tbuckley/cabot-search huggingface dataset:
Firefighter occupational exposures in forest fire settings – Three years of the FUMEXP project
Authors: Antonio Jorge Ferreira, Carlos Robalo Cordeiro, Pedro Ferreira, Ana Isabel Miranda, Vera Martins, Domingos Xavier Viegas
Journal: European Respiratory Journal (2011)

Introduction and objectives: There is a growing awareness that smoke produced during wildland fires can expose firefighters and populations to hazardous concentrations of several air pollutants. The FUMEXP Project was developed to evaluate the potential effects of smoke emissions on firemen health.

Methods: A sample of firefighters (n=38) was submitted to spirometry and responded to the SF-36® General Health Survey before the 2008 forest fire season, and again at the end of the 2010 season.

During three years (2008-2010), a subsample of 18 firefighters was tested before and after firefighting. Exhaled nitric oxide (eNO), carbon monoxide (CO) and% carboxy-haemoglobin were monitored.

Ten of these firefighters carried monitoring devices to assess particulate matter (PM2,5), NO2, volatile organic compounds (VOC's) and carbon monoxide, during prescribed/experimental an real forest fires.

Results: Values above international recommendations were measured: PM2.5 > 1,280 μg.m3; CO>73,000 μg.m-3; NO2 >4,670 μg.m-3. VOC values were also high.

Airway monitoring: there was a significant decrease (p<0.05) on the eNO, and a very significant increase on exhaled CO (p<0,001), pre and post firefighting.

Predicted FEV1, F25, F50 e MEF were lower at the end of the Project (p<0.05). Three questions of the SF-36 survey had scores significantly lower.

Conclusions: With the levels of exposure monitored, forest fire smoke inhalation can cause acute and long term health effects on exposed professionals. Suggested preventive measures include regular health evaluation, use of adequate protecting equipment and individual monitoring devices, planning of fire-fighting shifts and modelling of exposure.
The alveolitis of hypersensitivity pneumonitis
Authors: U Costabel
Journal: European Respiratory Journal (1988)

In the pathogenesis of hypersensitivity pneumonitis (HP) several immune mechanisms are involved. The initial phase, 4-48 h after antigen inhalation, appears to be immune complex mediated and is characterized by an early increase in bronchoalveolar lavage (BAL) neutrophils and the histopathologic features of oedema, neutrophil infiltration of the alveolar wall, and vasculitis. After 12 h to several days, the immune response possibly shifts to a cell-mediated reaction, and the alveolitis consists of cytotoxic effector cells as well as suppressor cells which may be required to modulate the B cell response of antibody production by plasma cells. In this phase, lymphocytes of the OKT8 positive phenotype, natural killer cells, and occasionally a few plasma cells are increased in BAL fluid. The characteristic histopathologic finding is a mononuclear infiltrate consisting of lymphocytes, plasma cells, and foamy histiocytes. After weeks to months, a delayed type hypersensitivity reaction may lead to a slight predominance of OKT4 positive cells in BAL fluid and to granuloma formation. Finally, after months to years, repeated immune-mediated injury to the alveolar wall with release of proteolytic enzymes and fibroblast growth factors may result in pulmonary fibrosis and end stage lung with concomitant increase in BAL neutrophils as in other fibrotic diseases.
Peripheral Arterial Occlusive Disease (PAOD) In Chronic Phase Chronic Myeloid Leukemia Patients Treated With Nilotinib
Authors: Young-Woo Jeon, Sung-Eun Lee, Soo-Young Choi, Soo-Hyun Kim, Jin-Eok Park, Hye-Rim Jeon, Eun-Jung Jang, Dong-Wook Kim
Journal: Blood (2013)
Validity and Reliability of the US National Cancer Institute’s Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
Authors: Amylou C. Dueck, Tito R. Mendoza, Sandra A. Mitchell, Bryce B. Reeve, Kathleen M. Castro, Lauren J. Rogak, Thomas M. Atkinson, Antonia V. Bennett, Andrea M. Denicoff, Ann M. O'Mara, Yuelin Li, Steven B. Clauser, Donna M. Bryant, James D. Bearden, Theresa A. Gillis, Jay K. Harness, Robert D. Siegel, Diane B. Paul, Charles S. Cleeland, Deborah Schrag, Jeff A. Sloan, Amy P. Abernethy, Deborah W. Bruner, Lori M. Minasian, Ethan Basch
Journal: JAMA Oncology (2015)

