbers, T-cell subsets, CD25+ T-cells and leukocyte endothelial adhesion molecules including P-selectin, E-selectin, intercellular adhesion molecule (ICAM)-1 and vascular adhesion molecule (VCAM)-1 were quantified in the bronchial biopsies. Paired samples were available from nine subjects. Following ozone exposure there was a threefold increase in the proportion of polymorphonuclear neutrophils (PMNs) (p=0.07) and epithelial cells (p=0.05) in BAL fluid. This was accompanied by increased concentrations of IL-8 (p=0.01), Gro-alpha (p=0.05) and total protein (p=0.058). A significant positive correlation was demonstrated between the two chemokines and proportion of PMNs in BAL fluid. After ozone exposure there was a significant decrease in the CD4/CD8 ratio (p=0.05) and the proportion of activated CD4+ (p=0.01) and CD8+ T-cells (p=0.04). However, no significant changes were demonstrable in any of the inflammatory markers studied in the biopsies. Short-term exposure of healthy humans to 0.2 ppm ozone induced a neutrophil influx in peripheral airways at 6 h post exposure, but no apparent inflammatory response in proximal airways. This response seems to be mediated at least in part by interleukin-8 and growth-related oncogene-alpha.
Radiochemotherapy After Transurethral Resection for High-Risk T1 Bladder Cancer: An Alternative to Intravesical Therapy or Early Cystectomy?
Authors: Christian Weiss, Carolin Wolze, Dirk Gerhard Engehausen, Oliver J. Ott, Frens S. Krause, Karl-Michael Schrott, Jürgen Dunst, Rolf Sauer, Claus Rödel
Journal: Journal of Clinical Oncology (2006)

Purpose For high-risk T1 bladder cancer, the most important issue is how to restrict radical cystectomy to selective patients with a high likelihood of tumor progression and to choose an initial bladder-sparing approach in others without affecting survival. Radiotherapy or radiochemotherapy (RT/RCT) may help to strike a balance between intravesical treatment and early cystectomy. Patients and Methods Between 1982 and 2004, 141 patients with high-risk T1 bladder cancer (84 patients with T1 grade 3 [T1G3]; others with T1G1/2 and associated carcinoma-in-situ, multifocality, tumor diameter &gt; 5 cm, or multiple recurrences) were treated with RT (n = 28) or platinum-based RCT (n = 113) after transurethral resection of bladder tumor (TURBT). Six weeks after RT/RCT, response was evaluated by restaging TURBT. Salvage cystectomy was recommended for patients with persistent disease and for tumor progression after initial complete response (CR). Median follow-up was 62 months; 65 patients have been observed for 5 years or more. Results CR was achieved in 121 of 137 patients (88%; four patients without restaging TURBT). Tumor progression for the entire group of 141 patients was 19% and 30% at 5 and 10 years, respectively (for 121 patients with CR, 15% and 29%; for 84 patients with T1G3, 13% and 29%, respectively). Disease-specific survival rates were 82% and 73% at 5 and 10 years (CR, 89% and 79%; T1G3, 80% and 71%, respectively). More than 80% of survivors preserved their bladder; 70.4% were “delighted” or “pleased” with their urinary function. Conclusion RT/RCT after TURBT with selective bladder preservation is a reasonable alternative to intravesical treatment or early cystectomy for high-risk T1 bladder cancer.
Update on treatment options for spinal brucellosis
Authors: A. Ulu-Kilic, A. Karakas, H. Erdem, T. Turker, A.S. Inal, O. Ak, H. Turan, E. Kazak, A. Inan, F. Duygu, H. Demiraslan, C. Kader, A. Sener, S. Dayan, O. Deveci, R. Tekin, N. Saltoglu, M. Aydin, E.S. Horasan, H.C. Gul, B. Ceylan, A. Kadanali, O. Karabay, G. Karagoz, U. Kayabas, V. Turhan, D. Engin, S. Gulsun, N. Elaldı, S. Alabay
Journal: Clinical Microbiology and Infection (2013)
EFFECTS OF BETA-BLOCKER ON HEART RATE REDUCTION AND COLLAGEN DEGRADATION IN PATIENTS WITH HEART FAILURE REDUCED EJECTION FRACTION
Authors: Miho Fukui, Shinichi Hirotani, Akiko Goda, Mitsuru Masaki, Ayumi Nakabo, Shohei Fujiwara, Masataka Sugahara, Masaaki Lee-Kawabata, Tohru Masuyama
Journal: Journal of the American College of Cardiology (2013)
Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry
Authors: Leonardo H Travassos, Leticia A M Carneiro, Mahendrasingh Ramjeet, Seamus Hussey, Yun-Gi Kim, João G Magalhães, Linda Yuan, Fraser Soares, Evelyn Chea, Lionel Le Bourhis, Ivo G Boneca, Abdelmounaaim Allaoui, Nicola L Jones, Gabriel Nuñez, Stephen E Girardin, Dana J Philpott
Journal: Nature Immunology (2009)
Tidal expiratory flow patterns in airflow obstruction.
Authors: M J Morris, D J Lane
Journal: Thorax (1981)

