tbuckley/cabot-search huggingface dataset:
Association of Antibody Induction with Short- and Long-Term Cause-Specific Mortality in Renal Transplant Recipients
Authors: Herwig-Ulf Meier-Kriesche, Julie A. Arndorfer, Bruce Kaplan
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. A total of 73,707 primary renal transplants reported to the USRDS between 1988 and 1997 were examined to investigate the cause-specific risk for patient death associated with anti-lymphocyte antibody induction therapy (ABI). Cox proportional hazard models were used to estimate the relative risk of the use of ABI and patient death. All Cox models were corrected for potential confounding variables, such as age, gender, race, HLA mismatch, panel reactive antibody, delayed graft function, cold ischemia time, time since start of dialysis, etiology of end-stage renal disease, cytomegalovirus risk group, donor source (living or cadaveric), era effect, and immunosuppressive therapy. Primary study end points were patient death with functioning graft (DWFG) and overall patient death, including death after graft loss. Early patient death (deaths within the first 6 mo after renal transplantation) and late death (deaths after 6 mo post–renal transplantation) were investigated separately. Additionally, specific causes of death were investigated. ABI was associated with a significant risk for late death after renal transplantation (relative risk [RR] = 1.1; P &lt; 0.001) but not for DWFG (RR = 0.94; P = 0.10). ABI conferred the highest RR for late malignancy–related death (RR = 1.35; P &lt; 0.001). ABI was significantly associated with early deaths due to infection and cardiovascular causes (RR = 1.32 [ P &lt; 0.001] and RR = 1.27 [ P &lt; 0.001], respectively). Kaplan Meier plots confirmed that the risk of ABI for patient death secondary to infectious complications was increased predominately early after transplantation as opposed to late for malignancy-related death. ABI was associated with a significant relative risk for patient death secondary to cardiovascular causes and infectious complications early in the posttransplant period. In addition, ABI was associated with a significant risk for long-term malignancy-related death. The risk of ABI should be taken in context with potential benefits of this therapy.
Mobilization of Peripheral-Blood Stem Cells by Concurrent Administration of Daniplestim and Granulocyte Colony-Stimulating Factor in Patients With Breast Cancer or Lymphoma
Authors: John F. DiPersio, Michael W. Schuster, Camille N. Abboud, Jane N. Winter, Vicki R. Santos, Denise M. Collins, Jeffrey W. Sherman, Charles M. Baum
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To evaluate the safety and hematopoietic activity of daniplestim administered concurrently with granulocyte colony-stimulating factor (G-CSF) for peripheral-blood stem-cell (PBSC) mobilization. PATIENTS AND METHODS: In the initial dose-escalation phase, 25 patients with adenocarcinoma of the breast (AB; 13 patients) or lymphoma (12 patients) were given daniplestim at doses ranging from 0.1 to 3.75 μg/kg/d plus G-CSF 10 μg/kg/d. In the randomized phase, 52 patients with AB (27 patients) or lymphoma (25 patients) were randomized within disease categories to the daniplestim dose chosen in the dose-escalation phase plus G-CSF 10 μg/kg/d (D+G) or placebo plus G-CSF 10 μg/kg/d (P+G) for up to 7 days. RESULTS: A daniplestim dose of 2.5 μg/kg/d was chosen for further study because it was hematopoietically active and had an acceptable side-effect profile. In the randomized phase, in patients with AB, D+G was associated with a higher probability (P = .0696) of collecting ≥ 2.5 × 10 6 CD34 + cells/kg and significantly higher circulating CD34 + cell counts (P = .0498) on days 6 through 9 after the initiation of dosing. The target level was more likely to be reached with additional leukaphereses in the patients given D+G. Patients given P+G did not benefit from additional leukaphereses beyond the first procedure. The type of mobilization did show a trend toward a shorter duration of neutropenia in the D+G group. The adverse events with D+G consisted largely of mild to moderate flu-like symptoms, including headache and fever, and occurred more frequently than with P+G. CONCLUSION: Daniplestim administered at 2.5 μg/kg/d is tolerable and active when combined with G-CSF, and the combination may prove more effective than G-CSF alone in promoting the collection of adequate numbers of CD34 + cells for PBSC infusion in patients with AB.
Treatment with PF-04449913, an oral smoothened antagonist, in patients with myeloid malignancies: a phase 1 safety and pharmacokinetics study
Authors: Giovanni Martinelli, Vivian G Oehler, Cristina Papayannidis, Rachel Courtney, M Naveed Shaik, Xiaoxi Zhang, Ashleigh O'Connell, Karen R McLachlan, Xianxian Zheng, Jerald Radich, Michele Baccarani, Hagop M Kantarjian, Wendy J Levin, Jorge E Cortes, Catriona Jamieson
Journal: The Lancet Haematology (2015)
Targeted Prodrug Approaches for Hormone Refractory Prostate Cancer
Authors: Herve Aloysius, Longqin Hu
Journal: Medicinal Research Reviews (2014)

