tbuckley/cabot-search huggingface dataset:
Studies of the epidemiology of bulimia nervosa
Authors: C G Fairburn, S J Beglin
Journal: American Journal of Psychiatry (1990)

Research on the epidemiology of bulimia nervosa has focused largely on the prevalence of the disorder. As methods have improved, consensus has increased regarding the prevalence rate among adolescent and young adult women--about 1%. However, the accuracy of this figure and its clinical significance must be questioned. In this synthesis of the epidemiological work to date, the authors review the literature from a clinical and research perspective. They recommend a shift in emphasis away from studies of the distribution of the disorder toward studies of the determinants of the whole spectrum of the disturbance that exists in the community.
Phase I and Pharmacokinetic Study of Temozolomide on a Daily-for-5-Days Schedule in Patients With Advanced Solid Malignancies
Authors: Lisa A. Hammond, John R. Eckardt, Sharyn D. Baker, S. Gail Eckhardt, Margaret Dugan, Kelly Forral, Pascale Reidenberg, Paul Statkevich, Geoffrey R. Weiss, David A. Rinaldi, Daniel D. Von Hoff, Eric K. Rowinsky
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To determine the principal toxicities, characterize the pharmacokinetics (PKs) and pharmacodynamics (PDs) of temozolomide (TMZ) on a daily-for-5-days schedule, and recommend a dose for subsequent disease-directed studies in both minimally pretreated (MP) and heavily pretreated (HP) patients. PATIENTS AND METHODS: Patients received TMZ as a single oral dose daily for 5 consecutive days every 28 days. TMZ doses were escalated from 100 to 150, and 150 to 200 mg/m 2 /d in separate cohorts of MP and HP patients. PK plasma was sampled on days 1 and 5. TMZ concentrations were analyzed and pertinent PK parameters were related to the principal toxicities of TMZ in PD analyses. RESULTS: Twenty-four patients were treated with 85 courses of TMZ. Thrombocytopenia and neutropenia were the principal dose-limiting toxicities (DLTs) of TMZ on this schedule. The cumulative rate of severe myelosuppressive effects was unacceptably high at TMZ doses exceeding 150 mg/m 2 /d in both MP and HP patients. TMZ was absorbed rapidly with maximum concentrations achieved in 0.90 hours, on average, and elimination was rapid, with a half-life and systemic clearance rate (Cl S/F ) averaging 1.8 hours and 115 mL/min/m 2 , respectively. When clearance was normalized to body-surface area (BSA), interpatient variability in Cl S/F was reduced from 20% to 13% on day 1 and from 16% to 10% on day 5. Patients who experienced DLT had significantly higher maximum drug concentration (median 16 v 9.5 μg/mL, P = .0084) and area under the concentration-time curve (median 36 v 23 μg-h/mL, P = .0019) values on day 5. CONCLUSION: Prior myelosuppressive therapy was not a determinant of toxicity. TMZ 150 mg/m 2 /d administered as a single oral dose daily for 5 days every 4 weeks is well tolerated by MP and HP patients, with higher doses resulting in unacceptably high rates of severe hematologic toxicity. TMZ doses should be individualized according to BSA rather than use of a prespecified oral dose for all individuals. TMZ is an optimal agent to develop in combination with other cytotoxic, biologic, and targeted therapeutics for patients with relevant malignancies.
Thymosin β4 affects the expression of annexin A1 with its signal pathway in cervical cancer cells
Authors: Hye-Sung Moon, Sun Hee Sung, Hye Young Park
Journal: Clinical Cancer Research (2006)

