tbuckley/cabot-search huggingface dataset:
Sirolimus-Eluting Stent for the Treatment of In-Stent Restenosis
Authors: J. Eduardo Sousa, Marco A. Costa, Alexandre Abizaid, Amanda G.M.R. Sousa, Fausto Feres, Luiz A. Mattos, Marinella Centemero, Galo Maldonado, Andrea S. Abizaid, Ibraim Pinto, Robert Falotico, Judith Jaeger, Jeffrey J. Popma, Patrick W. Serruys
Journal: Circulation (2003)

Background— We have previously reported the safety and effectiveness of sirolimus-eluting stents for the treatment of de novo coronary lesions. The present investigation explored the potential of this technology to treat in-stent restenosis. Methods and Results— Twenty-five patients with in-stent restenosis were successfully treated with the implantation of 1 or 2 sirolimus-eluting Bx VELOCITY stents in São Paulo, Brazil. Nine patients received 2 stents (1.4 stents per lesion). Angiographic and volumetric intravascular ultrasound (IVUS) images were obtained after the procedure and at 4 and 12 months. All vessels were patent at the time of 12-month angiography. Angiographic late loss averaged 0.07±0.2 mm in-stent and −0.05±0.3 mm in-lesion at 4 months, and 0.36±0.46 mm in-stent and 0.16±0.42 mm in-lesion after 12 months. No patient had in-stent or stent margin restenosis at 4 months, and only one patient developed in-stent restenosis at 1-year follow-up. Intimal hyperplasia by 3-dimensional IVUS was 0.92±1.9 mm 3 at 4 months and 2.55±4.9 mm 3 after 1 year. Percent volume obstruction was 0.81±1.7% and 1.76±3.4% at the 4- and 12-month follow-up, respectively. There was no evidence of stent malapposition either acutely or in the follow-up IVUS images, and there were no deaths, stent thromboses, or repeat revascularizations. Conclusion— This study demonstrates the safety and the potential utility of sirolimus-eluting Bx VELOCITY stents for the treatment of in-stent restenosis.
Immune Selection and Emergence of Aggressive Tumor Variants as Negative Consequences of Fas-Mediated Cytotoxicity and Altered IFN-γ-Regulated Gene Expression
Authors: Kebin Liu, Sheila A. Caldwell, Scott I. Abrams
Journal: Cancer Research (2005)

Antitumor responses can be induced in patients via active or adoptive immunotherapy, yet complete tumor eradication occurs infrequently. This paradox in tumor immunology led us to address two questions: (a) Does an antitumor response, which is intended to destroy the aberrant target population, also at the same time select for aggressive tumor variants (ATV) in vivo? (b) If this process does occur, what is the contribution of the perforin- or Fas-mediated effector mechanism in the immune selection of such ATV? Here, in an experimental mouse lung metastasis model, we showed that ATV generated either naturally in vivo or in vitro by anti-Fas selection resembled each other biologically and genetically as judged by enhanced tumor growth and genome-scale gene expression profiling, respectively. Furthermore, ATV that survived CTL adoptive immunotherapy displayed an even more profound loss of Fas expression and function as well as enhanced malignant proficiency in vivo. ATV, however, retained sensitivity to perforin-mediated lysis in vitro. Lastly, such ATV displayed a diminished responsiveness in their expression of IFN-gamma-regulated genes, including those mechanistically linked to Fas-mediated death (i.e., Fas and caspase-1). Overall, we showed that (a) immune selection did occur in vivo and played an important role in the emergence of ATV, (b) ATV bearing a Fas-resistant phenotype was a chief consequence of immune selection, and (c) an overall diminished responsiveness of IFN-gamma-regulated gene expression was characteristic of ATV. Thus, in this model, Fas-mediated cytotoxicity, in concert with IFN-gamma-regulated gene expression, mechanistically constituted significant determinants of immune selection of ATV in vivo.
Microenvironmental Regulation of Proliferation in Multicellular Spheroids Is Mediated through Differential Expression of Cyclin-Dependent Kinase Inhibitors
Authors: Karen E. A. LaRue, Mona Khalil, James P. Freyer
Journal: Cancer Research (2004)

