tbuckley/cabot-search huggingface dataset:
Phase I Trial of Intravenous Administration of PV701, an Oncolytic Virus, in Patients With Advanced Solid Cancers
Authors: Andrew L. Pecora, Naiyer Rizvi, Gary I. Cohen, Neal J. Meropol, Daniel Sterman, John L. Marshall, Stuart Goldberg, Peter Gross, James D. O’Neil, William S. Groene, M. Scot Roberts, Harvey Rabin, Michael K. Bamat, Robert M. Lorence
Journal: Journal of Clinical Oncology (2002)

PURPOSE: PV701, a replication-competent strain of Newcastle disease virus, causes regression of tumor xenografts after intravenous administration. This phase I study was designed to define the maximum-tolerated dose (MTD) and safety of single and multiple intravenous doses of PV701 as a single agent in patients with cancer. PATIENTS AND METHODS: Seventy-nine patients with advanced solid cancers that were unresponsive to standard therapy were enrolled. Four PV701 intravenous dosing regimens were evaluated: (1) single dose: one dose every 28 days; (2) repeat dose: three doses in 1 week every 28 days; (3) desensitizing: one lower dose followed by two higher doses in 1 week every 28 days; and (4) two week: one lower dose followed by five higher doses over 2 weeks every 21 days. RESULTS: A 100-fold dose intensification was achieved over 195 cycles. A first-dose MTD of 12 × 10 9 plaque-forming units (PFU)/m 2 was established for outpatient dosing. After an initial dose of 12 × 10 9 PFU/m 2 , patients tolerated an MTD for subsequent doses of 120 × 10 9 PFU/m 2 . The most common adverse events were flu-like symptoms that occurred principally after the first dose and were decreased in number and severity with each subsequent dose. Tumor site–specific adverse events and acute dosing reactions were also observed but not cumulative toxicity. Objective responses occurred at higher dose levels, and progression-free survival ranged from 4 to 31 months. Tumor tissue from one patient was obtained after 11 months of therapy and showed evidence of PV701 particles budding from the tumor cell membrane by electron microscopy and a pronounced lymphoplasmacytic infiltrate by histologic examination. CONCLUSION: PV701 warrants further study as a novel therapeutic agent for cancer patients.
Diagnostic Crossover in Anorexia Nervosa and Bulimia Nervosa: Implications for DSM-V
Authors: Kamryn T Eddy, David J Dorer, Debra L Franko, Kavita Tahilani, Heather Thompson-Brenner, David B Herzog
Journal: American Journal of Psychiatry (2008)

The Diagnostic and Statistical Manual of Mental Disorders (DSM) is designed primarily as a clinical tool. Yet high rates of diagnostic "crossover" among the anorexia nervosa subtypes and bulimia nervosa may reflect problems with the validity of the current diagnostic schema, thereby limiting its clinical utility. This study was designed to examine diagnostic crossover longitudinally in anorexia nervosa and bulimia nervosa to inform the validity of the DSM-IV-TR eating disorders classification system.A total of 216 women with a diagnosis of anorexia nervosa or bulimia nervosa were followed for 7 years; weekly eating disorder symptom data collected using the Eating Disorder Longitudinal Interval Follow-Up Examination allowed for diagnoses to be made throughout the follow-up period.Over 7 years, the majority of women with anorexia nervosa experienced diagnostic crossover: more than half crossed between the restricting and binge eating/purging anorexia nervosa subtypes over time; one-third crossed over to bulimia nervosa but were likely to relapse into anorexia nervosa. Women with bulimia nervosa were unlikely to cross over to anorexia nervosa.These findings support the longitudinal distinction of anorexia nervosa and bulimia nervosa but do not support the anorexia nervosa subtyping schema.
Prognostic value of breast cancer m-RNA transcripts (Ts) detection by RT-PCR in GCSF stimulated peripheral blood (PB) after adjuvant chemotherapy (ACT) in high-risk breast cancer patients (HRBCP)
Authors: M. Quintela-Fandino, R. Hitt, J. Martinez, S. Gamarra, A. Jimeno, M. L. Amador, C. Guzman, J. Montero, H. Cortes Funes
Journal: Journal of Clinical Oncology (2005)