A30  Objects: Thymosin β4 promotes cell migration and is important in angiogenesis, wound healing, and tumor metastasis. Annexins are involved in signal transduction, tissue growth and differentiation, and inflammation. This study investigated that the thymosin β4 affects the expression of annexin with its signal pathway in cervical cancer cells with clinical significance.Methods: Microarray with thymosin β4 virus infected SiHa cells was done. The mRNA expression of thymosin β4 and annexin A1was analyzed with Quantative Competitive Polymerase Chain Reaction in 11 normal cervix, 10 cervical intraepithelial neoplasia of cervix, and 34 invasive cervical carcinoma. The clinicopathologic factors were obtained from the review of patients9 charts. RT-PCR was done with thymosin β4 treated SiHa cells. Western blotting by Annexin A1, cyclin D1, and ERK1/2 antibody were done with those cells.Results: The mRNA expression of thymosin β4 in invasive cervical carcinoma was higher than that of normal cervix and cervical intraepithelial neoplasia (p
Having “Skin in the Game” and Allowing Cross-Border Importation of Drugs to Lower High Prices of Cancer Drugs
Authors: Hagop Kantarjian, Michael S. Mathisen, Jeffrey H. Lipton
Journal: JAMA Oncology (2015)

This Viewpoint discusses the differential prices of drugs in the United States vs Canada and England and cross-border drug importation. Competitive market forces would function better, lower cancer drug prices, and would benefit all parties.
Polymorphism at the Glutathione <i>S</i>-transferase GSTP1 Locus
Authors: ANTHONY A. FRYER, ANDREA BIANCO, MICHAEL HEPPLE, PETER W. JONES, RICHARD C. STRANGE, MONICA A. SPITERI
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Most genetic studies of asthma have concentrated on genes on chromosomes 11q and 5q and their association with the key asthma-related phenotypes of bronchial hyperresponsiveness (BHR) and atopy. Although asthma is characterized by airway inflammation, a critical component of which is oxidative stress, few data exist on genes involved in protecting against this insult. We describe an association study designed to examine whether allelic variation at the glutathione-S-transferase GSTP1 locus influences expression of the BHR and atopy phenotypes in asthma. The enzyme encoded by GSTP1 utilizes a variety of lipid and DNA products of oxidative stress, and polymorphic variants of this gene are associated with altered catalytic function of this enzyme. We found that the frequency of GSTP1 Val105/Val105 was significantly lower in asthmatic than in control subjects. Indeed, the presence of this genotype conferred a sixfold lower risk of asthma than did GSTP1 Ile105/Ile105. Remarkably, asthma risk in Val105 homozygotes was further reduced (by ninefold) after correction for atopic indices, age, and gender. Trend analysis after stratification according to the degree of bronchial reactivity/obstruction showed that the frequency of GSTP1 Val105/Val105 correlates with decreasing severity of airway dysfunction. Furthermore, subjects with GSTP1 Val105/Val105 have four- and 10-fold lower risks, respectively, of exhibiting atopy defined by skin test positivity and IgE level. These data show that GSTP1 polymorphism is strongly associated with asthma and related phenotypes, and provide an alternative explanation for the linkage of chromosome 11q13 with BHR and atopy.
Abstract 5510: ABT-737 synergizes with Vorinostat to induce apoptosis, mediated by Noxa upregulation, Bax activation and mitochondrial dysfunction in PTEN-intact malignant human glioma cell lines
Authors: Kimberly A. Foster, Daniel R. Premkumar, Esther P. Jane, Alejandro Morales, Ian F. Pollack
Journal: Cancer Research (2014)

