tbuckley/cabot-search huggingface dataset:
Phase II Trial Evaluating the Palliative Benefit of Second-Line Zoledronic Acid in Breast Cancer Patients With Either a Skeletal-Related Event or Progressive Bone Metastases Despite First-Line Bisphosphonate Therapy
Authors: Mark J. Clemons, George Dranitsaris, Wei S. Ooi, Geetha Yogendran, Tatjana Sukovic, Betty Y.L. Wong, Sunil Verma, Kathleen I. Pritchard, Maureen Trudeau, David E.C. Cole
Journal: Journal of Clinical Oncology (2006)

This study evaluated whether additional palliative benefits could be derived from the second-line use of the more potent bisphosphonate zoledronic acid in metastatic breast cancer patients with either progressive bone metastases or skeletal-related events (SRE), despite first-line therapy with either pamidronate or clodronate.This prospective study evaluated the impact of second-line zoledronic acid on pain, quality of life, and markers of bone turnover (for example, urinary N-telopeptide [NTX]). Patients received monthly zoledronic acid (4 mg) for 3 months. Study evaluations were made weekly during the first month and again at week 8. No changes in chemotherapy or endocrine therapy were allowed in the month before or after commencing study treatment.Thirty-one women completed this study. By week 8, patients had experienced significant improvements in pain control (P < .001). There was a downward trend in urinary NTX levels over the same time period (P = .008). Overall, there was a trend towards a positive correlation between improvement in pain control and reduction in week one urinary NTX relative to baseline (Spearman's rho r = 0.27; P = .15).This is the first study to demonstrate that patients with either progressive bone metastases or SREs while on clodronate or pamidronate can have relevant palliative benefits with a switch to the more potent bisphosphonate zoledronic acid. This is reflected by significant improvements in pain control and bone turnover markers. If confirmed in randomized trials, these findings have major implications to the use of bisphosphonates in both the metastatic and adjuvant settings.
Low density of sympathetic nerve fibres and increased density of brain derived neurotrophic factor positive cells in RA synovium
Authors: C Weidler
Journal: Annals of the Rheumatic Diseases (2004)

To investigate the correlation between density of nerve fibres and the presence of BDNF(+) cells.Densities of nerve fibres and BDNF(+) cells were detected by quantitative immunohistochemistry in fresh synovial tissue from 52 patients with RA, 59 with OA, and 26 controls (Co). BDNF was also detected by in situ hybridisation.Sympathetic nerve fibre density was similar in Co and OA but markedly reduced in RA (p = 0.002), whereas density of substance P positive (SP(+)) sensory nerve fibres was lower in OA than in Co and RA (p = 0.002). The ratio of sympathetic/SP(+) sensory nerve fibre density was highest in OA and Co, followed by RA. The correlation between density of sympathetic nerve fibres and SP(+) sensory nerve fibres in OA (R = 0.425, p = 0.001) was strongly positive, had a positive trend in Co (R = 0.243, NS), but was negative in RA (R = -0.292, p = 0.040). In RA and OA tissue the density of BDNF(+) cells was high in sublining areas but markedly lower in Co (p = 0.001). BDNF(+) cell density correlated positively with the ratio of sympathetic/SP(+) sensory nerve fibre density in Co (R = 0.433, p = 0.045) and in OA (R = 0.613, p = 0.015), but not in RA (R = 0.101, NS). Immunohistochemical double staining demonstrated that some macrophages and fibroblasts were positive for BDNF.The correlation of density of SP(+) sensory with sympathetic nerve fibres was positive in Co and OA but negative in RA. BDNF may have a stimulatory role on growth of sympathetic in relation to SP(+) sensory nerve fibres in Co and OA, but not in RA.
Stem-Cell Gene Therapy for the Wiskott–Aldrich Syndrome
Authors: Kaan Boztug, Manfred Schmidt, Adrian Schwarzer, Pinaki P. Banerjee, Inés Avedillo Díez, Ricardo A. Dewey, Marie Böhm, Ali Nowrouzi, Claudia R. Ball, Hanno Glimm, Sonja Naundorf, Klaus Kühlcke, Rainer Blasczyk, Irina Kondratenko, László Maródi, Jordan S. Orange, Christof von Kalle, Christoph Klein
Journal: New England Journal of Medicine (2010)