To integrate the patient perspective into adverse event reporting, the National Cancer Institute developed a patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).
Paclitaxel and carboplatin in combination in the treatment of advanced non-small-cell lung cancer: a phase II toxicity, response, and survival analysis.
Authors: C J Langer, J C Leighton, R L Comis, P J O'Dwyer, C A McAleer, C A Bonjo, P F Engstrom, S Litwin, R F Ozols
Journal: Journal of Clinical Oncology (1995)

PURPOSE To determine the activity and toxicity of combination paclitaxel (24 hours) and carboplatin in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Eligibility required measurable disease (stage IV or stage IIIB with malignant pleural effusion), Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, absolute neutrophil count &gt; or = 2,000/microL, platelet count &gt; or = 100,000/microL serum creatinine concentration &lt; or = 1.5 mg/dL, and bilirubin level &lt; or = 2 mg/dL. Paclitaxel was initially administered at a dose of 135 mg/m2/d, followed by carboplatin on day 2 at a targeted area under the concentration-time curve (AUC) of 7.5 using the Calvert formula. Granulocyte colony-stimulating factor (G-CSF) 5 micrograms/kg subcutaneously (SC) on days 3 to 17 was introduced during the second and subsequent cycles. In patients who sustained less than grade 4 myelosuppression, the paclitaxel dose was sequentially escalated 40 mg/m2 per cycle to a maximum of 215 mg/m2. Treatment was repeated at 3-week intervals for six cycles. RESULTS From June 1993 through February 1994, 54 patients were enrolled; 53 are assessable for toxicity and response. The median age was 62 years (range, 34 to 84). Sixty-nine percent were male, 65% had adenocarcinoma, and 93% had stage IV disease. Two hundred sixty-eight cycles were administered; 32 patients (59%) completed all six cycles. Twenty-five unanticipated hospitalizations occurred during treatment (9.3% of cycles) in 20 patients (37%). Myelosuppression was the principal toxicity; grade 3 or 4 granulocytopenia occurred in 57% of patients after the first cycle, but decreased to 35% during the second cycle after introduction of G-CSF and consistently remained &lt; or = 22% during subsequent cycles. Seven episodes of neutropenic fever occurred, all during the first cycle. Grade 3 or 4 thrombocytopenia and anemia occurred in 47% and 33% of patients, respectively. Eight patients (15%) required platelet transfusions and 16 (30%) required packed RBC support. Neuropathy, myalgias/arthralgias, and thrombocytopenia, although generally mild, were cumulative. The paclitaxel dose was boosted to 215 mg/m2 in &gt; or = 70% of patients who received three or more cycles. At an AUC of 7.5, the median first-cycle carboplatin dose was 424 mg/m2 (range, 273 to 709 mg/m2). The objective response rate was 62%, with five (9%) complete responses and 28 (53%) partial responses. The median progression-free survival time was 28 weeks and the median survival time 53 weeks. The 1-year survival rate is 54%. CONCLUSION The paclitaxel-carboplatin combination is active in advanced NSCLC and may enhance survival; it merits further investigation in phase III trials.
A Stitch in Time
Authors: Christopher J. Graber, Adam S. Lauring, Peter V. Chin-Hong
Journal: New England Journal of Medicine (2007)

A 64-year-old man with a history of coronary artery disease and peripheral vascular disease was admitted with a several-month history of fevers, chills, and fatigue. These symptoms began after he underwent percutaneous coronary intervention with placement of a stent in the left anterior descending coronary artery 10 months previously. A 5-day course of ciprofloxacin led to temporary relief of his symptoms, which returned 1 week after discontinuation of the antibiotic.
Review: After coronary DES placement, longer vs shorter DAPT increases major bleeding and death and reduces MI
Authors: Debabrata Mukherjee
Journal: Annals of Internal Medicine (2015)

Source Citation Spencer FA, Prasad M, Vandvik PO, et al. Longer versus shorter duration dual-antiplatelet therapy after drug-eluting stent placement: a systematic review and meta-analysis. Ann Intern Med. 2015 May 26. [Epub ahead of print]. 26005909
Inhibition of a New Differentiation Pathway in Neuroblastoma by Copy Number Defects of <i>N-myc</i>, <i>Cdc42</i>, and <i>nm23</i> Genes
Authors: Linda J. Valentijn, Arjen Koppen, Ronald van Asperen, Heather A. Root, Franciska Haneveld, Rogier Versteeg
Journal: Cancer Research (2005)