Abstract We have previously observed that glioma cells are differentially sensitive to ABT-737 and, when used as a single-agent, this drug failed to induce apopotsis. Identification of therapeutic strategies to enhance the efficacy of the Bcl-2 inhibitor ABT-737 in human glioma is of interest. Histone deacetylation inhibitors (HDACi) are currently being assessed clinically in patients with glioma, as regulation of epigenetic abnormalities is expected to produce pro-apoptotic effects. We hypothesized that cotreatment of glioma with a BH3-mimetic and HDACi may synergistically produce cell death. We assessed the combination of the Bcl-2 family inhibitor ABT-737 and the HDACi vorinostat in established and primary cultured glioma cells. We found that combined treatment with these agents led to significant cellular death when compared to either drug as a single agent and demonstrated activation of the caspase cascade. The enhanced apoptosis observed with the combination also appears dependent upon the loss of mitochondrial membrane potential, release of cytochrome c, smac/DIABLO and apoptosis-inducing factor to the cytosol. We observed that the upregulation of Noxa, truncation of Bid, and the activation of Bax caused by this combination were important factors for synergistic cell death. We demonstrated that Noxa functioned to occupy Mcl-1 in cells exposed to the combination, yet, contrary to studies in other malignancies, this combination in glioma occurred without the release of proapoptotic proteins Bim and Bak from Mcl-1. We showed this combination to be less effective in PTEN-deficient glioma cells. Both genetic manipulation of PTEN status and pharmacologic inhibition of PI3 kinase sensitized PTEN-deleted glioma cells to the combination. This study demonstrates that antagonizing apoptosis-resistance pathways, such as the Bcl-2 family, and regulating epigenetic aberrancies, such as histone regulation, may induce cell death. Moreover, we reiterate that therapies to target the PI3-kinase/Akt/mTor pathway may be additionally necessary in cancers lacking PTEN functionality. Citation Format: Kimberly A. Foster, Daniel R. Premkumar, Esther P. Jane, Alejandro Morales, Ian F. Pollack. ABT-737 synergizes with Vorinostat to induce apoptosis, mediated by Noxa upregulation, Bax activation and mitochondrial dysfunction in PTEN-intact malignant human glioma cell lines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5510. doi:10.1158/1538-7445.AM2014-5510
Abstract 3170: Acute Heart Failure: What Doesn’t Get Admitted May Come Back To Haunt You
Authors: Justin A Ezekowitz, Wei-Ching Chang, Cynthia M Westerhout, Paul W Armstrong
Journal: Circulation (2006)

Background: Previous epidemiologic studies of acute heart failure (AHF) have involved patients admitted to hospital therefore failing to account for an unknown proportion of pts discharged directly from the emergency department (ED). We evaluated discharge vs. admission rates of AHF pts as well as changes in evidence-based medication (EBM) prescriptions and whether their outcomes, including mortality, differed from those who were admitted. Methods: A population-based cohort was analyzed including all pts ≥65 years presenting to Alberta EDs with a most responsible diagnosis of heart failure (ICD9-CM 428.x) between 1998 and 2001. Pts were either discharged from the ED (DCED) or admitted to hospital (HOSP). Data includes procedures (angiogram, PCI, CABG, echo, nuclear, exercise tests, pacemakers), EBMs (ACE inhibitors, beta-blockers, spironolactone) and socioeconomic data, repeat ED (re-ED) visits, inpatient admissions (hosp and re-hosp) and death. Results: Of 4652 AHF pts evaluated in the ED, 29% were DCED ...
Long-lived cytotoxic T lymphocyte memory in mucosal tissues after mucosal but not systemic immunization.
Authors: W S Gallichan, K L Rosenthal
Journal: The Journal of Experimental Medicine (1996)

