tbuckley/cabot-search huggingface dataset:
Chemoimmunotherapy With Fludarabine, Cyclophosphamide, and Rituximab for Relapsed and Refractory Chronic Lymphocytic Leukemia
Authors: William Wierda, Susan O’Brien, Sijin Wen, Stefan Faderl, Guillermo Garcia-Manero, Deborah Thomas, Kim-Anh Do, Jorge Cortes, Charles Koller, Miloslav Beran, Alessandra Ferrajoli, Francis Giles, Susan Lerner, Maher Albitar, Hagop Kantarjian, Michael Keating
Journal: Journal of Clinical Oncology (2005)

The efficacy, toxicity, and tolerability of chemoimmunotherapy with the combination of fludarabine, cyclophosphamide, and rituximab (FCR) were evaluated in previously treated patients with chronic lymphocytic leukemia (CLL). The purpose of this study was to improve the complete remission (CR) rate for previously treated patients and evaluate the quality of bone marrow response.One hundred seventy-seven previously treated patients with CLL were evaluated. Treatment consisted of rituximab 375 mg/m(2) day 1 of course 1 and 500 mg/m(2) day 1 of courses 2 to 6; fludarabine 25 mg/m(2)/d days 2 to 4 of course 1 and days 1 to 3 of courses 2 to 6; and cyclophosphamide 250 mg/m(2)/d days 2 to 4 of course 1 and days 1 to 3 of courses 2 to 6. Courses were repeated every 4 weeks.CR was achieved in 25% of 177 patients, and nodular partial remission and partial remission were achieved in 16% and 32% of patients, respectively; the overall response rate was 73%. Twelve (32%) of 37 complete responders tested achieved molecular remission in bone marrow. Univariate and multivariate analyses were used to identify pretreatment patient characteristics associated with CR and overall remission, longer time to progression, and overall survival.The FCR regimen was an active and well-tolerated treatment for previously treated patients with CLL. Myelosuppression was the most common toxicity. FCR induced the highest CR rate reported in a clinical trial of previously treated patients with CLL. Furthermore, molecular remissions were achieved in a third of patients achieving CR.
Allografting with nonmyeloablative conditioning following cytoreductive autografts for the treatment of patients with multiple myeloma
Authors: David G. Maloney, Arthur J. Molina, Firoozeh Sahebi, Keith E. Stockerl-Goldstein, Brenda M. Sandmaier, William Bensinger, Barry Storer, Ute Hegenbart, George Somlo, Thomas Chauncey, Benedetto Bruno, Frederick R. Appelbaum, Karl G. Blume, Stephen J. Forman, Peter McSweeney, Rainer Storb
Journal: Blood (2003)
Myocardial microvascular function during acute coronary artery stenosis: effect of hypertension and hypercholesterolaemia
Authors: X.-Y. Zhu, E. Daghini, A. R. Chade, D. Versari, J. D. Krier, K. B. Textor, A. Lerman, L. O. Lerman
Journal: Cardiovascular Research (2009)

AimsCoronary collateral arteries (CCA) reduce cardiovascular events. We tested the hypothesis that new microvessels that proliferate in early atherosclerosis may be associated with myocardial protection during acute subtotal coronary artery obstruction (CAO).
Functional membrane androgen receptors in colon tumors trigger pro-apoptotic responses in vitro and reduce drastically tumor incidence in vivo
Authors: Shuchen Gu, Natalia Papadopoulou, Eva-Maria Gehring, Omaima Nasir, Konstantinos Dimas, Shefalee K Bhavsar, Michael Föller, Konstantinos Alevizopoulos, Florian Lang, Christos Stournaras
Journal: Molecular Cancer (2009)

Abstract Background Membrane androgen receptors (mAR) have been implicated in the regulation of cell growth, motility and apoptosis in prostate and breast cancer. Here we analyzed mAR expression and function in colon cancer. Results Using fluorescent mAR ligands we showed specific membrane staining in colon cell lines and mouse xenograft tumor tissues, while membrane staining was undetectable in healthy mouse colon tissues and non-transformed intestinal cells. Saturation/displacement assays revealed time- and concentration-dependent specific binding for testosterone with a K D of 2.9 nM. Stimulation of colon mAR by testosterone albumin conjugates induced rapid cytoskeleton reorganization and apoptotic responses, even in the presence of anti-androgens. The actin cytoskeleton drug cytochalasin B effectively inhibited the pro-apoptotic responses and caspase-3 activation. Interestingly, in vivo studies revealed that mAR activation resulted in a 65% reduction of tumor incidence in chemically induced Balb/c mice colon tumors. Conclusion Our results demonstrate for the first time that functional mARs are predominantly expressed in colon tumors and that their activation results in induction of anti-tumor responses in vitro and extensive reduction of tumor incidence in vivo .
Functional Data Analysis Applied to a Randomized Controlled Clinical Trial in Hemodialysis Patients Describes the Variability of Patient Responses in the Control of Renal Anemia
Authors: Robert M. West, Katie Harris, Mark S. Gilthorpe, Cae Tolman, Eric J. Will
Journal: Journal of the American Society of Nephrology (2007)