The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive primary immunodeficiency disorder associated with thrombocytopenia, eczema, and autoimmunity. We treated two patients who had this disorder with a transfusion of autologous, genetically modified hematopoietic stem cells (HSC). We found sustained expression of WAS protein expression in HSC, lymphoid and myeloid cells, and platelets after gene therapy. T and B cells, natural killer (NK) cells, and monocytes were functionally corrected. After treatment, the patients' clinical condition markedly improved, with resolution of hemorrhagic diathesis, eczema, autoimmunity, and predisposition to severe infection. Comprehensive insertion-site analysis showed vector integration that targeted multiple genes controlling growth and immunologic responses in a persistently polyclonal hematopoiesis. (Funded by Deutsche Forschungsgemeinschaft and others; German Clinical Trials Register number, DRKS00000330.).
Delayed union stress fractures of the anterior tibia: conservative management
Authors: M E Batt, S Kemp, R Kerslake
Journal: British Journal of Sports Medicine (2001)

Introduction —A conservative method of treating four delayed union stress fractures of the anterior mid-tibia is described, with an illustrative case history. Methods —Once diagnosed each of the patients was treated in a pneumatic lower leg brace with modified rest. The mean (range) age of the patients was 28 (24–32) years and all were involved in professional or amateur sports. The mean (range) duration of symptoms before diagnosis and definitive treatment of the four fractures was 9 (3–14) months. Results —Use of this technique avoided the need for surgery in this group of patients and allowed return to unrestricted activity an average of 12 months from presentation. Conclusion —The treatment is cost effective and avoids the often uncertain results and morbidity associated with surgery for these difficult stress fractures.
Interferon Regulatory Factor-1 Mediates the Proapoptotic but Not Cell Cycle Arrest Effects of the Steroidal Antiestrogen ICI 182,780 (Faslodex, Fulvestrant)
Authors: Kerrie B. Bouker, Todd C. Skaar, David R. Fernandez, Kerry A. O’Brien, Rebecca B. Riggins, Donghua Cao, Robert Clarke
Journal: Cancer Research (2004)

Abstract Antiestrogens induce both cytostasis (cell cycle arrest) and apoptosis, but the relationship between these end points and the signaling that regulates their induction are unclear. We have previously implicated the transcription factor and putative tumor suppressor IFN regulatory factor-1 (IRF-1) in acquired antiestrogen resistance (Gu et al., Cancer Res, 62: 3428–3437, 2002). We now show the functional significance of IRF-1 in affecting antiestrogen responsiveness in estrogen receptor-positive antiestrogen-sensitive models (MCF-7, T47D, and ZR-75-1), a model of acquired antiestrogen resistance (MCF7/LCC9; estrogen receptor positive), and a model of de novo antiestrogen resistance (MDA-MB-231; estrogen receptor negative). Basal IRF-1 mRNA expression is lower in MCF7/LCC9 cells when compared with MCF-7, T47D, and ZR-75-1 cells. IRF-1 transcriptional activity in MCF-7/LCC9 cells is 18-fold lower than that seen in the parental cells (MCF-7/LCC1) and is comparable with that in MDA-MB-231 cells. Although IRF-1 mRNA expression is induced by ICI 182,780 in sensitive cells, this regulation is lost in MCF-7/LCC9 and is absent in MDA-MB-231 cells. Loss of IRF-1 regulation appears specific to antiestrogen resistance—resistant cells induce IRF-1 mRNA in response to the cytotoxic drug doxorubicin. A dominant-negative IRF-1 eliminates the ICI 182,780-induced apoptotic response (reduced &amp;gt;4-fold) and reduces MCF-7 and T47D cell sensitivity to the antiproliferative effects of ICI 182,780. This effect is not mediated by changes in cell cycle distribution; rather, dominant-negative IRF-1 reduces ICI 182,780-induced apoptosis. These data identify a novel mechanism of antiestrogen resistance and implicate IRF-1 as a key component in signaling some ER-mediated effects on apoptosis/cell survival.
Epidemiology of whiplash: an international dilemma
Authors: R. FERRARI, A. S RUSSELL
Journal: Annals of the Rheumatic Diseases (1999)