Due to the propensity of relapse and resistance with prolonged androgen deprivation therapy (ADT), there is a growing interest in developing non-hormonal therapeutic approaches as alternative treatment modalities for hormone refractory prostate cancer (HRPC). Although the standard treatment for HRPC consists of a combination of ADT with taxanes and anthracyclines, the clinical use of chemotherapeutics is limited by systemic toxicity stemming from nondiscriminatory drug exposure to normal tissues. In order to improve the tumor selectivity of chemotherapeutics, various targeted prodrug approaches have been explored. Antibody-directed enzyme prodrug therapy (ADEPT) and gene-directed enzyme prodrug therapy (GDEPT) strategies leverage tumor-specific antigens and transcription factors for the specific delivery of cytotoxic anticancer agents using various prodrug-activating enzymes. In prostate cancer, overexpression of tumor-specific proteases such as prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) is being exploited for selective activation of anticancer prodrugs designed to be activated through proteolysis by these prostate cancer-specific enzymes. PSMA- and PSA-activated prodrugs typically comprise an engineered high-specificity protease peptide substrate coupled to a potent cytotoxic agent via a linker for rapid release of cytotoxic species in the vicinity of prostate cancer cells following proteolytic cleavage. Over the past two decades, various such prodrugs have been developed and they were effective at inhibiting prostate tumor growth in rodent models; several of these prodrug approaches have been advanced to clinical trials and may be developed into effective therapies for HRPC.
Prognostic value of ERCC1 expression in advanced non-small cell lung cancer (NSCLC)
Authors: Jens Kollmeier, Torsten Blum, Daniel Misch, Andreas Roth, Christian Boch, Wolfram Gruening, Catharina Crolow, Sergej Griff, Thomas Mairinger, Torsten T. Bauer
Journal: European Respiratory Journal (2012)

Background: The immunohistochemical (IHC) detection of the excision repair cross-complementation group 1” (ERCC1) protein in resected NSCLC is prognostically relevant. Pts with ERCC1-neg. tumors appear to benefit from adjuvant cisplatin-based chemotherapy (Ctx), whereas pts with ERCC1-pos. tumors do not.

Aim: We compared survival of pts with non-operated NSCLC III/IV according to ERCC1.

Methods: We analyzed 398 pts (m=248, f=150) newly diagnosed with NSCLC stage III/IV between 10/2009 and 12/2010. Prospectively, ERCC1 expression determined by IHC was measured and indicated as H-score. Pts where no IHC and/or no H-score could be performed were excluded.

Results : 271/398 cases (68%) were suitable for IHC. 175/271 (65%) of tumors were ERCC1 pos., 96/271 (35%) ERCC1 neg. 177/271 (65%) received platin. Survival times in days were (mean ± SEM): platin+/ERCC1- 404 ± 25 (n=67); platin+/ERCC1+ 346 ± 23 (n=110); platin-/ERCC1- 144 ± 23 (n=29); platin-/ERCC1+ 268 ± 33 (n=65). In Cox hazard regression analysis, the factors platinum (p<0.001) and ERCC1 (p=0.01) were not independent (p=0.001, interaction term).

![Figure][1] 



Conclusions : Pts with palliative platin-based Ctx for advanced NSCLC had significantly longer OS when the tumor showed no significant ERCC1 expression. In pts who did not have platin-based Ctx, the absence of ERCC1 expression was prognostically unfavorable. This study confirms observations from adjuvant therapy also for palliative Ctx.

 [1]: pending:yes
Muscle function in patients with COPD
Authors: Margareta Emtner, Mikael Andersson, Anne Marie Grönberg, Linda Moberg, Frode Slinde, Ulla Svantesson
Journal: European Respiratory Journal (2012)

Introduction: Patients with COPD are likely to decrease their level of physical activity due to dyspnea which often results in impaired muscle function. The aim of this study was to make a survey of muscle function in patients with COPD and to relate these findings to health related quality of life.

