tbuckley/cabot-search huggingface dataset:
Randomized Controlled Trial of a Structured Intervention to Facilitate End-of-Life Decision Making in Patients With Advanced Cancer
Authors: Rhea A. Stein, Louise Sharpe, Melanie L. Bell, Fran M. Boyle, Stewart M. Dunn, Stephen J. Clarke
Journal: Journal of Clinical Oncology (2013)

Purpose This study tested the efficacy of an intervention on end-of-life decision making for patients with advanced cancer. Patients and Methods One hundred twenty patients with metastatic cancer who were no longer being treated with curative intent (and 87 caregivers) were randomly assigned to the intervention (n = 55) or treatment as usual (n = 65). Primary outcome measures were the proportion of patients with do-not-resuscitate (DNR) orders, timing of DNR orders, and place of death. Secondary outcome measures were completed at study enrollment, 3 weeks later, and 3 months later, including patients' knowledge, mood, and caregiver burden. Results High, but equivalent, rates of DNR orders were observed in both groups. In per-protocol analyses, DNR orders were placed earlier for patients who received the intervention (median, 27 v 12.5 days; 95% CI, 1.1 to 5.9; P = .03) and they were more likely to avoid a hospital death (19% v 50% (95% CI, 11% to 50%; P = .004). Differences between the groups over time were evident for estimates of cardiopulmonary rehabilitation (CPR) success rates (P = .01) but not knowledge of CPR (P = .2). There was no evidence that the intervention resulted in more anxious or depressive symptoms. Caregivers experienced less burden in terms of disruption to schedule if the patient received the intervention (P = .05). Conclusion An intervention, consisting of an informational pamphlet and discussion, was associated with earlier placement of DNR orders relative to death and less likelihood of death in hospital. There was no negative impact of the intervention on secondary outcomes, although the sample may have been too small to detect differences.
Predictive markers of anthracycline benefit: a prospectively planned analysis of the UK National Epirubicin Adjuvant Trial (NEAT/BR9601)
Authors: John MS Bartlett, Alison F Munro, Janet A Dunn, Christopher McConkey, Sarah Jordan, Chris J Twelves, David A Cameron, Jeremy Thomas, Fiona M Campbell, Daniel W Rea, Elena Provenzano, Carlos Caldas, Paul Pharoah, Louise Hiller, Helena Earl, Christopher J Poole
Journal: The Lancet Oncology (2010)

The NEAT/BR9601 trial showed benefit for addition of anthracyclines to cyclophosphamide, methotrexate, and fluorouracil (CMF) as adjuvant treatment for early breast cancer. We investigated prospectively predictive biomarkers of anthracycline benefit including HER2 and TOP2A.
Anrukinzumab, an anti-interleukin 13 monoclonal antibody, in active UC: efficacy and safety from a phase IIa randomised multicentre study
Authors: Walter Reinisch, Julián Panés, Sunil Khurana, Gabor Toth, Fei Hua, Gail M Comer, Michelle Hinz, Karen Page, Margot O'Toole, Tara McDonnell Moorehead, Hua Zhu, YanHui Sun, Fabio Cataldi
Journal: Gut (2015)

<h3>Objective</h3> Interleukin 13 (IL-13) is thought to play a key role as an effector cytokine in UC. Anrukinzumab, a humanised antibody that inhibits human IL-13, was evaluated for the treatment of UC. <h3>Design</h3> In a multicentre, randomised, double-blind, placebo-controlled study, patients with active UC (Mayo score ≥4 and &lt;10) were randomised to anrukinzumab 200, 400 or 600 mg or placebo. Patients received five intravenous administrations over 14 weeks. The primary endpoint was fold change from baseline in faecal calprotectin (FC) at Week 14. Secondary endpoints included safety, pharmacokinetics and IL-13 levels. <h3>Results</h3> The modified intention-to-treat population included 84 patients (21 patients/arm). Fold change of FC from baseline at Week 14 was not significantly different for any treatment groups compared with the placebo. The study had a high dropout rate, in part, related to lack of efficacy. The exploratory comparisons of each dose were not significantly different from placebo in terms of change from baseline in total Mayo score, clinical response, clinical remission and proportion of subjects with mucosal healing. An increase in serum total IL-13 (free and bound to anrukinzumab) was observed for all anrukinzumab groups but not with placebo. This suggests significant binding of anrukinzumab to IL-13. The safety profile was not different between the anrukinzumab and placebo groups. <h3>Conclusions</h3> A statistically significant therapeutic effect of anrukinzumab could not be demonstrated in patients with active UC in spite of binding of anrukinzumab to IL-13. <h3>Trial registration number</h3> ClinicalTrials.gov number NCT01284062.
Roles of epidermal growth factor receptor activation in epithelial cell repair and mucin production in airway epithelium
Authors: P-R Burgel
Journal: Thorax (2004)

