tbuckley/cabot-search huggingface dataset:
We Should Desist Using RECIST, at Least in GIST
Authors: Robert S. Benjamin, Haesun Choi, Homer A. Macapinlac, Michael A. Burgess, Shreyaskumar R. Patel, Lei L. Chen, Donald A. Podoloff, Chuslip Charnsangavej
Journal: Journal of Clinical Oncology (2007)

Response Evaluation Criteria in Solid Tumors (RECIST) are insensitive in evaluating imatinib-treated gastrointestinal stromal tumors (GISTs). Response by Choi criteria, a 10% decrease in size or a 15% decrease in density on contrast-enhanced CT, correlated well in a small training set of patients who showed response as measured by positron emission tomography, and was more predictive of time to tumor progression (TTP) than response by RECIST. This study was designed to validate these observations in an independent data set.Fifty-eight patients with imatinib-treated GISTs were evaluated by RECIST and Choi criteria. TTP was compared with TTP in the training set. Patients were analyzed initially with follow-up to 28 months, extended to 60 months for survival analysis.Patients who met Choi response criteria on CT at 2 months had significantly better TTP than those who did not (P = .0002), whereas response group by RECIST was not significantly correlated with TTP. Even when the 98 patients from both sets were analyzed together, the response group by RECIST did not correlate significantly with TTP, whereas response group by Choi criteria did correlate significantly with TTP. Disease-specific survival (DSS) was also significantly correlated with response group by Choi criteria (P = .04), but not with response group by RECIST.Choi response criteria are reproducible, more sensitive, and more precise than RECIST in assessing the response of GISTs to imatinib mesylate. Response by Choi criteria, unlike response by RECIST, correlates significantly with TTP and DSS. Response by Choi criteria should be incorporated routinely into future studies of GIST therapy. We should desist using RECIST, at least in GIST.
180-W XPS GreenLight Laser Vaporisation Versus Transurethral Resection of the Prostate for the Treatment of Benign Prostatic Obstruction: 6-Month Safety and Efficacy Results of a European Multicentre Randomised Trial—The GOLIATH Study
Authors: Alexander Bachmann, Andrea Tubaro, Neil Barber, Frank d’Ancona, Gordon Muir, Ulrich Witzsch, Marc-Oliver Grimm, Joan Benejam, Jens-Uwe Stolzenburg, Antony Riddick, Sascha Pahernik, Herman Roelink, Filip Ameye, Christian Saussine, Franck Bruyère, Wolfgang Loidl, Tim Larner, Nirjan-Kumar Gogoi, Richard Hindley, Rolf Muschter, Andrew Thorpe, Nitin Shrotri, Stuart Graham, Moritz Hamann, Kurt Miller, Martin Schostak, Carlos Capitán, Helmut Knispel, J. Andrew Thomas
Journal: European Urology (2013)
Indium In 113m for Visualizing Body Organs
Authors: E. James Potchen
Journal: JAMA (1968)

Indium In 113m, a generator-produced radionuclide, has been useful as a protein-bound metal and a colloidal aggregate to scan the cardiac blood pool, placenta, liver, spleen, bone marrow, lung, and brain. The wide applicability and ease of preparation in addition to the physical characteristics of this radiopharmaceutical suggest that it may well be the most useful scanning agent devised to date.
Sepsis and spontaneous bacterial peritonitis in Thailand
Authors: Anusak Kerdsin, Surang Dejsirilert, Pathom Sawanpanyalert, Adisorn Boonnark, Wipa Noithachang, Duangdao Sriyakum, Somchai Simkum, Sukenya Chokngam, Marcelo Gottschalk, Yukihiro Akeda, Kazunori Oishi
Journal: The Lancet (2011)
Ibritumomab tiuxetan radioimmunotherapy for patients with relapsed or refractory non-Hodgkin lymphoma and mild thrombocytopenia: a phase II multicenter trial
Authors: Gregory A. Wiseman, Leo I. Gordon, Pratik S. Multani, Thomas E. Witzig, Stewart Spies, Nancy L. Bartlett, Russell J. Schilder, James L. Murray, Mansoor Saleh, Roberta S. Allen, Antonio J. Grillo-López, Christine A. White
Journal: Blood (2002)
A randomized EPOCH vs. CHOP front-line therapy for aggressive non-Hodgkin's lymphoma patients: Long-term results
Authors: H.M. Khaled, Z.K. Zekri, N. Mokhtar, N.M. Ali, T. Darwish, I. Elattar, R. Gaafar, M.S. Moawad
Journal: Annals of Oncology (1999)
Contribution of chronic diseases to disability in elderly people in countries with low and middle incomes: a 10/66 Dementia Research Group population-based survey
Authors: Renata M Sousa, Cleusa P Ferri, Daisy Acosta, Emiliano Albanese, Mariella Guerra, Yueqin Huang, KS Jacob, AT Jotheeswaran, Juan J Llibre Rodriguez, Guillermina Rodriguez Pichardo, Marina Calvo Rodriguez, Aquiles Salas, Ana Luisa Sosa, Joseph Williams, Tirso Zuniga, Martin Prince
Journal: The Lancet (2009)
Interaction of Phosphatidylserine-Phosphatidylcholine Liposomes with Sickle Erythrocytes
Authors: Robert S. Schwartz, Nejat Düzgüneş, Danny Tsun-Yee Chiu, Bertram Lubin
Journal: Journal of Clinical Investigation (1983)

