tbuckley/cabot-search huggingface dataset:
A Two-by-Two Factorial Trial Comparing Oral with Transdermal Estrogen Therapy and Fenretinide with Placebo on Breast Cancer Biomarkers
Authors: Andrea Decensi, Bernardo Bonanni, Laura Baglietto, Aliana Guerrieri-Gonzaga, Francesca Ramazzotto, Harriet Johansson, Chris Robertson, Irene Marinucci, Frederique Mariette, Maria Teresa Sandri, Cristina Daldoss, Vanda Bianco, Marco Buttarelli, Massimiliano Cazzaniga, Dorella Franchi, Enrico Cassano, Umberto Omodei
Journal: Clinical Cancer Research (2004)

Oral conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) increase breast cancer risk, whereas the effect of transdermal estradiol (E2) and MPA is less known. Fenretinide may decrease second breast malignancies in premenopausal women but not in postmenopausal women, suggesting a hormone-sensitizing effect. We compared the 6 and 12-month changes in insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP-3), IGF-I:IGFBP-3 ratio, sex-hormone binding-globulin, and computerized mammographic percent density during oral CEE or transdermal E2 with sequential MPA and fenretinide or placebo.A total of 226 recent postmenopausal healthy women were randomly assigned in a two-by-two factorial design to either oral CEE 0.625 mg/day (n = 111) or transdermal E2, 50 microg/day (n = 115) and to fenretinide 100 mg/twice a day (n = 112) or placebo (n = 114) for 12 months. Treatment effects were investigated by the Kruskall-Wallis test and analysis of covariance. P values were two-sided.After 12 months, oral CEE decreased IGF-I by 26% [95% confidence interval (CI), 22-30%] and increased sex-hormone binding-globulin by 96% (95% CI, 79-112%) relative to baseline, whereas no change occurred with transdermal E2 (P < 0.001 between groups). Fenretinide decreased IGFBP-3 relative to placebo (P = 0.04). Percentage of breast density showed an absolute increase of 3.5% (95% CI, 2.5-4.6%) during hormone therapy without differences between groups (P = 0.39).Oral CEE has more favorable changes than transdermal E2 on circulating breast cancer risk biomarkers but gives similar effects on mammographic density. Fenretinide exerted little modulation on most biomarkers. The clinical implications of these findings require additional studies.
Patients' acceptance of medical photography in a French adult and paediatric dermatology department: a questionnaire survey
Authors: F. Hacard, A. Maruani, M. Delaplace, A. Caille, L. Machet, G. Lorette, M. Samimi
Journal: British Journal of Dermatology (2013)

Despite the increasing use of medical photography by dermatologists, no study on patients' perceptions of photography in dermatology has been performed to date.Firstly, to evaluate patients' perceptions of medical photography. Secondly, to assess whether perceptions differed between patients in our adult department and parents accompanying a child in our paediatric department.An opinion survey was conducted at the Hospital of Tours (France) among adult patients (adult department) and accompanying parents (paediatric department) by completion of a questionnaire after any medical photography had been performed.We collected 272 questionnaires regarding 158 adults and 114 children. A camera used only in the department, and storage of the images in the department's records were the most accepted modalities (> 90%), especially in the paediatric survey. Respondents agreed with the sharing of the images with other practitioners and in medical meetings (> 85%) rather than distribution via publications (58·3%), e-mails (45·5%), health magazines (44·3%) and websites (32·0%). Most (78·8%) considered that the consent form should list all the possible uses of the images. Need for renewed consent for each use of the images was significantly more often expressed in the paediatric than the adult survey (44·5% vs. 24·5%, P = 0·001). More than 95% of respondents considered medical photography to be useful for improving diagnosis, monitoring of skin disease and aiding teaching.These findings could be used to improve practice, to increase the acceptability of medical photography and for devising a standardized consent form for medical practitioners performing medical photography.
Identification of mcl-1 as a BCR/ABL-dependent target in chronic myeloid leukemia (CML): evidence for cooperative antileukemic effects of imatinib and mcl-1 antisense oligonucleotides
Authors: Karl J. Aichberger, Matthias Mayerhofer, Maria-Theresa Krauth, Hans Skvara, Stefan Florian, Karoline Sonneck, Cahit Akgul, Sophia Derdak, Winfried F. Pickl, Volker Wacheck, Edgar Selzer, Brett P. Monia, Richard Moriggl, Peter Valent, Christian Sillaber
Journal: Blood (2004)
Inhibition of nitric oxide production aggravates myocardial hypoperfusion during exercise in the presence of a coronary artery stenosis.
Authors: D J Duncker, R J Bache
Journal: Circulation Research (1994)