The epithelial cells lining the airways serve protective functions. The "barrier function" of the epithelium protects the individual from damage by inhaled irritants. The epithelium produces mucins which become hydrated and form a viscoelastic gel which spreads over the epithelial surface. In healthy individuals inhaled foreign materials become entrapped in the mucus and are cleared by mucociliary transport and by coughing. In many chronic inflammatory airway diseases, however, excessive mucus is produced and is inadequately cleared, leading to mucous obstruction and infection. At present there is no specific treatment for hypersecretion. However, the discovery that an epidermal growth factor receptor (EGFR) cascade is involved in mucin production by a wide variety of stimuli suggests that blockade may provide specific treatment for hypersecretory diseases. EGFR pathways have also been implicated in the repair of damaged airway epithelium. The roles of EGFR in airway epithelial cell hypersecretion and epithelial damage and repair are reviewed and future potential treatments are suggested.
Differences in Glycosylation Patterns of Heat Shock Protein, gp96: Implications for Prostate Cancer Prevention
Authors: Robert Suriano, Salil K. Ghosh, Badithe T. Ashok, Abraham Mittelman, Yuangen Chen, Asesh Banerjee, Raj K. Tiwari
Journal: Cancer Research (2005)

Abstract Heat shock protein gp96 induces a tumor-specific protective immunity in a variety of experimental tumor models. Because the primary sequences of the glycoprotein, gp96 are identical between tumor and normal tissues, the peptides associated with gp96 and/or the posttranslational modifications of gp96, determine its immunogenicity. Gp96-associated peptides constitute the antigenic repertoire of the source tissue; thus, purified gp96-peptide complexes have clinical significance as autologous cancer vaccines. However, the role of altered glycosylation and its contribution in the biological as well as immunologic activity of gp96 still remains uncharacterized. We examined the cancer-specific glycosylation patterns of gp96. To this end, monosaccharide compositions of gp96 were compared between normal rat prostate and two cancerous rat prostate tissues, nonmetastatic/androgen-dependent Dunning G and metastatic/androgen-independent MAT-LyLu, as well as two human nonmetastatic prostate cancer cell lines, androgen-dependent LnCaP and androgen-independent DU145. Marked differences were observed between the gp96 monosaccharide compositions of the normal and cancerous tissues. Furthermore, gp96 molecules from more aggressive cellular transformations were found to carry decreasing quantities of several monosaccharides as well as sum total content of neutral and amino sugars. We believe that the unique glycosylation patterns contribute to cellular phenotype and that the posttranslational modifications of gp96 may affect its functional attributes.
Early malignant melanoma manifested as longitudinal melanonychia: subungual melanoma may arise from suprabasal melanocytes
Authors: K. Tomizawa
Journal: British Journal of Dermatology (2000)

A 51‐year‐old woman developed longitudinal melanonychia of 3 months’ duration on the right index fingernail. A biopsy specimen revealed that atypical melanocytes were distributed in the lower third of the matrix epithelium but were few in number at the basal layer. The involved nail matrix was resected because of continual growth of the lesion after the biopsy. It has been proven in normal nail matrices that melanocytes are distributed not only in the basal layer but also in the lower half of the epithelium. It is therefore understandable that malignant melanoma of the nail matrix can arise from melanocytes situated in the squamous epithelium above the basal layer. The present case is a good example in which malignant melanoma of the nail matrix may arise from the intraepithelial region where melanocytes normally reside.
Ultrasound of ovaries combats infertility
Authors: John Henahan
Journal: JAMA (1983)