The achievement of desirable hemoglobin levels in renal anemia that is treated with epoetins is often incomplete and subject to much variation of outcome values and applied dosage. The further development of clinical decision support for renal anemia requires the characterization of patient responses and an analysis of the dynamics of the dosage and response variables. In this methodologic article, the extended data of a randomized, controlled clinical trial comparing two epoetins were examined by the techniques of functional data analysis to establish how precisely the patterns of treatment response might be described and analyzed. The description of the trajectory of hemoglobin values in each patient as a mathematical function allowed the characterization of individual responses, with a wide variety of patterns being revealed. An analysis of the degree of system control in the management of the anemia was then possible through phase plotting. The analysis also allowed an expression of the dynamic characteristics of the entire experimental system, analyzed in summary group waveforms with standard statistical properties. In addition, a quantification of the notional instability of patient responses enabled the determination of a subset of patients for whom control might be improved in a modified management system. It is concluded that functional data analysis does provide the basis for further characterization and experimental study of the control of renal anemia.
Bone marrow reconstitution after high-dose chemotherapy and autologous peripheral blood progenitor cell transplantation: Effect of graft size
Authors: E. van der Wall, D.J. Richel, M.J. Holtkamp, I.C.M. Slaper-Cortenbach, C.E. van der Schoot, O. Dalesio, W.J. Nooijen, J.H. Schornagel, S. Rodenhuis
Journal: Annals of Oncology (1994)
β<sub>2</sub>-Receptor Polymorphisms in Patients Receiving Salmeterol with or without Fluticasone Propionate
Authors: Eugene R. Bleecker, Harold S. Nelson, Monica Kraft, Jonathan Corren, Deborah A. Meyers, Steven W. Yancey, Wayne H. Anderson, Amanda H. Emmett, Hector G. Ortega
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: Retrospective pharmacogenetic studies have questioned whether patients with asthma who are arginine homozygous at the β2-adrenergic receptor (position 16) should use long-acting β-agonists.Objectives: To examine whether the response to salmeterol alone or in combination with an inhaled corticosteroid is influenced by β- receptor polymorphisms.Methods: Subjects using only as-needed albuterol were screened and completed two sequential open-label run-in periods (8 wk on as-needed albuterol; 8 wk on as-needed ipratropium). Five hundred forty-four subjects were randomized by Arg16Gly genotype to salmeterol alone or with fluticasone propionate for 16 weeks. Change from baseline in morning peak expiratory flow was the primary endpoint.Measurements and Main Results: Lung function responses were sustained over treatment and no statistically significant changes from baseline between genotypes within treatments were observed. Overall mean changes in morning peak flow for salmeterol with fluticasone propionate were 32.6 L/min (Arg/Arg vs. Gly/Gly, 95% confidence interval [CI], −6.3, 22.1), 25.9 L/min (Arg/Arg vs. Arg/Gly, 95% CI, −7.1, 21.3), and 24.9 L/min (Arg/Gly vs. Gly/Gly, 95% CI, −13.0, 14.6), and for salmeterol alone were 19.4 L/min (Arg/Arg vs. Gly/Gly, 95% CI, −1.7, 21.4), 24.6 L/min (Arg/Arg vs. Arg/Gly, 95% CI, −13.0, 10.6), and 12.4 L/min (Arg/Gly vs. Gly/Gly, 95% CI, −0.2, 22.3) for Arg/Arg, Arg/Gly, and Gly/Gly genotypes, respectively. Other measures of asthma control showed similar responses.Conclusions: The results showed no evidence of a pharmacogenetic effect of β-receptor variation on salmeterol response.Clinical trial registered with www.clinicaltrials.gov (NCT 00102882).
Polysomy 17 in Breast Cancer: Clinicopathologic Significance and Impact on HER-2 Testing
Authors: Isabelle Vanden Bempt, Peter Van Loo, Maria Drijkoningen, Patrick Neven, Ann Smeets, Marie-Rose Christiaens, Robert Paridaens, Christiane De Wolf-Peeters
Journal: Journal of Clinical Oncology (2008)

