tbuckley/cabot-search huggingface dataset:
Surgical/pathologic-stage migration confounds comparisons of gastric cancer survival rates between Japan and Western countries.
Authors: A M Bunt, J Hermans, V T Smit, C J van de Velde, G J Fleuren, J A Bruijn
Journal: Journal of Clinical Oncology (1995)

PURPOSE Possible causes underlying the substantial differences in gastric cancer survival rates observed between Japan and the West were examined in a randomized trial comparing the Western R1 resection with limited lymphadenectomy and the Japanese R2 resection with extended lymphadenectomy. PATIENTS AND METHODS The effect of four factors associated with lymphadenectomy on microscopic tumor-node-metastasis (TNM) staging, and on stage-specific survival rates was assessed in 473 curatively resected patients. RESULTS After application of extended lymphadenectomy, additional information on N status was available, only in R2 resections with up-staging to N2 status in 30% of patients. The calculated effect of this stage migration on known 5-year survival rates was as follows: an increase of 1% in TNM stage Ia, 2% in Ib, 7% in II, 15% in IIIa, and 15% in IIIb. A further increase in survival was observed by stage migration to N3 or N4 status, due to selective extension of lymphadenectomy to clinically overt metastases located outside the allocated level of clearance (contamination). Incomplete lymphadenectomy of N1- or N2-level stations indicated for dissection (noncompliance) demonstrates that more migration can occur when strictly adhering to the protocol. Examining more nodes per N level (diligence) induces even more migration, since the number of nodes that were histologically examined per N level correlated significantly with nodal status (lymph node-negative [N-] or lymph node-positive [N+]). CONCLUSION These factors explain, at least partially, superior stage-specific survival rates after R2 compared with R1 resections, without a real survival benefit in individual patients.
Mutations in the filaggrin gene in Han Chinese patients with atopic dermatitis
Authors: H. Zhang, Y. Guo, W. Wang, M. Shi, X. Chen, Z. Yao
Journal: Allergy (2010)

Recently, loss-of-function mutations in the filaggrin gene (FLG) have been identified as the cause of ichthyosis vulgaris (IV) and also predisposing factors for atopic dermatitis (AD) and AD-associated phenotypes. Until now, over thirty mutations in FLG have been identified in patients with IV and AD, but the FLG mutation spectrum is not clear for Chinese Han patients with AD. This study aimed to investigate the role of FLG mutations in AD and AD-associated phenotypes in a Chinese population.We carried out a comprehensive sequencing of the entire FLG coding region in 261 Han AD patients.In our research, we identified ten novel mutations (R826X, 3222del4, R1140X, 4271delAA, Q1790X, 5757del4, 6834del5, 6950del8, S2706X and K4671X) and eight reported mutations (441delA, R501X, 3321delA, R1474X, Q2417X, E2422X, 7945delA and R4306X) in FLG. FLG mutations were present in 31.4% of our AD patients. Mutations 3321delA and K4671X, with a frequency of 14.6% and 9.2%, respectively, were two of the most common mutations in this AD cohort. FLG null alleles (compound genotypes) were significantly associated with AD (P < 0.001) and AD associated with food sensitization (P = 0.012). However, we did not observe a positive association between FLG mutations and other AD-associated phenotypes, including asthma, allergic rhinitis and elevated total serum IgE level.Our study increases the total number of reported FLG mutations. Moreover, we further confirm that FLG mutations are strong predisposing factors for AD in Han Chinese.
Treprostinil prodrugs for pulmonary arterial hypertension evaluated in cAMP profiling studies in live CHO-K1 cells
Authors: Kuan-Ju Chen, Jane Ong, Vlad Malinin, Franziska Leifer, Donna Omiatek, Zhili Li, Richard Chapman, Walter Perkins, Renu Gupta
Journal: European Respiratory Journal (2014)

