tbuckley/cabot-search huggingface dataset:
Escin/diethylammonium salicylate/heparin combination gels for the topical treatment of acute impact injuries: a randomised, double blind, placebo controlled, multicentre study
Authors: D Wetzel, W Menke, R Dieter, V Smasal, B Giannetti, M Bulitta
Journal: British Journal of Sports Medicine (2002)

Objectives: To investigate the clinical efficacy and safety of escin-containing gels in the topical treatment of blunt impact injuries. Methods: Competitors in soccer, handball, or karate competitions were enrolled within two hours of sustaining a strain, sprain, or contusion and treated three times with the trial gel within a period of eight hours. Patients were randomised to three parallel groups consisting of two active treatment gels, containing escin (1% or 2%), 5% diethylammonium salicylate, and 5000 IU heparin, or placebo gel. Tenderness produced by pressure was measured at 0 (baseline), 1, 2, 3, 4, 6, and 24 hours after enrolment (within two hours of the injury). Tenderness was defined as the amount of pressure (measured by a calibrated caliper at the centre of the injury) that first produced a pain reaction as reported by the patient. Results: A total of 158 patients were enrolled; 156 were evaluated in the intention to treat analysis. The primary efficacy variable was the area under the curve for tenderness over a six hour period. The gel preparations containing 1% and 2% escin were significantly more effective (a priori ordered hypotheses testing controlling the multiple α = 5% significance level) than placebo (p 1 = 0.0001 and p 2 = 0.0002 respectively). The treatment effects were 5.7 kp h/cm 2 (95% confidence interval (CI) 2.9 to 8.5) and 5.9 kilopond (kp) h/cm 2 (95% CI 2.9 to 8.8) between 1% escin and placebo and between 2% escin and placebo respectively. These results were supported by secondary efficacy variables. The time to reach the baseline contralateral tenderness value (resolution of pain) at the injured site was shorter in the treatment groups than in the placebo group (p&lt;0.0001). Both active gel preparations produced more rapid pain relief than the placebo gel. No relevant differences were detected between the two active gels. The safety and tolerability of the escin-containing gels were excellent. Conclusions: Escin/diethylammonium salicylate/heparin combination gel preparations are effective and safe for the treatment of blunt impact injuries.
The Effects of a Smoking Cessation Intervention on 14.5-Year Mortality
Authors: Nicholas R. Anthonisen
Journal: Annals of Internal Medicine (2005)