Abstract Multicellular spheroids composed of transformed cells are known to mimic the growth characteristics of tumors and to develop gradients in proliferation with increasing size. This progressive accumulation of quiescent cells is presumably an active process that occurs in response to the microenvironmental stresses that develop within the three-dimensional structure, and, yet, little is known regarding either the signals that induce the cell cycle arrest or the molecular basis for the halt in proliferation. We have previously reported that regulation of cyclin-dependent kinase (CDK) inhibitors (CKIs) differs in monolayer versus spheroid cell culture. In this study, we have examined the expression of three CKIs in EMT6 mouse mammary carcinoma and MEL28 human melanoma spheroids, as a function both of spheroid size and of location within the spheroid. We report that expression of the CKIs p18INK4c, p21waf1/cip1, and p27Kip1 all increase as the spheroid grows and develops a quiescent cell fraction. However, by examining protein expression in discrete regions of the spheroid, we have found that only p18INK4c and p27Kip1 expression positively correlate with growth arrest, whereas p21waf1/cip1 is expressed predominantly in proliferating cells. Further analysis indicated that, in the quiescent cells, p18INK4c is found in increasing association with CDK6, whereas p27Kip1 associates predominantly with CDK2. In MEL28 cells, CDK2 activity is completely abrogated in the inner regions of the spheroid, whereas in EMT6 cells, CDK2 activity decreases in accordance with a decrease in expression. We also observed a decrease in all cell cycle regulatory proteins in the innermost spheroid fraction, including CDKs, CKIs, and cyclins. Induction of CKIs from separate families, as well as their association with distinct target CDKs, suggests that there may be multiple checkpoints activated to ensure cell cycle arrest in non-growth-conducive environments. Furthermore, because very similar observations were made in both a human melanoma cell line and a mouse mammary carcinoma cell line, our results indicate that these checkpoints, as well as the signal transduction pathways that activate them, are highly conserved.
Randomized Phase III Trial of Gemcitabine Plus Docetaxel Plus Bevacizumab or Placebo As First-Line Treatment for Metastatic Uterine Leiomyosarcoma: An NRG Oncology/Gynecologic Oncology Group Study
Authors: Martee L. Hensley, Austin Miller, David M. O'Malley, Robert S. Mannel, Kian Behbakht, Jamie N. Bakkum-Gamez, Helen Michael
Journal: Journal of Clinical Oncology (2015)

Fixed-dose rate gemcitabine plus docetaxel achieves objective response in 35% of patients with uterine leiomyosarcoma (uLMS). This study aimed to determine whether the addition of bevacizumab to gemcitabine-docetaxel increases progression-free survival (PFS) in uLMS.In this phase III, double-blind, placebo-controlled trial, patients with chemotherapy-naive, metastatic, unresectable uLMS were randomly assigned to gemcitabine-docetaxel plus bevacizumab or gemcitabine-docetaxel plus placebo. PFS, overall survival (OS), and objective response rates (ORRs) were compared to determine superiority. Target accrual was 130 patients to detect an increase in median PFS from 4 months (gemcitabine-docetaxel plus placebo) to 6.7 months (gemcitabine-docetaxel plus bevacizumab). Treatment effects on PFS and OS were described by hazard ratios (HRs), median times to event, and 95% CIs.In all, 107 patients were accrued: gemcitabine-docetaxel plus placebo (n = 54) and gemcitabine-docetaxel plus bevacizumab (n = 53). Accrual was stopped early for futility. No statistically significant differences in grade 3 to 4 toxicities were observed. Median PFS was 6.2 months for gemcitabine-docetaxel plus placebo versus 4.2 months for gemcitabine-docetaxel plus bevacizumab (HR, 1.12; P = .58). Median OS was 26.9 months for gemcitabine-docetaxel plus placebo and 23.3 months for gemcitabine-docetaxel plus bevacizumab (HR, 1.07; P = .81). Objective responses were observed in 17 (31.5%) of 54 patients randomly assigned to gemcitabine-docetaxel plus placebo and 19 (35.8%) of 53 patients randomly assigned to gemcitabine-docetaxel plus bevacizumab. Mean duration of response was 8.6 months for gemcitabine-docetaxel plus placebo versus 8.8 months for gemcitabine-docetaxel plus bevacizumab.The addition of bevacizumab to gemcitabine-docetaxel for first-line treatment of metastatic uLMS failed to improve PFS, OS, or ORR. Gemcitabine-docetaxel remains a standard first-line treatment for uLMS.
THE BLOOD-TIGHT UTERUS AND ITS INFLUENCE ON INVOLUTION
Authors: C. N. Longridge
Journal: BMJ (1909)