Regulation of coronary vasomotor tone during myocardial hypoperfusion is incompletely understood. The present study was performed to test the hypothesis that endogenous production of nitric oxide contributes to resistance vessel dilation distal to a coronary artery stenosis that results in myocardial ischemia during exercise. Seven dogs instrumented with a Doppler velocity probe, hydraulic occluder, and indwelling microcatheter in the left anterior descending coronary artery (LAD) were studied during treadmill exercise in the presence of a coronary artery stenosis before and after intracoronary infusion of NG-nitro-L-arginine (LNNA, 20 mg/kg). This dose of LNNA inhibited the maximal increase in LAD flow produced by intracoronary acetylcholine by 82 +/- 5% but did not alter the response to intracoronary nitroprusside. Coronary pressure distal to the stenosis was maintained constant during the control period and after administration of LNNA. LNNA increased aortic and left ventricular systolic and end-diastolic pressures at rest and during exercise. During control in the absence of a stenosis, LNNA had no effect on coronary blood flow. In the presence of a stenosis that decreased distal coronary pressure to 55 +/- 2 mm Hg, mean myocardial blood flow measured with microspheres was 1.09 +/- 0.13 mL.min-1.g-1 in the LAD-dependent and 2.57 +/- 0.50 mL.min-1.g-1 in the posterior control region, respectively. With no change in distal coronary pressure, LNNA decreased mean myocardial blood flow in the LAD region to 0.68 +/- 0.11 mL.min-1.g-1 (P &lt; .01). To avoid systemic hemodynamic effects, LNNA was administered in a dose of 1.5 mg/kg IC to four additional dogs. This low dose inhibited the coronary blood flow increases produced by acetylcholine by 61 +/- 5% but was devoid of systemic hemodynamic effects. During exercise in the presence of a coronary stenosis that decreased coronary pressure to 52 +/- 1 mm Hg, this dose of LNNA decreased mean myocardial blood flow from 0.89 +/- 0.23 to 0.66 +/- 0.21 mL.min-1.g-1 (P &lt; .02). These data demonstrate that nitric oxide contributes to the maintenance of myocardial perfusion distal to a flow-limiting coronary artery stenosis during exercise.
Comorbidity of Borderline Personality Disorder With Other Personality Disorders in Hospitalized Adolescents and Adults
Authors: D F Becker, C M Grilo, W S Edell, T H McGlashan
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: The authors examined the comorbidity of borderline personality disorder with other personality disorders in a series of consecutively admitted adolescents. For comparison, the comorbidity of borderline personality disorder with other personality disorders was also examined in a series of adults consecutively admitted to the same hospital during the same period. METHOD: A total of 138 adolescents and 117 adults were reliably assessed with the Personality Disorder Examination, a semistructured diagnostic interview for DSM-III-R personality disorders. Sixty-eight adolescents and 50 adults met the diagnostic criteria for borderline personality disorder. The co-occurrence of other personality disorders in the group of subjects with borderline personality disorder was statistically compared to that in the group without borderline personality disorder, for adolescents and adults separately. RESULTS: For the adults, Bonferroni-corrected chi-square analysis revealed significant diagnostic co-occurrence with borderline personality disorder for antisocial personality disorder only. For the adolescents, borderline personality disorder showed significant co-occurrence with schizotypal and passive-aggressive personality disorders. CONCLUSIONS: In the adults, borderline personality disorder was significantly comorbid only with another cluster B disorder. The adolescents, by comparison, displayed a broader pattern of comorbidity of borderline personality disorder, encompassing aspects of clusters A and C. These results suggest that the borderline personality disorder diagnosis may represent a more diffuse range of psychopathology in adolescents than in adults.
Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype
Authors: So Yeon Park, Mithat Gönen, Hee Jung Kim, Franziska Michor, Kornelia Polyak
Journal: Journal of Clinical Investigation (2010)