Letters18 October 2005The Effects of a Smoking Cessation Intervention on 14.5-Year MortalityNicholas R. Anthonisen, MDNicholas R. Anthonisen, MDFrom University of Manitoba, Winnipeg, Manitoba R3A 1R8, Canada.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-143-8-200510180-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Dr. Mathew rightly points out that the Lung Health Study smoking cessation program was accompanied by the prescription of inhalers and believes that we may not have given them adequate consideration. He agrees that the content of the inhalers (placebo or bronchodilator) did not make a difference and appears to accept that it was differences in smoking habits that determined the improved survival in the special intervention group. It therefore follows that if the inhalers were important, it was because they made the smoking cessation program more effective. Maybe so, but we are unapologetic about attributing the smoking ...References1. Higenbottam TW, Feyeraband C, Clark TJ. Cigarette smoking in asthma. Br J Dis Chest. 1980;74:279-84. [PMID: 7426367] CrossrefMedlineGoogle Scholar2. Silverman RA, Boudreaux ED, Woodruff PG, Clark S, Camargo CA. Cigarette smoking among asthmatic adults presenting to 64 emergency departments. Chest. 2003;123:1472-9. [PMID: 12740263] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From University of Manitoba, Winnipeg, Manitoba R3A 1R8, Canada. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Effects of a Smoking Cessation Intervention on 14.5-Year Mortality Nicholas R. Anthonisen , Melissa A. Skeans , Robert A. Wise , Jure Manfreda , Richard E. Kanner , John E. Connett , and The Effects of a Smoking Cessation Intervention on 14.5-Year Mortality Milan C. Mathew The Effects of a Smoking Cessation Intervention on 14.5-Year Mortality Gregory J. Bombassei Metrics Cited ByA scoping review of studies on the health impact of electronic nicotine delivery systemsIntroduction to Lung DiseasesTobacco Use: A Chronic Illness? 18 October 2005Volume 143, Issue 8Page: 615KeywordsAsthmaBronchodilatorsLungsSmoking habits ePublished: 18 October 2005 Issue Published: 18 October 2005 CopyrightCopyright © 2005 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Infertility, infertility treatment, and congenital malformations: Danish national birth cohort
Authors: Jin Liang Zhu, Olga Basso, Carsten Obel, Camilla Bille, Jørn Olsen
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objectives</b> To examine whether infertile couples (with a time to pregnancy of &gt; 12 months), who conceive naturally or after treatment, give birth to children with an increased prevalence of congenital malformations. <b>Design</b> Longitudinal study. <b>Setting</b> Danish national birth cohort. <b>Participants</b> Three groups of liveborn children and their mothers: 50 897 singletons and 1366 twins born of fertile couples (time to pregnancy ≤ 12 months), 5764 singletons and 100 twins born of infertile couples who conceived naturally (time to pregnancy &gt; 12 months), and 4588 singletons and 1690 twins born after infertility treatment. <b>Main outcome measures</b> Prevalence of congenital malformations determined from hospital discharge diagnoses. <b>Results</b> Compared with singletons born of fertile couples, singletons born of infertile couples who conceived naturally or after treatment had a higher prevalence of congenital malformations—hazard ratios 1.20 (95% confidence interval 1.07 to 1.35) and 1.39 (1.23 to 1.57). The overall prevalence of congenital malformations increased with increasing time to pregnancy. When the analysis was restricted to singletons born of infertile couples, babies born after treatment had an increased prevalence of genital organ malformations (hazard ratio 2.32, 1.24 to 4.35) compared with babies conceived naturally. No significant differences existed in the overall prevalence of congenital malformations among twins. <b>Conclusions</b> Hormonal treatment for infertility may be related to the occurrence of malformations of genital organs, but our results suggest that the reported increased prevalence of congenital malformations seen in singletons born after assisted reproductive technology is partly due to the underlying infertility or its determinants. The association between untreated infertility and congenital malformations warrants further examination.
Antimalarials may influence the risk of malignancy in systemic lupus erythematosus
Authors: G Ruiz-Irastorza, A Ugarte, M V Egurbide, M Garmendia, J I Pijoan, A Martinez-Berriotxoa, C Aguirre
Journal: Annals of the Rheumatic Diseases (2007)

<b>Background:</b> Recent studies suggest that antimalarials have antineoplastic properties. <b>Objective:</b> To investigate whether antimalarials decrease the risk of cancer in systemic lupus erythematosus (SLE). <b>Methods:</b> An observational prospective cohort study was carried out. 235 patients were included in the study at the time of diagnosis (American College of Rheumatology criteria). The end point was the diagnosis of cancer. Kaplan–Meier cancer-free survival curves for patients treated and not treated with antimalarials were compared. A Cox proportional hazards model was fitted, with cancer as the dependent variable. Age at diagnosis, gender, treatment with azathioprine, cyclophosphamide and methotrexate, smoking, Systemic Lupus International Collaborating Clinics (SLICC) Damage Index 6 months after diagnosis, year of diagnosis and treatment with antimalarials were entered as independent variables. <b>Results:</b> 209 (89%) patients were women. 233 (99%) patients were white. Mean (SD) age at diagnosis was 37 (16) years. Median (range) follow-up was 10 (1–31) years. 156 (66%) patients had ever received antimalarials. 2/156 (1.3%) ever-treated patients compared with 11/79 (13%) never-treated patients had cancer (p&lt;0.001). Cumulative cancer-free survival in treated and not treated patients was 0.98 and 0.73, respectively (p&lt;0.001). Adjusted hazard ratio for cancer among malaria drug users compared with non-users was 0.15 (95% CI 0.02 to 0.99). <b>Conclusions:</b> This study launches the hypothesis of a protective action of antimalarials against cancer in patients with SLE. This effect should be confirmed in larger multicentre studies.
Risk of Adverse Events After Completion of Therapy for Childhood Acute Lymphoblastic Leukemia
Authors: Ching-Hon Pui, Deqing Pei, John T. Sandlund, Dario Campana, Raul C. Ribeiro, Bassem I. Razzouk, Jeffrey E. Rubnitz, Scott C. Howard, Nobuko Hijiya, Sima Jeha, Cheng Cheng, James R. Downing, William E. Evans, Mary V. Relling, Melissa Hudson
Journal: Journal of Clinical Oncology (2005)