Methods: One hundred patients with COPD (FEV1 % predicted, 43±17, stage II-IV) (59 % women) with a mean age of 64±7 years for the women and 67±6 years for the men participated in the study. All patients carried out performance based tests including isometric muscle strength of the quadriceps muscle, hand grip strength, and 30 meter walking test (self chosen and maximal speed). Health related quality of life was assessed with SF-36 and SGRQ.

Results: Muscle strength in the quadriceps muscle reached 85 % in patients with COPD in comparison with a reference group of healthy persons. Comparable values for hand grip strength were 90 % and walking speed 74-80 %. Maximal walking speed correlated with SF-36 (r=0.38, p<0.001) and SGRQ (r=0.36, p=0.001).

Conclusion: Muscle function is generally impaired in patients with COPD, and should be measured in addition to lung function.
Suppression of In Vivo Growth of Mouse Myelomas by Purified Rabbit Antibodies Against Mouse Myeloma Cells2
Authors: Masamichi Yutoku, Allan L. Grossberg, David Pressman
Journal: JNCI Journal of the National Cancer Institute (1974)

Tested for their effects on in vivo growth of different myeloma lines were antibodies against myeloma cell-surface antigens, prepared by the immunization of rabbits with BALB/c mouse myeloma cells- either MOPC104E (an IgM-producing line) or MOPC-21 (an IgG-producing line)- and purified by passage through mice. Anti-MOPC-I04E-cell antibodies most strongly inhibited growth of homologous MOPC-I04E and moderately suppressed growth of myelomas Adj-PC-5 (an IgG-producing line) and Adj-PC-22A (an IgA-producing line), as expected from their pattern of in vitro cytotoxic reactivity. However, they enhanced growth of MOPC-21 cells, which were only weakly sensitive to the in vitro cytotoxicity of anti-MOPC104E- cell antibodies. Anti-MOPC-21-cell antibodies suppressed growth of MOPC-I04E and myeloma Adj-PC-22A but did not inhibit growth of a lymphoma. Although moderately Cytotoxic in vitro for the rapidly growing, homologous MOPC-21 cells, they could not suppress growth of the myeloma in vivo under the injection schedule used to suppress growth of the slower growing MOPC-I04E and Adj-PC-22A myelomas.
Diagnostic value of vascular endothelial growth factor, glycosaminoglycan, cathepsin S, cathepsin H in the discrimination of transudate exudate and benign malignant patients with pleural effusion
Authors: Nalan Göloglu, Cengiz Özge, Gürbüz Polat, Serin Akbayir, Bahar Tasdelen, Eylem Sercan Özgür, Sibel Atis Nayci, Ahmet Ilvan
Journal: European Respiratory Journal (2012)

Pleural effusion is one of the most common problems and it was reported that 4% of the patients appliying internal clinics suffer from pleural effusion. Cathepsin S, cathepsin H, glycosaminoglycan and vascular endothelial growth factor (VEGF) recently parameters are started to be investigated. In this study, 90 patients, who are diagnosed as pleural effusion, were searched proteine, glycose, pH, albumine, lactate dehydrogenase (LDH), colesterol, triglyceride, C-reactive proteine (CRP), amilase and also diagnostic value of cathepsin S, cathepsin H, glycosaminoglycan and VEGF parameters were investigated for the discrimination of transudate exudate and beningn malignant patients with pleural effusions. PS/S cathepsin S, PS cathepsin H, PS/S cathepsin H, PS VEGF and PS/S VEGF parameters were found statistically significant (p=0.033, p=0.001, p=0.016, p=0.014, p=0.015). S cathepsinS, PS cathepsin H, PS/S cathepsin H, PS VEGF, PS/S VEGF, PS GAG parameters were detected statistically significant between transudate and exudate groups (p=0.037, p=0.008, p=0.009, p
Day care attendance, recurrent infections, wheezing and eczema
Authors: Borislav Kamenov, Hristina Stamenkovic, Tatjana Stankovic, Aleksandar Kamenov, Svetlana Kamenov
Journal: European Respiratory Journal (2012)

