tbuckley/cabot-search huggingface dataset:
Detorubicin--an active anthracycline in untreated metastatic melanoma.
Authors: S P Chawla, S S Legha, R S Benjamin
Journal: Journal of Clinical Oncology (1985)

A phase II study of detorubicin, the semisynthetic 14-diethoxyacetoxy ester of daunorubicin, was conducted in 42 patients with metastatic melanoma. The drug was administered in a dose range of 120 to 180 mg/m2 and repeated at 3-week intervals. One clinical complete remission (soft tissue) and seven partial responses (three visceral and four soft tissue) were observed among the 22 patients who had undergone no prior chemotherapy, a complete and partial response rate of 36%. The duration of response varied from 2 to 27 months with a median of 10 months. There were also four (19%) minor responses (one visceral and three soft tissue). In contrast, among the 20 patients who had undergone prior chemotherapy treatment, only three patients showed a minor response. General toxicities were acceptable and were similar to those of Adriamycin (Adria Laboratories, Columbus, Ohio). Cardiac toxicity was evaluated by cardiac biopsy and radionuclide scan. Cardiac biopsy changes were identical to those observed with Adriamycin and were progressive with cumulative dose. One patient had a high-grade biopsy at a cumulative detorubicin dose of 1,420 mg/m2. Similarly, a trend of decreasing ejection fraction with cumulative dose was noted. Only one patient developed congestive heart failure at a cumulative dose of 1,290 mg/m2, that was well compensated with digoxin and diuretics. In contrast to Adriamycin, detorubicin has shown activity in previously untreated patients with metastatic melanoma.
Reference data transition of whole-body plethysmography from infancy to childhood
Authors: Richard Kraemer, Aida Mashkouri Najafi, Ernst Stadlober
Journal: European Respiratory Journal (2011)

Rationale: Advances in plethysmographic measurement techniques have made it possible to obtain lung function data in infants [1] and children. However, application remains limited by the lack of appropriate transitional normative data from infancy to childhood, especially for effective specific airway resistance (sReff).

Objectives: On previously collected lung function data, updated prediction equations were modeled spanning from infant's years to childhood, using the LMS method.

Methods: Normative lung function data from 67 healthy young infants aged 2.3 to 28.2 (10.8±6.3) months and children aged 5.1 to 16.8 (10.4±2.9) years were evaluated, and prediction equations for functional residual capacity (FRCpleth), and sReff were computed. Applying the LMS method in R environment using GAMLSS package [2] the changing distribution of the measurements is summarized by three curves representing the median (M), coefficient of variation (S) and skewness (L) in relation to age.

Results: The present prediction equations feature the first attempt to provide continuous normative data of infants with a smooth transition into childhood (Table 1).

View this table:

Table 1





Conclusions: Updated prediction equations of plethysmographic data for infants and children applying LMS statistics provide a new basis for longitudinal evaluation of lung function in children with lung disease.

References: 

*   1. Respiration 1993, 60:1-8.

*   2. Statistics in Medicine 2004, 23:3053-3076.
Abstract 15630: Direct Renin Inhibition With Aliskiren Improves Ischemia-Induced Neovascularization
Authors: Michel Desjarlais, Sylvie Dussault, Wahiba Dhahri, Alain Rivard
Journal: Circulation (2014)

Background: The activation of the renin-angiotensin system is associated with impaired formation of new blood vessels (neovascularization) in response to ischemia. Aliskiren is the only direct renin inhibitor that is clinically used as an orally active antihypertensive drug. Here we tested the hypothesis that aliskiren might improve neovascularization following ischemia. Methods and Results: C57BL/6 mice were treated with a high dose of aliskiren (50 mg/kg), a low dose of aliskiren (10 mg/kg), or drinking water only. After two weeks of treatment, hindlimb ischemia was surgically induced by femoral artery removal. Treatment with aliskiren led to a significantly faster rate of blood flow recovery after hindlimb ischemia (Laser Doppler). Interestingly the lower dose of aliskiren, which did not reduce blood pressure, provided similar improvement of blood flow recuperation compared to the higher dose of aliskiren. At day 21 after surgery, Doppler flow ratios were significantly improved in mice treated with aliskiren (0.69+/-0.07 vs. 0.52+/-0.03; p&lt;0.05). This was associated with an increased expression of angiogenic factors in ischemic muscles, including VEGF and eNOS. Endothelial progenitor cells (EPCs) have been shown to have an important role in postnatal neovascularisation. We found that aliskiren significantly increased the number of bone marrow EPCs at day 7 after ischemia (172+/-7% increase; p&lt;0.05). Moreover, the adhesive properties of EPCs were significantly improved in mice treated with aliskiren (175+/-5% increase; p&lt;0.05). In vitro, aliskiren improves cellular migration and tubule formation in HUVECs. This is associated with an increased expression of nitric oxide (DAF staining), and a significant reduction of oxidative stress levels (DHE staining). Importantly, the antioxidant and angiogenic properties of aliskiren in HUVECs are abolished following treatment with the NOS inhibitor L-NAME. Conclusions: Direct renin inhibition with aliskiren leads to improved ischemia-induced neovascularization that is not dependant on blood pressure lowering. The mechanisms involve beneficial effects of aliskiren on NO and angiogenic pathways in ischemic tissues, together with an increase in the number and the functional activity of EPCs.
Abstract 12010: Penalizing Hospitals for Excess Heart Failure Readmissions: Probability of Hospital Misclassification Error
Authors: Eugene A Sosunov, Natalia N Egorova, Ken McCardle, Annetine C Gelijns, Alan J Moskowitz, Hung-Mo Lin
Journal: Circulation (2015)