Epidemiology of whiplash: an international dilemma* Whiplash associated disorders have become an international medicolegal and social dilemma.Physicians are not sure what the best therapeutic approach should be, and the courts are finding the topic growing ever more controversial.There are many evident paradoxes in the development and presentation of such disorders.We will focus particularly on the remarkable epidemiological findings covering the "natural history" of this problem, and provide a biopsychosocial model to explain these observations.
External-Beam Radiation Therapy (Ebrt) Use and Safety with Radium-223 Dichloride (Ra) in Patients (Pts) with Castration-Resistant Prostate Cancer (Crpc) and Symptomatic Bone Metastases (Mets) from the Alsympca Trial
Authors: J.M. O'Sullivan, O. Sartor, C. Parker, P. Hoskin, A. Widmark, B. Mellado, S.I. Helle, A. Aksnes, J.E. Garcia-Vargas, S. Nilsson
Journal: Annals of Oncology (2014)
Characterization of irritant patch test reactions to topical D vitamins and <i>all‐trans</i> retinoic acid in comparison with sodium lauryl sulphate. Evaluation by clinical scoring and multiparametric non‐invasive measuring techniques
Authors: A. FULLERTON, J. SERUP
Journal: British Journal of Dermatology (1997)

The study was a single-centre, double-blind randomized, placebo-controlled within-subject comparison of 42 healthy volunteers. Occlusive patch test for 48 h was performed with solutions of 1α,25(OH)2D3 (calcitriol), two vitamin D analogues (calcipotriol and KH 1060 (lexacalcitol)), all-trans retinoic acid and sodium lauryl sulphate (SLS) as reference irritant. Solution vehicles and an empty chamber was also included. Test evaluation was performed at day 2, day 3 and again on day 7. Test evaluation was based both on clinical scoring and on various non-invasive measuring methods. 1α,25(OH)2D3, calcipotriol and KH 1060 all showed mild irritation in the concentrations tested. The number and severity of test reactions was found to be dose dependent based both on clinical scoring and on non-invasive measurements. Irritation of the vitamin D analogues mainly affected the vasculature with vasodilation and increased cutaneous blood flow. All-trans retinoic acid showed irritant reactions with some similarity to the tested vitamin D analogues; however, the reactions were more prolonged. Transepidermal water loss (TEWL) was affected neither after application of vitamin D analogues nor after application of all-trans retinoic acid and it was thus concluded that these substances are non-corrosive. SLS showed the known irritant mechanism with corrosion and increase in TEWL as the primary event.
Acute Effects of Estrogen on Neuronal Physiology
Authors: Catherine S. Woolley
Journal: The Annual Review of Pharmacology and Toxicology (2006)

It has been known for more than 30 years that estrogen can alter the intrinsic and synaptic physiology of neurons within minutes. The physiological significance of these acute effects has been unclear, however, because some effects require higher concentrations of estrogen than are detected in plasma, and because estrogen secreted by the ovary rises and falls over a time course of days, not minutes. These concerns may be answered by new research demonstrating that estrogen is produced at high levels within the brain itself, and that production of estrogen in the brain may be regulated by neuronal activity. Additionally, recent studies indicate that classical estrogen receptor proteins are found not only in the nucleus where they regulate gene expression but also at extranuclear sites, including at synapses. These findings, together with evidence for new types of extranuclear estrogen receptors, suggest that estrogen might act directly at synapses to activate second messenger signaling, thereby rapidly altering neuronal excitability, synaptic transmission, and/or synaptic plasticity.
Prognostic Model for Survival in Patients with Metastatic Renal Cell Carcinoma: Results from the International Kidney Cancer Working Group
Authors: Judith Manola, Patrick Royston, Paul Elson, Jennifer Bacik McCormack, Madhu Mazumdar, Sylvie Négrier, Bernard Escudier, Tim Eisen, Janice Dutcher, Michael Atkins, Daniel Y.C. Heng, Toni K. Choueiri, Robert Motzer, Ronald Bukowski
Journal: Clinical Cancer Research (2011)