The induction and maintenance of long-term CTL memory at mucosal surfaces may be a critical component of protection against mucosal pathogens and is one goal towards development of effective mucosal vaccines. In these studies we have functionally evaluated short and long-term CTL memory in systemic and respiratory or genital-associated lymphoid tissues following mucosal or systemic routes of immunization. Our results indicate that shortly after immunizing mice with a recombinant adenovirus vector expressing glycoprotein B (gB) of herpes simplex virus (AdgB8), gB-specific CTL memory responses were observed in systemic and mucosal immune compartments regardless of the route of inoculation. In contrast, several months after immunization, anamnestic CTL responses compartmentalized exclusively to mucosal or systemic lymphoid tissues after mucosal or systemic immunization, respectively. Furthermore, the compartmentalized CTL memory responses in mucosal tissues were functionally observed for longer than 1.5 yr after intranasal immunization, and CTL precursor frequencies one year after immunization were comparable to those seen shortly after immunization. Therefore, to our knowledge, this is the first functional demonstration that the maintenance of anti-viral memory CTL in mucosal tissues is dependent on the route of immunization and the time of assessment. These results have important implications for our understanding of the development, maintenance, and compartmentalization of functional T cell memory and the development and evaluation of vaccines for mucosal pathogens, such as HSV and HIV.
Abstract 4182: Tri-Dimensional Fusion Image Improves the Evaluation of Myocardial Perfusion
Authors: Marcelo Goldstein, Guy Beersaerts, Yvan De Merlier, Marie-Antoinette Anckaert, Koen Erard, Philippe Lambert, Olivier De Coster, Frederic Chapelle, Angel Lozano, Sebastien Neirinckx, Fabienne Vandewynckel
Journal: Circulation (2008)
Brief Report: Leucine‐Rich α<sub>2</sub>‐Glycoprotein as a Potential Biomarker for Joint Inflammation During Anti–Interleukin‐6 Biologic Therapy in Rheumatoid Arthritis
Authors: Minoru Fujimoto, Satoshi Serada, Katsuya Suzuki, Ayumi Nishikawa, Atsushi Ogata, Toshihiro Nanki, Kunihiro Hattori, Hitoshi Kohsaka, Nobuyuki Miyasaka, Tsutomu Takeuchi, Tetsuji Naka
Journal: Arthritis & Rheumatology (2015)

To investigate whether leucine-rich α2 -glycoprotein (LRG) could be a biomarker for disease activity during interleukin-6 (IL-6) blockade treatment of rheumatoid arthritis (RA).In 59 RA patients who were treated with tocilizumab for 24 weeks, serum LRG levels were determined by enzyme-linked immunosorbent assay. RA disease activity was evaluated by the Clinical Disease Activity Index (CDAI). Receiver operating characteristic (ROC) curve analysis was used to examine the diagnostic performance of LRG and other biomarkers. In monkeys with experimental autoimmune arthritis, swollen joint counts, joint pathologic changes, and blood levels of C-reactive protein (CRP) and LRG were evaluated after treatment with anti-IL-6 receptor antibody.Among tocilizumab-treated RA patients, those with active disease (CDAI >2.8) had significantly higher serum LRG levels compared to those whose disease was in remission. ROC curve analysis suggested that the LRG level was more useful than the CRP or matrix metalloproteinase 3 level or the erythrocyte sedimentation rate in discriminating between remission and active disease during therapy with tocilizumab. In monkeys treated with IL-6 blockade, joint scores were more closely correlated with LRG levels than with CRP levels. Histologic analysis of joints revealed that LRG levels correlated significantly with granulomatous tissue formation, cartilage degeneration, and bone destruction in IL-6 blockade-treated monkeys with low levels of CRP.Under conditions of IL-6 inhibition, LRG was more useful than other biomarkers in discriminating between active and inactive disease in human RA and in detecting joint inflammation in experimental arthritis. LRG may serve as a convenient biomarker for RA disease activity during IL-6 blockade treatment.
The airway microbiota is significantly altered in subjects with eosinophilic asthma
Authors: Asger Sverrild, Pia Kiilerich, Celeste Porsbjerg, Anders Bergqvist, Jonas Erjefält, Karsten Kristiansen, Vibeke Backer
Journal: European Respiratory Journal (2014)

Rationale

In rodents commensal bacteria in gut are critical for normal maturation of the immune system and microbiota alterations have been linked to development of eosinophilic airway inflammation. However, no study has yet related airway microbiota composition and airway inflammation in humans with asthma.

Aim

To relate airway eosinophilia to the composition of the airway microbiota in subjects with asthma.

