tbuckley/cabot-search huggingface dataset:
Treatment of advanced non-small cell lung cancer with trofosfamide
Authors: Angelika Reissig, Mario Walther
Journal: European Respiratory Journal (2013)

Introduction: The aim of this retrospective study was to examine the effect of oral trofosfamide in patients with advanced non-small cell lung cancer (NSCLC).

Patients and Methods: Patients with histologically or cytologically proven NSCLC who had received at least two other therapies were enrolled. Primary clinical end point was progression-free survival (PFS); secondary end points included overall survival (OS), response rate and toxicity.

Results: Twenty-three patients were enrolled, one of whom was excluded due to non-compliance. The patients had received a median of three prior therapies (range 2–4). Regarding all 22 patients, median PFS was 14 weeks (95% confidence interval (CI) 9.96–18.04). The median OS was 119 weeks (95% CI 85.67–152.33). The median duration of trofosfamide therapy was 10.5 weeks (interquartile range 6.5–17.3). Twenty patients (90.9%) had stable disease; two were not assessable. Trofosfamide therapy was stopped in four patients (18.2%) due to side effects.

Conclusion: Trofosfamide is an orally applicable, well-tolerated and cost-effective drug that works in patients with advanced NSCLC who have undergone at least two lines of therapy. Trofosfamide seems to be a therapeutic option in NSCLC as a further therapy line. These preliminary data need to be confirmed in a larger trial.
Ifosfamide with mesna uroprotection and etoposide: an effective regimen in the treatment of recurrent sarcomas and other tumors of children and young adults.
Authors: J S Miser, T J Kinsella, T J Triche, M Tsokos, P Jarosinski, R Forquer, R Wesley, I Magrath
Journal: Journal of Clinical Oncology (1987)

One hundred twenty-four children and young adults with recurrent tumors, predominantly sarcomas, were treated with the combination of ifosfamide, etoposide, and the uroprotector, mesna (2-mercaptoethane sulphonate), in a phase II trial. The treatment regimen consisted of 12 cycles of therapy administered every 3 weeks. After evaluation of the tumor response to chemotherapy alone, radiation or surgery was used to eradicate residual sites of metastatic disease where possible. At the present time, 77 patients are evaluable for response to the chemotherapy; 43 of the patients have experienced a significant reduction in the tumor size in response to the chemotherapy alone (39 partial responses [PR] and four complete responses [CR]). Sixteen of 17 patients with Ewing's sarcoma, nine of 13 with rhabdomyosarcoma, four of eight with peripheral neuroepithelioma, three of eight with osteosarcoma, and 11 of 31 with other tumors have responded with a PR or CR. The toxicity of the regimen was acceptable. Moderate or severe toxicity evaluated on a per cycle basis included: neutropenia, 97%; thrombocytopenia, 32%; nephrotoxicity, less than 1%; mucositis, 1%; neurologic toxicity, 2%; nausea and vomiting, 13%; hemorrhagic cystitis, less than 1%. Fever was present after 33% of cycles and sepsis following 7%. One patient died due to sepsis and pancytopenia. At the present time, only seven of the 43 patients who responded to the chemotherapy regimen have relapsed, with a median follow-up of 10 weeks after the response. This drug combination is highly active in the treatment of recurrent sarcomas and other tumors in children and young adults.
Abstract 2625: The Demethylating Agent 5-aza-2′deoxycytidine (Decitabine) Restores Superoxide Dismutase 2 (SOD2) Expression and Reactive Oxygen Species Production in the Pulmonary Arteries of Fawn-hooded Rats with Pulmonary Hypertension
Authors: Hannah J Zhang, Peter T Toth, Dalia Urboniene, Stephen L Archer
Journal: Circulation (2008)
Relationship between exhaled nitric oxide and exacerbation frequency in COPD patients: A longitudinal study
Authors: Balazs Antus, Szabolcs Soter, Imre Barta
Journal: European Respiratory Journal (2011)