The sickle erythrocyte (RBC) is a pathologic RBC that contains multiple membrane abnormalities. Some of these abnormalities have been implicated in the pathophysiology of vasoocclusive crises characteristic of sickle cell disease; others have yet to be defined in terms of their clinical significance. Recent information has shown that sickle RBC adhere abnormally to cultured endothelial cells yet little is known about the ways in which sickle cells interact with model membranes of defined size and lipid composition. We investigated this phenomenon by interacting sickle RBC with artificial lipid vesicles (liposomes) containing acidic phospholipids. Our results demonstrate that sickle disease (hemoglobin SS) RBC bind more of these liposomes than do normal or sickle trait (hemoglobin AS) RBC and that these differences are accentuated by hypoxia-induced sickling. Binding of liposome phospholipid to sickled RBC was not attributable to phospholipid exchange between liposomes and RBC and was consistent with a mechanism involving both membrane fusion and a stable reversible adhesion of liposomes to the RBC membrane.
Lysis of RNA tumor viruses by human serum: direct antibody-independent triggering of the classical complement pathway.
Authors: N R Cooper, F C Jensen, R M Welsh, M B Oldstone
Journal: The Journal of Experimental Medicine (1976)

In earlier studies we found that human serum, but not serum from multiple other species, inactivated and lysed oncornaviruses from a number of diverse sources in the apparent absence of antibody. A detailed analysis of the role of the human complement (C) system in mediating this lytic process indicates that human C1q interacts directly, in the absence of immunoglobulin, with oncornaviruses. Binding of C1 via C1q in this manner leads to activation of C1r, C1s, and thus of the classical C pathway. Integrity of the classical pathway is an absolute requirement for lysis although activation of the alternative pathway considerably amplifies the amount of lysis obtained, possibly through involvement of the C3b-dependent feedback mechanism. Activation of C is accompanied by deposition of C components on the viral surface and lysis on completion of the C reaction sequence. Thus in this system, the C1q subunit of C1 subserves a specific recognition function normally associated with antibody. This ability of human serum to inactivate oncornaviruses may represent a natural defense mechanism operative in vivo which deters expression of intact oncornaviruses in human malignancies.
Relationship between body size, fill volume, and mass transfer area coefficient in peritoneal dialysis.
Authors: P Keshaviah, P F Emerson, E F Vonesh, J C Brandes
Journal: Journal of the American Society of Nephrology (1994)

A peritoneal dialysate fill volume of 2 L has become the standard of clinical practice, but the relationships between body size, fill volume, and mass transfer area coefficient (KoA) have not been well established. These relationships were studied in 10 stable peritoneal dialysis patients who underwent six peritoneal equilibration studies (2 h each) at fill volumes of 0.5, 1, 1.5, 2, 2.5, and 3 L. The concentration-time profiles for urea, creatinine, and glucose were measured at each fill volume, and residual volumes were calculated from the preceding dwell period. A modified Henderson equation was used to calculate the KoA for the three solutes as a function of fill volume. By normalizing the KoA for each solute to the value at 2 L, the data for all three solutes collapsed onto the same trend line when plotting the normalized KoA versus dialysate volume. Between 0.5- and 2-L fill volumes, the average normalized KoA increases in an almost linear fashion, its value almost doubling over this range. Between 2- and 3-L fill volumes, there is less than a 10% change in the normalized KoA. However, fill volumes for peak urea KoA were found to increase with increasing body surface area (R = 0.76), being around 2.5 L for an average-sized patient and increasing to between 3 and 3.5 L for body surface areas > 2 m2. To maximize solute transport, these relationships between body size, volume, and KoA should be considered when choosing fill volumes for continuous ambulatory peritoneal dialysis and automated peritoneal dialysis and when deciding reserve and tidal volumes for tidal peritoneal dialysis.
Lymphatic regulator PROX1 determines Schlemm’s canal integrity and identity
Authors: Dae-Young Park, Junyeop Lee, Intae Park, Dongwon Choi, Sunju Lee, Sukhyun Song, Yoonha Hwang, Ki Yong Hong, Yoshikazu Nakaoka, Taija Makinen, Pilhan Kim, Kari Alitalo, Young-Kwon Hong, Gou Young Koh
Journal: Journal of Clinical Investigation (2014)