Introduction: The Centers for Medicare &amp; Medicaid Services (CMS) adjust hospital payments for heart failure (HF) admissions if the estimate of risk-standardized excess readmission ratio (ERR) is above 1. The 2012 Inpatient Prospective Payment Systems Final Rule does not take into account the uncertainty of ERR measurement raising concerns about possible consequences. Hypothesis: Ignoring the uncertainty of ERR measurement results in significant probability of hospital misclassification error (HME) in HF, the most costly of applicable conditions. Methods: For a cohort of 1,085,568 Medicare fee-for-service patients undergoing 1,494,993 HF admissions in 4,930 U. S. hospitals between July 1, 2005 and June 30, 2008, we reproduced ERR distributions for individual hospitals using hierarchical logistic regression model and bootstrap method employed by CMS to obtain confidence intervals of ERR. Based on ERR distributions, we calculated probability of HME for each hospital and stratified results by hospital volume. Results: Mean probability of HME due to ignoring the uncertainty of ERR measurement is 28.2% (95% CI: 27.7%, 28.6%). Probability of HME varies with hospital volume: 41.5, 33.9, 26.9, 21.5, 16.7% in the 1st-5th volume quintiles (p&lt;.001). In the subset of 2,381 hospitals with ERR above 1 (subject to payment adjustment per existing regulations), the falsely penalized rate was 27.5% (95% CI: 26.7%, 28.3%). In the subset of 2,549 hospitals with point estimate ≤ 1 (not subject to payment adjustment), the probability of not penalizing a poorly performing hospital was 28.8% (95% CI: 28.2%, 29.4%). (Possible maximum of probability of HME is 50% equivalent to no discrimination). Conclusions: Ignoring uncertainty of ERR measurement leads to errors in imposing financial penalties on hospitals associated with heart failure readmissions: good performers are penalized and poor performers escape penalties with estimated probability ~30%. Furthermore, disparity exists among hospitals with different volume: probability of erroneous adjustment of payment is inversely related to hospital volume.
Reducing dose density in adjuvant chemotherapy (C) is detrimental in early breast cancer (EBC). A review of 872 adjuvant treatments in Centre François Baclesse
Authors: T. Delozier, C. Ségura, C. Levy, C. Delcambre, D. Allouache, O. Switsers, J.-M. Ollivier, B. Vié, F. Joly, J.-Y. Génot
Journal: Journal of Clinical Oncology (2004)