Introduction:  Treprostinil (TRE), a prostacyclin analogue used to treat pulmonary arterial hypertension (PAH), reportedly binds prostaglandin E receptor 2 (PTGER2) with high potency and increases cAMP levels in cells expressing PTGER2. Inclusion of human PTGER2 to pGloSensor TM  assay would increase the sensitivity of the assay enabling subtle changes in cAMP to be monitored in live cells. Here, we evaluated the functional activities of TRE and C2- to C16- alkyl chain derivatives of treprostinil (TRE-prodrugs) using an enhanced pGloSensor-human PTGER2 assay in CHO-K1 cells.   Methods:  CHO-K1 cells were transiently co-transfected with pGloSensor-22F and human PTGER2 plasmids. Transfected cells, thawed overnight and equilibrated at room temperature were treated with TRE and TRE-prodrugs. cAMP levels were measured every 5 minutes for 8 hours and the increase in activation relative to control was calculated. cAMP profiles and EC 50  values for TRE and TRE-prodrugs were determined.   Results:  The enhanced pGloSenor assay augmented cAMP sensitivity by almost 10 fold. Treatment with C2- to C16- derivatized TRE prodrugs displayed different delayed-released cAMP profiles with sustained activities that appeared to depend upon the length of alkyl chain added. TRE showed an immediate response which declined over time and then plateaued. EC 50  curves showed that all TRE-prodrugs were less potent than TRE.   Conclusions:  With the enhanced cAMP detection system, we were able to distinguish activities between TRE and TRE-prodrugs and predict that because of their slower conversion the longer alkyl chain TRE-prodrugs are possible candidates for an inhaled sustained delivery formulation.
Tuberculosis in Bucharest continues to be a concern
Authors: Emilia Tabacu, Gilda Popescu, Nicoleta Cioran, Cristian Didilescu
Journal: European Respiratory Journal (2013)

Bucharest, Romania's capital, a great urban agglomeration with almost 2 000 000 inhabitants and a population density of 8 528 inhabitants/Km², was confronted with a rate, sometimes wery high of tuberculosis cases for a long time period. Objective: The study of the main indicators of the TB endemic in Bucharest between years 2001 - 2012. Material and method: We used the information existing in the official documents of the information system within the National Program of Tuberculosis Control. Trends of TB endemic were constantly favorable in Bucharest in the recent years: number of new cases and relapses decreases with 1678 (number of new case with 1623 and of relapses with 155), incidence rate with 54,4% and incidence rate in children with 57,9%. Tuberculosis mortality in Bucharest, a marker for severity of the endemic were 11,7%ooo in 2001 and 5,1%ooo in 2010. The incidence continues to be greaterin males than in females. The source density was reduced from 12 sources/Km2 in 2001 to 5 sources/Km2 in 2012. A negative aspect of TB endemic in Bucharest is a number of severe forms of TB, TB-HIV, MDR-TB or deaths in children under 15 years old. DOTS strategy implemented in Bucharest proved to be an important weapon for TB control, success rate increase yearly. Conclusio n: The strict monitoring of the treatment is the medical key in fighting the tuberculosis.
Anti-DNA Antibody in Serum Measured by Radioimmunoassay (Fair Technique).
Authors: R. Manthorpe, J. Palif, G. Bendexen
Journal: Allergy (1978)

Anti‐DNA antibody determination in strum is increasingly used because it supports the diagnosis of systemic lupus erythematosus (SLE) with high selectivity. The present work evaluates several of the technical variables of the Fair radioimmunoassay for anti‐DNA antibody determination and describes a recommendable procedure, emphasizes the most important sources of error and gives the range of normal blood donors and a group of hospital patients without SLE.
Effect of pulmonary hemodynamics on the prognosis of patients with emphysematous COPD after LVRS
Authors: Motokimi Shiraishi, Yushi Yoshida, Takemasa Matumoto, Taishi Harada, Hiroshi Ishii, Masaki Fujita, Kentarou Watanabe
Journal: European Respiratory Journal (2014)

Objective :

Ventilation-perfusion ratio is different in emphysematous COPD and non-emphysematous COPD, depending on the destruction of pulmonary vascular bed and airway disease.To assess the relationship between the prognosis and pulmonary hemodynamics in patients with emphysematous COPD after Lung Volume Reduction Surgery (LVRS).