Tidal expiratory flow pattern was analysed in 99 subjects with a view to assessing it as a quantitative measurement of airflow obstruction. Fifteen normal volunteers, nine patients with dyspnoea referred for investigation in whom airway resistance was within normal limits, 24 patients with restrictive lung disorders, and 51 patients with airway obstruction were studied. The expiratory flow pattern against time had a quadrilateral configuration in airway obstruction, which differed from the more sinusoidal form that is seen in subjects without airflow obstruction. The rapid rise to tidal peak flow was analysed in two ways, percentage of volume expired at tidal peak flow (delta V/V) and percentage of expiratory time to tidal peak flow (delta t/t). Both these indices correlated significantly with conventional measurements of airway obstruction. The pattern of expiratory flow in airflow obstruction during quiet breathing resembles that of a forced expiratory maneuver at similar lung volumes. In some cases this may be caused by dynamic compression occurring during tidal breathing. In others, the pattern may result from the static recoil of the lung being permitted to drive flow freely in expiration, rather than being braked by postinspiratory contraction of inspiratory musculature.
Effects of Exercise on Cardiovascular Risk Factors in Type 2 Diabetes
Authors: Anna Chudyk, Robert J. Petrella
Journal: Diabetes Care (2011)

OBJECTIVE Exercise is a cornerstone of diabetes management and the prevention of incident diabetes. However, the impact of the mode of exercise on cardiovascular (CV) risk factors in type 2 diabetes is unclear. RESEARCH DESIGN AND METHODS We conducted a systematic review of the literature between 1970 and October 2009 in representative databases for the effect of aerobic or resistance exercise training on clinical markers of CV risk, including glycemic control, dyslipidemia, blood pressure, and body composition in patients with type 2 diabetes. RESULTS Of 645 articles retrieved, 34 met our inclusion criteria; most investigated aerobic exercise alone, and 10 reported combined exercise training. Aerobic alone or combined with resistance training (RT) significantly improved HbA1c −0.6 and −0.67%, respectively (95% CI −0.98 to −0.27 and −0.93 to −0.40, respectively), systolic blood pressure (SBP) −6.08 and −3.59 mmHg, respectively (95% CI −10.79 to −1.36 and −6.93 to −0.24, respectively), and triglycerides −0.3 mmol/L (95% CI −0.48 to −0.11 and −0.57 to −0.02, respectively). Waist circumference was significantly improved −3.1 cm (95% CI −10.3 to −1.2) with combined aerobic and resistance exercise, although fewer studies and more heterogeneity of the responses were observed in the latter two markers. Resistance exercise alone or combined with any other form of exercise was not found to have any significant effect on CV markers. CONCLUSIONS Aerobic exercise alone or combined with RT improves glycemic control, SBP, triglycerides, and waist circumference. The impact of resistance exercise alone on CV risk markers in type 2 diabetes remains unclear.
Intensification of Mercaptopurine/Methotrexate Maintenance Chemotherapy May Increase the Risk of Relapse for Some Children With Acute Lymphoblastic Leukemia
Authors: Kjeld Schmiegelow, Olle Björk, Anders Glomstein, Göran Gustafsson, Niels Keiding, Jon Kristinsson, Anne Mäkipernaa, Susanne Rosthøj, Carol Szumlanski, Tine M Sørensen, Richard Weinshilboum
Journal: Journal of Clinical Oncology (2003)

