Effect of N dose, fertilisation duration and application of a nitrification inhibitor on GHG emissions from a peach orchard.

Despite only occupying 5% of the worldwide arable area, fruit tree crops are of vital economic importance in many regions. Intensive cropping practices can lead to greenhouse gas (GHG) emissions. In order to reduce these emissions, numerous studies have been made on lowering N inputs or applying nitrification inhibitors (NIs) which tend to maintain or even increase yield while reducing N leaching and nitrogenous emissions to the atmosphere. However, very few studies have been conducted on potential GHG emissions from the peach crop. In this work, a three-year study was carried out in a commercial peach orchard with a split-plot design with three replicates, in which the main factor was N dose (25, 50 and 100 kg N ha-1 year-1, and 50 kg N ha-1 year-1 applied during a shorter period of time in 2015 and 2016; and only 70 kg N ha-1 year-1 in 2017). Subplots in the study were used to analyse the effect of the application of a NI (3,4-dimethylpyrazole phosphate; DMPP). The aim was to qualitatively compare the effect of these factors on N2O, N2O + N2, CH4 and CO2 emissions from a peach orchard soil in order to recommend agricultural practices that minimise emissions without concurrent yield reductions. We show that N2O and N2O + N2 emissions were linked to fertilisation and increased with N dose. The N2O emissions were mitigated (up to 49%) by DMPP up to the 50 kg N ha-1 dose (not significantly). It seems that between 70 and 100 kg N ha-1 the application of DMPP loses effectiveness. Methane oxidation increased with N dose and decreased with DMPP application; CO2 emissions increased with DMPP and were unaffected by N dose. The intermediate N dose (50 kg N ha-1) applied during a shorter period of time increased yield (not significantly) and NUE without increasing GHG emissions.

Ammonia volatilisation from pig slurry and ANS with DMPP applied to Westerwold ryegrass (Lolium multiflorum Lam., cv. Trinova) under Mediterranean conditions.

Ammonia volatilisation from agriculture represents an important nitrogen (N) loss which has both environmental and economic impacts. In regions where large amounts of manures are available, there is a need to find appropriate management strategies that help to reuse them without increasing ammonia volatilisation. A study was made of the effect on ammonia volatilisation and yield of fertilising ryegrass with pig slurry (PS) and ammonium nitrosulphate (ANS-26) alone and with the 3,4-dimethylpyrazol phosphate (DMPP) nitrification inhibitor added to them. The study was conducted under Mediterranean conditions at two different sites. The treatments (control, PS, PS + DMPP, ANS-26 and ENTEC®) were established in a randomised block design with three replicates. Ammonia was sampled daily after each fertilisation using semi-static volatilisation chambers. We hypothesised that PS could replace mineral fertiliser without substantially increasing ammonia volatilisation in the studied systems. Temperature positively correlated with ammonia emissions. On the whole, during the two years of the study, the PS treatments presented higher average cumulative ammonia volatilisation (25% of total ammonium nitrogen (TAN) applied at Site 1; 21% of TAN applied at Site 2) than the mineral ones (11% of TAN applied at Site 1; 10% of TAN applied at Site 2). At pre-sowing, ammonia volatilisation was significantly (p < .05) lower (51% at Site 1; 55% at Site 2) than after ryegrass cuts due to burying PS immediately after application. Overall, applying DMPP had no effect on ammonia volatilisation. There were no significant differences in average yield (from 13.7 to 15.8 kg ha-1 at Site 1; from 11.6 to 13.5 kg ha-1 at Site 2) between the fertilised treatments, though ENTEC® tended to increase it. Applying PS (pre-sowing fertilisation) in combination with mineral N or processed PS fractions after ryegrass cuts could be an interesting option for the recycling of this livestock by-product without increasing ammonia volatilisation while maintaining yields.

[Austrian syndrome: A rare manifestation of invasive pneumococcal disease. A case report and bibliographic review]. / Síndrome de Austrian: Una rara manifestación de la enfermedad neumocócica invasiva. Presentación de un caso y revisión bibliográfica.