9689 Background: The real prognostic value of residual tumor cells(in PB/bone marrow (BM)) is unknown. IHQ-based detection studies show irregular results. Inadequate designs may underestimate prognostic value. Assays commonly have been made using citokeratin 19 (CK19) but it is usually down-regulated in metastatic cells. Samples should be collected months after surgery and after ACT to ensure that detected tumor cells are not released to PB/BM due to a trauma and have overcome ACT. We studied micrometastatic disease (MMD) value in a homogeneous-risk cohort with a high sensitive technique. Methods: 83 HRBCP were studied; median age: 42 yrs.; affected nodes: 4–10:25%; >10: 75%; ACT: FEC (69); AC-Taxol (14); 4 weeks after last cycle GCSF 300μg bid was given for 10 days; apheresis was performed on days 7–10. Lastly, STAMP-V was administered. Radiotherapy and tamox. were administrated if indicated. Aliquots of apheresis-mononuclear blood cells were frozen for each patient. mRNA was isolated by MagNa Pure LC Instrument. A SAGE-defined panel of Ts that are present in almost 100% of breast cancer cells but absent in PB/BM (EGP2, PS2, p1B) (Clin Cancer Res, 8, 1871), CK19 and HER2 were chosen as targets. Target Ts were quantified relatively to control gene B-glucuronidase by RT-PCR on a Light Cycler using Taqman probes. Any Ts quantity detection was considered MMD. Statistics: Time to relapse was considered the end point. Age, tumor size, number of nodes, grade, ER, PR, Taxol Y/N and quantitative value of the Ts were included as prognostic factors for analysis. Descriptive, uni/bivariate (log-rank/Pearson) and multivariate (Cox model) analysis were performed. Results: To date EGP2, HER 2 and CK19 Ts have been quantified in PB. 38% of the 83 patients showed MMD. After a median follow up of 68.3 months, 46(55%) pts relapsed. In multivariate analysis only EGP2 produced an independent elevation of hazard ratio for relapse (HR:1.08, p<0.05). CK19 and HER2 assays detected only 16% and 23% of de MMD cases respectively. Conclusions: 1)MMD after ACT adds little prognostic value to classical factors 2)CK19 and HER2 Ts are not efficient for MMD detection. No significant financial relationships to disclose.
Respiration biofeedback assisted controlled breathing training to enhance shooting performance
Authors: Anuradha S Solanky
Journal: British Journal of Sports Medicine (2010)

Good breathing patterns are those that meet our needs and provide optimal conditions for health and performance. Only when corrective breathing is restored, performance can be enhanced to optimal levels. Purpose The present research was carried out to assist a national shooter who reported with hyperventilatory breathing patterns (averaging 22–23 breaths/min). Methods and materials The shooter (age 26 years) was preparing for an international competition. Breathing patterns were monitored using respiration biofeedback apparatus. Controlled breathing exercises were taught to him. Results Three weeks of respiration biofeedback training resulted in considerable decrease in respiration rate as well as jerky breathing patterns exhibited earlier. Following the training, he participated in an international competition where he reported that his performance showed considerable improvement. Conclusions The shooter reported to have been able to recover faster, prevent pre-competition anxiety and regulate concentration levels during competition. Corrective breathing patterns lead to enhanced performance levels.
Environmental and Sociodemographic Factors Associated With Food Allergy: A Nested Case-Control Study
Authors: Moshe Ben-Shoshan, Lianne Soller, Daniel Harrington, Megan Knoll, Sebastian La Vieille, Joseph Fragapane, Lawrence Joseph, Yvan St. Pierre, Kathi Wilson, Susan Elliott, Ann Elaine Clarke
Journal: Journal of Allergy and Clinical Immunology (2014)
Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction
Authors: K F Chung, I M Adcock
Journal: European Respiratory Journal (2008)

Chronic obstructive pulmonary disease is a leading global cause of morbidity and mortality that is characterised by inexorable deterioration of small airways obstruction with emphysema associated with cellular inflammation and structural remodelling. Other features include apoptosis as well as proliferation of cells, and both tissue repair and lack of tissue repair. Metalloprotease release, together with that of apoptotic factors, may underlie the emphysema, and, conversely, fibrosis of the small airways may be accounted for by the effects of growth factor activation. In advanced disease, influential factors include the development of autoimmunity, with activation of dendritic cells and T-helper cells of both type 1 and 2, and the senescence response. An inability of macrophages to ingest apoptosed cells and bacteria may exacerbate inflammatory responses. Systemic inflammation with concomitant cardiovascular disease and metabolic syndrome may reflect the effect of cigarette smoke on nonpulmonary cells. Corticosteroid resistance may be secondary to oxidative stress mechanisms, such as inactivation of histone deacetylases. The mechanisms of chronic obstructive pulmonary disease may be heterogeneous, according to severity, and clinical phenotypes need to be correlated with cellular and pathological processes. Treatments may be targeted to patients with specific mechanisms.
Electrical uncoupling and increase of extracellular resistance after induction of ischemia in isolated, arterially perfused rabbit papillary muscle.
Authors: A G Kléber, C B Riegger, M J Janse
Journal: Circulation Research (1987)