Intratumor genetic heterogeneity is a key mechanism underlying tumor progression and therapeutic resistance. The prevailing model for explaining intratumor diversity, the clonal evolution model, has recently been challenged by proponents of the cancer stem cell hypothesis. To investigate this issue, we performed combined analyses of markers associated with cellular differentiation states and genotypic alterations in human breast carcinomas and evaluated diversity with ecological and evolutionary methods. Our analyses showed a high degree of genetic heterogeneity both within and between distinct tumor cell populations that were defined based on markers of cellular phenotypes including stem cell-like characteristics. In several tumors, stem cell-like and more-differentiated cancer cell populations were genetically distinct, leading us to question the validity of a simple differentiation hierarchy-based cancer stem cell model. The degree of diversity correlated with clinically relevant breast tumor subtypes and in some tumors was markedly different between the in situ and invasive cell populations. We also found that diversity measures were associated with clinical variables. Our findings highlight the importance of genetic diversity in intratumor heterogeneity and the value of analyzing tumors as distinct populations of cancer cells to more effectively plan treatments.
Hypertension Prevalence and Stroke Mortality Across Populations
Authors: Jan A. Staessen
Journal: JAMA (2003)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
TYPHUS IN SERBIA
Authors: B. W. Howell
Journal: BMJ (1915)

I ''cm __ors5w813 exposure of twenty minutes or so.In the treatment of joints, lhowever, I prefer diathermiy.It seems on the wlhole to do a little better, and as the greatest heat is developed mnidway between the .electrodes, it should theoretically be more efficient.After twenty minutes, then, of either radiant lheat or diathermy a rlhythmically interrupted electric current is applied.Of titc rhythmically interrupted currents we have-The faradic as uised in the Bergouih apparattus.The sinusoidal, interrupted by such a device as the Lewis Jones initerrupter.
Phase I Pharmacokinetic and Pharmacodynamic Study of the First-in-Class Spliceosome Inhibitor E7107 in Patients with Advanced Solid Tumors
Authors: Ferry A.L.M. Eskens, Francisco J. Ramos, Herman Burger, James P. O'Brien, Adelaida Piera, Maja J.A. de Jonge, Yoshiharu Mizui, Erik A.C. Wiemer, Maria Josepa Carreras, José Baselga, Josep Tabernero
Journal: Clinical Cancer Research (2013)

To assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of E7107 administered as 5-minute bolus infusions on days 1, 8, and 15 in a 28-day schedule.Patients with solid tumors refractory to standard therapies or with no standard treatment available were enrolled. Dose levels of 0.6 to 4.5 mg/m(2) were explored.Forty patients [24M/16F, median age 61 years (45-79)] were enrolled. At 4.5 mg/m(2), dose-limiting toxicity (DLT) consisted of grade 3 diarrhea, nausea, and vomiting and grade 4 diarrhea, respectively, in two patients. At 4.0 mg/m(2), DLT (grade 3 nausea, vomiting, and abdominal cramps) was observed in one patient. Frequently occurring side effects were mainly gastrointestinal. After drug discontinuation at 4.0 mg/m(2), one patient experienced reversible grade 4 blurred vision. The maximum tolerated dose (MTD) is 4.0 mg/m(2). No complete or partial responses during treatment were observed; one patient at 4.0 mg/m(2) had a confirmed partial response after drug discontinuation. Pharmacokinetic analysis revealed a large volume of distribution, high systemic clearance, and a plasma elimination half-life of 5.3 to 15.1 hours. Overall drug exposure increased in a dose-dependent manner. At the MTD, mRNA levels of selected target genes monitored in peripheral blood mononuclear cells showed a reversible 15- to 25-fold decrease, whereas unspliced pre-mRNA levels of DNAJB1 and EIF4A1 showed a reversible 10- to 25-fold increase.The MTD for E7107 using this schedule is 4.0 mg/m(2). Pharmacokinetics is dose-dependent and reproducible within patients. Pharmacodynamic analysis revealed dose-dependent reversible inhibition of pre-mRNA processing of target genes, confirming proof-of-principle activity of E7107.
UK stocks up on antiviral drug to tackle flu outbreak
Authors: Rebecca Coombes
Journal: BMJ (2005)

The UK government is to build up a stockpile of millions of doses of an antiviral drug as its first line of defence against a likely influenza pandemic.