The Austrian syndrome is a pathology caused by disseminated Streptococcus pneumoniae infection and characterized for the triad of pneumonia, endocarditis and meningitis. It has an estimated incidence of 0.9-7.8 cases per ten millions people each year, and a mortality of 32%. Alcohol abuse, as the main risk factor, appears only in four out of ten patients. Moreover, 14% of patientes do not have any risk factor. Two out of three patients are males and it occurs in the middle aged of life. It is more frequently on native valve, aortic valve is injured in the half of the cases. Severe regurgitation occurs in two per three patients. Appropriate antimicrobial treatment and early endocarditis surgery decrease mortality. It is possible that Austrian syndrome epidemiology is changing by the introduction of 13-valent pneumococcal conjugated vaccine in the children´s calendar.

Effect of N dose on soil GHG emissions from a drip-fertigated olive (Olea europaea L.) orchard.

Agronomic practices may mitigate greenhouse gas emissions (GHG) from crops. Appropriate nitrogen (N) and irrigation management provide the potential to reduce nitrous oxide (N2O) and methane (CH4) emissions. However, there is little information about the combination of both practices on the GHG emissions from olive orchards. This four-year study was conducted to qualitatively compare the effect of N doses applied through two drip irrigation strategies on N2O and CH4 emissions in a super-intensive (1010 trees ha-1) olive orchard. The design (randomised blocks) was asymmetric: 0, 50 and 100 kg N ha-1 yr-1 were tested with full irrigation (FI; 2013 to 2016), but only 0 and 50 kg N ha-1 yr-1 were tested with regulated deficit irrigation (RDI; 2014 to 2016). The study shows that the soil acted as a main sink of N2O and CH4, regardless of the soil water content. Methane oxidation increased with N dose in the FI strategy (significant in 2013 and 2015). Overall, there was a tendency of yield to increase with the N dose without increasing emissions and without depending of the irrigation strategy. However, these results were not significant. Further confirmation of this tendency is necessary; particularly comparing FI + N100 (most promising treatment in terms of profitability) with the RDI + N100 (not available in this study) water-saving strategy.

Phase I-II study of paclitaxel, cisplatin, and gemcitabine in advanced transitional-cell carcinoma of the urothelium. Spanish Oncology Genitourinary Group.

PURPOSE: To determine the maximum-tolerated dose and the antitumor activity of a combination of paclitaxel, cisplatin, and gemcitabine in advanced transitional-cell carcinoma (TCC) of the urothelium. PATIENTS AND METHODS: Patients with measurable, previously untreated, locally advanced or metastatic TCC and with Eastern Cooperative Oncology Group performance status < or = 2 and creatinine clearance > or = 55 mL/min were eligible. Cisplatin was given on day 1 at a fixed dose of 70 mg/m(2). Paclitaxel and gemcitabine were given on days 1 and 8 at increasing dose levels. Cycles were repeated every 21 days to a maximum of six cycles. RESULTS: Sixty-one patients were registered. In phase I, 15 patients were entered at four different dose levels. Dose-limiting toxicity consisted of early onset (after the first cycle) grade 2 asthenia (two of six patients) and grade 3 asthenia (one of six patients) at dose level 4. A paclitaxel dose of 80 mg/m(2) and gemcitabine 1,000 mg/m(2) was recommended for phase II, and 46 additional patients were entered at this level for a total of 49 patients. Main nonhematologic toxicity was grade 2 asthenia in 18 patients, with early onset in five patients, and grade 3 in four patients. Grade 3/4 neutropenia and thrombocytopenia occurred in 27 (55%) and 11 (22%) patients, respectively. Overall, febrile neutropenia was seen in 11 patients, and one toxic death occurred because of neutropenic sepsis. The combination was active at all dose levels. In total, 58 of 61 eligible patients were assessable for response; 16 complete responses (27.6%) and 29 partial responses (50%) were observed for an overall response rate of 77.6% (95% confidence interval, 60% to 98%). The median survival time (MST) available for the phase I part of the study is 24.0 months. MST has not been reached for the whole group with the current follow-up. CONCLUSION: This combination of paclitaxel, cisplatin, and gemcitabine is feasible and highly active in patients with advanced TCC of the urothelium. Further evaluation of this regimen in patients with TCC is warranted.