Abstract The best studied oncogenic mechanisms are inactivating defects in both alleles of tumor suppressor genes and activating mutations in oncogenes. Chromosomal gains and losses are frequent in human tumors, but for many regions, like 1p36 and 17q in neuroblastoma, no mutated tumor suppressor genes or oncogenes were identified. Amplification of N-myc in neuroblastoma is strongly correlated with loss of 1p36 and gain of 17q. Here we report that N-myc down-regulates the mRNA expression of many genes with a role in cell architecture. One of them is the 1p36 gene Cdc42. Restoring the Cdc42 expression in neuroblastoma cells strongly induced differentiation. N-myc also inhibited Cdc42 functioning at the protein level. This was mediated by nm23-H1 and nm23-H2, which are located in the amplified 17q region. Nm23-H1 and nm23-H2 are strongly up-regulated downstream targets of N-myc. Nm23-H1 was shown to bind Cdc42 and prevented the induction of differentiation. Overexpression of Nm23 due to gain of 17q and induction by N-myc combined with weak expression of Cdc42 due to loss of 1p36 and down-regulation by N-myc can thus block differentiation. Although this marks Cdc42 as a candidate tumor suppressor gene, no mutations were found. Further silencing of Cdc42 by small interfering RNA induced massive apoptosis, indicating that tumor cell survival requires a minimal Cdc42 activity. Three regions of chromosomal gain and loss thus affect genes functioning in one pathway in neuroblastoma. They converge to bring the pathway out of balance and prevent Cdc42 mediated differentiation.
Abstract 13510: Discovery of Orally Active Transient Receptor Potential Vanilloid 4 (TRPV4) Blockers for the Treatment of Pulmonary Edema in Heart Failure
Authors: Kevin S Thorneloe, Weike Bao, Hasan Alsaid, Ming-Yuan Jian, Melissa Costell, Kristeen Maniscalco, Alan Olzinski, Earl Gordon, Irina Lozinskaya, Lou Elefante, Pu Qin, Daniel Matasic, Lorena Kallal, Anna Waszkiewicz, Elizabeth Davenport, Jonathan Larkin, Mark Burgert, Hiliary Eidam, Krista Goodman, John R Toomey, Theresa Roethke, Beat Jucker, Christine Schnackenberg, Mui Cheung, Mary I Townsley, John J Lepore, Robert N Willette
Journal: Circulation (2011)
Epidermal growth factor receptor (EGFR) gene and protein expression in renal cell carcinoma (RCC)
Authors: Martin Anne-Marie, Kay Tatsuoka, Michal Magid-Slav, Patrick Warren, Kathleen Danenberg, Tal Z. Zaks
Journal: Clinical Cancer Research (2006)

A84   The epidermal growth factor receptor (EGFR) tyrosine kinase is over-expressed in numerous tumor types, where in some instances the level of expression correlates with disease outcome and tumor response to targeted EGFR therapies. Although immunohistochemistry (IHC) is the most frequently used diagnostic method to assess the over-expression of EGFR protein, other more quantitative methods such as real-time polymerase chain reaction q(RT)PCR should be considered. To this end, we compared q(RT)PCR measurements of EGFR in renal cell carcinoma (RCC) tumors that had been previously stained and scored by IHC using the DAKO EGFR PharmDx Kit to determine whether this assay provides an accurate and objective alternative for the determination of EGFR  status.Methods: Forty RCC tumors receiving a semi-quantitative IHC score of 0, 1+, 2+ and 3+ were evaluated using TaqMan  technology. Four housekeeping genes were used to normalize the EGFR measurements and reduce variability.Results: A statistically significant association (p-value 0.0002) between IHC and q(RT)PCR measurements for EGFR was observed. Conclusion: The data show that the results obtained for gene expression  by q(RT) PCR correlate well with results obtained by IHC. These data suggest that q(RT)PCR analysis is a viable alternative for assessing the expression of EGFR in RCC. Further, the greater dynamic range of measurement and quantitative nature of q(RT)PCR suggest that a combined IHC and real-time PCR approach for the determination of EGFR status in RCC patients may be a more effective and efficient strategy for patient stratification than IHC alone.
Familial Chronic Lymphocytic Leukemia&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN4"&gt;4&lt;/xref&gt;
Authors: Carolyn Y. Neuland, William A. Blattner, Dean L. Mann, Mary C. Fraser, Shien Tsai, Douglas M. Strong
Journal: JNCI Journal of the National Cancer Institute (1983)