Background: The majority of studies of recurrent infections, wheezing and eczema are seeking for genetic background, possible immunodeficiency, and atopy. Exposure to pathogens, particularly viruses seems to be very important for aberrations in the development of the immune system that may lead to chronic conditions later in life.  Methods: In order to determine the importance of day care attendance in the pathogenesis of recurrent infections, wheezing and eczema, children aged one to two years, with recurrent infections, wheezing or/and eczema and attending day care were analyzed. The parents from all children were advised to withdraw from day care attendance. On the criterion of the acceptance of withdrawing patients were divided in two groups: I that accepted (53) and II that did not accept such advice (32). Both groups were followed up next 12 months, for the incidence of infections, wheezing and eczema episodes. The excluding criteria for the study were: intolerance/allergy to cow milk and other nutritional allergens, treatment with steroids and antyleukotriens.  Results: During one year follow up in the group that was withdrawn from day care attendance the symptom scores related to respiratory infections reduced by 76%, wheezing by 36% and eczema by 29%.  Conclusion: Our results indicate that withdrawing from day care attendance reduces the symptom scores related to recurrent infections, wheezing and eczema episodes. This suggests that viral infections, the most frequent infections in this age are important for inappropriate development of the immune system and may be a pathogenetic factor in chronic inflammation, asthma and eczema development.
Randomised controlled trial of chest pain units is needed
Authors: S. Goodacre
Journal: BMJ (2000)

EDITOR—Collinson et al audited prognostically important myocardial damage in patients discharged from the emergency department—a large and important healthcare problem.1 The commentary by Kennedy touches on several key issues as well as the obvious limitations of such a study. As Kennedy says, further follow up data on the seven patients with raised concentrations of troponin would be useful.

Kennedy also touched on the issue of definitions. The seven missed Mayday patients …
NCCN Task Force Report: Estrogen Receptor and Progesterone Receptor Testing in Breast Cancer by Immunohistochemistry
Authors: D. Craig Allred, Robert W. Carlson, Donald A. Berry, Harold J. Burstein, Stephen B. Edge, Lori J. Goldstein, Allen Gown, M. Elizabeth Hammond, James Dirk Iglehart, Susan Moench, Lori J. Pierce, Peter Ravdin, Stuart J. Schnitt, Antonio C. Wolff
Journal: Journal of the National Comprehensive Cancer Network (2009)

The NCCN Task Force on Estrogen Receptor and Progesterone Receptor Testing in Breast Cancer by Immunohistochemistry was convened to critically evaluate the extent to which the presence of the estrogen receptor (ER) and progesterone receptor (PgR) biomarkers in breast cancer serve as prognostic and predictive factors in the adjuvant and metastatic settings, and the ability of immunohistochemical (IHC) detection of ER and PgR to provide an accurate assessment of the expression of these biomarkers in breast cancer tumor tissue. The task force is a multidisciplinary panel of 13 experts in breast cancer who are affiliated with NCCN member institutions and represent the disciplines of pathology, medical oncology, radiation oncology, surgical oncology, and biostatistics. The main overall conclusions of the task force are ER is a strong predictor of response to endocrine therapy; ER status of all samples of invasive breast cancer or ductal carcinoma in situ (DCIS) should be evaluated by IHC; IHC measurements of PgR, although not as important clinically as ER, can provide useful information and should also be performed on all samples of invasive breast cancer or DCIS; IHC is the main testing strategy for evaluating ER and PgR in breast cancer and priority should be given to improve the quality of IHC testing methodologies; all laboratories performing IHC assays of ER and PgR should undertake formal validation studies to show both technical and clinical validation of the assay in use; and all laboratories performing IHC assays of hormone receptors in breast cancer should follow additional quality control and assurance measures as outlined in the upcoming guidelines from the American Society of Clinical Oncology and College of American Pathologists.
Differences in Incidence of Reported Asthma Related to Age in Men and Women
Authors: ROBERTO de MARCO, FRANCESCA LOCATELLI, JORDY SUNYER, PETER BURNEY
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Sex differences in asthma prevalence and morbidity, assessed with different methods in different populations, have raised several hypotheses about the different susceptibility to asthma in men and women. However, information on the incidence of asthma by age and sex is limited. The aim of this study was to estimate the age- and sex-specific incidence of asthma from birth to 44 yr of age in men and women across several countries, and to evaluate the main factors influencing asthma incidence in young adults. The data of the European Community Respiratory Health Survey, an international, cross-sectional, population-based survey, which were collected in 16 countries from 1991 to 1993 according to a common protocol, and which pertained to 18,659 subjects, were analyzed retrospectively, using the reported age of the first attack as the onset of asthma. During childhood, girls had a significantly lower risk of developing asthma than did boys (relative risk [RR]: 0.74 and 0.56 in the 0- to 5-yr and 5- to 10-yr age classes, respectively). Around puberty, the risk was almost equal in the two sexes (RR = 0.84; 95% confidence interval [CI]: 0.65 to 1.10 in the 10 to 15-yr age class). After puberty, the risk in women was always significantly higher than that in men (RR: 1.38 to 5.91). This pattern was consistent in all of the 16 countries studied, and was not influenced by recall or cohort effects. When the effects of airway caliber and smoking were studied with a case–control design, the results showed that women's greater susceptibility to asthma in early adulthood was at least partly, explained by their smaller airway caliber (the OR decreased from 2.04 [95% CI: 1.32 to 3.15] to 1.47 [95% CI: 0.89 to 2.44] after controlling for height-adjusted FEV1); while smoking did not increase the risk. This analysis strongly confirms that the incidence of asthma shows a sex reversal during puberty, and suggests that airway caliber, in addition to hormonal factors, could play an important role in explaining the different patterns of asthma incidence in men and women.
Clinical course and outcome of patients with status asthmaticus in a tertiary care centre in Pakistan over the last ten years
Authors: Ali Zubairi, Shahid Javed Husain, Zeeshan Waheed
Journal: European Respiratory Journal (2011)