Methods

In 20 steroid-free, non-smoking subjects with asthma bacterial DNA was extracted from broncho-alveolar lavage (BAL) and subjected to Illumina MiSeq sequencing of the 16S rDNA V4 region. Eosinophils in submucosa were quantified by immunohistochemichal identification and computerized image analysis. Asthmatics were divided into eosinophil low and eosinophil high using the median as cut-off.

Results

Microbiota diversity was lower and microbiota composition was significantly different in BAL from eosinophil high asthma compared to eosinophil low asthma. Bacteroidetes, Firmicutes, Proteobacteria, Fusobacteria and Actinobacteria were identified in all samples and accounted for more than 97% of the microbial load. The proportion of Bacteroidetes was reduced in eosinophil high asthma compared to eosinophil low (median [IQR]: 0.17 [0.11] vs. 0.29 [0.16], p=0.009), whereas the proportion of Proteobacteria was increased (median [IQR]: 0.33 [0.11] vs. 0.25 [0.09], p=0.035). The degree of eosinophilia was negatively correlated with the proportion of Bacteroidetes, rho(s): -0.69, p=0.001.

Conclusion

The airway microbiota is significantly altered in eosinophil high asthma, suggesting dysbiosis of the airway microbiome corresponding to the degree of eosinophilia.
A controlled trial of recombinant human granulocyte-macrophage colony- stimulating factor after total body irradiation, high-dose chemotherapy, and autologous bone marrow transplantation for acute lymphoblastic leukemia or malignant lymphoma
Authors: H Link, MA Boogaerts, AM Carella, A Ferrant, H Gadner, NC Gorin, I Harabacz, JL Harousseau, P Herve, J Holldack
Journal: Blood (1992)
Abstract 13178: Bicuspid Aortic Valve and Marfan Syndrome: Two Strikes?
Authors: Kathryn W Holmes, G M Silberbach, Preiss Liliana, Cheryl L Maslen, H C Dietz, William J Ravekes, Scott A LeMaire, Dianna M Milewicz, Richard Devereux, Mary J Roman, Reed E Pyeritz, Ralph Shohet, Nazli McDonnell, Barbara Y Kroner, Eagle Kim, Jennifer P Habashi, Eser Tolunay, Howard K Song
Journal: Circulation (2013)

Objective: To determine the morbidity associated with a diagnosis of bicuspid aortic valve (BAV) and Marfan syndrome (MFS) versus MFS alone. Methods: We performed a retrospective cross-sectional an...
Costs of exacerbations in COPD
Authors: Sven-Arne Jansson, Helena Backman, Eva Rönmark, Bo Lundbäck, Anne Lindberg
Journal: European Respiratory Journal (2012)

Background   Chronic obstructive pulmonary disease (COPD) is one of the most common chronic and disabling diseases worldwide, and exacerbations affect resource burden and healthcare costs.   Aim   To examine the costs of exacerbations in relation to degree of severity of COPD and of exacerbations.   Methods   The study sample was identified in earlier clinical examinations of general population cohorts within the OLIN (Obstructive Lung Disease in Northern Sweden) studies. The cohort consisted initially of 993 subjects with COPD according to the GOLD spirometric criteria. In 2009-2010, telephone interviews on resource utilization were made to a sample of 244 subjects, stratified by disease severity. Interviews were performed quarterly to minimize the risk of recall bias. Exacerbations were identified by asking questions on extra resource use due to respiratory problems, and were divided into different levels of severity, depending on intensity of resource use.   Results   At least one exacerbation was reported by 84 subjects (36%). A significant relationship was found between severity of exacerbations and costs. The mean annual total cost per exacerbation was: €9 (mild), €21 (mild/moderate), €205 (moderate), and €2,715 (severe). A significant relationship was also found between severity of COPD and costs. The mean annual total cost according to disease severity was: €71 (mild), €209 (moderate), €1,133 (severe), and €3,298 (very severe). The prevalence-weighted cost of all exacerbations for an average subject with COPD was about €200, accounting for about 35% of the direct costs of COPD.   Conclusions   The costs for exacerbations increase considerably by severity of exacerbation and also by severity of COPD. The prevention of exacerbations could be very cost-effective.
Influence of acupuncture on type I hypersensitivity itch and the wheal and flare response in adults with atopic eczema – a blinded, randomized, placebo‐controlled, crossover trial
Authors: F. Pfab, J. Huss‐Marp, A. Gatti, J. Fuqin, G. I. Athanasiadis, D. Irnich, U. Raap, W. Schober, H. Behrendt, J. Ring, U. Darsow
Journal: Allergy (2009)