Chronic lymphocytic leukemia (CLL) was previously documented in a father and 4 of his 5 offspring. Follow-up studies revealed spontaneous regression of the disease in 1 patient and shifts in the clinical patterns in the other patients; the unaffected sibling developed lung adenocarcinoma. Cell surface analysis showed that 2 of these patients shared a common surface immunoglobulin profile with mu- and delta-type heavy chains and kappa-type light chains, whereas a 3d sibling with CLL had elevated mu- and kappa-chains. The patient with spontaneous disease remission had a perturbation in the percentage of cells bearing these same markers, consistent with a subclinical persistence of her lympho-proliferative process. Immunogenetic markers were associated with the occurrence of CLL, but these B-cell alloantigens were not linked to HLA. Two patients had abnormalities of chromosome 12 in B- but not T-cells: One had trisomy 12; the other had a mixture of dicentrics and translocations involving the same chromosome.
The Slippery Slope of Broadening Treatment Eligibility and Weak End Points
Authors: Howard (Jack) West
Journal: JAMA Oncology (2015)

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UNBS3157, a new amonafide derivative with improved in vivo efficacy and decreased toxicity
Authors: Patrick Dumont, Fabrice Ribaucour, Eric Van Quaquebeke, Francis Darro, Robert Kiss
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4703 

Amonafide is a member of the naphthalimide family of anti-tumor molecules. It is a DNA intercalating agent that interferes with topoisomerase II (topo II) catalytic cycle and, more specifically, acts as a topo II poison. In phase II clinical trials, amonafide showed promising activity in advanced breast cancer. However, its development was hampered by its toxicity, namely a severe and dose-limiting myelosuppression. The toxicity of amonafide was later attributed to its in vivo metabolization by the enzyme N-acetyltransferase 2 (NAT2). The NAT2 locus is highly polymorphic and two distinct phenotypes have been described. Amonafide was markedly more toxic in fast acetylators than in slow acetylators, the toxicity being proportional to the extent of N-acetylation. With the purpose of reducing this toxicity, we synthesized a series of 40 new amonafide derivatives. This chemical modulation program was directed towards the amino group that is the target of the in vivo N-acetylation. The compounds were first characterized in vitro (IC50 determination) and in vivo on the L1210 mouse leukemia model. From this screen, 4 molecules were selected for further analysis based on their decreased toxicity and drastically improved in vivo anti-tumor activity. Because amonafide is severely hematotoxic, we next performed a toxicological analysis aimed to assess the effects of the molecules on blood parameters. These experiments revealed that, as opposed to amonafide, UNBS3157 was not hematotoxic: no significant decrease in platelet, red blood cell or white blood cell counts was recorded in healthy mice chronically treated with the molecule. The high in vivo anti-tumor activity of UNBS3157, the lead compound, was also confirmed on the MXT-HI mouse mammary syngeneic and the human PC-3 prostate cancer models. In addition, data indicate that UNBS3157 has a mechanism of action different, at least partly, from that of amonafide. UNBS3157 is a DNA intercalating agent, although 5 times less potent in terms of intercalation than amonafide. In vitro assays revealed that UNBS3157 does not act as a topo II poison. Moreover, UNBS3157 does not induce the tumor suppressor p53 in MCF-7 cells, while amonafide, consistent with its topo II poisoning activity, triggers a rapid activation of p53. Current experiments involve additional in vivo evaluations of the anti-tumor activity of UNBS3157 in different human xenograft cancer models. Additionally, in order to better understand its mechanism of action, we are performing a genome-wide expression profiling of the genes responsive to UNBS3157. This is done in vivo on human PC-3 prostate cancer cells implanted orthotopically in immunodeficient mice.
Multi-center phase II study of S-1 plus cisplatin in patients with advanced gastric carcinoma (AGC)
Authors: J. A. Ajani, A. Phan, J. C. Yao, F.-C. Lee, D. A. Singh, D. Haller, A. B. Benson, H.-J. Lenz, R. H. Yanagihara, D. Strumberg
Journal: Journal of Clinical Oncology (2005)