Gemcitabine/carboplatin in advanced urothelial cancer.

Transitional cell carcinoma of the urothelium is a highly chemosensitive tumor. Combination chemotherapy can provide both palliation and a modest survival advantage in patients with advanced disease. As shown in a recent phase III trial, the new gold standard should be considered gemcitabine/cisplatin, although toxicity remains important. Bladder cancer is a common tumor in our population (Spain), usually affecting elderly patients with comorbid diseases and renal impairment. Thus, most of these patients may not benefit from cisplatin-based regimens. The development of new combinations for treating such patients is, therefore, of vital importance. The identification of new active agents against transitional cell carcinoma, such as taxanes and gemcitabine, is promising. We believe that the combination of gemcitabine plus carboplatin could also be useful in this subset of patients. On this basis, we treated bladder cancer patients in two trials using gemcitabine 1,000 mg/m(2) on days 1 and 8, and carboplatin (area under the curve 5) on day 1, every 21 days. The overall response rate for evaluable patients with and without renal impairment was 60%, with a 95% confidence interval of 40% to 72%. The potential clinical benefit of this new doublet in the treatment of transitional cell carcinoma warrants testing in future phase III studies. Semin Oncol 28 (suppl 10):19-24.

Ifosfamide and irinotecan in solid tumors: a phase I dose-finding trial.

The combination of ifosfamide and irinotecan was tested in a dose-finding study. The preliminary results of the combination in this phase I study did not show any major toxicity that could help to define the dose-limiting toxicity. The escalation continues even after nine levels; the study is therefore ongoing. The main toxicity is gastrointestinal, with mild nausea, vomiting, and diarrhea. There was some other irrelevant toxicity, which was easily manageable with the usual supportive therapy. When responses were evaluated, stable disease was found in some cases, suggesting some activity for the combination.

Second-line chemotherapy for non-small cell lung cancer.

BACKGROUND: The role of second-line chemotherapy for the treatment of patients with non-small cell lung cancer (NSCLC) who have relapsed or failed to respond to first-line treatment was unclear. OBJECTIVES: To determine the effectiveness of any second-line chemotherapy in patients with NSCLC. SEARCH STRATEGY: Bibliographic databases were searched. Handsearching and contact with experts was also performed. SELECTION CRITERIA: Randomised controlled clinical trials in which any second-line chemotherapy was compared with BSC in patients with NSCLC who had previously failed to any previous chemotherapy regimen. DATA COLLECTION AND ANALYSIS: Data was extracted by 2 independent reviewers and revised by all authors. MAIN RESULTS: Only one study was included. It randomised 204 patients to receive either doxetaxel or BSC. Following an unacceptably high toxic death rate the dose of doxetaxel was reduced from 100 mg/m(2) to 75 mg/m(2). Doxetaxel gave an extra 2.4 months of survival - an average of 7.0 months vs 4.6 months on BSC. At 1 year after diagnosis 29% of doxetaxel treated patients were alive compared with 19% of the BSC group. REVIEWER'S CONCLUSIONS: Definitive recommendations cannot be made since evidence is only available from one randomised controlled trial which, though of reasonable quality, had a number of limitations. There is currently no evidence to support second-line treatment of patients with poor performance status. Larger, well-designed controlled trials are needed to further evaluate whether the benefits of second-line chemotherapy to patients with NSCLC outweigh its risks and costs.

Second-line chemotherapy for non-small cell lung cancer.