Schlemm’s canal (SC) is a specialized vascular structure in the eye that functions to drain aqueous humor from the intraocular chamber into systemic circulation. Dysfunction of SC has been proposed to underlie increased aqueous humor outflow (AHO) resistance, which leads to elevated ocular pressure, a factor for glaucoma development in humans. Here, using lymphatic and blood vasculature reporter mice, we determined that SC, which originates from blood vessels during the postnatal period, acquires lymphatic identity through upregulation of prospero homeobox protein 1 (PROX1), the master regulator of lymphatic development. SC expressed lymphatic valve markers FOXC2 and integrin α9 and exhibited continuous vascular endothelial–cadherin (VE-cadherin) junctions and basement membrane, similar to collecting lymphatics. SC notably lacked luminal valves and expression of the lymphatic endothelial cell markers podoplanin and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1). Using an ocular puncture model, we determined that reduced AHO altered the fate of SC both during development and under pathologic conditions; however, alteration of VEGF-C/VEGFR3 signaling did not modulate SC integrity and identity. Intriguingly, PROX1 expression levels linearly correlated with SC functionality. For example, PROX1 expression was reduced or undetectable under pathogenic conditions and in deteriorated SCs. Collectively, our data indicate that PROX1 is an accurate and reliable biosensor of SC integrity and identity.
<i>BRAF</i> Gene Is Somatically Mutated but Does Not Make a Major Contribution to Malignant Melanoma Susceptibility: The Italian Melanoma Intergroup Study
Authors: Milena Casula, Maria Colombino, Maria P. Satta, Antonio Cossu, Paolo A. Ascierto, Giovanna Bianchi-Scarrà, Daniele Castiglia, Mario Budroni, Carla Rozzo, Antonella Manca, Amelia Lissia, Annangela Carboni, Elisabetta Petretto, Sabrina M.R. Satriano, Gerardo Botti, Michela Mantelli, Paola Ghiorzo, Michael R. Stratton, Francesco Tanda, Giuseppe Palmieri
Journal: Journal of Clinical Oncology (2004)

Purpose Oncogenic activation of the BRAF gene has been demonstrated to be involved in the pathogenesis of malignant melanoma (MM). In this study, we investigated the contribution of BRAF to melanoma susceptibility, also making a comparison with frequency of CDKN2A germline mutations in MM patients from different areas in Italy. Patients and Methods Using a combination of denaturing high-performance liquid chromatography analysis and automated sequencing on genomic DNA from peripheral blood or tumor tissue samples, 569 MM patients (211 from northern Italy and 358 from southern Italy) were screened for BRAF mutations. Results Three BRAF germline sequence variants (M116R, V599E, and G608H) were identified in four (0.7%) of 569 MM patients. The most common BRAF mutation, V599E, was detected in one germline DNA sample only; M116R and G608H were newly described mutations. A high frequency (59%) of BRAF mutations was instead observed in tumor samples from patients also undergoing germline DNA analysis; at the somatic level, substitution of valine 599 was found to account for the majority (88%) of BRAF mutations. We then estimated the germline mutation rates in BRAF and CDKN2A among 358 consecutively collected patient samples originating in southern Italy; a low (2.5%) or very low (0.29%) prevalence of CDKN2A and BRAF mutations, respectively, was detected. Conclusion Mutation analysis of either blood DNA from a large collection of MM patients or matched MM tissues from a subset of such patients revealed that BRAF is somatically mutated and does not play a major role in melanoma susceptibility. The present study further suggests that patient origin may account for different mutation rates in candidate genes.
Human macrophage inflammatory protein alpha (MIP-1 alpha) and MIP-1 beta chemokines attract distinct populations of lymphocytes.
Authors: T J Schall, K Bacon, R D Camp, J W Kaspari, D V Goeddel
Journal: The Journal of Experimental Medicine (1993)