Thioguanine nucleotides (TGNs) mediate the cytotoxicity of mercaptopurine (MP). Methylated MP metabolites (formed by thiopurine methyltransferase [TPMT]) and methotrexate (MTX) polyglutamates can inhibit de novo purine synthesis. We explored whether dose adjustment of MP and MTX by erythrocyte (E) levels of TGN and MTX (including polyglutamates) could improve outcome in childhood acute lymphoblastic leukemia (ALL).A total of 538 children with ALL were randomly assigned to have their oral MP/MTX maintenance therapy adjusted by white cell counts (WBC), E-TGN, and E-MTX (pharmacology group), or by WBC only (control group).After a median follow-up of 7.8 years, 79 patients had relapsed. Cox regression analysis showed an increased risk of relapse for boys (P =.00003), high WBC at diagnosis (P =.03), pharmacology arm (6.6 times increased relapse hazard for girls), high TPMT activity (P =.002), and high average neutrophil counts during maintenance therapy (P =.0009), with a significant interaction between sex and randomization group (P =.0007). For girls, the relapse risk was 5% in the control group and 19% in the pharmacology group (P =.001) because of an increased relapse hazard during the first year after cessation of therapy. TPMT activity was the most significant predictor of relapses among girls in the pharmacology arm (P <.0001). Overall, the TPMT activity was higher for patients who relapsed after cessation of therapy compared with those who stayed in remission (girls 19.5 v 17.4 U/mL, P =.03; boys 19.3 v 18.0 U/mL, P =.04).Adding pharmacologically guided treatment intensification to dose adjustments by blood counts may not be warranted for girls, whereas new approaches to optimize maintenance therapy are needed for boys.
Oxidative stress activates ADAM17/TACE and induces its target receptor shedding in platelets in a p38-dependent fashion
Authors: A. Brill, A. K. Chauhan, M. Canault, M. T. Walsh, W. Bergmeier, D. D. Wagner
Journal: Cardiovascular Research (2009)

Oxidative stress accompanies inflammatory and vascular diseases. The objective of this study was to explore whether reactive oxygen species can activate shedding of platelet receptors and thus suppress platelet function. Hydrogen peroxide and glucose oxidase were chosen to model oxidative stress in vitro. We demonstrate that oxidative damage activated tumour necrosis factor-α-converting enzyme (TACE) and induced shedding of its targets, glycoprotein (GP) Ibα and GPV, in murine and human platelets. Also, 12-HpETE, a peroxide synthesized in the platelet lipoxygenase pathway, induced TACE-mediated receptor cleavage. The TACE activation was independent of platelet activation, as α-granule secretion, activation of αIIbβ3, or phosphatidylserine expression was not observed. TACE activation induced by hydrogen peroxide was dependent on p38 mitogen-activated protein kinase signalling, whereas protein kinase C, phosphoinositide 3-kinase, and caspases were not involved. Inhibition of p38 cytoplasmic targets, phospholipase A2 and heat shock protein 27, did not prevent shedding, whereas blocking 12-lipoxygenase or Src kinase slightly inhibited TACE activation. The loss of the GPIbα receptor induced by oxidative stress rendered platelets unable to incorporate into a growing thrombus in vivo. Oxidative stress can render platelets functionally less active by shedding key adhesion receptors via the activation of p38. This suggests that oxidative injury of platelets may attenuate their function.
General Quality of Life 2 Years Following Treatment for Prostate Cancer: What Influences Outcomes? Results From the Prostate Cancer Outcomes Study
Authors: David F. Penson, Ziding Feng, Alan Kuniyuki, Dale McClerran, Peter C. Albertsen, Dennis Deapen, Frank Gilliland, Richard Hoffman, Robert A. Stephenson, Arnold L. Potosky, Janet L. Stanford
Journal: Journal of Clinical Oncology (2003)

