tbuckley/cabot-search huggingface dataset:
Lymphopenia in Rheumatoid Arthritis
Authors: D P M Symmons, M Farr, M Salmon, P A Bacon
Journal: Journal of the Royal Society of Medicine (1989)

Lymphopenia is a recognized but poorly studied feature of rheumatoid arthritis (RA). We set out to establish the prevalence and significance of lymphopenia in RA. A group of 66 RA patients was studied for one year. During this time 10 (15%) had persistent lymphopenia (lymphocyte count less than 1.00 X 10(9)/l) without evidence of Felty's syndrome. A separate study of lymphocyte subsets in 13 lymphopenic RA patients showed marked reduction in T-cell numbers with normal circulating B-cell numbers. The numbers of CD4 and CD8 positive T-cells were equally depressed. Lymphopenia may indicate more severe disease. It was not influenced by changes in disease activity or therapy.
Endocrine Therapy Trials of Aromatase Inhibitors for Breast Cancer in the Adjuvant and Prevention Settings
Authors: James N. Ingle
Journal: Clinical Cancer Research (2005)

The recent past has witnessed the appearance of substantial data relating to endocrine therapy of breast cancer. In the adjuvant therapy setting in early breast cancer, several large, well-conducted, randomized, double-blind clinical trials have provided evidence for the value of the third-generation aromatase inhibitors (AI) anastrozole, exemestane, and letrozole. The three major studies to date [i.e., Arimidex, tamoxifen alone, or in combination (ATAC), International Exemestane Study (IES), and letrozole after 5 years of tamoxifen (MA.17)] evaluated three different populations of women from the standpoints of duration of prior tamoxifen and thus time since the treatment of the primary breast cancer. A consistent pattern of improvement in disease-free survival was seen whether the control arm was tamoxifen (ATAC and IES) or placebo following tamoxifen (MA.17). From a toxicity standpoint, the major findings with the AIs were a decreased incidence of thromboembolic events and endometrial cancers but an increase in musculoskeletal complaints and potential for decreasing bone density. The last issue should be clarified with ongoing studies addressing the impact of the three AIs on bone density and fractures. In summary, based on ATAC, IES, and MA.17, respectively, the following conclusions can be drawn relating to postmenopausal women with hormone receptor positive early breast cancer: anastrozole is a reasonable choice for initial endocrine adjuvant therapy, exemestane should be considered for women who have received 2 to 3 years of tamoxifen, and letrozole should be considered for those who have completed about 5 years of tamoxifen. In the prevention setting, tamoxifen has been evaluated in multiple trials involving >28,000 women and, despite clear evidence of benefit, the level of acceptance of this agent by women seems to be low. Two recently developed prevention trials, IBIS 2 and MAP.3, involve the study of aromatase inhibitors against a placebo control rather than tamoxifen. Whereas the recent adjuvant trials have established the value of the third-generation aromatase inhibitors in early-stage breast cancer, the marked reductions in contralateral breast cancers seen in these trials suggest they will be of value in the prevention setting in women at increased risk of developing the disease.
Hydroxyurea‐associated acral erythema in a patient with polycythemia vera
Authors: Daniel Butler, Vinod E. Nambudiri, Tina Nandi
Journal: American Journal of Hematology (2014)

