10 research outputs found
Angiotensin II and Prostaglandin Interactions on Systemic andRenal Effects of L-NAME in Humans
No full textFor investigation of whether interactions between
prostaglandins and angiotensin II modulate renal response to
acute nitric oxide synthesis inhibition in humans, seven young
volunteers who were kept on a 240-mM Na diet underwent
four experiments with 90 min of infusion of 3.0 mg/kg.min21
NG-nitro-L-arginine methyl ester (L-NAME), each preceded by
a 3-d treatment with placebo (PL), 50 mg of losartan (LOS), 75
to 125 mg of indomethacin (IND), or both drugs. Mean arterial
pressure (MAP), GFR, effective renal plasma flow (ERPF),
and Na excretion rate (UNaV) were measured at baseline and
from 0 to 45 min and 45 to 90 min of L-NAME infusion. After
PL, L-NAME reduced GFR by 5% at 45 min (P , 0.05) and by
9% at 90 min (P , 0.001), ERPF by 11 to 17% (P , 0.001),
and UNaV by 28 to 45% (P , 0.001). MAP, unchanged at 45min, rose by 5% (P , 0.001) at 90 min. LOS prevented pressor
but not renal effects of L-NAME. With L-NAME1IND, MAP
rose even at 45 min (15%; P , 0.001 versus baseline) with a
10% rise at 90 min (P , 0.001). Changes in GFR (213 to
220%), ERPF (219 to226%), and UNaV (251 to270%) were
greater than those with L-NAME1PL or L-NAME1LOS (P ,
0.05 to 0.001). With L-NAME1IND1LOS, MAP did not increase,
and GFR, ERPF, and UNaV fell much less than with
L-NAME1IND alone (P , 0.02 to 0.001) with no differences
versus PL or LOS alone. Angiotensin II blockade does not affect
renal changes caused by L-NAME but prevents their potentiation
by prostaglandin inhibition. Thus, endogenous prostaglandins
counteract renal actions of endogenous angiotensin II in Na repleted humans even when nitric oxide synthesis is inhibite
Long-term results of PRRT in advanced bronchopulmonary carcinoid
No full textPurpose: Peptide receptor radionuclide therapy (PRRT) for the treatment of neuroendocrine tumours (NET) has been explored for almost two decades, but there are still few trials that have exclusively investigated well-differentiated and moderately differentiated NET arising from the respiratory tree. Thus, the aim of this study was to explore the outcome in patients affected by bronchopulmonary carcinoid (BPC) following PRRT. Methods: We retrospectively analysed 114 patients with advanced stage BPC consecutively treated with PRRT at the European Institute of Oncology, Milan, from 1997 to 2012 and followed until October 2014. The objective responses, overall survival (OS) and progression-free survival (PFS) were rated, and three different PRRT protocols (90Y-DOTATOC vs. 177Lu-DOTATATE vs. 90Y-DOTATOC + 177Lu-DOTATATE) were compared with regard to their efficacy and tolerability. Results: The median OS (evaluated in 94 of the 114 patients) was 58.8 months. The median PFS was 28.0 months. The 177Lu-DOTATATE protocol resulted in the highest 5-year OS (61.4 %). Morphological responses (partial responses + minor responses) were obtained in 26.5 % of the cohort and were associated with longer OS and PFS. The 90Y-DOTATOC + 177Lu-DOTATATE protocol provided the highest response rate (38.1 %). Adverse events were mild in the majority of patients. However, haematological toxicity negatively affected survival. No severe (grade 3/4) serum creatinine increase was observed. Patients treated with 90Y-DOTATOC alone more frequently showed a mild/moderate decrease in renal function. In patients treated with chemotherapy before PRRT had a shorter OS and PFS, and a higher risk of developing nephrotoxicity. Conclusion: In a large cohort of patients with advanced BPC treated in a âreal-worldâ scenario and followed up for a median of 45.1 months (range 2 â 191 months), PRRT proved to be promising in prolonging survival and delaying disease progression. Despite the potential selection biases, considering the risk-benefit ratio, 177Lu-DOTATATE monotherapy seems the best option for PRRT. Our results indicate that the use of PRRT in earlier stages of the disease could provide a more favorable outcome
Egan's stage theory : an exploratory study of its use in the analysis of science textbooks
No full textThesis (M.Ed.)--University of Melbourne, 1985Kieran Egan (1979) has challenged educationists to consider the need for a Theory of Development which is specifically Educational. Such a need is discussed and examined in the context of science teaching. Egan's Theory was applied to the selection of science text material for a group of eleven and twelve year old students. The students' responses to the materials were compared with Egan's descriptions of certain developmental stages, particularly of his Romantic Stage. The author concluded that Egan's theoretical proposition assisted in interpeting certain student behaviour and preferences. Possible classroom uses of Egan's theory are discussed, implications for text usage and design are outlined, and some areas of research are suggested
Final data of an Italian multicentric survey about counseling for smoking cessation in patients with diagnosis of a respiratory disease
No full textSmoking is the major risk factor for cancer and several respiratory diseases. Quitting smoking at any point of life may increase the effectiveness of treatments and improve prognosis of patients with any pulmonary disease, including lung cancer. However, few institutions in Europe offer to patients adequate counseling for smoking cessation
Rationale for Treatment and Study Design of TAILOR: A Randomized Phase III Trial of Second-line Erlotinib Versus Docetaxel in the Treatment of Patients Affected by Advanced Non-Small-Cell Lung Cancer With the Absence of Epidermal Growth Factor Receptor Mutations