We previously demonstrated that fractional exhaled nitric oxide (FENO) level determined at hospital admission predicts response to treatment in COPD patients hospitalized with acute exacerbations. The optimum cut point for FENO was 27 ppb. In this longitudinal study we assessed the relationship between FENO and frequency of hospitalization-associated exacerbations in patients with COPD.  66 COPD patients (mean age: 65.6±1.4 years; 31 males, 35 females) with FENO level lower (n=39, group 1) or higher (n=27, group 2) than 27 ppb were followed over a 33.9±1.1 months period of time. In patients in group 2 the exacerbation frequency (1.0±0.19 vs. 0.37±0.09 exacerbations/patient-year; p 0.05) in these patients. In patients in group 1 positive sputum culture results were more often obtained (group 1: 24 pos. and 15 neg. vs. group 2: 9 pos. and 18 neg.; p 0.05).  Our data suggest that the rate of exacerbations requiring hospitalization is reduced in COPD patients who have higher (>27 ppb) FENO level during exacerbation. FENO may have a role in detecting different COPD phenotypes.
Activity outcomes correlation of 6 monitors in COPD, a field study part of the PROactive project
Authors: Santiago Giavedoni, Roberto Rabinovich, Yogini Raste, Nicholas Hopkinson, Hans Van Remoortel, Eloisa M. Gatti Regueiro, Daniel Langer, Zafiris Louvaris, Ioannis Vogiatzis, Barry Peterson, Frederick Wilson, Thierry Troosters
Journal: European Respiratory Journal (2011)

Background: Monitoring Physical activity (PA) in COPD patients is a new outcome to assess effects of interventions. It is unknown to what extent outcomes of different Physical activity monitors (PAM) interrelate when used in patients with low PA. A monitor will be part of the assessment platform created by PROactive project. We assessed the correlation between different outcomes of six PAM.

Methods: PA was measured for 2 weeks in 64 COPD patients (Age 68years (55-83), FEV1 57% (16-95), 6MWD 429m (149-675)). Patients wore at least 3 PAM simultaneously: SenseWear Armband (SW n=57); RT3 (n=27); Actiwatch Spectrum (AW n=30); Actigraph GT3X (AG n=30); MiniMod Dynaport (MM n=37) or Lifecorder Plus Kenz (KZ n=27). Correlations are provided in Table 1.

![Figure][1] 



Results: PAM providing a general PA outcome (KZ, AG, RT3) correlate modestly (R=0.62-0.64). Walking specific outcomes (MM, SW) relate stronger (R=0.77) while energy expenditure (EE) estimates correlation is less (R=0.22).

Conclusion: Different outcomes measuring Physical activity of daily life in COPD patients, show significant correlations when compared in between activity monitors. Monitors, however, assess different aspects of PA reflecting specific or overall movement or EE. Selection of a device and validation in COPD population is mandatory.

 [1]: pending:yes
Oxaliplatin combined with leucovorin plus 5-FU (FOLFOX) in patients with advanced/metastatic biliary tract carcinoma
Authors: J. Y. Lim, J. Y. Cho, Y. H. Paik, S. J. Lee, J. Y. Won, J. H. Kim, D. S. Yoon, D. K. Lee
Journal: Journal of Clinical Oncology (2006)