583 Background: Dose density is a key in the efficacy of C. This concept has been tested in increasing dose density especially in the adjuvant setting. Side effects of C such as leukopenia can induce delay in dose administration, leading to a decrease in dose density. The aim of the study was to evaluate the impact of reducing dose density in adjuvant C in EBC. We compared disease free survival and overall survival according to dose density expressed in treatment duration for women treated with the same C in our institution. Methods: We reviewed data from 872 women who received 6 cycles of C using the FEC60 regimen (5FU : 600 mg/m2, Epirubicin : 60 mg/m2, cyclophosphamide: 600 mg/m2 on day one repeated every three weeks). All estradiol receptor positive (ER+) patients received adjuvant tamoxifen for 5 years. According to the protocol, C administration was postponed for one week if patients presented leukopenia on day one. No reduction in the applied dose was performed. Overall, 181 patients (group 1) underwent their 6 cycles of C without any delay. In 343 patients (group 2) C was delayed up to three times: treatment duration between 110 and 130 days. C was delayed more than 3 times in 350 patients (group 3): treatment duration greater than 130 days. The distribution of main characteristics was similar in the groups. The median duration of treatment was 125 (100–195) days. Median age was 47 (25–69) years, 66% were premenopausal, 63% node positive, 66% ER positive. The median follow-up is 4 years. Results: Overall, 35, 75 and 117 patients relapsed in the three groups, respectively, leading to a 4-year disease-free survival (DFS) rate of 79.4%, 76.0% and 66.1% respectively (p=0.09). Patients who underwent C in more than 130 days had a higher risk of relapse (p=0.03). No difference was observed in overall survival. Conclusion: We conclude that although no survival disadvantage is noted, the non respect of time schedule in C is detrimental in early breast cancer patients. No significant financial relationships to disclose.
Synergistic Cytotoxic Effect of the Combination of Amrubicin and Erlotinib in Nsclc Without Egfr Mutation
Authors: Sakiko Otani, Jiichiro Sasaki, Masumi Tanaka, Sachiyo Maki, Akira Takakura, Shinichiro Ryuge, Tomoya Fukui, Kazuya Okamoto, Kuniko Masuda, Noriyuki Masuda
Journal: Annals of Oncology (2014)
Abstract 92: Effect of Epinephrine Administration During Out-of-Hospital Cardiac Arrest: a Nationwide, Population-Based Cohort Study
Authors: Hiroshi Kaneko, Tetsuo Hatanaka, Hideharu Tanaka, Hiroshi Takyu, Aki Nagase, Hiroko Noguchi, Yoshio Tahara, Kazuo Kimura
Journal: Circulation (2010)

Effectiveness of prehospital epinephrine administration remains controversial. The aim of this study was to compare the outcome of cardiac arrest patients with and without prehospital epinephrine a...
Reduction of Dialysate Calcium Level Reduces Progression of Coronary Artery Calcification and Improves Low Bone Turnover in Patients on Hemodialysis
Authors: Ercan Ok, Gulay Asci, Selen Bayraktaroglu, Huseyin Toz, Mehmet Ozkahya, Mumtaz Yilmaz, Fatih Kircelli, Ebru Sevinc Ok, Naim Ceylan, Soner Duman, Mustafa Cirit, Marie-Claude Monier-Faugere, Hartmut H. Malluche
Journal: Journal of the American Society of Nephrology (2015)

Exposure to high Ca concentrations may influence the development of low–turnover bone disease and coronary artery calcification (CAC) in patients on hemodialysis (HD). In this randomized, controlled study, we investigated the effects of lowering dialysate Ca level on progression of CAC and histologic bone abnormalities in patients on HD. Patients on HD with intact parathyroid hormone levels ≤300 pg/ml receiving dialysate containing 1.75 or 1.50 mmol/L Ca ( n =425) were randomized to the 1.25-mmol/L Ca (1.25 Ca; n =212) or the 1.75-mmol/L Ca (1.75 Ca; n =213) dialysate arm. Primary outcome was a change in CAC score measured by multislice computerized tomography; main secondary outcome was a change in bone histomorphometric parameters determined by analysis of bone biopsy specimens. CAC scores increased from 452±869 (mean±SD) in the 1.25 Ca group and 500±909 in the 1.75 Ca group ( P =0.68) at baseline to 616±1086 and 803±1412, respectively, at 24 months ( P =0.25). Progression rate was significantly lower in the 1.25 Ca group than in the 1.75 Ca group ( P =0.03). The prevalence of histologically diagnosed low bone turnover decreased from 85.0% to 41.8% in the 1.25 Ca group ( P =0.001) and did not change in the 1.75 Ca group. At 24 months, bone formation rate, trabecular thickness, and bone volume were higher in the 1.25 Ca group than in the 1.75 Ca group. Thus, lowering dialysate Ca levels slowed the progression of CAC and improved bone turnover in patients on HD with baseline intact parathyroid hormone levels ≤300 pg/ml.
Planned Parenthood “sting” film makers are indicted in Texas
Authors: Owen Dyer
Journal: BMJ (2016)

The Planned Parenthood Federation of America—much criticized since July when undercover videos purported to show its officials offering to sell tissue from aborted fetuses—has been handed an unexpected victory by a Texas grand jury. The women’s health organization was cleared of any wrongdoing, and the two anti-abortion activists who made the films were indicted instead.