   ![][1] 

Scientists from a joint WHO and Food and Agriculture Organization conference on avian flu tour a chicken farm in Vietnam

Credit: RICHARD VOGEL/AP

The order for 14.6 million courses of oseltamivir was announced this week along with …

 [1]: /embed/graphic-1.gif
Capecitabine plus oxaliplatin (CapOx) versus capecitabine plus gemcitabine (CapGem) versus gemcitabine plus oxaliplatin (mGemOx): final results of a multicenter randomized phase II trial in advanced pancreatic cancer
Authors: S. Boeck, T. Hoehler, G. Seipelt, R. Mahlberg, A. Wein, A. Hochhaus, H.-P. Boeck, B. Schmid, E. Kettner, M. Stauch, F. Lordick, Y. Ko, M. Geissler, K. Schoppmeyer, G. Kojouharoff, A. Golf, S. Neugebauer, V. Heinemann
Journal: Annals of Oncology (2007)
A8.27 Control of the humoral response by regulatory B cells
Authors: Christophe Jamin, Achouak Achour, Pierre Youinou, Jacques-Olivier Pers
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Follicular helper T (Tfh) cells are instrumental in the development of humoral responses. They support the terminal differentiation of B cells into memory and antibody-producing cells within germinal centers. Regulatory B (Breg) cells can modulate inflammatory reactions through the control of dendritic cell maturation and function, and through the control of T cell proliferation and Th1 polarization. Our aimed was to evaluate the control of humoral responses by Breg cells. <h3>Materials and Methods</h3> We developed in vitro models of human Tfh cell polarisation and function. They were obtained by stimulation of purified T cells with anti-CD3 and anti-CD28 Abs in the presence of IL-12 and IL-21. Expression of Bcl-6, IL-21, ICOS, CXCR5 and PD-1, all characteristics of Tfh cells were determined by flow cytometry. Tfh functions were studied by co-cultures with non-stimulated purified B cells. Their differentiation into memory and plasma cells was appraised by flow cytometry and by ELISA to measure the production of immunolgobulins. Breg cells were obtained by stimulation of purified B cells with CpG-ODN on CD40L-transfected fibroblasts. Their effect on Tfh cell maturation and function were studied in co-culture experiments. <h3>Results</h3> in vitro Tfh cells were obtained. Thus, Bcl-6 was up-regulated, IL-21 induced and ICOS, CXCR5 and PD-1 expression increased after stimulation. Furthermore, differentiated Tfh cells fostered the maturation of IgD-CD27 + memory B cells and CD138 + plasma cells, and triggered the secretion of IgM, IgG and IgA. Added to the T cells, Breg cells restrained the expression of Tfh markers. In the co-cultures of Tfh with B cells, Breg cells inhibited the induction of IgD-CD27 + and CD138 + B cells. They also impeded the secretion of immunoglobulins. Using blocking antibodies, suppressive activities of Bregs were found to be dependent on IL-10 and TGFbeta and based on direct contact with Tfh cells involving CD40, CD80, CD86 and CD54 molecules. <h3>Conclusions</h3> Human Breg cells can modulate the development of humoral responses through the control of Tfh cell polarization and of Tfh-dependent terminal differentiation of B cells. Whether these properties are impaired and responsible for abnormal humoral responses in autoimmune diseases needs now to be established.
Improved survival in ARDS: chance, technology or experience?
Authors: S BAUDOUIN
Journal: Thorax (1998)

Randomised, clinical controlled trials in ARDS have shown that the use of historical control groups can produce misleading results.1 If , for example, the 90% mortality of the 1979 National Heart and Lung Institute ARDS Extracorporeal Membrane Oxygenation (ECMO) trial2 is used as a baseline, then all subsequent studies of ARDS would demonstrate an apparent increase in survival . Examination of the entry criteria and case mix of this study highlights many of the potential pitfalls in examining changes in mortality from ARDS over time. Abnormalities of gas exchange were the major entry criteria whilst no adjustment was made for the fact that many patients were admitted with severe, atypical pneumonia. Subsequent work has shown that the initial severity of gas exchange is not a strong predictor of survival in ARDS while case mix (in terms of patient selection, severity of disease, patient age and predisposing factors) is very important.3 

Problems with patient selection have, to some extent, been overcome by the adoption of recent European/North American consensus conference definitions of ARDS.4 Gas exchange, plain chest radiology and, if available, haemodynamic data define ARDS in the context of an “at risk” patient. However, the ease of use of these criteria does not guarantee the selection of a homogeneous population. The …
Inhibiting the Complement System Does Not Reduce Injury in Renal Ischemia Reperfusion
Authors: PIERCE PARK, MARK HAAS, PATRICK N. CUNNINGHAM, JESSY J. ALEXANDER, LIHUA BAO, JOEL M. GUTHRIDGE, DAMIAN M. KRAUS, V. MICHAEL HOLERS, RICHARD J. QUIGG
Journal: Journal of the American Society of Nephrology (2001)