14093 Background: Biliary tract carcinoma is often diagnosed at advanced stage, with median survival rarely exceeding 6 months. There is currently no established palliative standard of care. A phase II trial was conducted to study a FOLFOX regimen as first- or second- line therapy in biliary tract carcinoma. Methods: Patients with unresectable or metastatic intrahepatic or extrahepatic biliary duct carcinoma and gallbladder carcinoma were enrolled. Eligible patients were between 18 and 75 years of age and had histologically confirmed, measurable adenocarcinoma. Patients were stratified according to prior chemotherapy(6) and no prior chemotherapy(15). Treatment consisted of intravenous oxaliplatin (100mg/m 2 ) as a 2 hours infusion on day 1 followed by leucovorin 100mg/m 2 on day1 and 5-FU 1000∼1200mg/m 2 as a 24 hours infusion on day 1,2. Treatment was repeated every 3 weeks for up to 6 cycles. Tumor response, survival and safety were determined Results: A total of 21 patients were evaluable;12 men and 9 women with a median age of 57(range 37–71). Tumor sites were: intrahepatic (n=7) and extrahepatic biliary duct (n=9); gallbladder (n=4); and ampulla (n=1). Total 115 cycles were administered (median 5 cycles, range 2∼12). According to RECIST criteria, partial response 3(14.3%), stable disease 10(47.7%) and disease progression.8(38%). The overall response rate with and without prior chemotherapy were 0%(0/6) and 20%(3/15), respectively. In patients without prior chemotherapy (15), median progression-free-survival and overall survival were 6.6(range, 1.2∼12.8) and 8.7(range, 3.7∼19.3) months. Grade 1–2 neurotoxicity, fatigue, diarrhea, anorexia, nausea were common. Grade 3 neutropenia and thrombocytopenia occurred in 23% and 4.7% of the patients respectively. There was no treatment related death. Conclusions: FOLFOX should be considered an active and well tolerated first-line combination chemotherapy regimen for patients with advanced/metastatic biliary tract carcinoma. No significant financial relationships to disclose.
The Value of Screening for Diabetes in Patients with Skin Sepsis
Authors: C Baynes, S Caplan, P Hames, R Swift, S Poole, J Wadsworth, R Touquet, R S Elkeles
Journal: Journal of the Royal Society of Medicine (1993)

Four hundred and eighty-two patients with spontaneous skin and superficial sepsis and 291 controls of similar age and sex underwent random capillary blood glucose measurements in order to assess whether screening for diabetes in patients presenting with skin sepsis to an Accident &amp; Emergency Department detects a greater number of cases than that present in the background population. All subjects with a concentration &gt;7.8 mmol/l were subsequently followed up with a 75 g oral glucose tolerance test. Forty-two (8.7%) of the 482 skin sepsis patients had a capillary blood glucose &gt;7.8 mmol/l compared to eight (2.7%) of the 291 without sepsis (χ 2 =9.71, P&lt;0.002). Of these, 26 of the skin sepsis group and 7 of the control group attended for follow up. Of those who attended, 13 of the skin sepsis group had an abnormal glucose tolerance test (seven diabetes, six impaired glucose tolerance — IGT) compared to two (one diabetes, one IGT) of the control group (χ 2 =2.87, P&lt;0.1). The difference in cases of frank diabetes between the two groups was not statistically significant. Of the total eight diabetic cases identified, five (on direct questioning) had symptoms of hyperglycaemia (thirst, polyuria and/or weight loss) and two of the others were obese, one of whom had documented ischaemic heart disease. Thus, while most cases of diabetes in patients with skin sepsis could be detected by specifically asking about hyperglycaemic symptoms and performing a blood glucose estimation when these are present, we suggest that the screening of patients with skin sepsis over 40 years of age provides an opportunistic method of screening. This strategy should yield clinically significant numbers of abnormal cases.
COPD and concomitant arterial hypertension: The efficacy and safety of slow-release formulation of indapamide
Authors: Zara Nersesyan, Svetlana Ovcharenko, Tatyana Morozova
Journal: European Respiratory Journal (2014)