David Daleiden, founder of the Center for Medical Progress, a non-profit organization that sent impostors with hidden cameras to try to buy tissue from Planned Parenthood, has been charged with a felony count of tampering with government property, as has Sandra Merritt, who with Daleiden posed as an executive of BioMax Procurement Services, a fictional intermediary for research institutes seeking fetal tissue.1 The …
Relation between Deep Vein Thrombosis and Pulmonary Embolism in Surgical Patients
Authors: L.P. Le Quesne
Journal: New England Journal of Medicine (1974)

ON the basis of autopsy evidence, it has been established that clots can be found in the lower-limb veins of 30 to 50 per cent1 2 3 of patients dying after a surgical operation, and pulmonary emboli in a similar percentage.4 The figure for both far exceeds the expectation based on clinical evidence before death. Until recently, the study of both deep vein thrombosis and pulmonary embolism in the living has been hampered not only by the unreliability of clinical examination but also by the lack of any dependable, readily applicable diagnostic technic. In recent years, the introduction of new technics, notably . . .
Histopathologic Studies on Liver Tumorigenesis Induced in Mice by Technical Polychlorinated Biphenyls and Its Promoting Effect on Liver Tumors Induced by Benzene Hexachloride 2
Authors: Nobuyuki Ito, Hiroshi Nagasaki, Masayuki Arai, Sachio Makiura, Seiichi Sugihara, Kazuya Hirao
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Histopathologic Studies on Liver Tumorigenesis Induced in Mice by Technical Polychlorinated Biphenyls and Its Promoting Effect on Liver Tumors Induced by Benzene Hexachloride Get access Nobuyuki Ito, M.D., Nobuyuki Ito, M.D. 3Cancer Center Institute, Nara Medical University, Kashihara, Nara 634, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Hiroshi Nagasaki, M.D., Hiroshi Nagasaki, M.D. 4Department of Hygiene, Nara Medical University, Kashihara, Nara 634, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Masayuki Arai, M.D., Masayuki Arai, M.D. 3Cancer Center Institute, Nara Medical University, Kashihara, Nara 634, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Sachio Makiura, M.D., Sachio Makiura, M.D. 3Cancer Center Institute, Nara Medical University, Kashihara, Nara 634, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Seiichi Sugihara, M.D., Seiichi Sugihara, M.D. 3Cancer Center Institute, Nara Medical University, Kashihara, Nara 634, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Kazuya Hirao, M.D. Kazuya Hirao, M.D. 3Cancer Center Institute, Nara Medical University, Kashihara, Nara 634, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 5, November 1973, Pages 1637–1646, https://doi.org/10.1093/jnci/51.5.1637 Published: 01 November 1973 Article history Received: 21 May 1973 Accepted: 30 July 1973 Published: 01 November 1973
Potential clinical prognostic factors in non-small cell lung cancer (NSCLC) patients treated with gefitinib
Authors: V. M. Villaflor, C. R. Polowy, J. S. Coon, W. T. Leslie, I. Lukic, G. Kanevsky, M. Gale, I. Stewart, P. Bonomi
Journal: Journal of Clinical Oncology (2004)

7088 Background: Phase II studies have shown that gefitinib (Iressa) produces approximately a 10% response rate in previously treated patients (pts) with NSCLC. Currently, little is known about which pts are likely to benefit from treatment with gefitinib. Tobacco, gender, and histologic subtype may be important factors in response to gefitinib(M Kris et.al.,V Miller et.al.). Our objective is to evaluate potential clinical prognostic factors in NSCLC pts treated with gefitinib. Methods: Response rate, progression free interval(PFI) and survival were evaluated for 126 patients (64 female/62 male, median age 68; 67 adenocarcinomas/59 other histologies; 72 PS 0–1/53 PS 2+; 110 used tobacco/ 16 no tobacco use) who were treated with gefitinib (500 mg po day 1, then 250 mg po daily) and evaluated monthly on the expanded access trial. CT scans were performed every two months. We collected data on the pts' age, sex, performance status(PS), tobacco use, number of previous chemotherapies and date of last prior chemotherapy Results: Median follow-up was 169 days(d). Overall response rate was 5.6%(1CR,6PR) and 24 pts (19%) had stable disease. Median Kaplan-Meier survival and PFI were 172 and 59 d, respectively. The Fisher's Exact Test was used to evaluated associations. A greater proportion of patients with adenocarcinoma 85% (6/7) responded than did other histologies 14% (1/7) p=.08. Median survival was 484 d for nonsmokers and 167 d for smokers. Similarly, PFI was146 days-nonsmokers and 59 days-smokers (p<.04). Significant differences in survival were also observed for pts with PS 0–1, 231 d and PS2+, 119 d (p=.0005). A significant association was also observed between tobacco use and gender; a larger proportion of females never used tobacco. Conclusions: Longer survival and PFI were observed in pts treated with gefitinib who have never used tobacco and have PS 0–1. These data suggest further investigation of tobacco usage and PS as predictive factors of response to gefitinib, as well as the relationship between tobacco use and gender is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca
Primary cutaneous lymphomas in Peru
Authors: B. Beltran, A. Carrasco, L. Vera, E. Salinas, M. Ticona, K. Portugal
Journal: Journal of Clinical Oncology (2006)