Extracellular and intracellular longitudinal resistances (ro and ri), transmembrane potentials, and conduction velocity were determined in arterially blood-perfused rabbit papillary muscles. Cable analysis was made possible by placing the muscle in a H2O-saturated gaseous environment, which acted as an electrical insulator. Ischemia was produced by exchanging the O2 in the atmosphere by N2 (94% N2-6% CO2) in addition to arresting coronary flow. The first 10-15 minutes of ischemia were characterized by an increase in ro, while ri remained constant. The early part of the increase in ro coincided with the drop in perfusion pressure and was probably due to the diminution of intravascular volume. Rapid electrical uncoupling, reflected by an increase in ri (threefold within 5 minutes), occurred thereafter. The dissociation between the early increase in ro and the delayed increase in ri produced an initial increase in the ratio ro:ri, which subsequently decreased. The decrease in conduction velocity was less than observed in intact hearts with ischemia. This difference is explained by the relatively small changes in resting membrane potential and action potential amplitude in the preparation used. Our results suggest that in the early, reversible phase of ischemia, the increase in ro contributes to a small but significant extent to the slowing of conduction. After 15-20 minutes, the rapid cellular uncoupling, which was most likely coincident with breakdown of cellular homeostasis, may contribute to the occurrence of arrhythmias during this phase of ischemia. Moreover, the early change in the ratio ro:ri will influence the amplitude of the extracellular electrograms following coronary occlusion (TQ-segment and ST-segment shifts).
Phase III Double-Blind, Randomized, Placebo-Controlled Crossover Trial of Black Cohosh in the Management of Hot Flashes: NCCTG Trial N01CC<sup>1</sup>
Authors: Barbara A. Pockaj, James G. Gallagher, Charles L. Loprinzi, Philip J. Stella, Debra L. Barton, Jeff A. Sloan, Beth I. Lavasseur, Radha M. Rao, Tom R. Fitch, Kendrith M. Rowland, Paul J. Novotny, Patrick J. Flynn, Elliott Richelson, Abdul H. Fauq
Journal: Journal of Clinical Oncology (2006)

Hot flashes can cause significant morbidity in postmenopausal women undergoing or finished with breast cancer treatment. Black cohosh has been used to treat hot flashes, but definitive clinical data about efficacy have been equivocal.A double-blind, randomized, cross-over clinical trial with two 4-week periods, was used to study the efficacy of black cohosh (1 capsule, Cimicifuga racemosa 20 mg BID) for the treatment of hot flashes in women. Participants kept a daily hot flash diary during a baseline week and then during two 4-week crossover treatment periods. Hot flash scores were measured by assigning points (1 to 4 for mild to very severe) to each hot flash based on severity and then adding the points for a given time period.Between October 31, 2003, to March 4, 2004, 132 patients were randomly assigned. Toxicity was minimal and not different by treatment group. Patients receiving black cohosh reported a mean decrease in hot flash score of 20% (comparing the fourth treatment week to the baseline week) compared with a 27% decrease for patients on placebo (P = .53). Mean hot flash frequency was reduced 17% on black cohosh and 26% on placebo (P = .36). Patient treatment preferences were measured after completion of both treatment periods by ascertaining which treatment period, if any, the patient preferred. Thirty-four percent of patients preferred the black cohosh treatment, 38% preferred the placebo, and 28% did not prefer either treatment.This trial failed to provide any evidence that black cohosh reduced hot flashes more than the placebo.
HyperCVAD for VAD-resistant multiple myeloma
Authors: Meletios A. Dimopoulos, Donna Weber, Hagop Kantarjian, Kay B. Delasalle, Raymond Alexanian
Journal: American Journal of Hematology (1996)