Polysomy 17 is frequently found in breast cancer and may complicate the interpretation of HER-2 testing results. We investigated the impact of polysomy 17 on HER-2 testing and studied its clinicopathologic significance in relation to HER2 gene amplification.In 226 patients with primary invasive breast carcinoma, HER2 gene and chromosome 17 copy numbers were determined by dual-color fluorescent in situ hybridization (FISH). The interpretation of FISH results was based on either absolute HER2 gene copy number or the ratio HER2/chromosome 17. Results were correlated with HER-2 protein expression on immunohistochemistry (IHC), HER2 mRNA expression by reverse transcriptase polymerase chain reaction (RT-PCR), and with various clinicopathologic parameters.All cases with an equivocal HER-2 result by FISH, either by absolute HER2 copy number (44 of 226 patients; 19.5%) or by the ratio HER2/chromosome 17 (three of 226 patients; 1.3%), displayed polysomy 17. On its own, polysomy 17 was not associated with HER-2 overexpression on IHC or increased HER2 mRNA levels by RT-PCR. Moreover, and in contrast with HER2 gene amplification, polysomy 17 was not associated with high tumor grade, hormone receptor negativity, or reduced disease-free survival.Polysomy 17 affects HER-2 testing in breast cancer and is a major cause of equivocal results by FISH. We show that tumors displaying polysomy 17 in the absence of HER2 gene amplification resemble more HER-2-negative than HER-2-positive tumors. These findings highlight the need for clinical trials to investigative whether polysomy 17 tumors benefit from HER-2-targeted therapy.
Matching of oligoclonal immunoglobulin transcriptomes and proteomes of cerebrospinal fluid in multiple sclerosis
Authors: Birgit Obermeier, Reinhard Mentele, Joachim Malotka, Josef Kellermann, Tania Kümpfel, Hartmut Wekerle, Friedrich Lottspeich, Reinhard Hohlfeld, Klaus Dornmair
Journal: Nature Medicine (2008)
Psychiatric Disorders: A Conceptual Taxonomy
Authors: Peter Zachar, Kenneth S. Kendler
Journal: American Journal of Psychiatry (2007)

This article summarizes six conceptual dimensions that underlie common assumptions about what counts as an adequate category of psychiatric disorder. These dimensions are 1) causalism-descriptivism, 2) essentialism-nominalism, 3) objectivism-evaluativism, 4) internalism-externalism, 5) entities-agents, and 6) categories-continua. Four different versions of the medical model are described and compared with respect to these dimensions. The medical models vary in several ways, but all can be considered “essentialistic.” As a counter to the essentialist homogeneity among the medical models, two nominalist analyses of psychiatric classification are reviewed. In order to fill out the space defined by the conceptual dimensions, two alternatives to medical model approaches are also described. After making some suggestions about where DSM-V might best be aligned with respect to the conceptual dimensions, the authors review the distinction between empirical and nonempirical aspects of classification—and argue that nonempirical aspects of classification are legitimate and necessary.
Human bile contains MicroRNA-laden extracellular vesicles that can be used for cholangiocarcinoma diagnosis
Authors: Ling Li, David Masica, Masaharu Ishida, Ciprian Tomuleasa, Sho Umegaki, Anthony N. Kalloo, Christos Georgiades, Vikesh K. Singh, Mouen Khashab, Stuart Amateau, Zhiping Li, Patrick Okolo, Anne-Marie Lennon, Payal Saxena, Jean-Francois Geschwind, Todd Schlachter, Kelvin Hong, Timothy M. Pawlik, Marcia Canto, Joanna Law, Reem Sharaiha, Clifford R. Weiss, Paul Thuluvath, Michael Goggins, Eun Ji Shin, Haoran Peng, Vivek Kumbhari, Susan Hutfless, Liya Zhou, Esteban Mezey, Stephen J. Meltzer, Rachel Karchin, Florin M. Selaru
Journal: Hepatology (2014)