4024 Background: A Phase I study of S-1 (tegafur, oxonic acid, and CDHP) plus cisplatin performed in Western patients defined the MTD (S-1 50mg/m2/d taken orally on d 1–21 and cisplatin 75 mg/m2 given iv on d 1; q 28-d cycles) and led to this phase II study. Methods: Eligible patients had untreated AGC, histologic proof, KPS ≥70, adequate liver, kidney, and marrow functions, and written consent. Patients received S-1 plus cisplatin at the MTD. All reported responses were confirmed by the RECIST criteria and externally reviewed. Results: Target accrual of 41 evaluable patients has been achieved. Currently, safety data for 30 patients and efficacy data for 20 patients are available. There were 23 men; median age = 57 years; and median KPS: 80%). 50% had GEJ involvement. Median no. of cycles was 3.5. Overall RR was 65% (13 of 20 patients evaluated so far; 95% CI 41%–85%). Median duration of response in the 13 responders was 4.8 months. Median TTP was 4.8 months. Median survival was not reached. At least one grade 3/4 toxicity occurred in 53% of patients. The most frequent grade 3/4 toxicities (occurring in >10% of patients) included: fatigue (33%), nausea (20%), vomiting (17%), anorexia (20%), diarrhea (17%), and neutropenia (13%). No grade 4 diarrhea was observed. Conclusions: S-1 plus cisplatin appears very active against AGC and the tolerance and convenience profile is extremely desirable. An international phase III study comparing S-1 plus cisplatin to 5-FU plus cisplatin is planned. (Supported by Taiho Pharma USA). Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Response Genetics, Taiho Roche, Sanofi, Pfizer, Genentech, Bristol-Myers Squibb, ImClone, Taiho NCI, NIH, Taiho
Acute effect of chest wall muscle stretching on chest wall volumes distribuition in chronic obstructive pulmonary disease: A randomized controlled trial
Authors: Rafaela Sá, Shirley Campos, Maira Pessoa, Ana Gabriela Cavalcanti, Cyda Reinaux, Catarina Rattes, Guilherme Fregonezi, Andrea Aliverti, Armele Dornelas de Andrade
Journal: European Respiratory Journal (2012)

Inspiratory muscles function is compromised in COPD due to increased loads, reduced mechanical advantage, and increased ventilatory requirements. The hyperinflation of COPD reduces the flow and pressure-generating capacity of the diaphragm  Aims:  To analyze the acute effects of chest wall muscle stretching on chest wall volumes distribuition in subjects with COPD.  Methods:  It was a randomized controlled trial, involving 28 COPD patients divided into two groups: 14 subjects to treatment group (TG, mean age 61.79±8.31years) and 14 to control group (CG, 62.38±8.33years). TG was composed for patients that received a program of chest wall muscle stretching and patients allocated in CG remained at rest in the similar conditions as in GT. Respiratory variables were measured during quiet breathing by Opto-Electronic plethysmography (OEP) before and after one intervention. Statistical analysis was performed using independent samples t-test.  Results:  Tidal volume (Vt) presented a significant increase immediately after the chest wall muscle stretching in rib cage pulmonary compartment (Vt,rcp, p=0.02), in rib cage abdominal compartment (Vt,rca, p=0.04) and their percentages regarding thoracic wall, Vt,rcp%(p=0.04) and Vt,rca% (p=0.022). Thus, there was a reduction in respiratory rate(p=0.011) and minute ventilation(p=0.03), and a increase in a expiratory time p=0.026).  Conclusions:  The chest wall muscle stretching has beneficial acute effects on chest wall volume distribuition in patients with COPD. For reason, this technique should be considered to treat these patients.  Supported by: CAPES-NF, CNPq, FACEPE.
Adult human and mouse ovaries lack DDX4-expressing functional oogonial stem cells
Authors: Hua Zhang, Sarita Panula, Sophie Petropoulos, Daniel Edsgärd, Kiran Busayavalasa, Lian Liu, Xin Li, Sanjiv Risal, Yan Shen, Jingchen Shao, Meng Liu, Susann Li, Dongdong Zhang, Xiaoxi Zhang, Romana Raphaela Gerner, Mona Sheikhi, Pauliina Damdimopoulou, Rickard Sandberg, Iyadh Douagi, Jan-Åke Gustafsson, Lin Liu, Fredrik Lanner, Outi Hovatta, Kui Liu
Journal: Nature Medicine (2015)