TEE-BLOOD-TIGHT UTERUS AND INVOLUTION.T4M9 brevity I will epitomize Dr. Haultain's conclusion.He says that at first sight the upright position would seem to favour a backward and downward displacement of the uterus, but this is not borne out by clinical facts, and that -only 2 per cent. of his 100 cases showed displacements.
Pridopidine for the treatment of motor function in patients with Huntington's disease (MermaiHD): a phase 3, randomised, double-blind, placebo-controlled trial
Authors: Justo Garcia de Yebenes, Bernhard Landwehrmeyer, Ferdinando Squitieri, Ralf Reilmann, Anne Rosser, Roger A Barker, Carsten Saft, Markus K Magnet, Alastair Sword, Åsa Rembratt, Joakim Tedroff
Journal: The Lancet Neurology (2011)
Enhancement in antioxidant-based hepatoprotective activity of trolox by its conjugation to lactosylphenylpyranoside
Authors: Tai-Wing Wu, Zdenek B. Pristupa, Ling-Hua Zeng, Jian-Xun Au, Jun Wu, Hiroshi Sugiyama, Doug Carey
Journal: Hepatology (1992)

When Trolox (a polar analog of vitamin E) is conjugated to p-aminophenyl-β-D-lactopyranoside, the resulting lactosylphenyl Trolox becomes a markedly more stable and effective hepatoprotector than Trolox. In primary rat hepatocytes exposed to xanthine oxidase-hypoxanthine, lactosylphenyl Trolox prolonged cell survival better than did Trolox, mannitol or ascorbate. In rats that underwent 80-min partial hepatic ischemia, infusion of lactosylphenyl Trolox at 2.9 to 5.7 μmol/kg body wt just before reoxygenation salvaged the organ more extensively than did Trolox. Mechanistically, we showed (a) that lactosylphenyl Trolox does not inhibit xanthine oxidase; (b) that lactosylphenyl Trolox effectively scavenges oxyradicals generated with xanthine oxidase and the peroxyl radicals produced with 2,2′-azo- bis (2-amidinopropane) HCl; (c) that both in hepatocytes and in vivo , lactosylphenyl Trolox is distinctly more cytoprotective than either or both of its precursors; and (d) that lactosylphenyl Trolox is amphipathic (i.e., it has both hydrophilic and hydrophobic properties), which enable it to better access and protect the lipid and aqueous milieus of the cell than the lipophile vitamin E and the moderately polar Trolox. Thus there are strong fundamental reasons for lactosylphenyl Trolox being an effective antioxidant-based hepatoprotector. (Hepatology 1992;15:454-458).
Prognosis of Depression in Old Age Compared to Middle Age: A Systematic Review of Comparative Studies
Authors: Alex J Mitchell, Hari Subramaniam
Journal: American Journal of Psychiatry (2005)

Depression in old age has a poor long-term prognosis; equal evidence shows that the same is true of depression in middle age. The authors sought to identify research that has compared the prognosis of depression in late life with depression in midlife under similar conditions.The authors separated studies that examined age at presentation/recruitment from studies of age at first episode of depression, studies that examined remission/response from those that examined relapse/recurrence, and those that examined mortality/risk of dementia.Evidence suggests that response and remission rates to pharmacotherapy and ECT are not sufficiently different in old-age depression and middle-age depression to be clinically significant. Older patients at study entry appear to have a higher risk of further episodes, which informs the debate about the duration of continuation treatment for depression in older people. However, older patients and patients with late-onset depression are at increased risk of medical comorbidity. Medical comorbidity is a risk factor for inferior treatment response and poor antidepressant tolerability. Elderly patients with early-onset depression are more likely to have had a higher number of previous episodes, which also adversely influences prognosis compared to elderly depressed patients with late onset of illness.With control for confounding variables, remission rates of depression in patients in late life are little different from those in midlife, but relapse rates appear higher. Findings underline the importance of assessing factors related to patient age and not just to age itself in evaluations of risk factors for poor prognosis.
<i>Tgfbr1</i>Haploinsufficiency Is a Potent Modifier of Colorectal Cancer Development
Authors: Qinghua Zeng, Sharbani Phukan, Yanfei Xu, Maureen Sadim, Diana S. Rosman, Michael Pennison, Jie Liao, Guang-Yu Yang, Chiang-Ching Huang, Laura Valle, Antonio Di Cristofano, Albert de la Chapelle, Boris Pasche
Journal: Cancer Research (2009)