A 64-year old man presented with 3 years of progressive redness, burning, and peeling of his palms and soles. His past medical history included cutaneous squamous cell carcinoma, malignant melanoma, gout, and polycythemia vera which had been diagnosed 10 years earlier and complicated by a significant gastrointestinal bleed. Genetic analysis demonstrated a mutant JAK-2 V617F allele. He had been treated with therapeutic phlebotomies and with hydroxyurea 1 g daily, with dose escalation to 1.5 g daily over the last 3 years for management of his polycythemia and worsening splenomegaly. On examination, he had desquamating erythema of the palms and soles, extending proximally to the flexures of the wrists and heels (Images 1A, 1B, 1C). The patient reported that his symptom worsened as the dose of hydroxyurea was increased over the previous 3 years. A diagnosis of hydroxyurea-associated acral erythema was made. Erythema and desquamation of the palms and soles—referred to as acral erythema, palmar-plantar erythrodysesthesia, toxic erythema of chemotherapy, or hand-foot syndrome—are associated with a variety of medications, particularly chemotherapeutic agents. Severe cases may result in focal formation of bullae. The National Cancer Institute grading scale for palmoplantar erythrodysesthesia based on the extent of skin involvement and functional limitation ranges from Grade 1 (minimal skin changes without pain) to Grade 3 (severe skin changes limiting self-care and activities of daily living) 1. Hydroxyurea-associated acral erythema is associated with long-term hydroxyurea use, usually at doses equal to or greater than 1 g daily. Symptoms may begin anywhere from weeks to years after initiation of hydroxyurea 2, 3. The histopathology of acral erythema typically demonstrates an interface dermatitis at the dermal-epidermal junction with a sparse inflammatory infiltrate 4. The reaction is variably reversible with discontinuation of the medication but symptoms of pain and discomfort can persist for months. The exact pathogenesis of this condition is unknown. Previous cases have been described in association with hydroxyurea for chronic myeloid leukemia and sickle cell disease 5, 6. In a large retrospective review of patients with myeloproliferative neoplasms treated with hydroxyurea, fewer than 10% of patients with treated with hydroxyurea developed any mucocutaneous toxicities, with more than 80% of comprising cutaneous ulceration and oral mucosal aphthae.7 We present this case of acral erythema as a rarely encountered adverse reaction associated with the use of hydroxyrea to raise awareness of this medication-related cutaneous toxicity.
Abstract 368: Detection of circulating tumor cells in peripheral blood of renal cell carcinoma patients is correlated with survival.
Authors: Steffen Goebel, Karen Bluemke, Udo Bilkenroth, Axel Meye, Susanne Fuessel, Christine Lautenschlaeger, Andres Melchior, Hans Heynemann, Paolo Fornara, Helge Taubert
Journal: Cancer Research (2013)

Abstract Purpose: The aim of this study was to evaluate the clinical relevance of the presence of disseminated tumor cells in peripheral blood [so called circulating tumor cells (CTCs)] for renal cell carcinoma (RCC) patients after a median follow-up time of 81 months. Methods: 233 peripheral blood samples from 154 RCC patients were investigated for the presence of disseminated tumor cells (DTCs) by autoMACS technique and immunocytochemical (ICC) staining of cytokeratin. The frequency of CTCs was analyzed statistically for correlation with relevant clinical data. Results: Two kinds of tumor cells were detected: Those with expression of cytokeratin 8/18 (CK+), but also cells without a detectable CK+ expression, which we called large blue stained cells (Bl+) with a tumor-like morphology. We hypotesized, that the latter cells could be “sleeping” tumor cells. After following the CD45 autoMACS depletion protocol, we identified CTCs in 96 out of 233 peripheral blood samples (41%), which originated from 81 out of 154 (53%) RCC patients. An update to follow up the RCC patients was conducted in 2012. Besides a significant correlation between the detection of CTCs before and after primary tumor resection a significant association with prognosis was found (p &amp;lt; 0.002; Chi-squared test). RCC patients with CK+ CTCs in their peripheral blood had a 5 times risk of tumor-related death compared to patients without these cells. In a Kaplan-Meier-Analysis these results were confirmed (p &amp;lt; 0.001). Patients with large blue stained cells (Bl+) also had a shorter survival time. Conclusion: In summary, for RCC patients, the presence of CTCs was associated with a poor overall survival and significantly correlated with an increased risk of tumor-related death. It is important to evaluate CK+ tumor cells to determine the role of CTCs in tumor behavior and disease progression. Detection of CK+ CTCs in peripheral blood is a significant and independent prognostic factor for renal cell carcinoma patients. Citation Format: Steffen Goebel, Karen Bluemke, Udo Bilkenroth, Axel Meye, Susanne Fuessel, Christine Lautenschlaeger, Andres Melchior, Hans Heynemann, Paolo Fornara, Helge Taubert. Detection of circulating tumor cells in peripheral blood of renal cell carcinoma patients is correlated with survival. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 368. doi:10.1158/1538-7445.AM2013-368
Microtubule-Associated Protein-tau is a Bifunctional Predictor of Endocrine Sensitivity and Chemotherapy Resistance in Estrogen Receptor–Positive Breast Cancer
Authors: Fabrice Andre, Christos Hatzis, Keith Anderson, Christos Sotiriou, Chafika Mazouni, Jaime Mejia, Bailiang Wang, Gabriel N. Hortobagyi, W. Fraser Symmans, Lajos Pusztai
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The clinical outcome for patients with breast cancer is influenced by the metastatic competence of the cancer and its sensitivity to endocrine therapy and chemotherapy. A molecular marker may be prognostic of outcome or predictive of response to therapy, or a combination of both. Experimental Design: We examined separately the prognostic and predictive values of tau mRNA expression in estrogen receptor (ER)–positive primary breast cancers in three patient cohorts. We used gene expression data from 209 untreated patients to assess the pure prognostic value of tau, data from 267 patients treated with adjuvant tamoxifen to assess predictive value for endocrine therapy, and data from 82 patients treated with preoperative paclitaxel followed by 5-fluorouracil, doxorubicin, and cyclophosphamide (paclitaxel/FAC) to assess predictive value for chemotherapy response. Wilcoxon rank sum test was used to compare tau expression between different outcome groups. Results: Higher tau mRNA expression showed borderline nonsignificant association with better prognosis in the absence of systemic adjuvant therapy. Higher tau mRNA expression was significantly associated with no recurrence (at 5 and 10 years, P = 0.005 and P = 0.05, respectively) in patients treated with tamoxifen, indicating a predictive value for endocrine therapy. Tau expression was significantly lower in patients who achieved pathologic complete response to paclitaxel/FAC chemotherapy (P &amp;lt; 0.001). Conclusion: This study suggests that high tau mRNA expression in ER-positive breast cancer indicates an endocrine-sensitive but chemotherapy-resistant disease. In contrast, low tau expression identifies a subset of ER-positive cancers that have poor prognosis with tamoxifen alone and may benefit from taxane-containing chemotherapy.
p55 Tumour necrosis factor receptor in bone marrow-derived cells promotes atherosclerosis development in low-density lipoprotein receptor knock-out mice
Authors: Sofia Xanthoulea, Marion J.J. Gijbels, Ingeborg van der Made, Hilda Mujčić, Melanie Thelen, Monique N. Vergouwe, Matheus H.C. Ambagts, Marten H. Hofker, Menno P.J. de Winther
Journal: Cardiovascular Research (2008)