Purpose: The goal of this study was to determine the relationship between primary treatment, urinary dysfunction, sexual dysfunction, and general health-related quality of life (HRQOL) in prostate cancer. Methods: A sample of men with newly diagnosed prostate cancer between 1994 and 1995 was randomly selected from six population-based Surveillance, Epidemiology, and End Results registries. A baseline survey was completed by 2,306 men within 6 to 12 months of diagnosis, and these men also completed a follow-up HRQOL survey 2 years after diagnosis. Logistic regression models were used to determine whether primary treatment, urinary dysfunction, and sexual dysfunction were independently associated with general HRQOL outcomes approximately 2 years after diagnosis as measured by the Medical Outcomes Study 36-item Short Form Health Survey. The magnitude of this effect was estimated using least square means models. Results: After adjustment for potential confounders, primary treatment was not associated with 2-year general HRQOL outcomes in men with prostate cancer. Urinary function and bother were independently associated with worse general HRQOL in all domains. Sexual function and bother were also independently associated with worse general HRQOL, although the relationship was not as strong as in the urinary domains. Conclusion: Primary treatment is not associated with 2-year general HRQOL outcomes in prostate cancer. Although both sexual and urinary function and bother are associated with quality of life, men who are more bothered by their urination or impotence are more likely to report worse quality of life. This implies that future research should be directed toward finding ways to improve treatment-related outcomes or help patients better cope with their posttreatment urinary or sexual dysfunction.
Inhibition of Neointima Formation After Experimental Coronary Artery Stenting
Authors: Eckhard Alt, Iris Haehnel, Christine Beilharz, Klaus Prietzel, Daniel Preter, Axel Stemberger, Thilo Fliedner, Wolf Erhardt, Albert Schömig
Journal: Circulation (2000)