Subjects :

Twenty-sevenpatients with emphysematous COPD who had undergone right heart catheterization (RHC) within 6 months after LVRS at our hospital from April 1997 to March 2000 (BMI 1.9±3.1; %FVC 90±18%; %FEV1 39±15%) were enrolled for the study. RHC was performed under both room air and 100% oxygen breathing. Prognosis at the time of March 2010 was compared using Kaplan-Meier survival curve. Death from cancer and cerebral infarction were excluded from the analysis.

Results :

Cardiac Index (CI) , stroke Index (SI) and mean pulmonary arterial pressure (Pap) were 2.8±0.4L/min/m2, 37±11 mL/beat/m2 and 22.4±4.9 mmHg, respectively, under the room air breathing. Under 100% oxygen breathing, CI, SI and Ppa were 2.6±0.4 L/min/m2, 37±9 mL/beat/m2 and 19.6±4.2 mmHg, respectively. Kaplan-Meier survival curves comparing two groups divided by the median values of %FVC, %FEV1, CI, SI and Ppa demonstrated that patients with lower SI had a shorter survival than those with higher SI under room air breathing (p<0.05) , and patients with higher Ppa tended to be worse in prognosis than those with lower Ppa under 100% oxygen breathing (p=0.053).

Conclusion :

Impaired cardiac function may have a greater effect on the survival than impaired ventlatory function, and fixed higher Ppa refractory to 100% oxygen may show a poorer prognosis in patients with emphysematous COPD after LVRS.
Phase I Study of Recombinant Human CD40 Ligand in Cancer Patients
Authors: Robert H. Vonderheide, Janice P. Dutcher, Jeanne E. Anderson, S. Gail Eckhardt, Katherine F. Stephans, Betty Razvillas, Susan Garl, Michael D. Butine, Vicki P. Perry, Richard J. Armitage, Richard Ghalie, Dania A. Caron, John G. Gribben
Journal: Journal of Clinical Oncology (2001)

To determine the toxicity, maximum-tolerated dose (MTD), and pharmacokinetics of recombinant human CD40 ligand (rhuCD40L) (Avrend; Immunex Corp, Seattle, WA), suggested in preclinical studies to mediate cytotoxicity against CD40-expressing tumors and immune stimulation.Patients with advanced solid tumors or intermediate- or high-grade non-Hodgkin's lymphoma (NHL) received rhuCD40L subcutaneously daily for 5 days in a phase I dose-escalation study. Subsequent courses were given until disease progression.Thirty-two patients received rhuCD40L at three dose levels. A total of 65 courses were administered. The MTD was 0.1 mg/kg/d based on dose-related but transient elevations of serum liver transaminases. Grade 3 or 4 transaminase elevations occurred in 14%, 28%, and 57% of patients treated at 0.05, 0.10, and 0.15 mg/kg/d, respectively. Other toxicities were mild to moderate. At the MTD, the half-life of rhuCD40L was calculated at 24.8 +/- 22.8 hours. Two patients (6%) had a partial response on study (one patient with laryngeal carcinoma and one with NHL). For the patient with laryngeal cancer, a partial response was sustained for 12 months before the patient was taken off therapy and observed on no additional therapy. Three months later, the patient was found to have a complete response and remains biopsy-proven free of disease at 24 months. Twelve patients (38%) had stable disease after one course, which was sustained in four patients through four courses.The MTD of rhuCD40L when administered subcutaneously daily for 5 days was defined by transient serum elevations in hepatic transaminases. Encouraging antitumor activity, including a long-term complete remission, was observed. Phase II studies are warranted.
Mean radiation dose to the heart in patients with left breast cancer with and without breath-hold technique.
Authors: Geraldine M. Jacobson, Christopher Nicholas Watson, Jianjun Zhang, Sijin Wen, Nicole Helen Bunda-Randall
Journal: Journal of Clinical Oncology (2014)