Lymphocyte trafficking is an essential process in immune and inflammatory functions which can be thought to contain at least two main components: adhesion and migration. Whereas adhesion molecules such as the selections are known to mediate the homing of leukocytes from the blood to the endothelium, the chemoattractant substances responsible for the migration of specific subsets of lymphocytes to sites of infection or inflammation are largely unknown. Here we show that two molecules in the chemokine (for chemoattractant cytokine) superfamily, human macrophage inflammatory protein 1 alpha (MIP-1 alpha) and MIP-1 beta, do not share identical attractant activities for lymphocyte subpopulations. When analyzed in vitro in microchemotaxis experiments, HuMIP-1 beta tends to attract CD4+ T lymphocytes, with some preference for T cells of the naive (CD45RA) phenotype. HuMIP-1 alpha, when tested in parallel with HuMIP-1 beta, is a more potent lymphocyte chemoattractant with a broader range of concentration-dependent chemoattractant specificities. HuMIP-1 alpha at a concentration of 100 pg/ml attracts B cells and cytotoxic T cells, whereas at higher concentrations (10 ng/ml), the migration of these cells appears diminished, and the migration of CD4+ T cells is enhanced. Thus, in this assay system, HuMIP-1 alpha and -1 beta have differential attractant activities for subsets of immune effector cells, with HuMIP-1 alpha having greater effects than HuMIP-1 beta, particularly on B cells.
Response of rat intracranial 9L gliosarcoma to microbeam radiation therapy
Authors: F. A. Dilmanian, T. M. Button, G. Le Duc, N. Zhong, L. A. Pena, J. A.L. Smith, S. R. Martinez, T. Bacarian, J. Tammam, B. Ren, P. M. Farmer, J. Kalef-Ezra, P. L. Micca, M. M. Nawrocky, J. A. Niederer, F. P. Recksiek, A. Fuchs, E. M. Rosen
Journal: Neuro-Oncology (2002)

Radiotherapeutic doses for malignant gliomas are generally palliative because greater, supposedly curative doses would impart clinically unacceptable damage to nearby vital CNS tissues. To improve radiation treatment for human gliomas, we evaluated microbeam radiation therapy, which utilizes an array of parallel, microscopically thin (<100 microm) planar beams (microbeams) of synchrotron-generated X rays. Rats with i.c. 9L gliosarcoma tumors were exposed laterally to a single microbeam, 27 pm wide and 3.8 mm high, stepwise, to produce irradiation arrays with 50, 75, or 100 microm of on-center beam spacings and 150, 250, 300, or 500 Gy of in-slice, skin-entrance, single-exposure doses. The resulting array size was 9 mm wide and 10.4 mm high (using three 3.8-mm vertical tiers); the beam's median energy was -70 keV. When all data were collated, the median survival was 70 days; no depletion of nerve cells was observed. However, when data from the highest skin-entrance dose and/or the smallest microbeam spacings were excluded, the median survival time of the subset of rats was 170 days, and no white matter necrosis was observed. Others have reported unilateral single-exposure broad-beam irradiation of i.c. 9L gliosarcomas at 22.5 Gy with a median survival of only -34 days and with severe depletion of neurons. These results suggest that the therapeutic index of unidirectional microbeams is larger than that of the broad beams and that an application for microbeam radiation therapy in treating certain malignant brain tumors may be found in the future.
Differential Regulation of Cardiac Angiotensin Converting Enzyme Binding Sites and AT <sub>1</sub> Receptor Density in the Failing Human Heart
Authors: Lawrence S. Zisman, Koji Asano, Darrin L. Dutcher, Anthony Ferdensi, Alastair D. Robertson, Matthew Jenkin, Erik W. Bush, Teresa Bohlmeyer, M. Benjamin Perryman, Michael R. Bristow
Journal: Circulation (1998)

Background —The regulation and interaction of ACE and the angiotensin II (Ang II) type I (AT 1 ) receptor in the failing human heart are not understood. Methods and Results —Radioligand binding with 3 H-ramiprilat was used to measure ACE protein in membrane preparations of hearts obtained from 36 subjects with idiopathic dilated cardiomyopathy (IDC), 8 subjects with primary pulmonary hypertension (PPH), and 32 organ donors with normal cardiac function (NF hearts). 125 I-Ang II formation was measured in a subset of hearts. Saralasin ( 125 I-{Sar 1 ,Ile 8 }-Ang II) was used to measure total Ang II receptor density. AT 1 and AT 2 receptor binding were determined with the AT 1 receptor antagonist losartan. Maximal ACE binding ( B max ) was 578±47 fmol/mg in IDC left ventricle (LV), 713±97 fmol/mg in PPH LV, and 325±27 fmol/mg in NF LV ( P &lt;0.001, IDC or PPH versus NF). In IDC, PPH, and NF right ventricles (RV), ACE B max was 737±78, 638±137, and 422±49 fmol/mg, respectively ( P =0.02, IDC versus NF; P =0.08, PPH versus NF). 125 I-Ang II formation correlated with ACE binding sites ( r =0.60, P =0.00005). There was selective downregulation of the AT 1 receptor subtype in failing PPH ventricles: 6.41±1.23 fmol/mg in PPH LV, 2.37±0.50 fmol/mg in PPH RV, 5.38±0.53 fmol/mg in NF LV, and 7.30±1.10 fmol/mg in NF RV ( P =0.01, PPH RV versus PPH LV; P =0.0006, PPH RV versus NF RV). Conclusions —ACE binding sites are increased in both failing IDC and nonfailing PPH ventricles. In PPH hearts, the AT 1 receptor is downregulated only in the failing RV.
Contractile Adaptations Preserving Cardiac Output Predispose the Hypertrophied Canine Heart to Delayed Afterdepolarization–Dependent Ventricular Arrhythmias
Authors: S. H. Marieke de Groot, Marieke Schoenmakers, Mirella M. C. Molenschot, Jet D. M. Leunissen, Hein J. J. Wellens, Marc A. Vos
Journal: Circulation (2000)