BACKGROUND: The role of second-line chemotherapy for the treatment of patients with non-small cell lung cancer (NSCLC) who have relapsed or failed to respond to first-line treatment was unclear. OBJECTIVES: To determine the effectiveness of any second-line chemotherapy in patients with NSCLC. SEARCH STRATEGY: Medline (1966-July 2001), Embase (1974-July 2001), Cancerlit (1993-July) and the Cochrane Controlled Trials Register (CENTRAL, issue 2 2001) were searched. In addition a handsearch was performed and experts in the field contacted to identify any further studies that had not been found by the electronic searches. SELECTION CRITERIA: Randomised controlled clinical trials in which any second-line chemotherapy was compared with placebo or best supportive care in patients with NSCLC who had previously failed to any previous chemotherapy regimen. DATA COLLECTION AND ANALYSIS: Data were extracted by 2 independent reviewers and revised by a third author. MAIN RESULTS: Only one study was included. This study included a total of 204 patients who were randomised to receive either doxetaxel or best supportive care. Following an unacceptably high toxic death rate the dose of doxetaxel was reduced from 100 mg/m(2) to 75 mg/m(2). Docetaxel gave an extra 2.4 months survival - an average of 7.0 months vs 4.6 months on best supportive care. At 1 year after diagnosis 29% of doxetaxel treated patients were alive compared with 19% of the best supportive care group. REVIEWER'S CONCLUSIONS: Definitive recommendations cannot be made since evidence is only available from one randomised controlled trial which, though of reasonable quality had a number of limitations. There is currently no evidence to support second-line treatment of patients with poor performance status. Larger, well-designed controlled trials are needed to further evaluate whether the benefits of second-line chemotherapy to patients with non-small cell lung cancer outweigh its risks and costs.

[Prospective assessment of clinical outcomes in patients with lung cancer]. / Evaluación prospectiva de resultados clínicos en los pacientes con cáncer de pulmón.

BACKGROUND: The aim of this study was to assess the outcome in patients with lung cancer. PATIENTS AND METHODS: Prospective study in 93 patients with lung cancer in 3 community hospitals. In each evaluation (4-6 weeks) the following results were obtained: a) questionnaire on the quality of life or performance status (QoL/PS), based on different instruments (Karnofsky Performance Scale [KPS], ECOG, QLQ-C30, and the Nottingham Health Profile [NHP], and b) a clinical questionnaire. Active follow-up was for 18 months and survival tracking was to five years. A descriptive analysis of the outcome variables and a survival analysis (Kaplan-Meier) were done. The prognostic value of each instrument (Cox) and the correlation between the instruments (Spearman) were also evaluated. RESULTS: The mean values recorded at the time of diagnosis between 60% and 70% of the maximum value possible. Mean survival was 12.4 months; accumulated survival was 30% to one year and 4% to 55 months. Only 17% of patients presented any disease-free period. Toxicity of treatment was almost always irrelevant. The correlation between the KPS, the QLQ-30 and the NHP was acceptable and their initial values were important prognostic factors. The QoL/PS scores for the survivors were similar to their initial values, but the global values were 11%. CONCLUSIONS: The outcomes measures used in this study provide very useful information, although registration and analysis of the necessary data should be systematic. The KPS was comparable to the other QoL/PS indicators used, but it is shorter, more acceptable and easier to use. Better QoL/PS measurement instruments are needed to evaluate outcomes in the practice of clinical oncology.

Weekly administration of docetaxel in combination with estramustine and celecoxib in patients with advanced hormone-refractory prostate cancer: final results from a phase II study.

The objective of this study was to evaluate the efficacy and safety profile of weekly docetaxel, estramustine and celecoxib in patients with advanced hormone-refractory prostate cancer. Forty-eight patients received 35 mg m(-2) of weekly docetaxel for 3 out of every 4 weeks, 280 mg of estramustine twice daily on days 1-3, 8-10, 15-17 and 400 mg of celecoxib twice daily until progression or toxicity. Cycles were repeated every 28 days for at least six cycles. Patients were evaluated for response and toxicity. Patients received a median of four cycles (range: 1-9). On an intention-to-treat analysis, prostate-specific antigen (PSA) was decreased greater than 50% in 28 out of 48 patients (overall response rate: 58%, 95% confidence interval (CI): 44-72) and median duration of PSA response was 8.0 months (95% CI: 6.9-9.0). After a median follow-up of 11.3 months, the median time to progression was 7.1 months and the median overall survival was 19.2 months. The most frequent severe toxicity was asthenia (15% of patients), diarrhoea and stomatitis (8% of patients, each). Grade 3/4 neutropenia was reported in two patients. There was a toxic death during the study due to a gastric perforation. Celecoxib with weekly docetaxel and estramustine is an effective and safe treatment for patients with hormone-refractory prostate cancer, but it does not seem to add any benefit to docetaxel.