Tumour necrosis factor (TNF) is a pivotal pro-inflammatory cytokine with a clear pathogenic role in many chronic inflammatory diseases, and p55 TNF receptor (TNFR) mediates the majority of TNF responses. The aim of the current study was to investigate the role of p55 TNFR expression in bone marrow-derived cells, in atherosclerotic lesion development.Irradiated low-density lipoprotein receptor knock-out mice were reconstituted with either p55 TNFR knock-out or control haematopoietic stem cells to generate chimeras deficient or wild-type for p55 TNFR specifically in bone marrow-derived cells, including macrophages. Upon high fat feeding, p55 TNFR knock-out transplanted mice developed smaller atherosclerotic lesions. These lesions were characterized by the presence of smaller foam cells and a reduced macrophage foam cell area. They did not differ in other compositional characteristics as determined by quantification of inflammatory T-cell and neutrophil influx, apoptotic and necrotic cell death, and collagen content. In vitro studies confirmed a significant defect in modified lipoprotein endocytosis by p55 TNFR knock-out macrophages due to reduced scavenger receptor class A expression. Interestingly, plasma cytokine/chemokine profile analysis indicated that monocyte chemoattractant protein-1 (MCP-1) levels, a major chemokine involved in atherogenesis, were consistently and significantly lower in p55 TNFR knock-out transplanted mice compared with controls, before and after high fat feeding.p55 TNFR expression in bone marrow-derived cells contributes to the development of atherosclerosis by enhancing lesional foam cell formation and by promoting the expression of pro-atherosclerotic chemokines such as MCP-1.
Decreased susceptibility of leukemic cells with PIG-Amutation to natural killer cells in vitro
Authors: Shoichi Nagakura, Sonoko Ishihara, Daniel E. Dunn, Jun-ichi Nishimura, Tatsuya Kawaguchi, Kentaro Horikawa, Michihiro Hidaka, Tadashi Kagimoto, Nozomu Eto, Hiroaki Mitsuya, Taroh Kinoshita, Neal S. Young, Hideki Nakakuma
Journal: Blood (2002)
Effects of CTLA4-Ig on monocyte/macrophage differentiation and cytokine production
Authors: M. J. Martinez-Calatrava, J. Zwerina, R. Bragado, A. L. Corbi, R. Largo, G. Schett, G. Herrero-Beaumont
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> Cytotoxic T lymphocyte antigen 4 (CTLA4) is a surface protein on T lymphocytes that binds to the surface of antigen-presenting cells through the CD80/86 molecules regulating their co-stimulation. The authors hypothesised that Abatacept (CTLA4-Ig) might bind to monocyte/macrophages regulating the differentiation of monocytes to macrophages, and the production of pro-inflammatory and anti-inflammatory cytokines by macrophages. <h3>Material and methods</h3> Human peripheral blood mononuclear cells were isolated from buffy coats from four normal donors by Ficoll gradient cell separation. Then, monocytes were purified by CD14 positive selection, and they were differentiated in vitro to classic and alternative macrophages by culturing in the presence of granulocyte-macrophage colony stimulating factor or macrophage-colony stimulating factor (M-CSF) respectively. The authors analysed the CTLA4-Ig binding to classic and alternative macrophages by flow cytometry. After demonstrating that CTLA4-Ig binds to classic and alternative macrophages, the effect of CTLA4-Ig on macrophage differentiation and cytokines production were tested. <h3>Results</h3> CTLA4-Ig binds to human macrophages. In addition, CTLA4-Ig reduced, in a dose-dependent fashion, the macrophage differentiation in monocytes cultures stimulated with M-CSF. This results did not evidence any effect of CTLA4-Ig on the IL-10 or tumour necrosis factor production by neither classical nor alternative macrophages. <h3>Conclusion</h3> These data show that CTLA4-Ig directly affects macrophage differentiation in vitro. Therefore, the beneficial effect of Abatacept in rheumatoid arthritis patients could be achieved at least partially through a direct mechanism of action on the monocyte/macrophage line cell.
Pilot series of radiofrequency ablation of Barrett’s esophagus with or without neoplasia
Authors: J. Hernandez, S. Reicher, D. Chung, B. Pham, F. Tsai, G. Disibio, S. French, V. Eysselein
Journal: Endoscopy (2008)