We studied the frequency, causes, and predictors of adverse events in children with acute lymphoblastic leukemia (ALL) who had completed treatment on contemporary clinical protocols between 1984 and 1999. Our goal was to use the information to further refine therapy and advance cure rates.Cumulative incidence functions of any post-treatment failure or any post-treatment relapse were estimated by the method of Kalbfleisch and Prentice and compared with Gray's test. The Cox proportional hazards model was used to identify independent prognostic factors.Of the 827 patients who completed all treatment while in initial complete remission, 134 patients subsequently had major adverse events, including 90 leukemic relapses, 40 second malignancies, and four deaths in remission. The cumulative incidence of any adverse event was 14.0% +/- 1.2% (SE) at 5 years and 16.9% +/- 1.4% at 10 years. The risk of any leukemic relapse was 10.0% +/- 1.1% at 5 years and 11.4% +/- 1.2% at 10 years. Male sex was the only independent predictor of relapse (hazard ratio, 1.74; 95% CI, 1.11 to 2.74; P = .02).Further treatment refinements for children with ALL should aim not only to decrease the leukemic relapse rate, but also to reduce the risk of development of second malignancies.
Do you know what your patient is thinking?
Authors: R. Snow
Journal: BMJ (2015)

Do you know what your patient is thinking?Rosamund Snow patient editor, The BMJThe way GP surgery and hospital outpatient encounters are organised-limited time, the power relations in the room-means that many things are left unsaid.As a patient this frustrates me; it's a missed opportunity.I have a long term condition that means I see healthcare professionals a lot.I've experienced a range of attitudes and types of care: from care that was so good it still makes me smile in gratitude 20 years later to dangerously bad care that reduced me to angry sobbing once I'd left the clinic.
Specific Recruitment of CC Chemokine Receptor 4–Positive Regulatory T Cells in Hodgkin Lymphoma Fosters Immune Privilege
Authors: Takashi Ishida, Toshihiko Ishii, Atsushi Inagaki, Hiroki Yano, Hirokazu Komatsu, Shinsuke Iida, Hiroshi Inagaki, Ryuzo Ueda
Journal: Cancer Research (2006)

Abstract Hodgkin lymphoma (HL) is characterized by the presence of a small number of tumor cells in a rich background of inflammatory cells, but the contribution of the abundant nontumor cells to HL pathogenesis is poorly understood. We showed that migratory CD4+ cells induced by HL cells were hyporesponsive to T-cell receptor stimulation and suppressed the activation/proliferation of the effector CD4+ T cells in an autologous setting. We further showed that HL cells in the affected lymph nodes were surrounded by a large number of lymphocytes expressing both CC chemokine receptor 4 (CCR4) and FOXP3. These findings indicate that the migratory cells induced by HL cells function as regulatory T (Treg) cells so that these cells create a favorable environment for the tumor cells to escape from host immune system. In addition, we showed that a chimeric anti-CCR4 monoclonal antibody (mAb) could deplete CCR4+ T cells and inhibit the migration of CD4+CD25+ T cells in vitro. Recognition of the importance of CCR4+ Treg cells in the pathogenesis of HL will allow rational design of more effective treatments, such as use of an anti-CCR4 mAb, to overcome the suppressive effect of CCR4+ Treg cells on the host immune response to tumor cells. (Cancer Res 2006; 66(11): 5716-22)
Protecting sight with F4/80
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