85 Background: Mean heart dose (MHD) from breast irradiation has been correlated with late risk of ischemic heart disease. We previously reported using 3-D conformal radiation with field-in-field forward planning and heart blocking; MHD is substantially lower than described for patients treated before 2001. To further reduce MHD, we treated eligible patients with left breast cancer with breath hold technique. We compared the MHD with and without breath hold technique. Methods: We reviewed 45 radiation treatment plans of patients treated to the left breast from 5/2013-5/2014. All patients were evaluated for breath hold technique. Criteria were ability to hold the breath for 20 seconds and a stable chest position. 18 patients were treated with breath hold (BH), 27 patients with non-breath hold (NBH). All treatment plans were CT-based, 3-D conformal with field-in- field forward planning and heart blocking. Two treatment regimens were used: hypofractionation (HF) (16 x 2.66 Gy, no boost) or standard fractionation (SF) (46.8-50.4 Gy, +/- 10 Gy boost). Fisher's exact test and t-test were used to assess the data between MHD with breath hold (BH) and without (NBH). Results: Average MHD was 1.03 Gy (0.59-1.7) in BH patients, in comparison to 1.57 Gy (0.89-2.50) in NBH patients p&lt;0.0001). MHD was associated with total breast dose (p=0.01) and BH patients were younger, average age 55.78 years (21.41-48.37) vs NBH, average 62.78 years (38-82). There was no association between breath hold and BMI. BH BMI average 34.12 (21.41-48.37), NBH average BMI 32.6 (20.58-44.71) p=0.46. Conclusions: Patients treated with radiation to the left breast with breath hold technique had significantly lower MHD than those treated with non-breath hold. (p=0.0001) Breath hold eligible patients tended to be younger; there was no relation between breath hold eligibility and BMI.
Update on Immunotherapy for Melanoma
Authors: Antoni Ribas
Journal: Journal of the National Comprehensive Cancer Network (2006)

Several experimental immunotherapy approaches and standard therapy with high doses of interleukin (IL)-2 can cause prolonged objective responses in some patients with metastatic melanoma. Experimental immunotherapy approaches in clinical development include 1) cytokines such as IL-7 and IL-21, 2) cytokine–antibody fusion proteins or immunocytokines, 3) whole tumor cell vaccines, 4) genetically modified tumor cells, 5) heat shock protein vaccines, 6) peptide vaccines, 7) dendritic cells pulsed with tumor antigens, 8) tumor antigen-naked DNA vectors, 9) recombinant viral vectors (either alone or in a prime boost schedule), 10) adoptive transfer of cloned tumor antigen-specific T cells, 11) Toll-like receptor ligands, 12) antagonistic antibodies to the cytotoxic T-lymphocyte antigen 4 (CTLA4, CD152), and 13) activating antibodies to CD40 and CD137 (41-BB). These improved approaches to induce cytotoxic T-cell responses to tumors are based on a more detailed understanding of the immune system activation and regulation. The higher response rates with modern immunotherapy approaches may allow exploration of the molecular mechanisms that make tumor targets sensitive or resistant to immunotherapy.
Evaluation of carotis intima media thickness in COPD patients
Authors: Fahri Halit Besir, Leyla Yilmaz Aydin, Omer Yazgan, Talha Dumlu, Melih Engin Erkan, Elif Onder, Hulya Coskun
Journal: European Respiratory Journal (2012)