Radiofrequency ablation is a rapidly evolving therapeutic modality for Barrett's esophagus. The aim of this ongoing 12-month trial is to assess Barrett's esophagus eradication after radiofrequency ablation using a balloon-based (HALO-360) and a plate-based (HALO-90) device. We report here our experience with the first 10 patients (out of 40) who have completed 12 months of follow-up.Following radiofrequency ablation using the HALO-360 device all patients were maintained on double-dose proton pump inhibitor therapy. Endoscopic evaluation was performed at 3 and 12 months postablation. Patients with residual Barrett's esophagus at 3 months underwent repeat ablation. Ten patients, seven with nondysplastic Barrett's esophagus, two with low-grade and one with high-grade dysplasia have completed the study to date.Complete Barrett's esophagus eradication was achieved in seven patients, and partial eradication was achieved in three. There were no major complications. One case of buried Barrett's metaplasia was encountered and successfully re-ablated, with complete Barrett's esophagus eradication achieved at 12 months.In this study, Barrett's eradication rates were comparable to previously published reports. One case of buried Barrett's metaplasia was identified out of 247 biopsies and was eradicated with repeat ablation.
Molecular Mechanisms Underlying Ionic Remodeling in a Dog Model of Atrial Fibrillation
Authors: Lixia Yue, Peter Melnyk, Rania Gaspo, Zhiguo Wang, Stanley Nattel
Journal: Circulation Research (1999)

Abstract —The rapid atrial rate during atrial fibrillation (AF) decreases the ionic current density of transient outward K + current, L-type Ca 2+ current, and Na + current, thereby altering cardiac electrophysiology and promoting arrhythmia maintenance. To assess possible underlying changes in cardiac gene expression, we applied competitive reverse transcriptase–polymerase chain reaction to quantify mRNA concentrations in dogs subjected to 7 (group P7 dogs) or 42 (group P42 dogs) days of atrial pacing at 400 bpm and in sham controls. Rapid pacing reduced mRNA concentrations of Kv4.3 (putative gene encoding transient outward K + current; by 60% in P7 and 74% in P42 dogs; P &lt;0.01 and P &lt;0.001, respectively, versus shams), the α 1c subunit of L-type Ca 2+ channels (by 57% in P7 and 72% in P42 dogs; P &lt;0.01 versus shams for each) and the α subunit of cardiac Na + channels (by 18% in P7 and 42% in P42; P =NS and P &lt;0.01, respectively, versus shams) genes. The observed changes in ion channel mRNA concentrations paralleled previously measured changes in corresponding atrial ionic current densities. Atrial tachycardia did not affect mRNA concentrations of genes encoding delayed or Kir2.1 inward rectifier K + currents (of which the densities are unchanged by atrial tachycardia) or of the Na + ,Ca 2+ exchanger. Western blot techniques were used to quantify protein expression for Kv4.3 and Na + channel α subunits, which were decreased by 72% and 47%, respectively, in P42 dogs ( P &lt;0.001 versus control for each), in a manner quantitatively similar to measured changes in mRNA and currents, whereas Na + ,Ca 2+ exchanger protein concentration was unchanged. We conclude that chronic atrial tachycardia alters atrial ion channel gene expression, thereby altering ionic currents in a fashion that promotes the occurrence of AF. These observations provide a potential molecular basis for the self-perpetuating nature of AF.
A recombinant human enzyme for enhanced interstitial transport of therapeutics
Authors: L.H. Bookbinder, A. Hofer, M.F. Haller, M.L. Zepeda, G.-A. Keller, J.E. Lim, T.S. Edgington, H.M. Shepard, J.S. Patton, G.I. Frost
Journal: Journal of Controlled Release (2006)
Abstract P2-10-08: Understanding potential gaps in treatment discussions between caregivers/patients with advanced breast cancer and oncologists
Authors: Musa Mayer, Helen L Coons, Stephen Jones, Deana Percassi
Journal: Cancer Research (2015)