To minimize acute stent thrombosis and development of restenosis, stents coated with biodegradable and nonbiodegradable polymers have been proposed to serve as sustained-release drug carriers.In both a sheep and a pig model, we examined the vascular response to standard and high-pressure implantation of coronary Palmaz-Schatz stents coated with a 10-microm layer of polylactic acid (MW 30 kDa) releasing recombinant polyethylene glycol (r-PEG)-hirudin and the prostacyclin analogue iloprost, both drugs with antithrombotic and potentially antiproliferative effects. Study observation time was 28 days. Between the corresponding stent groups, no differences were observed with regard to preplacement and postplacement implantation parameters. The morphometric analysis demonstrated that the coating was associated with a greater lumen diameter through a reduction in the mean restenosis area by 22.9% (P<0.02) in the standard-pressure model (sheep) and by 24.8% (P<0.02) in the overstretch pig model compared with uncoated control stents without inducing a local inflammatory response.The results from this study demonstrate beneficial effects of a polymeric stent coating with polylactic acid releasing r-PEG-hirudin and iloprost on the development of restenosis after coronary stent placement at 4 weeks, independent of the extent of vascular injury. Future studies are proposed to investigate the integration of other substances to further enhance the potential of the stent coating on reducing neointimal formation.
Phase I Trial of Combretastatin A-4 Phosphate with Carboplatin
Authors: Joshua H. Bilenker, Keith T. Flaherty, Mark Rosen, Lisa Davis, Maryann Gallagher, James P. Stevenson, Weijing Sun, David Vaughn, Bruce Giantonio, Ross Zimmer, Mitchell Schnall, Peter J. O'Dwyer
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Preclinical evidence of synergy led to a phase I trial employing combretastatin A-4 phosphate (CA4P), a novel tubulin-binding antivascular drug, in combination with carboplatin. Experimental Design: Based on preclinical scheduling studies, patients were treated on day 1 of a 21-day cycle. Carboplatin was given as a 30-minute i.v. infusion and CA4P was given 60 minutes later as a 10-minute infusion. Results: Sixteen patients with solid tumors received 40 cycles of therapy at CA4P doses of 27 and 36 mg/m2 together with carboplatin at area under the concentration-time curve (AUC) values of 4 and 5 mg min/mL. The dose-limiting toxicity of thrombocytopenia halted the dose escalation phase of the study. Four patients were treated at an amended dose level of CA4P of 36 mg/m2 and carboplatin AUC of 4 mg min/mL although grade 3 neutropenia and thrombocytopenia were still observed. Three lines of evidence are adduced to suggest that a pharmacokinetic interaction between the drugs results in greater thrombocytopenia than anticipated: the carboplatin exposure (as AUC) was greater than predicted; the platelet nadirs were lower than predicted; and the deviation of the carboplatin exposure from predicted was proportional to the AUC of CA4, the active metabolite of CA4P. Patient benefit included six patients with stable disease lasting at least four cycles. Conclusion: This study of CA4P and carboplatin given in combination showed dose-limiting thrombocytopenia. Pharmacokinetic/pharmacodynamic modeling permitted the inference that altered carboplatin pharmacokinetics caused the increment in platelet toxicity.
THE THICKNESS OF THE STRATUM COENEUM IN ACNE VULGARIS
Authors: CICELY BLAIR
Journal: British Journal of Dermatology (1968)

SUMMARY. The number of layers of cells in the stratum corneum of a group of patients suffering from acne vulgaris was measured and compared with that of a group of controls, matched as nearly as was possible. Punch biopsy specimens were taken from uninvolved skin from the inter-scapular region. They were treated according to the method of Christophers and Kligman in which fresh frozen sections are exposed to sodium hydroxide solution. The resultant swelling renders the cells easily recognizable. The mean number of cell layers was recorded. The differences between cases and controls was not significant. These observations are discussed in relation to the interpretation of quantitative studies of surface lipids and to the pallor which is a conspicuous clinical feature in many patients with acne.
Cationic liposomes as non‐viral carriers of gene medicines: Resolved issues, open questions, and future promises
Authors: Priya Prakash Karmali, Arabinda Chaudhuri
Journal: Medicinal Research Reviews (2006)

Abstract The clinical success of gene therapy is critically dependent on the development of efficient and safe gene delivery reagents, popularly known as “transfection vectors.” The transfection vectors commonly used in gene therapy are mainly of two types: viral and non‐viral. The efficiencies of viral transfection vectors are, in general, superior to their non‐viral counterparts. However, the myriads of potentially adverse immunogenic aftermaths associated with the use of viral vectors are increasingly making the non‐viral gene delivery reagents as the vectors of choice. Among the existing arsenal of non‐viral gene delivery reagents, the distinct advantages associated with the use of cationic transfection lipids include their: (a) robust manufacture; (b) ease in handling and preparation techniques; (c) ability to inject large lipid:DNA complexes; and (d) low immunogenic response. The present review highlights the major achievements in the area of designing efficacious cationic transfection lipids, some of the more recent advances in the field of cationic liposomes‐mediated gene transfer and targeted gene delivery, some unresolved issues and challenges in liposomal gene delivery, and future promises of cationic liposomes as gene‐carriers in non‐viral gene therapy. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 5, 696–722, 2007