Background: Chronic obstructive pulmonary disease (COPD) and atherosclerosis may occur due to similar risk factors and have a significant cause of morbidity and mortality. In this study to assess the relationship between COPD and atherosclerosis; carotis intima media thickness (CIMT) of COPD patients and adult healthy individuals with normal BMI and metabolic parameters compared.  Method: 2230 participants aged between 18 -92; 46 patients diagnosed with COPD according to clinical features and pulmonary function tests the study, 47 healthy controls who do not have exclusion criteria were evaluated. Doppler ultrasound was performed for the assessment of CIMT to all participants.  Results: Mean CIMT in COPD group and control group were 0.79 ± 0.16 mm and 0.616 ± 0.1 mm, respectively (p   Conclusion: Persistent low-grade systemic inflammation in COPD and atherosclerotic disease may possibly have been reported a factor in both pathologies. Early atherosclerosis and cardiovascular risks in adults with COPD increases independent of other risk factors. CIMT which shows direct proportion with age and inverse proportion with FEV1% is a non-invasive, easily applicable and cheap method that can be used in determining the risk of atherosclerosis.
Evaluation of genome-wide chromatin library of Stat5 binding sites in human breast cancer.
Authors: Matthew J LeBaron, Jianwu Xie, Hallgeir Rui
Journal: Molecular Cancer (2005)

There is considerable interest in identifying target genes and chromatin binding sites for transcription factors in a genome-wide manner. Such information may become useful in diagnosis and treatment of disease, drug target identification, and for prognostication. In cancer diagnosis, patterns of transcription factor binding to specific regulatory chromatin elements are expected to complement and enhance current diagnostic predictions of tumor behavior based on protein and mRNA analyses. Signal transducer and activator of transcription-5 (Stat5) is a cytokine-activated transcription factor implicated in growth and progression of many malignancies, including hematopoietic, prostate, and breast cancer. We have explored immunoaffinity purification of Stat5-bound chromatin from breast cancer cells to identify Stat5 target sites in an unbiased, genome-wide manner. In this report, we evaluate the efficacy of a Stat5-bound chromatin library to identify valid Stat5 chromatin binding sites within the oncogenome of T-47D human breast cancer cells. A general problem with cloning of immunocaptured, transcription factor-bound chromatin fragments is contamination with non-specific chromatin. However, using an optimized strategy, five out of ten randomly selected clones could be experimentally verified to bind Stat5 both in vitro and in vivo as tested by electrophoretic mobility shift assay and chromatin immunoprecipitation, respectively. While there was no binding to fragments lacking a Stat5 consensus binding sequence, presence of a Stat5 binding sequence did not assure binding. A chromatin library coupled with experimental validation may productively identify novel in vivo Stat5 chromatin binding sites in cancer, including abnormal regulatory sites in tumor-specific neochromatin.
Isolation of an amikacin-resistant Escherichia coli strain after tobramycin treatment of previous recurrent episodes of respiratory tract infections caused by Pseudomonas aeruginosa
Authors: J. Ruiz, S. Bertran, G. Sauca, A. Julià, X. Vila, E. Gómez, M. T. Jiménez de Anta, J. Vila
Journal: Clinical Microbiology and Infection (2005)
Androgen Deprivation Therapy–Linked Cardiovascular Disease Risk: Still Unresolved:
Authors: Anna Azvolinsky
Journal: JNCI Journal of the National Cancer Institute (2015)

In a new study, men with prostate cancer who received androgen deprivation therapy (ADT) in the form of gonadotropin-releasing hormone (GnRH) agonists had a 21% higher risk of cardiovascular disease (CVD) than same-age men without prostate cancer. Appearing in the Journal of Clinical Oncology, the study (doi:10.1200/JCO.2014.59.1792) adds evidence to the still-unresolved question of whether ADT is associated with an increased risk of CVD. Those men who had a surgical orchiectomy (testicle removal) to lower androgen levels had a 16% higher risk of CVD than the control group.
Successful treatment of multidrug-resistant tuberculosis through a binational consortium
Authors: Rafael Laniado-Laborin, Kathleen Moser, Julia Estrada-Guzman, Hector Perez
Journal: European Respiratory Journal (2011)