Background —In dogs, chronic complete atrioventricular block (CAVB) results in structural (biventricular hypertrophy) and electrical (delayed repolarization) remodeling, which predisposes the heart to torsade de pointes arrhythmias. We assessed the contractile alterations in the CAVB dog and tested the hypothesis that these adaptations increase delayed afterdepolarization (DAD)–dependent triggered arrhythmias. Methods and Results —Steady-state and dynamic (fast pacing: 1 to 68 stimuli) left and right ventricular systolic and diastolic parameters were determined by positive and negative inotropic interventions at acute AVB and CAVB. Concomitantly, left and right ventricular endocardial monophasic action potentials were registered. In CAVB, all systolic contractile parameters were markedly increased, resulting in preserved cardiac output. The increase was most pronounced at low heart rates, altering the force-frequency response. At both acute AVB and CAVB, the degree of potentiation of cardiac function with pacing was dependent on the number of stimuli and showed a maximum at 8 to 13 stimuli. With CAVB, this potentiation curve was shifted upward, and it was only then that pacing resulted in DADs (in 8 of 10 dogs) and ectopic beats (EBs, in 6 of 10 dogs). The incidence of EBs in relation to the number of stimuli also had a maximum at 8 to 13 stimuli. Ouabain increased the incidence of DADs and EBs, whereas the negative inotropic interventions prevented them completely. Conclusions —The alterations responsible for improvement in systolic contractile function in CAVB dogs predispose the hypertrophied heart to DAD-dependent triggered arrhythmias during positive inotropic interventions.
Patterns of Nonadherence to Antiepileptic Drug Therapy in Children With Newly Diagnosed Epilepsy
Authors: Avani C. Modi
Journal: JAMA (2011)

Because of epilepsy's common occurrence, the narrow therapeutic and safety margins of antiepileptic medications, and the recognized complications of medication nonadherence in adults with epilepsy, identifying the rates, patterns, and predictors of nonadherence in children with epilepsy is imperative. The onset and evolution of antiepileptic drug nonadherence in children with newly diagnosed epilepsy remains unknown.To identify and characterize trajectories of adherence in children with newly diagnosed epilepsy over the first 6 months of therapy and to determine sociodemographic and epilepsy-specific predictors of adherence trajectories.Prospective, longitudinal observational study of antiepileptic drug adherence in a consecutive cohort of 124 children (2-12 years old) with newly diagnosed epilepsy at Cincinnati Children's Hospital Medical Center. Patients were recruited from April 2006 through March 2009, and final data collection occurred in September 2009.Objective adherence measured using electronic monitors.Fifty-eight percent of children with newly diagnosed epilepsy demonstrated persistent nonadherence during the first 6 months of therapy. Group-based trajectory models identified 5 differential adherence patterns (Bayesian information criterion = -23611.8): severe early nonadherence (13%; 95% confidence interval [CI], 8%-20%), severe delayed nonadherence (7%; 95% CI, 3%-12%), moderate nonadherence (13%; 95% CI, 8%-20%), mild nonadherence (26%; 95% CI, 19%-34%), and near-perfect adherence (42%; 95% CI, 33%-50%). The adherence pattern of most patients was established by the first month of therapy. Socioeconomic status was the sole predictor of adherence trajectory group status (χ(4)(2) = 19.3 [n = 115]; P < .001; partial r(2) = 0.25), with lower socioeconomic status associated with higher nonadherence.Five trajectory patterns were identified that captured the spectrum of nonadherence to antiepileptic drugs among children with newly diagnosed epilepsy; the patterns were significantly associated with socioeconomic status.