Itch is a major symptom of allergic skin disease. Acupuncture has been shown to exhibit a significant effect on histamine-induced itch in healthy volunteers. We investigated the effect of acupuncture on type I hypersensitivity itch and skin reaction in a double-blind, randomized, placebo-controlled, crossover trial.An allergen stimulus (house dust mite or grass pollen skin prick) was applied to 30 patients with atopic eczema before (direct effect) and after (preventive effect) two experimental approaches or control observation: acupuncture at points Quchi and Xuehai [verum acupuncture (VA), dominant side], 'placebo-point' acupuncture (PA, dominant side), no acupuncture (NA). Itch intensity was recorded on a visual analogue scale. After 10 min, wheal and flare size and skin perfusion (via LASER-Doppler) were measured at the stimulus site, and the validated Eppendorf Itch Questionnaire (EIQ) was answered.Mean itch intensity was significantly lower in VA (35.7 +/- 6.4) compared to NA (45.9 +/- 7.8) and PA (40.4 +/- 5.8) regarding the direct effect; and significantly lower in VA (34.3 +/- 7.1) and PA (37.8 +/- 5.6) compared to NA (44.6 +/- 6.2) regarding the preventive effect. In the preventive approach, mean wheal and flare size were significantly smaller in VA (0.38 +/- 0.12 cm(2)/8.1 +/- 2.0 cm(2)) compared to PA (0.54 +/- 0.13 cm(2)/13.5 +/- 2.8 cm(2)) and NA (0.73 +/- 0.28 cm(2)/15.1 +/- 4.1 cm(2)), and mean perfusion in VA (72.4 +/- 10.7) compared to NA (84.1 +/- 10.7). Mean EIQ ratings were significantly lower in VA compared to NA and PA in the treatment approach; and significantly lower in VA and PA compared to NA in the preventive approach.Acupuncture at the correct points showed a significant reduction in type I hypersensitivity itch in patients with atopic eczema. With time the preventive point-specific effect diminished with regard to subjective itch sensation, whereas it increased in suppressing skin-prick reactions.
Mental health status and community adjustment after treatment in a residential treatment program for homeless veterans
Authors: C Leda, R Rosenheck
Journal: American Journal of Psychiatry (1992)

An uncontrolled outcome study was conducted to examine clinical improvement and the relationship of psychiatric and substance abuse problems, community adjustment, and housing status among homeless veterans who participated in a multisite residential treatment program.The study was performed at three U.S. Department of Veterans Affairs medical centers in Florida, Ohio, and California. Baseline, discharge, and 3-month postdischarge follow-up data were collected for 255 veterans admitted to the Domiciliary Care for Homeless Veterans Program. Multiple dimensions of outcome were examined, including psychiatric symptoms, alcohol abuse, drug abuse, social contacts, income, employment, and housing.Program participation was found to be associated with improvement in all areas of mental health and community adjustment. Improvement in psychiatric symptoms was associated with superior housing outcomes and improvement in community adjustment. When correlates of improvement in alcohol and drug abuse were examined, only one of eight possible relationships was found to be significant: improvement in alcohol problems was positively associated with improvement in employment.Homeless mentally ill veterans derive clear benefits from participation in a multidimensional residential treatment program. Improvement in mental health problems, however, is weakly linked to improvement in other areas, suggesting that treatment programs may have to attend separately to multiple domains of life adjustment.