Cholangiocarcinoma (CCA) presents significant diagnostic challenges, resulting in late patient diagnosis and poor survival rates. Primary sclerosing cholangitis (PSC) patients pose a particularly difficult clinical dilemma because they harbor chronic biliary strictures that are difficult to distinguish from CCA. MicroRNAs (miRs) have recently emerged as a valuable class of diagnostic markers; however, thus far, neither extracellular vesicles (EVs) nor miRs within EVs have been investigated in human bile. We aimed to comprehensively characterize human biliary EVs, including their miR content. We have established the presence of extracellular vesicles in human bile. In addition, we have demonstrated that human biliary EVs contain abundant miR species, which are stable and therefore amenable to the development of disease marker panels. Furthermore, we have characterized the protein content, size, numbers, and size distribution of human biliary EVs. Utilizing multivariate organization of combinatorial alterations (MOCA), we defined a novel biliary vesicle miR-based panel for CCA diagnosis that demonstrated a sensitivity of 67% and specificity of 96%. Importantly, our control group contained 13 PSC patients, 16 with biliary obstruction of varying etiologies (including benign biliary stricture, papillary stenosis, choledocholithiasis, extrinsic compression from pancreatic cysts, and cholangitis), and 3 with bile leak syndromes. Clinically, these types of patients present with a biliary obstructive clinical picture that could be confused with CCA. Conclusion : These findings establish the importance of using extracellular vesicles, rather than whole bile, for developing miR-based disease markers in bile. Finally, we report on the development of a novel bile-based CCA diagnostic panel that is stable, reproducible, and has potential clinical utility. (Hepatology 2014;60:896–907)
Diet and Breast Cancer: Evidence That Extremes in Diet Are Associated With Poor Survival
Authors: Pamela J. Goodwin, Marguerite Ennis, Kathleen I. Pritchard, Jarley Koo, Maureen E. Trudeau, Nicky Hood
Journal: Journal of Clinical Oncology (2003)

Purpose: Diet has been postulated to influence breast cancer prognosis; however, existing evidence is weak and inconsistent. Previous studies have sought evidence of a linear relationship between diet and breast cancer outcomes. Because of a U-shaped association of body mass index (BMI) with survival in breast cancer, we hypothesized that a nonlinear association also existed for dietary variables. Patients and Methods: Four hundred seventy-seven women with surgically resected T1 to T3, N0/1, M0 breast cancer completed the Block Food Frequency Questionnaire 9.3 ± 4.6 weeks (mean ± standard deviation) after diagnosis, reporting intake over the preceding 12 months. Data on tumor-related factors, treatment, and outcomes were obtained prospectively from medical records. A series of Cox models was performed, modeling the association of dietary factors with breast cancer survival linearly and quadratically, adjusting for total energy intake, tumor- and treatment-related variables, and BMI. Results: Significant nonlinear survival associations were found for protein, oleic acid, cholesterol, polyunsaturated-saturated fat ratio, and for percentage of calories from fat and percentage of calories from carbohydrates in multivariate models. The shape of the survival associations varied across nutrients. Hazard ratios for highest risk quintiles ranged from 2.1 to 6.5. For total fat, adjustment for BMI reduced the multivariate P value obtained from nonlinear Cox models from .05 to .10. No significant linear associations were identified. Conclusion: The association of key dietary variables with breast cancer survival may be U-shaped rather than linear. Our data suggest that midrange intake of most major energy sources is associated with the most favorable outcomes, and extremes are associated with less favorable outcomes.
Cough frequency and cough receptor sensitivity to citric acid challenge during a simulated ascent to extreme altitude
Authors: NP Mason, PW Barry, G Despiau, B Gardette, JP Richalet
Journal: European Respiratory Journal (1999)