More effective and safer regimens are needed for patients who have advanced multiple myeloma resistant to or relapsing despite prior treatment with alkylating agents and VAD. We treated 58 such patients using the combination of twice daily cyclophosphamide (total dose 1.8 g/m2) and VAD (hyperCVAD). Treatment was given to outpatients followed by G-CSF at 5 microgram/kg/d until granulocyte recovery. Twenty-three patients responded (40%), with a median duration of granulocyte depression to less than 500/microliter of 4 days and a mortality rate of 2%. The median survival time for all patients was 15 months, and the median remission time of responding patients was 8 months. Patients who had low LDH, low B2M, or primary resistant disease lived significantly longer than patients without these features. The combination of fractionated cyclophosphamide and VAD provided an effective and safe rescue treatment for many patients who had advanced myeloma resistant to standard therapies.
[<sup>18</sup>F]Fluorodeoxyglucose Positron Emission Tomography–Computed Tomography in Breast Cancer: When… and When Not?
Authors: David A. Mankoff, Jennifer M. Specht, William B. Eubank, Larry Kessler
Journal: Journal of Clinical Oncology (2012)

Diagnostic imaging plays an important role in the care of patients with breast cancer and is used for breast cancer detection, diagnosis, staging, and therapeutic response evaluation. 1 Advances in imaging technology, especially relatively newer technologies such as magnetic resonance imaging (MRI) and positron emission tomography without or with integrated computed tomography (PET or PET/CT) provide powerful diagnostic tools, but also generate questions and controversy regarding where and when to use these new modalities.Early studies of new imaging approaches most often come from centers that are scientifically invested in the development of the technology.Typically, small and highly selected patient populations are evaluated, and these preliminary studies often indicate excellent diagnostic performance.Later on, when large multicenter trials are performed with more clinically representative patient populations, the new test invariably performs less well.Nevertheless, the excitement surrounding early results from a new imaging technology and the increasing public access to these early results fuel the desire by patients for access to new forms of diagnostic imaging.Physicians and patients share the wish for diagnostic certainty in excluding cancer spread at the time of diagnosis and may reason that a purely diagnostic procedure, even if untested, can do no harm.These factors, combined with the challenge and expense of carrying out larger scale diagnostic imaging trials, can lead to the early adoption of new imaging studies into clinical practice, often before their performance and optimal use have been fully determined.However, the use of a new imaging technology in populations of patients unlikely to benefit from its use can add anxiety, expense, unnecessary procedures, and delay in care.Equally important, inappropriate use in the wrong patient population can obfuscate benefit in other clinical settings where the imaging might be helpful.These dilemmas have been aptly demonstrated in the application of [ 18 F]fluorodeoxyglucose (FDG) PET and PET/CT to early breast cancer staging.Early studies of FDG PET for breast cancer axillary staging (reviewed in Eubank et al 2 ) demonstrated high sensitivity and specificity (85%-90% or better for both) and created considerable enthusiasm for FDG PET as a noninvasive method for detecting axillary nodal metastases.However, these studies were heavily biased towards patients with advanced disease, often with larger and more aggressive
Abstract P5-09-02: The CYP19 RS4646 polymorphism is related to the prognosis of stage I–II and operable stage III breast cancers
Authors: Xiying Shao, Xiaojia Wang, Yangbing Zheng, Ping Huang, Jian Huang
Journal: Cancer Research (2015)