Ultrasound is being used with increasing success to determine time of ovulation and to enhance the chances of pregnancy for infertile women who undergo hormone therapy, artificial insemination, or, more recently, in vitro fertilization, according to a large number of presentations made at the XI World Congress of Fertility and Sterility in Dublin.  The technique involves applying an ultrasonic transducer to the abdominal area overlying the ovaries to assess maturation of the ovarian follicles (as seen on the viewing screen) and to judge when fertilization seems most likely to occur.  However, considerable debate erupted over the safety aspects of a new modification of the technique in which ultrasound is used to guide removal of the oocyte from the ovary before in vitro fertilization.  Still, there was little doubt that employing ultrasound to monitor follicular development is quite useful and can better indicate when ovulation occurs than traditional hormone measurements. Participants
Points from Letters: Place of Vasectomy
Authors: M. Altman
Journal: BMJ (1972)

the dose we prescribed facilitate further rehabilitation of the patients.Our experience, however, does confinn the findings of other workers that very large doses of the drug do not produce any parallel increase in iatrogenic Parkinsonian symptoms.We felt reluctant to inject the drug more frequently than once a week.The advantage of a longacting parenteral phenothiazine drug lies in its infrequent administration.Daily injection at the dose suggested by Kline et al. negates any advantage that parenteral therapy may have over oral phenothiazines.-Weare, etc.,
Ibrutinib and novel BTK inhibitors in clinical development
Authors: Akintunde Akinleye, Yamei Chen, Nikhil Mukhi, Yongping Song, Delong Liu
Journal: Journal of Hematology & Oncology (2013)

Abstract Small molecule inhibitors targeting dysregulated pathways (RAS/RAF/MEK, PI3K/AKT/mTOR, JAK/STAT) have significantly improved clinical outcomes in cancer patients. Recently Bruton’s tyrosine kinase (BTK), a crucial terminal kinase enzyme in the B-cell antigen receptor (BCR) signaling pathway, has emerged as an attractive target for therapeutic intervention in human malignancies and autoimmune disorders. Ibrutinib, a novel first-in-human BTK-inhibitor, has demonstrated clinical effectiveness and tolerability in early clinical trials and has progressed into phase III trials. However, additional research is necessary to identify the optimal dosing schedule, as well as patients most likely to benefit from BTK inhibition. This review summarizes preclinical and clinical development of ibrutinib and other novel BTK inhibitors (GDC-0834, CGI-560, CGI-1746, HM-71224, CC-292, and ONO-4059, CNX-774, LFM-A13) in the treatment of B-cell malignancies and autoimmune disorders.
Allergic contact dermatitis due to an epoxy acrylate
Authors: JAMES R. NETHERCOTT
Journal: British Journal of Dermatology (1981)

Journal Article Allergic contact dermatitis due to an epoxy acrylate Get access JAMES R. NETHERCOTT JAMES R. NETHERCOTT Department of Medicine (Dermatology), Contact Dermatitis Clinic, St Michael's Hospital, University of Toronto, 30 Bond Street, Toronto, Canada, M5B 1W8 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 104, Issue 6, 1 June 1981, Pages 697–703, https://doi.org/10.1111/j.1365-2133.1981.tb00758.x Published: 01 June 1981 Article history Accepted: 05 July 1980 Published: 01 June 1981
Recalcitrant necrobiotic xanthogranuloma responding to pulsed high-dose oral dexamethasone plus maintenance therapy with oral prednisolone
Authors: T.A. Chave, M.M.U. Chowdhury, P.J.A. Holt
Journal: British Journal of Dermatology (2001)

A patient with the rare condition necrobiotic xanthogranuloma was treated from 1992 to 1999 with multiple therapies, none of which was effective. Her disease was progressive, causing significant disability. In September 1999 a trial of high-dose pulsed oral dexamethasone with maintenance corticosteroids led to a substantial improvement in her condition.
Effect of intravenous hydrocortisone on nocturnal airflow limitation in childhood asthma
Authors: A.M. Landstra, H.M. Boezen, D.S. Postma, W.M.C. van Aalderen
Journal: European Respiratory Journal (2003)