Clinical experience with tegafur and low dose oral leucovorin: a dose-finding study.

Tegafur is an effective oral fluoropyrimidine that shows the same activity as 5-fluorouracil for a similar spectrum of cancers. Their biochemical modulation with oral Leucovorin (LV) attempts to simulate treatment with a continuous infusion of 5-fluorouracil and LV with the added advantage of outpatient administration. Thirty-three patients with advanced adenocarcinoma were included in the study. The treatment consisted of tegafur, 0.75 g/m2/day, for 21 days, with oral LV at different dose levels, 15, 30, 45, 60 and 90 mg/day, in a 28-day cycle. A correlation between the LV dose and an increase in grade III/IV toxicity (especially diarrhea, oral mucositis and fatigue) was established in the nonlinear regression model, reaching a plateau at 60 mg of LV. For the tegafur dose used, the recommended dose of LV is in the range of 45-60 mg/day. This schedule could be considered to evaluate the possible therapeutic effect in phase II trials.

Intraoperative colonoscopy in patients with colorectal cancer.

Sixty-seven patients underwent intraoperative colonoscopy during elective surgery for colorectal cancer. Complete examination of the colon was achieved in 65 patients (97 per cent), albeit with insertion through a colotomy in three (4 per cent). A synchronous carcinoma was found in six patients (9 per cent), which necessitated a change of planned surgical procedure. Synchronous polyps were detected and removed in 24 patients (36 per cent); two had polyps with carcinoma in situ. The mean age of patients with synchronous carcinoma was significantly higher than that of those without (74.1 versus 61.2 years, P = 0.02). Intraoperative colonoscopy took a mean of 15 min surgical time and only two minor complications (serosal lacerations) were encountered. In patients with colorectal cancer, intraoperative colonoscopy allows complete assessment of the colon and identifies synchronous lesions.

Carboplatin-gemcitabine treatment of patients with transitional cell carcinoma of the bladder and impaired renal function.

INTRODUCTION: Bladder cancer is a frequently occurring tumour in Spain and usually affects elderly patients with renal impairment. The development of new combination therapies for such patients is thus of vital importance. PATIENTS AND METHODS: Between 1997 and 1998, 17 patients with locally advanced non-surgical or metastatic bladder tumours were treated at our centres. Treatment consisted of 1,000 mg/m(2) of gemcitabine administered on days 1 and 8, and carboplatin (area under the concentration curve = 5) on day 1, every 21 days. RESULTS: The mean age of the patients [4 females (26%) and 13 males] was 69 years (range: 54-78 years). The average Karnofsky performance status was 80% (range: 50-100%). Mean creatinine clearance was 45.4 ml/min (range: 21-55 ml/min). There were 2 complete responses, 7 partial responses (RO: 56%; range 31-81%), 6 patients had stable disease and 1 disease progression. Haematological toxicities were as follows: grade I anaemia in 2 patients, grade III in 3; grade I granulocytopenia in 2 patients, grade III-IV in 4 patients; grade III thrombocytopenia in 3 patients. Toxic death occurred in the course of one grade IV neutropenic event. Non-haematological toxicities were as follows: grade I-II vomiting in 3 patients and grade III in 1. One patient had grade III hepatic toxicity. One patient had grade III renal toxicity, and 3 patients grade II alopecia. CONCLUSIONS: The above-mentioned treatment has low toxicity, is easy to administer and offers promising results in this group of patients.

Protracted treatment with tegafur and low dose oral leucovorin in patients with advanced colorectal carcinoma.