Abstract Background: Aromatase, encoded by the CYP19 gene, catalyzes the final step of the conversion of androgens to estrogens. In premenopausal women, estrogen is mainly produced by the ovary, while in postmenopausal women, aromatization of androgen in extragonadal tissue, for example, adipose tissue, is the main source. Given the critical role of CYP19 in estrogen synthesis and the association of clinical outcome with rs4646 polymorphism, we investigated the clinical relevance of CYP19 rs4646 genotypes in early breast cancer. Methods: Genotype for CYP19 rs4646 variants was performed on 406 Chinese women with early breast cancer. Associations were examined between rs4646 genotypes with histopathological characteristics and disease-free survival. Results: In patients younger than 50 years, women who are homozygous for the minor allele (AA) have a longer disease-free survival (DFS)compared with those carrying the major allele(CC or AC) (87 months versus 48.7 months; HR 0.560; 95CI 0.318-0.985; P =0.041). This differences was further demonstrated by a multivariate analysis (HR 0.456; 95CI 0.249-0.836; P=0.011). Conversely, the same variants(AA) were found to be associated with a poorer DFS in women with age above 50 years (AA versus AC or CC: 38.9months versus 79.7 months; HR 2.758; 95% CI: 1.432-5.313; P=0.002). Furthermore, the differences was proved by the COX proportional hazards model (HR 2.983; 95CI 1.494-5.955; P=0.002). Conclusions: The present study indicates that CYP19 rs4646 polymorphism is associated with DFS in early breast cancer and that the prognosis index of the homozygous for the minor allele (AA) may depend on circulating estrogens levels due to the different age. The founding is novel, if confirmed in a larger prospective independent cohort, rs4646 genotypes may provide useful information for routine management in breast cancer. Citation Format: Xiying Shao, Xiaojia Wang, Yangbing Zheng, Ping Huang, Jian Huang. The CYP19 RS4646 polymorphism is related to the prognosis of stage I–II and operable stage III breast cancers [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 P5-09-02.
The Two-Edged Sword
Authors: William B. Smith
Journal: JAMA (1979)

A unanimous opinion of the Supreme Court is an unusual phenomenon today, when it seems that almost every other decision of that august court is determined by a single vote. Furthermore, it is encouraging to read the opinion written by Chief Justice Warren Burger in the case of<i>Addington vs Texas</i>. The reader must appreciate the wisdom and sensitivity disclosed by the careful analysis in that opinion, which deals with the legal problems inherent in the civil commitment of the mentally ill. The Court's determination of the standard of proof required by the due process clause of the Fourteenth Amendment for an involuntary commitment to a state mental hospital is wrapped in a comprehensive delineation of rights and duties. The main argument centered on use of the same standard of proof required in criminal actions, ie, proof beyond a reasonable doubt, as opposed to the more moderate standard of clear
Endothelin-1-induced airway and parenchymal mechanical responses in guinea-pigs: the roles of ETA and ETB receptors
Authors: Á. Adamicza, F. Peták, T. Asztalos, L. Tiszlavicz, M. Boros, Z. Hantos
Journal: European Respiratory Journal (2001)

Endothelin-1 (ET-1) has been shown to have a constrictor effect on the airways and parenchyma; however, the roles of the ET A and ET B receptors in the ET-1-induced changes in the airway and tissue compartments have not been fully explored. Low-frequency pulmonary impedance ( Z L ) was measured in anaesthetized, paralysed, open-chest guinea-pigs. Z L spectra were fitted by a model to estimate airway resistance ( R aw ) and inertance ( I aw ), and coefficients of tissue damping (G) and elastance (H), and hysteresivity (η=G/H). Two successive doses of ET-1 (0.05 and 0.2 nmol·kg −1 ) each evoked significant dose-related increases in R aw , G, H and η. Pretreatment with 20 nmol·kg −1 BQ-610 (a highly selective ET A receptor antagonist) resulted in a significantly decreased elevation only in H after the lower dose of ET-1. However, all parameters changed significantly less on the administration of ET-1 after pretreatment with 80 nmol·kg −1 BQ-610, with 20 nmol·kg −1 ETR-P1/fl (a novel ET A receptor antagonist) or with 20 nmol·kg −1 IRL 1038 (an ET B receptor antagonist). The results of the separate assessments of the airway and tissue mechanics demonstrate that endothelin-1 induces airway and parenchymal constriction via stimulation of both receptor types in both compartments.
Bisphosphonates for the prevention and treatment of osteoporosis
Authors: Spyridoula Maraka, Kurt A Kennel
Journal: BMJ (2015)

Osteoporosis is a systemic skeletal disorder characterized by bone loss, which leads to impaired bone strength and an increased risk of fractures. Two million fractures are attributed to osteoporosis annually in the United States and they are associated with serious morbidity and mortality. Bisphosphonates reduce the risk of fracture by suppressing bone resorption and increasing bone strength, and they have been widely used for the prevention and treatment of osteoporosis. However, the use of these drugs for the management of osteoporosis remains a clinical challenge. There are several important considerations including appropriate patient selection, pretreatment evaluation, potential adverse effects, patient preferences, and adherence. This review will discuss the evidence informing the clinical strategy for using bisphosphonates in patients with osteoporosis and those at high risk of fracture, focusing on the benefits and risks of treatment. We will also consider issues related to the monitoring and duration of treatment.