Treatment of COPD patients with concomitant arterial hypertension is associated with such significant complications as increasing of bronchial obstruction, hyperinflation, electrolytes balance changing and others.   Aims : To investigate the efficacy and safety of slow-release (SR) formulation of indapamide in the treatment of COPD and concomitant hypertension.   Methods : 33 out-patients with COPD and concomitant hypertension were recruited (27 male, mean age of 60.8±10.5, %FEV1 58.4±11.5%, index smoker 42.3±11.5). COPD duration was 10.5±3.5 years, hypertension duration was 14.3±7.4 years. All patients were received indapamide SR 1.5 mg/day for 3 months. Ambulatory blood pressure (BP) monitoring, spirometry and bodyplethysmography, serum potassium levels, respiratory symptoms (cough, sputum production, dyspnea severity) by CAT and MRC were assessed at baseline and after 3 month of treatment.   Results : After 3 months of treatment it was noted: daily pattern of BP normalization (n=26), decreasing of the average diastolic BP at night-time (92.3±7.4 vs 71.4±3.8 mm Hg), decreasing of the average systolic (56.4±29.4 vs 30.4±21.5%) and diastolic (47.2±23.5 vs 31.6±21.7%) BP load at night-time, decreasing of the average night-time systolic BP variability (12.9±3.7 vs 9.5±2.5 mm Hg), p    Conclusions : Using of indapamide SR in complex therapy of COPD and concomitant hypertension is efficacy and safety antihypertensive treatment that doesn9t affect the existing hyperinflation and electrolytes balance.
Involvement of striate and extrastriate visual cortical areas in spatial attention
Authors: A. Martínez, L. Anllo-Vento, M. I. Sereno, L. R. Frank, R. B. Buxton, D. J. Dubowitz, E. C. Wong, H. Hinrichs, H. J. Heinze, S. A. Hillyard
Journal: Nature Neuroscience (1999)
Biotoxicological pattern and related respiratory impairments in chemical laboratory workers
Authors: Felicia Gradinariu, Carmen Croitoru, Brigitte Scutaru, Razvan Danulescu, Micaela Margineanu, Madalina Ipate, Mirela Ghitescu, Eugenia Danulescu
Journal: European Respiratory Journal (2011)

Aim:  To evaluate the relations between the changes in blood/urine markers and respiratory outcomes in workers from a chemical research institute   Material/Methods:  161 workers (73%women, 23% smokers, having mean age 44.6±13 yrs; mean exposure 20.8±14 yrs) were investigated by spirometry, blood/urine biomarkers, including exposure/effect ones. Workplace air solvents level was below upper threshold limits, but noxious cumulative index varied between 1 and 2.   Results:  Urinary total phenols releases correlated with TBARS (r=0.22; p 10 yrs length of exposure, SOD correlated with Ig M level (r=0.20; p   Conclusions:  Immunological and oxidative stress markers might be related to respiratory changes, even in the early stage of occupational-induced respiratory diseases.
Abstract 997: Cardiovascular Risk Associated With Concurrent Proton Pump Inhibitor and Clopidogrel Therapy: How Much? How Specific?
Authors: Nathaniel L Hall, Katy D Mathews, Heidi T May, Tami L Bair, Benjamin D Horne, John F Carlquist, Donald L Lappe, Joseph B Muhlestein, Jeffrey L Anderson
Journal: Circulation (2009)

Background:  Clopidogrel (CLOP) is a prodrug activated by hepatic CYP450 enzymes, principally CYP2C19. CLOP is widely used after acute coronary interventions to prevent thrombosis. Because CLOP increases the bleeding risk, a proton pump inhibitor (PPI) often is given concurrently. Omeprazole (O), and to a lesser extent other PPIs, inhibits CYP2C19, and  ex vivo  studies indicate that concurrent O reduces the generation of CLOP active metabolite. However, evidence for a clinical interaction is inconclusive.   Methods:  We prospectively analyzed patient data from the Intermountain Heart Collaborative Study Registry to assess 1-y risk for death/myocardial infarction (D/MI) of CLOP + PPI vs. CLOP alone (N=10,703; age 60±15, 62% male). Subanalyses assessed trends by PPI type, with prospective risk hypothesized to be O (n=3912) > lansoprazole (L; n=5020) > pantoprazole (P; n=1733), based on  ex vivo  pharmacodynamics (PD). Hazard ratios (HR) were adjusted (adj) for multiple potential confounders.   Results:  Results are shown in the Table. D/MI was higher for CLOP + PPI than CLOP. Risk was substantially but not completely reduced by adjustment, with an adj HR of 1.64, 95% confidence interval 1.41–1.90, p   Conclusions:  PPIs are associated with an increase in risk of D/MI in cardiovascular patients receiving CLOP. None of the PPIs are free of apparent risk. However, failure to show increased risk in an order consistent with  ex vivo  data raises the question of selection bias (uncorrected confounding) or a direct toxic effect of PPIs, as well as an interaction with CYP2C19. The issue of causation should be addressed by a randomized clinical trial. Meanwhile,  routine  use of PPIs with CLOP should be discouraged.
Ultrasound biomicroscopy of sclerotomy sites after pars plana vitrectomy for diabetic vitreous hemorrhage11The authors have no proprietary interest in any of the materials used in this study.
Authors: Muna Bhende, Satish G Agraharam, Lingam Gopal, Kallakuri Sumasri, Balusamy Sukumar, Joshua George, Tarun Sharma, Mahesh P Shanmugam, Pramod S Bhende, Nitin S Shetty, Rajat N Agrawal, Dhanashree A Deshpande
Journal: Ophthalmology (2000)
Radiation-Induced Hair-Follicle Damage and Tumor Formation in Mouse and Rat Skin&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R. E. Albert, F. J. Burns, P. Bennett
Journal: JNCI Journal of the National Cancer Institute (1972)