Abstract. The complex pathogenesis of ischemia reperfusion injury (IRI) includes endothelial expression of adhesion molecules, leukocyte recruitment and activation, reactive oxygen species production, and apoptotic and necrotic cell death. A role for complement in IRI of different organs, including kidney, has been proposed on the basis of results of experiments that used pharmacologic inhibitors as well as animals that were deficient in individual complement proteins. Here, renal IRI in mice was examined. Animals that were deficient in C3 had partial protection from IRI induced by 27.5 min of bilateral renal ischemia, followed by 20 h of reperfusion (blood urea nitrogen [BUN] values, 46.6 ± 6.9 and 68.4 ± 7.9 mg/dl in C3 -/- and C3 +/+ mice; n = 7 and 8, respectively; P = 0.033). Given the reduction in IRI in C3 -/- mice, it was investigated, by use of the rodent C3 convertase inhibitor CR 1- r elated gene/protein y -Ig (Crry-Ig), whether exogenous administration of a complement inhibitor could lessen renal injury. Despite the use of Crry-Ig in high doses, there was no significant reduction of injury induced by 20 to 30 min of ischemia followed by up to 30 h of reperfusion. Histologic examination revealed acute tubular necrosis and neutrophilic infiltration, both of which correlated significantly with BUN values ( P &lt; 0.001). Of interest, C3 deposition around renal tubules was significantly less in animals with IRI, compared with that in unmanipulated controls ( P &lt; 0.001). In Crry-Ig—treated animals, C3 deposition was inversely proportional to BUN values ( r = -0.63; P &lt; 0.001), which presumably indicates that severe vascular IRI allowed access of the 160 kD Crry-Ig to the interstitium. Thus, renal IRI in mice may have a partial complement dependence, yet pharmacologic inhibition of the complement system does not seem to be effective, likely because of the presence of other mediator systems that operate in parallel.
STA‐21, a Promising STAT‐3 Inhibitor That Reciprocally Regulates Th17 and Treg Cells, Inhibits Osteoclastogenesis in Mice and Humans and Alleviates Autoimmune Inflammation in an Experimental Model of Rheumatoid Arthritis
Authors: Jin‐Sil Park, Seung‐Ki Kwok, Mi‐Ae Lim, Eun‐Kyung Kim, Jun‐Geol Ryu, Sung‐Min Kim, Hye‐Joa Oh, Ji Hyeon Ju, Sung‐Hwan Park, Ho‐Youn Kim, Mi‐La Cho
Journal: Arthritis & Rheumatology (2013)

To investigate the impact of STA-21, a promising STAT-3 inhibitor, on the development and progression of inflammatory arthritis and to determine the possible mechanisms by which STA-21 has antiarthritic effects in interleukin-1 receptor antagonist-knockout (IL-1Ra-KO) mice, an animal model of rheumatoid arthritis (RA).IL-1Ra-KO mice were treated with intraperitoneal injections of STA-21 (0.5 mg/kg) or vehicle 3 times per week for 3 weeks. The mouse joints were assessed for clinical and histologic features of inflammatory arthritis. CD4+CD25+FoxP3+ Treg cells and CD4+IL-17+ cells were defined. Human peripheral blood mononuclear cell-derived monocytes or mouse bone marrow-derived monocyte/macrophage (BMM) cells were cultured in the presence of macrophage colony-stimulating factor alone or together with RANKL and various concentrations of STA-21, followed by staining of the cells for tartrate-resistant acid phosphatase activity to determine osteoclast formation.STA-21 suppressed inflammatory arthritis in IL-1Ra-KO mice. The proportion of Th17 cells was decreased and the proportion of Treg cells expressing FoxP3 was markedly increased in the spleens of STA-21-treated mice. Adoptive transfer of CD4+CD25+ T cells obtained from STA-21-treated IL-1Ra-KO mice markedly suppressed inflammatory arthritis. In vitro treatment with STA-21 induced the expression of FoxP3 and repressed IL-17 expression in both mouse and human CD4+ T cells. Moreover, STA-21 prevented both mouse BMM cells and human monocytes from differentiating into osteoclasts in vitro.STA-21 improved the clinical course of arthritis in IL-1Ra-KO mice. It increased not only the number of Treg cells but also the function of the Treg cells. It also suppressed Th17 cells and osteoclast formation. These data suggest that STA-21 might be an effective treatment for patients with RA.