The aim of this study was to determine the frequency of cough and the citric acid cough threshold during hypobaric hypoxia under controlled environmental conditions. Subjects were studied during Operation Everest 3. Eight subjects ascended to a simulated altitude of 8,848 m over 31 days in a hypobaric chamber. Frequency of nocturnal cough was measured using voice-activated tape recorders, and cough threshold by inhalation of increasing concentrations of citric acid aerosol. Spirometry was performed before and after each test. Subjects recorded symptoms of acute mountain sickness and arterial oxygen saturation daily. Air temperature and humidity were controlled during the operation. Cough frequency increased with increasing altitude, from a median of 0 coughs (range 0-4) at sea level to 15 coughs (range 3-32) at a simulated altitude of 8,000 m. Cough threshold was unchanged on arrival at 5,000 m compared to sea level (geometric mean difference (GMD) 1.0, 95% confidence intervals (CI) 0.5-2.1, p=0.5), but fell on arrival at 8,000 m compared to sea level (GMD 3.3, 95% CI 1.1-10.3, p=0.043). There was no relationship between cough threshold and symptoms of acute mountain sickness, oxygen saturation or forced expiratory volume in one second. Temperature and humidity in the chamber were controlled between 18-24 degrees C and 30-60%, respectively. These results confirm an increase in cough frequency and cough receptor sensitivity associated with hypobaric hypoxia, and refute the hypothesis that high altitude cough is due to the inhalation of cold, dry air. The small sample size makes further conclusions difficult, and the cause of altitude-related cough remains unclear.
A Psychiatric Epidemiological Study of Postpartum Chinese Women
Authors: Dominic T.S. Lee, Alexander S.K. Yip, Helen F.K. Chiu, Tony Y.S. Leung, Tony K.H. Chung
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Epidemiological studies in the 1980s have suggested that depression is rare in the Chinese population and there is no postpartum depression among Chinese women. However, subsequent small-scale studies of postpartum depression in China have yielded contradictory and inconsistent findings. Furthermore, after two decades of profound socioeconomic transformation, depression may no longer be rare in the contemporary population. The authors conducted a psychiatric epidemiological study among postpartum Chinese women using rigorous methodology and a representative sample. METHOD: A total of 959 consecutive women were recruited at the antenatal clinic of a university hospital in Hong Kong. At 3 months postpartum, the prevalence and incidence rates of depression were measured with a two-phase design. The participants were first stratified by means of the 12-item General Health Questionnaire. Subsequently, all high scorers and 10% of low scorers were assessed with the nonpatient version of the Structured Clinical Interview for DSM-III-R. The 1-month and 3-month prevalence and incidence rates were estimated by using reverse weighting. RESULTS: The 1-month prevalence rates for major and minor depression were 5.5% and 4.7%, respectively. At 3 months, the corresponding prevalence rates were 6.1% and 5.1%. Together, 13.5% of the participants suffered from one or more forms of psychiatric disorder in the first 3 months postpartum. CONCLUSIONS: Postpartum depression is common among contemporary Chinese women. A universal postpartum depression-screening program would be useful for early detection. Our data suggest that depression may no longer be rare in the Chinese population.
High association of mycobacterial infections with polymyositis in a non-endemic country for tuberculosis
Authors: A. Airio, M. Kauppi, H. Kautiainen, M. Hakala, V. Kinnula
Journal: Annals of the Rheumatic Diseases (2007)

consistent with the competitive inhibition of glucosamine by glucose for transport from the gastrointestinal tract.Furthermore, higher serum levels might be expected because glucose would competitively inhibit the uptake of glucosamine into the liver, thus allowing a higher concentration of glucosamine to enter the peripheral circulation.We do not believe that the minimal raising or extending glucosamine levels would be of significant therapeutic benefit.
DNA aneuploidy in ulcerative colitis.
Authors: J B Fozard, P Quirke, M F Dixon, G R Giles, C C Bird
Journal: Gut (1986)

The prevalence of deoxyribonucleic acid (DNA) aneuploidy in 297 samples from 38 patients with ulcerative colitis of varying duration was investigated by flow cytometry. In 12 patients colitis was complicated by the development of colorectal carcinoma: one had three synchronous carcinomas. Only four of 14 carcinomas were DNA aneuploid. Deoxyribonucleic acid aneuploidy occurred focally in the colorectal mucosa in the presence and absence of carcinoma: rates of aneuploidy (67% in cancer patients and 42% in non-cancer patients), were not significantly different (chi 2 = 1.0962, p = 0.295). A higher rate of DNA aneuploidy was found in dysplastic tissues (21%) compared with non-dysplastic tissues (15%), but again these differences did not reach statistical significance (chi 2 = 1.0747, p = 0.299). Deoxyribonucleic acid aneuploidy and dysplastic change occurred more often with increasing duration of ulcerative colitis (p less than 0.001, p less than 0.005 respectively). We conclude that flow cytometric analysis of cellular DNA content should not replace present morphological methods of assessment of premalignancy in ulcerative colitis, but may be a useful adjunct in the identification of abnormal mucosa.
Deafness Following Standard Intravenous Dose of Ethacrynic Acid
Authors: W. Delano Meriwether
Journal: JAMA (1971)

Two nonuremic patients experienced neurosensory hearing loss after the intravenous administration of standard doses of ethacrynic acid. Both were receiving nontoxic doses of aminoglycoside antibiotics concurrently. Total deafness occurred within 15 minutes of the administration of ethacrynic acid and was not accompanied by vertigo, nausea, or vomiting. The impairment of hearing was clearly transient in one patient. In the other patient, results of histologic examination of the inner ear at the time of autopsy were normal.
Recognition of continuous speech requires top-down processing
Authors: Kenneth N. Stevens
Journal: Behavioral and Brain Sciences (2000)

The proposition that feedback is never necessary in speech recognition is examined for utterances consisting of sequences of words. In running speech the features near word boundaries are often modified according to language-dependent rules. Application of these rules during word recognition requires top-down processing. Because isolated words are not usually modified by rules, their recognition could be achieved by bottom-up processing only.