Abstract Transforming growth factor-β (TGF-β) signaling is frequently altered in colorectal cancer. Using a novel model of mice heterozygous for a targeted null mutation of Tgfbr1 crossed with ApcMin/+ mice, we show that ApcMin/+;Tgfbr1+/− mice develop twice as many intestinal tumors as ApcMin/+;Tgfbr1+/+ mice, as well as adenocarcinoma of the colon, without loss of heterozygosity at the Tgfbr1 locus. Decreased Smad2 and Smad3 phosphorylation and increased cellular proliferation are observed in the colonic epithelium crypts of ApcMin/+; Tgfbr1+/− mice. Smad-mediated TGF-β signaling is preserved in both ApcMin/+;Tgfbr1+/+ and ApcMin/+;Tgfbr1+/− intestinal tumors, but cyclin D1 expression and cellular proliferation are significantly higher in ApcMin/+;Tgfbr1+/− tumors. These results show that constitutively reduced Tgfbr1-mediated TGF-β signaling significantly enhances colorectal cancer development and results in increased tumor cell proliferation. These findings provide a plausible molecular mechanism for colorectal cancer development in individuals with constitutively altered TGFBR1 expression, a recently identified common form of human colorectal cancer. [Cancer Res 2009;69(2):678–86]
Emergency surgery in ulcerative colitis.
Authors: T A Boxall
Journal: Gut (1966)

EDITORIAL COMMENT In reviewing a series of cases of ulcerative colitis which required emergency surgical intervention, the author stresses the lowered mortality which may be obtained if sur- gery is undertaken before deterioration is advanced.Ileostomy and subtotal colectomy is the operation of choice, and is preferable to conservative measures even in desperately ill patients.Ulcerative colitis in its milder manifestations may be managed by conservative methods.If these are un- successful, or, in the presence of more severe disease, a planned surgical procedure, either subtotal colec- tomy or proctocolectomy, is the alternative method of treatment.On occasion, however, the rapidity of progression of the disease forces the issue: con- servative measures, if any have been instituted, have to be abandoned, and emergency surgery becomes obligatory.The results of such surgery are markedly worse in terms of mortality than interval or definitive procedures (Tables I andII).One possible method of improving this serious discrepancy between interval and emergency surgery could be an earlier resort to surgery in certain situa- tions.This paper presents an analysis of a group of patients with ulcerative colitis treated by emergency surgery because there was marked clinical deteriora- TABLE I RESULTS OF EMERGENCY SURGERY FOR ULCERATIVE COLITIS
Complete response of deep neutrophilic dermatosis associated with myelodysplastic syndrome to 5-azacytidine
Authors: K. Raj, A. Ho, J.D. Creamer, A.W.P. du Vivier, J.R. Salisbury, G.J. Mufti
Journal: British Journal of Dermatology (2007)

Cutaneous manifestations of myelodysplastic syndromes (MDS) may predict disease progression and a poorer prognosis. We describe a patient in whom a deep neutrophilic dermatosis preceded evolution of disease from refractory anaemia to RAEB (refractory anaemia with excess blasts) and resolved completely on treating the disease with 5-azacytidine. The dermatological response was accompanied by complete bone marrow remission and trilineage haematological improvement. We suggest that 5-azacytidine should be considered in the treatment of immune mediated cutaneous manifestations of MDS.
The voltage-gated Kv1.3 K+ channel in effector memory T cells as new target for MS
Authors: Heike Wulff, Peter A. Calabresi, Rameeza Allie, Sung Yun, Michael Pennington, Christine Beeton, K. George Chandy
Journal: Journal of Clinical Investigation (2003)

Through a combination of fluorescence microscopy and patch-clamp analysis we have identified a striking alteration in K+ channel expression in terminally differentiated human CCR7–CD45RA– effector memory T lymphocytes (TEM). Following activation, TEM cells expressed significantly higher levels of the voltage-gated K+ channel Kv1.3 and lower levels of the calcium-activated K+ channel IKCa1 than naive and central memory T cells (TCM). Upon repeated in vitro antigenic stimulation, naive cells differentiated into Kv1.3highIKCa1low TEM cells, and the potent Kv1.3-blocking sea anemone Stichodactyla helianthus peptide (ShK) suppressed proliferation of TEM cells without affecting naive or TCM lymphocytes. Thus, the Kv1.3highIKCa1low phenotype is a functional marker of activated TEM lymphocytes. Activated myelin-reactive T cells from patients with MS exhibited the Kv1.3highIKCa1low TEM phenotype, suggesting that they have undergone repeated stimulation during the course of disease; these cells may contribute to disease pathogenesis due to their ability to home to inflamed tissues and exhibit immediate effector function. The Kv1.3highIKCa1low phenotype was not seen in glutamic acid decarboxylase, insulin-peptide or ovalbumin-specific and mitogen-activated T cells from MS patients, or in myelin-specific T cells from healthy controls. Selective targeting of Kv1.3 in TEM cells may therefore hold therapeutic promise for MS and other T cell–mediated autoimmune diseases.
Bortezomib plus rituximab versus rituximab alone in patients with relapsed, rituximab-naive or rituximab-sensitive, follicular lymphoma: a randomised phase 3 trial
Authors: Bertrand Coiffier, Evgenii A Osmanov, Xiaonan Hong, Adriana Scheliga, Jiri Mayer, Fritz Offner, Simon Rule, Adriana Teixeira, Jan Walewski, Sven de Vos, Michael Crump, Ofer Shpilberg, Dixie-Lee Esseltine, Eugene Zhu, Christopher Enny, Panteli Theocharous, Helgi van de Velde, Yusri A Elsayed, Pier Luigi Zinzani
Journal: The Lancet Oncology (2011)
A Randomized Controlled Trial of Psychoanalytic Psychotherapy or Cognitive-Behavioral Therapy for Bulimia Nervosa
Authors: Stig Poulsen, Susanne Lunn, Sarah I. F. Daniel, Sofie Folke, Birgit Bork Mathiesen, Hannah Katznelson, Christopher G. Fairburn
Journal: American Journal of Psychiatry (2013)