The dorsal skin of 158 Swiss Millerton mice was irradiated with electrons in single exposures at 6 dose levels from 500–4,000 rods. The mice were observed for skin-tumor formation every 4 weeks for 88 weeks. At death each tumor was examined histologically, and whole-skin mounts were used to determine the survival of intact hair follicles and the incidence of atrophic follicles. These data were compared with the dose-response characteristics for tumor induction and hair-follicle survival in the rat from previous experiments. The incidence of epithelial skin tumors was markedly lower in mice than in rats. This difference was due to the failure of mice to develop adnexal tumors, which are the predominant type of skin tumor in the rat. The radiation sensitivity of mouse skin for hair-follicle destruction was at least twice that of the rat. The relatively low level of atrophic follicle formation in the mouse skin as a consequence of radiation damage may be related to the failure to develop adnexal skin tumors.—J Natl Cancer Inst 49: 1131–1137, 1972.
A20 targets caspase-8 and FADD to protect HTLV-I-infected cells
Authors: Y Saitoh, A Hamano, K Mochida, A Kakeya, M Uno, E Tsuruyama, H Ichikawa, F Tokunaga, A Utsunomiya, T Watanabe, S Yamaoka
Journal: Leukemia (2015)
Interactions Between High- and Low-Risk HPV Types Reduce the Risk of Squamous Cervical Cancer
Authors: Karin Sundström, Alexander Ploner, Lisen Arnheim-Dahlström, Sandra Eloranta, Juni Palmgren, Hans-Olov Adami, Nathalie Ylitalo Helm, Pär Sparén, Joakim Dillner
Journal: JNCI Journal of the National Cancer Institute (2015)

The clinical significance of co-infections with high-risk (HR) and low-risk (LR) human papillomavirus (HPV) in the etiology of cervical cancer is debated, as prospective evidence on this issue is limited. However, the question is of increasing relevance in relation to HPV-based cancer prevention. In two population-based nested case-control studies among women participating in cervical screening with baseline normal smears, we collected 4659 smears from women who later developed cancer in situ (CIS; n = 524) or squamous cervical cancer (SCC; n = 378) and individually matched control subjects who remained free of disease during study follow-up. The median follow-up until diagnosis was 6.4 to 7.8 years. All smears were tested for HPV. We used conditional logistic regression models with two-way interaction terms to estimate relative risks (RRs) for CIS and SCC, respectively. All statistical tests were two-sided. Compared with women who were infected with HRHPV only, women who were also infected with LRHPV had a lower risk for SCC (RR = 0.2, 95% confidence interval [CI] = 0.04 to 0.99, P = .049). This interaction was not shown for CIS (RR = 1.1, 95% CI = 0.4 to 3.6). Women who were positive for both HRHPV and LRHPV had, on average, a 4.8 year longer time to diagnosis of SCC than women who were positive for HRHPV only (P = .006). Results were highly robust in sensitivity analyses. Co-infection with LRHPV is associated with a lower risk of future invasive disease and longer time to diagnosis than infection with HRHPV alone. We propose that co-infection with LRHPV interferes with the rate of progression to invasive cervical cancer.
STOP-Bang questionnaire as a preoperative screening tool for obstructive sleep apnea in bariatric surgery patients
Authors: Ali Khodabandeh, Ryan Chua, Antonio De Gorordo Arzamendi, Julia Tassinari, Anthony McCluney, Nicole Pecquex, Armin Ernst, Katherine Hendra
Journal: European Respiratory Journal (2012)