Abstract Purpose: To develop a single validated model for survival in metastatic renal cell carcinoma (mRCC) using a comprehensive international database. Experimental Design: A comprehensive database of 3,748 patients including previously reported clinical prognostic factors was established by pooling patient-level data from clinical trials. Following quality control and standardization, descriptive statistics were generated. Univariate analyses were conducted using proportional hazards models. Multivariable analysis using a log–logistic model stratified by center and multivariable fractional polynomials was conducted to identify independent predictors of survival. Missing data were handled using multiple imputation methods. Three risk groups were formed using the 25th and 75th percentiles of the resulting prognostic index. The model was validated using an independent data set of 645 patients treated with tyrosine kinase inhibitor (TKI) therapy. Results: Median survival in the favorable, intermediate and poor risk groups was 26.9 months, 11.5 months, and 4.2 months, respectively. Factors contributing to the prognostic index included treatment, performance status, number of metastatic sites, time from diagnosis to treatment, and pretreatment hemoglobin, white blood count, lactate dehydrogenase, alkaline phosphatase, and serum calcium. The model showed good concordance when tested among patients treated with TKI therapy (C statistic = 0.741, 95% CI: 0.714–0.768). Conclusions: Nine clinical factors can be used to model survival in mRCC and form distinct prognostic groups. The model shows utility among patients treated in the TKI era. Clin Cancer Res; 17(16); 5443–50. ©2011 AACR.
Ataxia and Paroxysmal Dyskinesia in Mice Lacking Axonally Transported FGF14
Authors: Qing Wang, Mark E. Bardgett, Michael Wong, David F. Wozniak, Junyang Lou, Benjamin D. McNeil, Chen Chen, Anthony Nardi, David C. Reid, Kelvin Yamada, David M. Ornitz
Journal: Neuron (2002)
Bone marrow-derived multidrug resistance protein ABCB4 protects against atherosclerotic lesion development in LDL receptor knockout mice☆
Authors: M PENNINGS, R HILDEBRAND, D YE, C KUNNE, T VANBERKEL, A GROEN, M VANECK
Journal: Cardiovascular Research (2007)

Objective Several members of the ATP binding cassette (ABC)-transporter super family expressed in macrophages protect against atherosclerosis by promoting macrophage cholesterol and phospholipid efflux. Systemic disruption of ABCB4 in mice results in a virtual absence of phospholipids in bile and a strongly impaired biliary cholesterol secretion, indicating that ABCB4 plays an essential role in cellular lipid efflux. The aim of the current study was to determine the role of bone marrow-derived ABCB4 in atherosclerotic lesion development.
Elimination of HIV in South Africa through Expanded Access to Antiretroviral Therapy: A Model Comparison Study
Authors: Jan A. C. Hontelez, Mark N. Lurie, Till Bärnighausen, Roel Bakker, Rob Baltussen, Frank Tanser, Timothy B. Hallett, Marie-Louise Newell, Sake J. de Vlas
Journal: PLoS Medicine (2013)

Using nine structurally different models, Jan Hontelez and colleagues investigate timeframes for HIV elimination in South Africa using a universal test and treat strategy. Please see later in the article for the Editors' Summary
Pervasive Adaptive Evolution in Mammalian Fertilization Proteins
Authors: Willie J Swanson, Rasmus Nielsen, Qiaofeng Yang
Journal: Molecular Biology and Evolution (2003)

Mammalian fertilization exhibits species specificity, and the proteins mediating sperm-egg interactions evolve rapidly between species. In this study, we demonstrate that the evolution of seven genes involved in mammalian fertilization is promoted by positive Darwinian selection by using likelihood ratio tests (LRTs). Several of these proteins are sperm proteins that have been implicated in binding the mammalian egg coat zona pellucida glycoproteins, which were shown previously to be subjected to positive selection. Taken together, these represent the major candidates involved in mammalian fertilization, indicating positive selection is pervasive amongst mammalian reproductive proteins. A new LRT is implemented to determine if the dN/dS ratio is significantly greater than one. This is a more refined test of positive selection than the previous LRTs which only identified if there was a class of sites with a dN/dS ratio >1 but did not test if that ratio was significantly greater than one.
Sleep Disturbance and Depression Recurrence in Community-Dwelling Older Adults: A Prospective Study
Authors: Hyong Jin Cho, Helen Lavretsky, Richard Olmstead, Myron J. Levin, Michael N. Oxman, Michael R. Irwin
Journal: American Journal of Psychiatry (2008)

A prior depressive episode is thought to increase the risk of depression. However, among older adults with prior depression, it is unclear whether sleep disturbance predicts depression recurrence independent of other depressive symptoms.A 2-year prospective cohort study was conducted with 351 community-dwelling older adults ages 60 years and older: 145 persons with a history of major or nonmajor depression in full remission and 206 without a prior history of depression or any mental illness. The participants were assessed at baseline, 6 weeks, 1 year, and 2 years for depressive episodes, depressive symptoms, sleep quality, and chronic medical disease.Twenty-three subjects (16.9%) with prior depression developed depressive episodes during follow-up, compared to only one person in the group without prior mental illness (0.5%). Within the group with prior depression, depression recurrence was predicted by sleep disturbance, and this association was independent of other depressive symptoms, chronic medical disease, and antidepressant medication use.This study is the first to demonstrate that sleep disturbance acts as an independent risk factor for depression recurrence in community-dwelling older adults. To identify older adults at risk for depression, a two-step strategy can be employed, which involves assessment of the presence of a prior depressive episode along with sleep disturbance.
Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Cancer: A Panacea or Just an Obstacle Course for the Patient?
Authors: Vijay P. Khatri
Journal: Journal of Clinical Oncology (2009)