Low endogenous cortisol levels appear to contribute to the pathophysiology of nocturnal asthma. Lower cortisol levels are associated with lower forced expiratory volume in one second (FEV 1 ) levels in children with asthma. The aim of the present study was to identify whether substitution of low serum cortisol with intravenous hydrocortisone decreases 24-h FEV 1 variation and/or indirect measures of airway inflammation. Hydrocortisone was given over 24 h in a double-blind randomised crossover design to 26 subjects. FEV 1 was measured every 4 h during 24 h; blood eosinophils and airway responsiveness to methacholine and adenosine 5′-monophosphate (AMP) were measured at 04:00 h and 16:00 h. Cortisol levels increased during the night and morning hours. FEV 1 values were higher at all time points in children with nocturnal asthma (n=10; 24-h FEV 1 variation ≥15%) which was significant at 08:00 h, unlike in the non-nocturnal asthma (NA−) group (n=16). Numbers of eosinophils (10 9 ·L −1 ) at 04:00 h decreased in the asthma group (median 0.61 (range 0.05–1.42) versus 0.52 (0.05–1.79)). Provocative dose causing a 20% fall in FEV 1 (PD 20 ) methacholine did not change, whereas PD 20 AMP improved only at 16:00 h in the NA− group (72.0 (0.13–144.0) versus 144.0 (2.25–144.0) mg·mL −1 ). These results show that substitution of lower endogenous 24-h values of cortisol contribute to higher forced expiratory volume in one second values and a decrease of blood eosinophils as an inflammatory marker in more severe airway obstruction.
Mitochondrial morphology and cardiovascular disease
Authors: S.-B. Ong, D. J. Hausenloy
Journal: Cardiovascular Research (2010)

Mitochondria are dynamic and are able to interchange their morphology between elongated interconnected mitochondrial networks and a fragmented disconnected arrangement by the processes of mitochondrial fusion and fission, respectively. Changes in mitochondrial morphology are regulated by the mitochondrial fusion proteins (mitofusins 1 and 2, and optic atrophy 1) and the mitochondrial fission proteins (dynamin-related peptide 1 and mitochondrial fission protein 1) and have been implicated in a variety of biological processes including embryonic development, metabolism, apoptosis, and autophagy, although the majority of studies have been largely confined to non-cardiac cells. Despite the unique arrangement of mitochondria in the adult heart, emerging data suggest that changes in mitochondrial morphology may be relevant to various aspects of cardiovascular biology—these include cardiac development, the response to ischaemia–reperfusion injury, heart failure, diabetes mellitus, and apoptosis. Interestingly, the machinery required for altering mitochondrial shape in terms of the mitochondrial fusion and fission proteins are all present in the adult heart, but their physiological function remains unclear. In this article, we review the current developments in this exciting new field of mitochondrial biology, the implications for cardiovascular physiology, and the potential for discovering novel therapeutic strategies for treating cardiovascular disease.
Number and Proliferation of Basal and Parabasal Cells in Normal Human Airway Epithelium
Authors: JAMES E. BOERS, ANTON W. AMBERGEN, FREDERIK B. J. M. THUNNISSEN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Two roles have been suggested for basal cells on the basis of studies performed with laboratory animals: (1) anchoring of the tracheobronchial epithelium; and (2) being the epithelial stem cell. Parabasal cells located just above the basal cells have also been shown to contribute to cell renewal. However, a systematic study of the composition and proliferation of basal and parabasal cells in normal human lungs is lacking. The aims of this study were to determine in normal human conducting-airway epithelium: (1) the number of basal and parabasal cells; and (2) the contribution of basal and parabasal cells to the proliferation fraction. Samples of histologically normal tissue, free of pulmonary disease, were taken from seven lungs obtained by autopsy. Immunohistochemical staining was performed with the primary antibody MIB-1 as a proliferation marker and the antikeratin antibody 34betaE12 as a marker for basal and parabasal cells. In the largest conducting airways (diameter >= 4 mm), the percentages of basal and parabasal cells were 31% and 7%, respectively; the contribution to the proliferation compartment was 51% for basal and 33% for parabasal cells. In the smallest airways (diameter < 0.5 mm), 6% of epithelial cells were basal cells, with a 30% contribution to the proliferation compartment, whereas parabasal cells were absent. The high fraction of basal and parabasal cells contributing to the proliferation compartment of normal human conducting-airway epithelium supports the theory that cells at or near the basement membrane are likely to be progenitor cells.
Mannose Receptor and Its Putative Ligands in Normal Murine Lymphoid and Nonlymphoid Organs: In Situ Expression of Mannose Receptor by Selected Macrophages, Endothelial Cells, Perivascular Microglia, and Mesangial Cells, but not Dendritic Cells
Authors: Sheena A. Linehan, Luisa Martínez-Pomares, Philip D. Stahl, Siamon Gordon
Journal: The Journal of Experimental Medicine (1999)