Introduction: 

STOP (snoring, tiredness, observed apnea, high blood pressure) questionnaire is a screening tool to identify surgical patients with high risk of obstructive sleep apnea (OSA). Incorporating BMI, age, neck size, and gender (Bang) has been shown to further increase the sensitivity and negative predictive value. The STOP-Bang questionnaire has not been validated as a screening tool for OSA in patients undergoing bariatric surgery.

Method: 

We retrospectively reviewed prospective data on bariatric surgery patients. Patients were asked to answer the STOP questionnaire during their preoperative assessment. The BMI, age, neck circumference and gender were documented. All patients underwent overnight polysomnography as one of the assessments prior to bariatric surgery.

Results: 

A total of 49 patients were included. The mean age was 42 ± 12.2 years; 29% males; BMI 48 ± 8.2 kg/m2. We classified 43 patients (88%) as high risk based on the STOP-Bang questionnaire (≥3 positive responses). A total of 36 patients (73%) were diagnosed with OSA (AHI>5); 13 patients as mild, 10 patients as moderate (30>AHI>15) and 13 patients as severe OSA (AHI>30). The sensitivity of the STOP-Bang questionnaire for all OSA patients (AHI > 5) and for moderate and severe OSA patients (AHI > 15) was 92% and 100%, respectively. The specificity was 33% and 23%. The positive predictive value was 81% and 54%. The negative predictive value was 57% and 100%.

Conclusions: 

The preliminary results of the STOP-Bang questionnaire suggest a high sensitivity to detect bariatric surgery patients with obstructive sleep apnea. The negative predictive value was high only in patients with moderate and severe OSA.
Pathogenesis of Tumor Desmoplasia. II. Collagens Synthesized By Line 1 And Line 10 Guinea Pig Carcinoma Cells And By Syngeneic Fibroblasts In Vitro&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: D M Form, L VanDeWater, H F Dvorak, B D Smith
Journal: JNCI Journal of the National Cancer Institute (1984)

For the investigation of the pathogenesis of desmoplasia, the capacities to synthesize collagen in vitro of 2 bile duct carcinomas (lines 1 and 10) of Sewall-Wright inbred strain 2 guinea pigs and of syngeneic dermal fibroblasts were studied. Line 10 cells synthesized collagen type IV as judged by sensitivity to bacterial collagenase, by immunoprecipitation, by migration of pro alpha (IV) chains and pepsin-resistant fragments on sodium dodecyl sulfate-polyacrylamide gels, and by immunofluorescence. Line 1 cells also synthesized small amounts of collagenase-sensitive protein. Neither line 1 nor line 10 cells synthesized detectable collagen type I, III, or V. Only about 1% of [14C]proline incorporated by tumor cells was found in collagenase-sensitive protein. In contrast, dermal fibroblasts synthesized 4 and 128 times as much collagenase-sensitive protein as line 10 and line 1 cells, respectively, amounting to 20% of total protein synthesized. Fibroblasts produced mostly collagen types I and III, in a ratio of 7:1, and smaller amounts of collagen type V. Thus lines 1 and 10 carcinoma cells produce primarily basement membrane collagen, whereas interstitial collagens, abundant in desmoplastic tumor stroma, are fibroblast products.
Nonsteroidal anti-inflammatory drugs in community-acquired pneumonia
Authors: Emma Crawford, Martin Allen, Naveed Mustfa, Helen Stone
Journal: European Respiratory Journal (2015)

We read with interest the editorial by Riccard and Medissa [1], which accompanied the paper by Tagami et al. [2] that reviewed the effects of corticosteroids on mortality in community-acquired pneumonia (CAP). Advising against NSAIDs is an inappropriate interpretation of current evidence and may increase patient morbidity <http://ow.ly/LAxiu>