Navelbine International Trialist Association (ANITA) randomized trial. Int J Radiat Oncol Biol Phys 72:695-701, 2008 15. Olaussen K, Dunant A, Fouret P, et al: DNA repair by ERCC1 in non-smallcell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med 355:983-991, 2006 16. Le Chevalier T: Long-term results of the International Lung Cancer trial evaluation of adjuvant cisplatin-based chemotherapy in resected non–small-cell lung cancer. J Clin Oncol 26:398s, 2008 (abstr 7507)
Reduced Plasma RNA Integrity in Nasopharyngeal Carcinoma Patients
Authors: Blenda C.K. Wong, K.C. Allen Chan, Anthony T.C. Chan, Sing-Fai Leung, Lisa Y.S. Chan, Katherine C.K. Chow, Y.M. Dennis Lo
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Recent research has shown the feasibility of detecting cell-free RNA markers in human subjects. As elevated RNase activity has previously been described in the circulation of cancer patients, we hypothesized that cancer patients may have reduced plasma RNA integrity. In this study, we used nasopharyngeal carcinoma (NPC) as a model system to test this hypothesis. Experimental Design: Plasma RNA integrity was determined using the ratio of the concentrations of transcript sequences corresponding to the 3′ to those from the 5′ end of a housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Transcript concentrations were measured using real-time quantitative reverse transcription-PCR assays targeting the 5′ and 3′ regions. We analyzed the plasma RNA integrity in 49 untreated NPC patients and 53 healthy controls. We also assessed the plasma samples from 19 NPC patients before and after radiotherapy to further show the clinical potential of this marker. Results: The 3′ to 5′ GAPDH ratio was significantly lower in the plasma of untreated NPC patients when compared with healthy controls (0.0252 versus 0.0485, P = 0.024). Statistical analysis showed that plasma GAPDH ratio was correlated with tumor stage but not with sex and age. Moreover, 14 of 19 NPC patients (74%) showed significant increase in the plasma GAPDH ratio following radiotherapy (P = 0.003). All of these patients were in clinical remission after treatment. Conclusions: Our findings suggest that NPC is associated with disturbances in the integrity of cell-free circulating RNA, raising the possibility that measurement of plasma RNA integrity may serve as a useful marker for the diagnosis and monitoring of malignant diseases.
Experimental arthritis of rabbits caused by intra-articular injection of autologous Fab2 produced by digestion of IgG with cathepsin D.
Authors: K Fehr, M Velvart, A Boni, H Watanabe, M A Spycher, J R Ruttner
Journal: Annals of the Rheumatic Diseases (1976)

Intra-articularly injected autologous Fab2 produced from IgG by homologous cathepsin D induces in animals not given prior immunization acute synovitis after 1 and 3 injections, acute synovitis after 6 injections, and chronic synovitis after 12 injections. Histologically, the chronic synovitis is similar to synovitis in rheumatoid arthritis (RA). In the joint, cathepsin D Fab2 appears to act as a fairly strong antigen. Evidence for this is provided by the infiltration of large numbers of polymorphonuclear leucocytes, the marked phagocytic activity of the exudate leucocytes and tissue phagocytes, and the stimulation of the synthesis of specific antibodies (homoreactants) in the synovial plasma cells. The immediate action of injected Fab2 suggests that it forms biologically active immune complexes with homoreactants already present. These complexes are phagocytosed, the homoreactants being demonstrable immunohistochemically in inclusions of the exudate and tissue phagocytes. In addition, the local synthesis of antigammaglobulins of rheumatoid factor type is also induced. These react with heat-aggregated homologous as well as human IgG and are likewise found in inclusions in the exudate and tissue phagocytes. In the serum of the animals the titre of rheumatoid factor-like antigammaglobulins increases to an extent depending on the number of injections given. These histochemical and serological findings show striking parallels with the findings in human RA.