BACKGROUND: Protracted oral administration of tegafur (TG) and leucovorin (LV) attempts to simulate the continuous infusion of 5-fluorouracil, with a higher intracellular folate pool. In a prior dose-finding study with a fixed TG dose of 0.75 g/m2/day for a period of 21 days and continuous oral LV, the recommended dose of LV was 45 mg/day in 28-day cycles. METHODS: Thirty-nine patients with histologic confirmation of adenocarcinoma of the colon or rectum, either advanced or metastatic disease, and who were not candidates for radical treatment were included in a Phase II study using this schedule. RESULTS: One hundred sixty-three cycles of chemotherapy were delivered (median, 4 cycles per patient). Toxicity was observed in the form of diarrhea, which was severe in 12 patients (30.7%). Grade 3 (according to the World Health Organization criteria) oral mucositis was recorded in 7 patients (18%). Asthenia was severe in 10% of the patients. Recuperation from toxicity was rapid and managed primarily on an outpatient basis. Two complete (5.1%) and 13 partial (33.3%) responses were observed, with a global response index of 38.5% (95% confidence interval, 23.2-53.6%). The median overall survival was 11.3 months. CONCLUSIONS: The results of this study show that an all-oral regimen of tegafur and leucovorin can obtain biochemical modulation, with a significant response rate, in patients with advanced colorectal carcinoma. Randomized trials are needed to assess the possible advantage of this regimen over intravenous schedules.

Alternating chemotherapy in advanced non-small cell lung cancer: a phase II study.

Fifty-three patients with advanced non-small cell lung cancer (NSCLC) were treated with alternating two-drug schedules cisplatin/vindesine and ifosfamide/mitomycin. Objective response (complete and partial response) was obtained in 31% (confidence limits 18.6-44%) of patients. The median duration of response was 26 weeks. The median survival was 25 weeks, with 24% of patients alive at 1 year. The toxicity was acceptable. The still poor antitumor activity of the chemotherapy schedules used and the lack of non-cross-resistance are factors that could explain the low antitumor activity of alternating chemotherapy.

Phase II study of estramustine and vinorelbine in hormone-refractory prostate carcinoma patients.

The purpose of this study was to evaluate the antitumor activity of vinorelbine and oral estramustine phosphate in patients with metastatic, hormone-refractory prostate cancer. We evaluated the activity of this association using the following schedule: estramustine phosphate 600 mg/m2/day orally days 1-42 and vinorelbine 25 mg/m1 days 1, 8, 22, 29 cycles repeated every 56 days. Twenty-five patients were included in the study, 24 being evaluable for response and 25 for toxicity. Out of 5 patients with measurable disease, none had an objective response. Of the 24 assessable patients with bone metastases, 9 patients had a > or = 65% decline in pretreatment prostate-specific antigen (PSA) level, stable disease was observed in 10 and 5 patients progressed. Toxicities were minimal. Anemia was observed in 5 patients, alopecia in 4 and nausea and vomiting was observed in 6 patients. Anorexia and weight loss of more than 10% were observed in 2 patients. This combination is active and well tolerated in hormone-resistant prostate cancer. These results support the therapeutic strategy of combining agents that impair microtubule function.

[Chronic theophylline treatment in chronic airflow obstruction. Relations between doses, blood levels and expiratory flow]. / Tratamiento crónico con teofilinas en la limitación crónica al flujo aéreo. Relación entre dosis, niveles séricos y flujo espiratorio.

We evaluated 31 patients from the ABS La Gavarra in Cornellà de Llobregat who fulfilled the following criteria: they were male, they had mild to moderate chronic limitation to airflow (CLAF), their disease and/or other accompanying conditions were stable, and they were receiving chronic slow release theophylline therapy. We investigated theophylline blood levels in these patients, attempting to correct the doses when appropriate, and we correlated the therapeutic levels with the subjective clinical improvement, which was also assessed by peak flow meter values. A total of 60% of patients had therapeutic levels. After correcting the dose, 64% had therapeutic levels with an increase of spirometric values of 4%. This improvement has small clinical relevance as it does not reach the expected 15%. The results of this study help to reassess the leading role of theophyllines in the therapeutic armamentarium available for CLAF.