Objectives: To describe the clinical course and predictors of poor outcome in patients with status asthmaticus at a tertiary care centre in Pakistan.

Methods: Data was collected in patients aged 16 and above with status asthmaticus on demographics, co-morbids, home medications, APACHE II score, use of mechanical ventilation, length of hospital stay, complications, and mortality.

Results: A total of 46 patients were studied, 40 (87%) were females. The mean age was 54±21 years. Ventilatory support was required in 34 (73.9%) patients, 17 (50%) required non invasive (BiPAP) ventilatory support, and 17 (50%) required invasive mechanical ventilation.

Hospital course was complicated by cardiac arrhythmias in 7 (15%) patients, sepsis in 5 (11%) and pneumothorax in 1 (2%) patient.

Three (6.5%) died, 2 due to sepsis and 1 due to respiratory failure. All three non-survivors were females and required invasive mechanical ventilation. Mean APACHE II score was 9.30±4.39 vs 13.66±2.08, mean PaCO2 was 53.83±23.07 mmHg vs 80.0±15.13 mmHg and arterial pH was 7.33±0.11 vs 7.21±0.09 among survivors and non survivors respectively.

Conclusion: Our study showed that requirement of ventilatory support was associated with prolonged hospital stay. High APACHE II scores, elevated PaCO2, and decreased arterial pH on admission were associated with increased mortality.
Lung inflammation is significantly reduced by recovery of neutrophil apoptosis in vivo
Authors: Klaus Unfried, Ulrich Sydlik, Matthias Kroker, Adnana Paunel-Görgülü, Stefanie Keymel, Christian Heiss, Malte Kelm, Joachim Windolf, Andreas Bilstein, Jean Krutmann
Journal: European Respiratory Journal (2012)

INTRODUCTION: Neutrophil apoptosis is considered to be a major regulator of neutrophil driven lung inflammation. The compatible solute ectoine has been described to act preventive against lung inflammation induced by environmental particles (Sydlik et al., Am J Respir Crit Care Med 2009). As a therapeutic approach, here, we investigated the influence of this compound on neutrophil apoptosis in the inflammatory microenvironment.  METHODS: Human neutrophils were treated ex vivo with particles or inflammatory mediators in the presence or absence of ectoine in order to study apoptosis rates and pro-apoptotic signalling. Lung inflammation was induced in rats by intra-tracheal application of 2.5 mg/kg environmental particles and studied in lung lavages after control or ectoine intervention.  RESULTS: Apoptosis rates of human neutrophils from COPD patients and volunteers, which were significantly reduced by the inflammatory stimuli, recovered significantly in the presence of ectoine. Mechanistic analyses demonstrated the preventive effect of ectoine of pro-apoptotic signalling events via Akt and Mcl-1. The in vivo relevance of the data was shown by significantly reduced neutrophil inflammation after ectoine intervention which correlated with restored neutrophil apoptosis rates in the lung.  CONCLUSIONS: The current studies demonstrate the effectivity to prevent anti-apoptotic signalling in neutrophils by the compatible solute ectoine. This effect led to recovered apoptosis rates and a reduction of environmentally induced lung inflammation. The relevance of ectoine treatment for humans is demonstrated by the EFECT study which will be presented on the same meeting.
Hypoxia Induces Production of L-2-Hydroxyglutarate
Authors: Andrew M. Intlekofer, Raymond G. Dematteo, Sriram Venneti, Lydia W.S. Finley, Chao Lu, Alexander R. Judkins, Ariën S. Rustenburg, Patrick B. Grinaway, John D. Chodera, Justin R. Cross, Craig B. Thompson
Journal: Cell Metabolism (2015)