Background:  Multidrug resistant tuberculosis (MDR-TB) is expensive to diagnose and treat, and requires a high degree of expertise by the laboratory and medical team, resources that may be scarce in regions with the highest rates of MDR-TB. Baja California, a Mexican state that shares the international border with California, United State of America (USA) has the highest rate of tuberculosis in the country.   Methods:  A binational consortium constituted by USA and Mexico partners started a program dedicated to the diagnosis and treatment of MDR-TB in the region. All regimens were individualized according to drug susceptibility tests with a mean of 5.38 drugs used per regimen. Strict directly observed therapy was enforced in every case.Funding from USAID, Rotary International and private donors has augmented existing program funds   Results:  From June 2006 through December 2010 forty patients started treatment. The lapse between their initial diagnosis and the referral to the program was 43.6 months; they had received 2.15 treatment regimens in the past. Their strains were resistant to 4.15 drugs; 2 patients (5.1%) had an XDR-TB strain.  All patients converted their culture on treatment, on average after 4.0 months. Nineteen patients (47.5%) have been discharged as cured (mean follow-up after discharge 6.8 months), 3 patients died (7.5%) and one patient abandoned (2.5%).   Conclusions:  Highly resistant cases can be cured under a well organized, outpatient program. In this consortium the USA partner introduced program elements that have been gradually integrated into the state TB program. After 5 years, the consortium continues to fine-tune sustainable interventions and provides quality control.
Exercise ventilatory inefficiency is an independent predictor of mortality in patients with pulmonary arterial hypertension
Authors: Eloara Ferreira, Roberta Ramos, Jaquelina Arakaki, Priscila Barbosa, Erika Treptow, L. Eduardo Nery, Fabrício Valois, J. Alberto Neder
Journal: European Respiratory Journal (2012)

Rationale:  An excessive ventilatory (V´E) response to CO 2  output (V´CO 2 ) during incremental exercise is a strong prognosticator in cardiovascular diseases. The role of ΔV´E/ΔV9CO 2  to predict mortality in pulmonary arterial hypertension (PAH), however, remains to be demonstrated.  Objective : To investigate the value of increased ΔV9E/ΔV9CO 2  as a negative prognostic marker in PAH.  Methods : 80 patients with PAH who underwent a ramp-incremental cardiopulmonary exercise test (CPET) were followed-up for 5 yrs. ΔV9E/ΔV9CO 2  slope was calculated to the respiratory compensation point (ΔV9E/ΔV9CO 2(start-RCP) ) or to peak exercise (ΔV9E/ΔV9CO 2(start-PEAK) ).  Results:  14 patients (17.5 %) died of PAH-related causes. Compared to survivors, deceased patients were younger and had lower peak O 2  uptake, O 2  pulse, and oxyhemoglobin saturation but, regardless the method of calculation, higher ΔV9E/ΔV9CO 2  (p 0.05). The best cutoff to death prediction was higher for ΔV9E/ΔV9CO 2(start-PEAK)  (>55) than ΔV9E/ΔV9CO 2(start-RCP)  (>45). An univariate analysis revealed that the former variable was superior to the later on this regard (p= 0.004  vs.  0.02).In fact, a multiple regression analysis showed that resting heart rate (hazard ratio (95% CI)= 1.04 (1.00-1.08); p=0.03) and ΔV9E/ΔV9CO 2(start-PEAK)  (1.04 (1.01-1.07); p= 0.006) were the only independent predictors of mortality.  Conclusions : A resting variable (heart rate) and an effort-independent marker of ventilatory inefficiency (ΔV9E/ΔV9CO 2(start-PEAK) ) are clinically-useful markers of poor prognosis in patients with PAH.