The mannose receptor (MR) has established roles in macrophage (Mφ) phagocytosis of microorganisms and endocytic clearance of host-derived glycoproteins, and has recently been implicated in antigen capture by dendritic cells (DCs) in vitro. MR is the founder member of a family of homologous proteins, and its recognition properties differ according to its tissue of origin. Given this heterogeneity and our recent discovery of a soluble form of MR in mouse serum, we studied the sites of synthesis of MR mRNA and expression of MR protein in normal mouse tissues. We demonstrate that synthesis and expression occur at identical sites, and that mature Mφ and endothelium are heterogeneous with respect to MR expression, additionally describing MR on perivascular microglia and glomerular mesangial cells. However, MR was not detected on DCs in situ, or on marginal zone or subcapsular sinus Mφ, both of which have MR-like binding activities. We also compared expression of MR to the binding of a recombinant probe containing the cysteine-rich domain of MR. We show that MR and its putative ligand(s) are expressed at nonoverlapping sites within lymphoid organs, consistent with a transfer function for soluble MR. Therefore, in addition to endocytic and phagocytic roles, MR may play an important role in antigen recognition and transport within lymphoid organs.
Impact of Caring for a Child With Cancer on Parents’ Health-Related Quality of Life
Authors: Anne F. Klassen, Robert Klaassen, David Dix, Sheila Pritchard, Rochelle Yanofsky, Maureen O'Donnell, Amie Scott, Lillian Sung
Journal: Journal of Clinical Oncology (2008)

To compare the health-related quality of life (QOL) of parents of children who are undergoing treatment for cancer with that of Canadian population norms and to identify important parent and child predictors of parental QOL.A total of 411 respondents of 513 eligible parents were recruited from five pediatric oncology centers in Canada between November 2004 and February 2007. Parents were asked to complete a questionnaire booklet that included a measure of adult QOL (SF-36), a measure of child health status (functional status IIR), and questions to assess health-promoting self-care actions (eg, sleep, diet, and exercise habits) and characteristics of the child with cancer (eg, relapse status, time since diagnosis, prognosis, treatment intensity).Compared with population norms, parents of children with cancer reported poorer physical and psychosocial QOL in all psychosocial domains (effect sizes range, -0.71 to -1.58) and in most physical health domains (effect sizes range, -0.08 to -0.63). Parent characteristics associated with better parental QOL included better eating, exercise and sleep habits, younger age, and higher income. Child characteristics associated with better parental QOL included better child health status (functional status IIR scores), lower treatment intensity, and longer time since diagnosis.Parents of children with cancer report poorer QOL compared with population norms. Interventions directed at parents should be included as part of the treatment plan for a child with cancer. Modifiable variables associated with poorer parental QOL, such as sleep quality and diet and exercise habits, indicate those parents most likely to experience poor QOL and may be potential areas for intervention.
Cannabinoids suppress inflammatory and neuropathic pain by targeting α3 glycine receptors
Authors: Wei Xiong, Tanxing Cui, Kejun Cheng, Fei Yang, Shao-Rui Chen, Dan Willenbring, Yun Guan, Hui-Lin Pan, Ke Ren, Yan Xu, Li Zhang
Journal: The Journal of Experimental Medicine (2012)

Certain types of nonpsychoactive cannabinoids can potentiate glycine receptors (GlyRs), an important target for nociceptive regulation at the spinal level. However, little is known about the potential and mechanism of glycinergic cannabinoids for chronic pain treatment. We report that systemic and intrathecal administration of cannabidiol (CBD), a major nonpsychoactive component of marijuana, and its modified derivatives significantly suppress chronic inflammatory and neuropathic pain without causing apparent analgesic tolerance in rodents. The cannabinoids significantly potentiate glycine currents in dorsal horn neurons in rat spinal cord slices. The analgesic potency of 11 structurally similar cannabinoids is positively correlated with cannabinoid potentiation of the α3 GlyRs. In contrast, the cannabinoid analgesia is neither correlated with their binding affinity for CB1 and CB2 receptors nor with their psychoactive side effects. NMR analysis reveals a direct interaction between CBD and S296 in the third transmembrane domain of purified α3 GlyR. The cannabinoid-induced analgesic effect is absent in mice lacking the α3 GlyRs. Our findings suggest that the α3 GlyRs mediate glycinergic cannabinoid-induced suppression of chronic pain. These cannabinoids may represent a novel class of therapeutic agents for the treatment of chronic pain and other diseases involving GlyR dysfunction.