Deconstructing I B kinaseOn page 1677, Ruocco et al. show that the formation of bone-resorbing osteoclasts is crippled when the ␤ subunit of the NF-B-activating I B kinase (IKK) complex is missing.The absence of IKK ␤ also protected mice against inflammatoryinduced bone loss, a complication of inflammatory diseases such as rheumatoid arthritis (RA) that is caused by excessive activation of osteoclasts.The osteoclast growth factor RANKL (receptor activator of NF-B ligand) activates the transcription factor NF-B, which promotes osteoclast development.NF-B activation requires the upstream IKK complex (IKK ␣ , ␤ , ␥ ), which releases NF-B from its inhibitor protein.Although a recent report showed that the IKK complex is required for osteoclast development, the relative importance of the two catalytic subunits of IKK ( ␣ , ␤ ) in this process remained unclear.Ruocco et al. now show that mice lacking IKK ␤ were unable to generate osteoclasts and developed severe osteopetrosis (increased bone formation), whereas those lacking IKK ␣ activity had no apparent bone abnormalities.The IKK ␤ -deficient mice failed to transmit RANKL signals and had increased TNF-induced apoptosis in osteoclast precursors.Osteoclast formation was partially restored in mice that lacked both IKK ␤ and the type I TNF receptor.IKK ␤ -deficient mice were also resistant to inflammatory bone loss and this resistance was dependent on TNF-derived signals.Thus the authors suggest that drugs designed to block IKK ␤ may prevent bone loss in patients.However, they caution that such drugs, if developed, should perhaps not be combined with anti-TNF therapy (commonly used to treat RA) as the combination may not be effective.
Enhanced Aldosterone Signaling in the Early Nephropathy of Rats with Metabolic Syndrome
Authors: Miki Nagase, Shigetaka Yoshida, Shigeru Shibata, Takashi Nagase, Takanari Gotoda, Katsuyuki Ando, Toshiro Fujita
Journal: Journal of the American Society of Nephrology (2006)

Metabolic syndrome is an important risk factor for proteinuria and chronic kidney disease independent of diabetes and hypertension; however, the underlying mechanisms have not been elucidated. Aldosterone is implicated in target organ injury of obesity-related disorders. This study investigated the role of aldosterone in the early nephropathy of 17-wk-old SHR/NDmcr-cp, a rat model of metabolic syndrome. Proteinuria was prominent in SHR/NDmcr-cp compared with nonobese SHR, which was accompanied by podocyte injury as evidenced by foot process effacement, induction of desmin and attenuation of nephrin. Serum aldosterone level, renal and glomerular expressions of aldosterone effector kinase Sgk1, and oxidative stress markers all were elevated in SHR/NDmcr-cp. Mineralocorticoid receptors were expressed in glomerular podocytes. Eplerenone, a selective aldosterone blocker, effectively improved podocyte damage, proteinuria, Sgk1, and oxidant stress. An antioxidant tempol also alleviated podocyte impairment and proteinuria, along with inhibition of Sgk1. As for the mechanisms of aldosterone excess, visceral adipocytes that were isolated from SHR/NDmcr-cp secreted substances that stimulate aldosterone production in adrenocortical cells. The aldosterone-releasing activity of adipocytes was not inhibited by candesartan. Adipocytes from nonobese SHR did not show such activity. In conclusion, SHR/NDmcr-cp exhibit enhanced aldosterone signaling, podocyte injury, and proteinuria, which are ameliorated by eplerenone or tempol. The data also suggest that adipocyte-derived factors other than angiotensin II might contribute to the aldosterone excess of this model.
Synthetic peptides define critical contacts between elongin C, elongin B, and the von Hippel-Lindau protein
Authors: Michael Ohh, Yuichiro Takagi, Teijiro Aso, Charles E. Stebbins, Nikola P. Pavletich, Bert Zbar, Ronald C. Conaway, Joan Weliky Conaway, William G. Kaelin
Journal: Journal of Clinical Investigation (1999)

The von Hippel-Lindau tumor suppressor protein (pVHL) negatively regulates hypoxia-inducible mRNAs such as the mRNA encoding vascular endothelial growth factor (VEGF). This activity has been linked to its ability to form multimeric complexes that contain elongin C, elongin B, and Cul2. To understand this process in greater detail, we performed a series of in vitro binding assays using pVHL, elongin B, and elongin C variants as well as synthetic peptide competitors derived from pVHL or elongin C. A subdomain of elongin C (residues 17–50) was necessary and sufficient for detectable binding to elongin B. In contrast, elongin B residues required for binding to elongin C were not confined to a discrete colinear domain. We found that the pVHL (residues 157–171) is necessary and sufficient for binding to elongin C in vitro and is frequently mutated in families with VHL disease. These mutations preferentially involve residues that directly bind to elongin C and/or alter the conformation of pVHL such that binding to elongin C is at least partially diminished. These results are consistent with the view that diminished binding of pVHL to the elongins plays a causal role in VHL disease.
Challenging Cytokine Redundancy: Inflammatory Cell Movement and Clinical Course of Experimental Autoimmune Encephalomyelitis Are Normal in Lymphotoxin-deficient, but Not Tumor Necrosis Factor–deficient, Mice
Authors: D. Sean Riminton, Heinrich Körner, Deborah H. Strickland, Frances A. Lemckert, John D. Pollard, Jonathon D. Sedgwick
Journal: The Journal of Experimental Medicine (1998)