Two years of psychoanalytic psychotherapy and 5 months of CBT with follow up visits for bulimia nervosa were compared. The proportions of patients who had stopped binging and purging at 2 years were 15% for psychoanalytic psychotherapy and 44% for CBT. Both treatments improve other eating disorder features and general psychopathology, but CBT does so faster, and therapists can learn CBT through videoconferencing.
Laser monitoring of chest wall displacement
Authors: T Kondo, T Uhlig, P Pemberton, PD Sly
Journal: European Respiratory Journal (1997)

We developed a prototype laser monitor, consisting of a single laser sensor, to observe chest wall displacement during respiration. With this monitor, respiratory waveforms are expressed as an anterioposterior motion of the chest wall. The purpose of this study was to examine the characteristics and performance of this prototype. Performance was assessed: 1) under static conditions; 2) using a lung model ventilated in both conventional and high frequency oscillation (HFOV) modes; and 3) during spontaneous breathing in normal adults. In vitro, the monitor performed well both under static conditions and during mechanical ventilation. Reliable "respiratory" wave forms, with no frequency-dependent change in the relationship between displacement and volume, were produced during both conventional ventilation and HFOV at 15 Hz. In vivo, abdominal displacement, measured in the midline, was linearly correlated with the tidal volume signal integrated from flow. The waveforms produced by the monitor were adequate for monitoring respiration and for calculating respiratory timing variables. While a single laser sensor is unlikely to be sufficient for monitoring respiration in spontaneously breathing subjects, the performance of the prototype monitor was sufficiently impressive to encourage further development and further study of this type of truly noninvasive respiratory monitor.
Family Focused Grief Therapy: A Randomized, Controlled Trial in Palliative Care and Bereavement
Authors: David Kissane
Journal: American Journal of Psychiatry (2006)

Objective: The aim of family focused grief therapy is to reduce the morbid effects of grief among families at risk of poor psychosocial outcome. It commences during palliative care of terminally ill patients and continues into bereavement. The authors report a randomized, controlled trial. Method: Using the Family Relationships Index, the authors screened 257 families of patients dying from cancer: 183 (71%) were at risk, and 81 of those (44%) participated in the trial. They were randomly assigned (in a 2:1 ratio) to family focused grief therapy (53 families, 233 individuals) or a control condition (28 families, 130 individuals). Assessments occurred at baseline and 6 and 13 months after the patient's death. The primary outcome measures were the Brief Symptom Inventory, Beck Depression Inventory, and Social Adjustment Scale. The Family Assessment Device was a secondary outcome measure. Analyses allowed for correlated family data and employed generalized estimating equations based on intention to treat and controlling for site. Results: The overall impact of family focused grief therapy was modest, with a reduction in distress at 13 months. Significant improvements in distress and depression occurred among individuals with high baseline scores on the Brief Symptom Inventory and Beck Depression Inventory. Global family functioning did not change. Sullen families and those with intermediate functioning tended to improve overall, whereas depression was unchanged in hostile families. Conclusions: Family focused grief therapy has the potential to prevent pathological grief. Benefit is clear for intermediate and sullen families. Care is needed to avoid increasing conflict in hostile families.
Chronic Asymptomatic Hepatitis B Presenting With Metastatic Hepatocellular Carcinoma
Authors: Ashok Pai, Albert Lin
Journal: Journal of Clinical Oncology (2008)

with CNS involvement has shown that those who receive cranial irradiation have significantly longer survival compared with the others (P ϭ .004). 3 Our patient was treated with intrathecal liposomal cytarabine associated with systemic chemotherapy.He obtained only a transient response and died after 42 days, confirming the poor prognosis of patients with CNS involvement.