No full textWe present the rationale and study design of the Tarceva Italian Lung Optimization trial phase III, multicenter, open-label, randomized trial on efficacy of second-line therapies in different subgroups of non small-cell lung cancer (NSCLC) patients identified using molecular and clinical evaluations. To date, we can assume that advanced NSCLC epidermal growth factor receptor (EGFR) mutated patients benefit from EGFR tyrosine kinase inhibitors, such as gefitinib and erlotinib, whereas their role in the treatment of patients who do not have EGFR mutations is controversial. The aim of this study is to assess whether it is possible to optimize second-line treatment in NSCLC patients with absence of EGFR mutations. Moreover, the predictive value of the K-ras mutation, EGFR protein expression, and EGFR gene copy number, as well as a smoking habit and histotype for determining a different effect of erlotinib, compared with chemotherapy will be assessed in patients who do not have EGFR mutations. The primary endpoint, is overall survival; the secondary endpoints are progression-free survival, response rate, quality of life, and toxicity. We have planned to collect blood samples to identify different prognosis-related polymorphisms and to assess their sensitivity and specificity in the detection of EGFR and K-ras mutations with respect to histologic samples
Angiotensin II and Prostaglandin Interactions on Systemic and Renal Effects of L-NAME in Humans
No full textFinal data of an Italian multicentric survey about counseling for smoking cessation in patients with diagnosis of a respiratory disease
No full textIntroductionSmoking is the major risk factor for cancer and several respiratory diseases. Quitting smoking at any point of life may increase the effectiveness of treatments and improve prognosis of patients with any pulmonary disease, including lung cancer. However, few institutions in Europe offer to patients adequate counseling for smoking cessation.ObjectivesAim of this study was to investigate the level of counseling for smoking cessation offered by healthcare professionals to patients and their appreciation towards the intervention itself.MethodsBetween January 2013 and February 2016, 490 patients, diagnosed with a respiratory diseases, were prospectively evaluated with an anonymous survey developed by WALCE (Women Against Lung Cancer in Europe).ResultsThe majority of patients enrolled (76%) declared to have stopped smoking after the diagnosis of a respiratory disease, 17% to smoke less, 7% to continue smoking. Patients who reported to have never received any counseling for smoking cessation were 38%. Almost 73% of the other patients reported a positive judgment about the quality of healthcare's intervention. Despite these favorable considerations, 83% of patients have disclosed they simply quit smoking overnight without help, 5% have used electronic cigarettes, 5% nicotine replacement treatments, 4% dedicated books, 3% have attended a referral clinic.ConclusionsConsidering all the smoking-related side effects, greater efforts should be made in order to better support patients in smoking cessation. Smoking should be considered as a real physical disorder and similar surveys should be encouraged with the aim to fight the stigma' of smoking that still exists among patients
Expression and activation of SHC/MAP kinase pathway in primary acute myeloid leukemia blasts
No full textCetuximab and gemcitabine in elderly or adult PS2 patients with advanced non-small-cell lung cancer: The cetuximab in advanced lung cancer (CALC1-E and CALC1-PS2) randomized phase II trials.
No full textTwo parallel randomized phase 2 trials were performed to choose the
optimal way of combining cetuximab with gemcitabine in the first-line treatment
of elderly (CALC1-E) and adult PS2 (CALC1-PS2) patients with advanced NSCLC.
METHODS: Stage IV or IIIB NSCLC patients, aged > or =70 years with PS 0-2 for
CALC1-E or aged <70 with PS2 for CALC1-PS2, not selected for EGFR expression,
were eligible. Patients were randomized to concomitant (gemcitabine, for a
maximum of 6 cycles, plus cetuximab until progression) or sequential
(gemcitabine, for a maximum of 6 cycles, followed by cetuximab) strategy. A
selection design, with 1-year survival rate as the primary endpoint, was applied,
requiring 58 elderly and 42 PS2 patients. RESULTS: All planned patients were
randomized. In sequential arms, 34.5% and 60.0% patients were not able to receive
cetuximab after gemcitabine in CALC1-E and CALC1-PS2, respectively. Survival
rates (95% CI) at 1-year for concomitant and sequential arms were 41.4%
(23.5-61.1) and 31.0% (15.3-50.8) in CALC1-E and 27.3% (10.7-50.2) and 35.0%
(15.4-59.2) in CALC1-PS2. In both studies, survival curves crossed at about 10
months and the worse arm until that time became the better one at 1-year.
Toxicity was similar across treatment groups. In concomitant arm of CALC1-E (but
not of CALC1-PS2), survival was longer for patients who developed skin toxicity
within the first two cycles of treatment. CONCLUSION: In both groups of patients,
sequential strategy cannot be proposed for future trials because of low
compliance. Inconsistency of survival outcomes makes also concomitant treatment
not a candidate for further testing in unselected elderly and PS2 NSCLC patients
Comprehensive analyses of somatic TP53 mutation in tumors with variable mutant allele frequency
No full text© The Author(s) 2017. Somatic mutation of the tumor suppressor gene TP53 is reported in at least 50% of human malignancies. Most high-grade serous ovarian cancers (HGSC) have a mutant TP53 allele. Accurate detection of these mutants in heterogeneous tumor tissue is paramount as therapies emerge to target mutant p53. We used a Fluidigm Access Array™ System with Massively Parallel Sequencing (MPS) to analyze DNA extracted from 76 serous ovarian tumors. This dataset has been made available to researchers through the European Genome-phenome Archive (EGA; EGAS00001002200). Herein, we present analyses of this dataset using HaplotypeCaller and MuTect2 through the Broad Institute's Genome Analysis Toolkit (GATK). We anticipate that this TP53 mutation dataset will be useful to researchers developing and testing new software to accurately determine high and low frequency variant alleles in heterogeneous aneuploid tumor tissue. Furthermore, the analysis pipeline we present provides a valuable framework for determining somatic variants more broadly in tumor tissue