Lymphotoxin (LT) is widely regarded as a proinflammatory cytokine with activities equivalent to tumor necrosis factor (TNF). The contribution of LT to experimental autoimmune encephalomyelitis (EAE) was examined using TNF/LTα−/− mice, TNF−/− mice, and a new LTα−/− line described here. All mice were generated directly in the C57BL/6 strain and used for the preparation of radiation bone marrow chimeras to reconstitute peripheral lymphoid organs and restore immunocompetence. This approach overcame the problems related to the lack of lymph nodes that results from LTα gene targeting. We show here that when LT is absent but TNF is present, EAE progresses normally. In contrast, when TNF is absent but LT is present, EAE is delayed in onset and inflammatory leukocytes fail to move normally into the central nervous system parenchyma, even at the peak of disease. In the absence of both cytokines, the clinical and histological picture is identical to that seen when TNF alone is deficient, including demyelination. Furthermore, the therapeutic inhibition of TNF and LTα with soluble TNF receptor in unmanipulated wild-type or TNF−/− mice exactly reproduces these outcomes. We conclude from these studies that TNF and LT are functionally distinct cytokines in vivo, and despite sharing common receptors, show no redundancy of function nor mutual compensation.
Complete inhibition of the expression of an idiotype by a mechanism of B-cell dominance.
Authors: B M Eig, S T Ju, A Nisonoff
Journal: The Journal of Experimental Medicine (1977)

Mice of the C.AL-20 strain, which express genes controlling CH regions of the AL/N strain on a BALB/c background, normally synthesize antibodies to the p-azophenylarsonate group (anti-Ar antibodies) with an idiotype characteristic of the A strain. The synthesis of the idiotype, as quantitated by a sensitive assay, can be completely inhibited by the transfer of leukocytes from BALB/c mice producing anti-Ar antibodies, which lack the idiotype. A number of control experiments show that the inhibition is not attributable to suppressor T cells and that the synergistic action of such cells is not required. The results indicate that B-cell dominance, mediated by secondary cells, can completely prevent the expression of unprimed cells with receptors of the same specificity. It is uncertain whether this effect is due entirely to selective capture of antigen by the secondary cells, or whether some type of active suppression by B cells is involved.
A requirement for FcγR in antibody-mediated bacterial toxin neutralization
Authors: Nareen Abboud, Siu-Kei Chow, Carolyn Saylor, Alena Janda, Jeffery V. Ravetch, Matthew D. Scharff, Arturo Casadevall
Journal: The Journal of Experimental Medicine (2010)

One important function of humoral immunity is toxin neutralization. The current view posits that neutralization results from antibody-mediated interference with the binding of toxins to their targets, a phenomenon viewed as dependent only on antibody specificity. To investigate the role of antibody constant region function in toxin neutralization, we generated IgG2a and IgG2b variants of the Bacillus anthracis protective antigen–binding IgG1 monoclonal antibody (mAb) 19D9. These antibodies express identical variable regions and display the same specificity. The efficacy of antibody-mediated neutralization was IgG2a &amp;gt; IgG2b &amp;gt; IgG1, and neutralization activity required competent Fcγ receptor (FcγR). The IgG2a mAb prevented lethal toxin cell killing and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase cleavage more efficiently than the IgG1 mAb. Passive immunization with IgG1 and IgG2a mAb protected wild-type mice, but not FcγR-deficient mice, against B. anthracis infection. These results establish that constant region isotype influences toxin neutralization efficacy of certain antibodies through a mechanism that requires engagement of FcγR. These findings highlight a new parameter for evaluating vaccine responses and the possibility of harnessing optimal FcγR interactions in the design of passive immunization strategies.