Abstract Approximately 232,670 cases of breast cancer will be diagnosed in the US in 2014, of which 86,088 (37%) cases will involve cancer that has spread regionally or metastasized. The 2013 Global Count Us, Know Us, Join Us survey found that 53% of women with advanced breast cancer (ABC; breast cancer that has spread to distant parts of the body) surveyed in the US wish they had more time to discuss their needs during clinic visits, and 60% believe their cancer treatment options are limited. To better understand unmet patient needs and potential communication gaps in treatment discussions with physicians, surveys were developed for women with ABC, their caregivers, and oncologists. The Make Your Dialogue Count survey will be conducted online, by paper, and by telephone in the US from June through August 2014. Survey respondents must be (1) women ≥21 years of age diagnosed with ABC; (2) their caregivers who attend at least half the clinic visits; or (3) licensed US medical oncologists who treat ≥5 women with ABC per month. Patient and caregiver data were not weighted. Oncologist data regarding geographic region and years in practice by gender were weighted to align with actual proportions in the population. Final results of the full survey are expected by September 30, 2014. The Make Your Dialogue Count survey will explore issues such as the emotional impact of diagnosis of ABC; the doctor-patient relationship, including the quality of communications and information exchange during clinic visits; and the effect of side effects on treatment choice and satisfaction, from the perspectives of patients, their caregivers, and oncologists. Findings from the Make Your Dialogue Count survey will provide insight into the doctor-patient relationship from multiple perspectives. Comparing responses given by patients, caregivers, and oncologists can identify potential communication gaps that could be affecting the quality of care provided. Considering the number of women living with ABC, our findings could help oncologists to meet the emotional and informational needs of their patients, and provide patients with the supportive treatment environment they seek and the most relevant disease and treatment information possible. Citation Format: Musa Mayer, Helen L Coons, Stephen Jones, Deana Percassi. Understanding potential gaps in treatment discussions between caregivers/patients with advanced breast cancer and oncologists [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-10-08.
William Lees Price Sir Douglas Ranger Keith William Reynolds Alastair Irvine Gordon Robertson Basil Roebuck Nigel Richard Saunders Harold Schnieden Edward Theodore Shennan Alan Sopwith Simpson Kenneth Swire Southam James Maryons ("Jim") Stansfeld Edmund Louis Ward Henry Robin Watson-Baker Anthony John White
Authors: J. Cochrane, L P Le Quesne, J. Pendower, L. Kaufman, J. Walton, M. Muers, J. Stewart, V. Schnieden, D W K Evans, A. S Simpson, D. Wilkins, L. Stansfeld, A W Craft, A E Ward, C B Willey, G. White
Journal: BMJ (1998)

He came from a medical family and began his career in general practice.During the war he served in the Royal Army Medical Corps and was based in the Middle East, where he specialised in anaesthetics.After demobilisation he continued with this and returned to take up various hospital appointments in Birmingham.
Arnold Appleby Alasdair Patrick Barden Benjamin Tillett Davis William Ferguson Kenneth Macrae Leighton Harry Naftali Levitt Frederick ("Fred") Smart Melville Kevin Lorne Merrett John Sinclair Miller Herbert Jan Penkala Philip Vernon Reading
Authors: V L McAllister, M. Walker, E. Barden, P. G. Bevan, A. Valle, J. M Ferries, D. Munro, D. Levitt, D. W Melville, A. Mahoney, P. Young, B. Thom, A. Penkala, O H Shaheen
Journal: BMJ (1998)

He trained in radiology after serving in the Royal Navy during the Korean war.A dedicated, highly skilled radiologist, Arnold contributed much