17566 Background: The clinicopathologic characteristics of malignant lymphomas vary according to geography. The aim of this study was to determine the relative frequency of cutaneous lymphomas and to examine the clinical relevance of the new WHO/EORTC classification in Peruvian cases of cutaneous lymphoma. Methods: We conducted a clinicopathologic retrospective study of a collection of 68 primary cutaneous lymphomas, diagnosed from 1997 to 2004 in a National General Hospital. The clinical records, haematoxylin &amp; eosin-stained slides and immunohistochemical stains from 67 patients with malignant lymphomas of the skin were reviewed. HTLV-1 serology was made using ELISA and Western Blot methods. The statistical method was descriptive and survival was calculated using the Kaplan-Meier method. Results: Mean age at presentation was 62 years and the female/male ratio 1.5:1. T cell lymphomas were 88.6% and 11.4% were B-cell lymphomas. The most frequent cutaneous lymphoma was mycosis fungoides (MF) 30/67 (44.7%), Adult T-cell leukemia/lymphoma (ATLL) 13/67 (19.4%), unspecified peripheral T-cell lymphoma 4/67 (6%), lymphomatoid papulosis 2/67 (3%), leg-type diffuse large B-cell lymphoma 2/67 (3%), diffuse large B-cell lymphoma 2/67 (3%), subcutaneous panniculitis-like T-cell lymphoma 2/67 (3%), anaplastic large cell lymphoma 1/67 (1.4%), Sézary síndrome 1/67 (1.4%), nasal type extranodal NK/T-cell lymphoma 1/67 (1.4%), marginal zone B-cell lymphoma 1/67 (1.4%), follicle center lymphoma 1/67 (1.4%), intravascular lymphoma 1/67 (1.4%) and unclassifiable 5/67 ( 7.4%). Clinical stages of MF were: 60% stage I; 30% stage II; 3% stage III and 7% stage IV. 5-year survival was 77%. In ATLL group, 3 had smouldering type and 10 had cutaneous type. 5-year survival was 18%. Conclusions: In this retrospective analysis, cutaneous T cell lymphomas were prevalent; both MF and ATLL had the most frequency among primary cutaneous lymphomas in our hospital. ATLL had a poor 5-year survival. No significant financial relationships to disclose.
Abstract 16758: Cardiosphere Derived Cells From Pediatric End-Stage Heart Failure Patients Have Enhanced Functional Activity Due to the Heat Shock Response Regulating the Secretome
Authors: Sudhish Sharma, Rachana MIshra, David Simpson, Evan J Colletti, savitha Deshmukh, Ling Chen, Brody P Wehman, shalesh Kaushal, Sunjay Kaushal
Journal: Circulation (2014)

Rationale: Results from pre-clinical studies and a Phase I clinical study demonstrates promising functional recovery by adult cardiosphere derived cells (CDCs) to repair damaged myocardium. We have previously demonstrated that age regulates the functional recovery of neonatal CDCs due to their more effective secretome. However, how advanced failure pediatric hearts regulate their derived CDC’s functional activity is still unknown. Objective: Our aim was to compare the functional potency between pediatric CDCs derived from normal myocardium of congenital heart disease (CHD) patients and from dysfunctional myocardium of pediatric end stage failing heart (ESHF) patients and determine the mechanisms involved. Methods and Results: ESHF derived hCDCs had a higher number of cardiac stem cells expressing c-kit+, Islet-1+, and Sca-1+. When transplanted in an infracted rodent model, ESHF derived hCDCs had a significantly higher preservation of ventricular function, prevented adverse remodeling, and enhanced angiogenesis when compared with CHD derived CDCs. The superior functional recovery of the ESHF derived hCDCs was mediated in part by increased SDF-1α and VEGF-A secretion which recruited more endogenous stem cells and proliferation of cardiomyocytes. The mechanism for the superior secretome is due to the heat shock response (HSR) which is supported by three lines of evidence. First, gain of function studies demonstrated that the HSR induced the low functioning CHD derived CDCs to significantly recover the injured myocardium to the same extent as ESHF derived CDCs. Secondly, loss-of function studies targeting the HSR down regulated the ability of the ESHF derived CDCs to functionally recover the injured myocardium. Finally, the HSR alone increased the number of the c-kit+ CSCs both in vitro and in vivo. Conclusion: These findings suggest that the HSR enhances the functional activity of ESHF derived CDCs by regulating their secretome.