Phase I study of dose-escalated paclitaxel, ifosfamide, and cisplatin (PIC) combination chemotherapy in advanced solid tumours

Based on the already known in vitro synergy between paclitaxel (taxol), cisplatin and oxazophosphorine cytostatics and the broad spectrum of activity of the above drugs we sought to evaluate the paclitaxel (taxol)-ifosfamide-cisplatin (PIC) combination in the outpatient setting in individuals with a variety of advanced solid tumours. Cohorts of patients were entered into six successive dose levels (DLs) with drug doses ranging as follows: paclitaxel 135–215 mg m−2day 1 – (1 h infusion), ifosfamide 4.5–6.0 g m−2(total dose) – divided over days 1 and 2, and cisplatin 80–100 mg m−2(total) – divided over days 1 and 2. Granulocyte colony-stimulating factor was given from day 5 to 14. Forty-two patients were entered. Eighteen patients had 2–8 cycles of prior chemotherapy with no taxanes or ifosfamide (cisplatin was allowed). The regimen was tolerated with outpatient administration in 36/42 patients. Toxicities included: grade 4 neutropenia for ≤ 5 days in 27% of cycles; 5 episodes of febrile neutropenia in three patients at DL-III, -V and -VI. Grade 3/4 thrombocytopenia and cumulative grade 3 anaemia were seen in 7% and 13% of cycles respectively. Three cases of severe grade 3 neuromotor/sensory neuropathy were recorded at DL-II, -III, and -V, all after cycle 3. The maximum tolerated dose was not formally reached at DL-V, but because of progressive anaemia and asthenia/fatigue, it was decided to test a new DL-VI with doses of paclitaxel 200 mg m−2, ifosfamide 5.0 g m−2and cisplatin 100 mg m−2; this appeared to be tolerable and is recommended for further phase II testing. The response rate was 47.5% (complete response + partial response: 20/42). The PIC regimen appears to be feasible and safe in the outpatient setting. Care should be paid to neurotoxicity. Phase II studies are starting in non-small-cell lung cancer, ovarian cancer and head and neck cancer at DL-VI. © 2000 Cancer Research Campaig

A computational framework for complex disease stratification from multiple large-scale datasets.

BACKGROUND: Multilevel data integration is becoming a major area of research in systems biology. Within this area, multi-'omics datasets on complex diseases are becoming more readily available and there is a need to set standards and good practices for integrated analysis of biological, clinical and environmental data. We present a framework to plan and generate single and multi-'omics signatures of disease states. METHODS: The framework is divided into four major steps: dataset subsetting, feature filtering, 'omics-based clustering and biomarker identification. RESULTS: We illustrate the usefulness of this framework by identifying potential patient clusters based on integrated multi-'omics signatures in a publicly available ovarian cystadenocarcinoma dataset. The analysis generated a higher number of stable and clinically relevant clusters than previously reported, and enabled the generation of predictive models of patient outcomes. CONCLUSIONS: This framework will help health researchers plan and perform multi-'omics big data analyses to generate hypotheses and make sense of their rich, diverse and ever growing datasets, to enable implementation of translational P4 medicine

The change in the specific leaf area of maize grown under Mediterranean conditions

The change in the specific leaf area (ie the leaf area per dry matter weight unit) of 2 single maize hybrids was studied in 4 field experiments carried out in central and northern Greece in 1987 and 1988. It was found that the overall specific leaf area of maize takes an initial value much lower than the values suggested for central European conditions and decreases as a function of the development stage of the crop, independent of location, cultivar, plant density (within the normal range), soil conditions, irrigation management and crop growth. A methodology for calculating the development stage based on the accumulated thermal units method is also discussed. Further, the validity of the produced empirical relation between specific leaf area and development stage was tested for 13 more maize plantings grown in western Greece in 1991. A fairly good agreement with the measured values especially before flowering (end of leaf growth) was found, suggesting that the empirical relation may be used in modern crop growth models simulating maize growth under Greek and more generally Mediterranean conditions.Modification de la surface foliaire spécifique du maïs dans les conditions culturales méditerranéennes. La modification de la surface foliaire spécifique (surface foliaire par unité de poids de matière sèche) de 2 hybrides de maïs a été étudiée, dans 4 expérimentations au champ, dans le centre et le nord de la Grèce en 1987 et 1988. Il a été constaté que la surface foliaire spécifique totale a une valeur initiale assez faible par rapport aux valeurs qui sont proposées pour les conditions d'Europe centrale. Elle diminue avec le stade de développement de la culture indépendamment du lieu, de la variété, de la densité de plantation (dans la gamme couramment utilisée), des conditions du sol, de la gestion de l'irrigation et de la croissance des plantes. Une méthode de calcul du stade de développement, basée sur la méthode des sommes de températures, a été aussi discutée. En outre, la validité de la relation empirique obtenue entre la surface foliaire spécifique et le stade du développement a été testée sur 13 cultures de maïs dans l'ouest de la Grèce en 1991. Une bonne concordance a été constatée, particulièrement pour les valeurs obtenues avant la floraison (fin du développement des feuilles), montrant que cette relation empirique pourrait être utilisée dans des modèles modernes de simulation du développement des plantes et spécialement du développement du maïs dans les conditions culturales grecques et plus généralement méditerranéennes

The role of rock fragments in evaporation from cultivated soils under Mediterranean climatic conditions

status: publishe

Evaporation from cultivated soils containing rock fragments

Evaporation from bare soil surfaces represents an important water loss for agriculture in semi-arid regions, Numerous efforts have been undertaken to modify the topsoil characteristics (mulching, tillage) in order to create a thin dry topsoil that reduces evaporation. However, little attention was paid to the role of natural rock fragments in topsoils with respect to evaporation. This paper presents the results of laboratory experiments simulating evaporation from initially wet and air-dry soils containing a range of rock fragment contents, and compares them to field conditions, Evaporation was stimulated by blowing fans at one (high) evaporative demand (E(o) = 7.7-9.2 mm day(-1)). Time domain reflectometry (TDR) was used to investigate the relation between the water content of the topsoil and the actual evaporation rate. For soils at field capacity, initial fine earth water content decreases with rock fragment content, and consequently evaporation rates decrease in the same order. For air-dry soils that received a limited amount of rain (10 and 20 mm), an opposite behaviour was observed. Initial fine earth water content and evaporation rates increase with rock fragment content. A strong positive sigmoidal relation between relative evaporation rate (actual over open-pan evaporation rates) and fine earth water content in the centre of the wetted soil section was observed during the laboratory experiments. Except for the columns covered with a mulch, there were no systematic differences in this relation between the treatments, A rock fragment mulch reduces evaporation rate at a given soil water content significantly, These trends explain the often ambivalent effects of rock fragments on evaporation rates in the field.status: publishe

Impact of iliac crest bone graft harvesting on fusion rates and postoperative pain during instrumented posterolateral lumbar fusion

This study aims to evaluate the influence of bone harvesting on postoperative pain and fusion rates. Group 1 patients received iliac crest bone graft (ICBG) either alone or augmented with local bone. Group 2 received only local bone. No statistical significance was found in radiological union or in the Oswestry Disability Index scores. Visual Analogue Scale scores showed less pain in group 2. Logistic regression showed no correlation between residual pain and occurrence of fusion. Harvesting ICBG did not appear to increase fusion rates and no relation was found between radiological non-union and pain