Topotecan in the treatment of relapsed small cell lung cancer

Small cell lung cancer (SCLC) represents about 15% to 20% of all lung cancers. Chemotherapy is the cornerstone of the treatment, cisplatin–etoposide combination being the most used combination as first-line therapy. Despite high initial chemosensitivity, most SCLC patients will experience relapse sooner or later. Unfortunately, second-line chemotherapy does not result in a high response rate like first-line therapy, most patients having developed wide chemoresistance. This chemoresistance is far more important in refractory patients, ie, those who never responded to first-line therapy or who relapsed within 3 months after the end of chemotherapy, than in sensitive patients, ie, those who relapse more than 3 months after the end of chemotherapy. Topotecan, a topoisomerase I inhibitor, is the most studied drug in this second-line setting and has proved its efficacy as a single agent and in combination. A phase III trial comparing oral topotecan to best supportive care (BSC) in relapsed SCLC demonstrated a significant survival benefit as well as a better quality of life. Although the usual schedule is 1.5 mg/m2, days 1–5 intravenously, it is not convenient for patients with relapsed SCLC, especially those who are refractory because of their short survival expectation. Oral topotecan is of similar efficacy and much more convenient with limited stay in a treatment unit and has a comparable toxicity profile for these patients with short expected survival. Combination of topotecan with platinum salts or taxanes does not seem to improve further the outcome of the patients and thus single-agent therapy with topotecan is the standard treatment for relapsed SCLC

Lifetime of Gas Turbines Hot Section Parts in an O&G Environment

TutorialThe main driver to define the time between overhauls of a gas turbine is the life of the hot components. For an Oil&Gas operator, a turbine overhaul represents a major cost and therefore is a key point for performance improvement. This paper reviews the main damaging mechanisms of the hot sections of gas turbines, the available models, and provides orders of magnitudes of the impact of the different factors in the life of components. It also presents the operational experience of Total through cases for which the time between overhauls was successfully extended

Lifetime of Gas Turbines Hot Section Parts in an O&G Environment

TutorialThe main driver to define the time between overhauls of a gas turbine is the life of the hot components. For an Oil&Gas operator, a turbine overhaul represents a major cost and therefore is a key point for performance improvement. This paper reviews the main damaging mechanisms of the hot sections of gas turbines, the available models, and provides orders of magnitudes of the impact of the different factors in the life of components. It also presents the operational experience of Total through cases for which the time between overhauls was successfully extended

Subsynchronous Vibrations On Turboexpanders Equipped With Magnetic Bearings Assessment, Understanding And Solutions

LectureIn most natural gas applications, turboexpanders are operating close to or on the dew point line and a mixture entering the turboexpander impeller is a combination of liquid and gas phases of the natural gas. The presence of the liquid phase may induce rotordynamic instabilities during operation. Special care should be taken in the case of magnetic bearings. This paper will present a revamp of two turboexpander-compressors equipped with active magnetic bearings (AMB). The application is liquid natural gas (LNG) rejection and gas injection on a Floating Production, Storage and Offloading (FPSO) barge. Prior to upgrade, the turboexpanders had accumulated more than 250 thousand hours in operation. The objective of the upgrade was to adapt to new process conditions and to increase the power of the turboexpanders. After the re-wheeling of turboexpanders, numerous trips due to violent subsynchronous vibrations were experienced. The root-cause analysis revealed that the presence of liquids in the front wheel labyrinth seals caused fluid-induced non-synchronous vibrations (NSV). Methods used in the redesign of the impellers and labyrinth seals that allowed the problem to be solved will be described in detail

Glucose and Pharmacological Modulators of ATP-Sensitive K+ Channels Control [Ca2+]c by Different Mechanisms in Isolated Mouse α-Cells

OBJECTIVE—We studied how glucose and ATP-sensitive K+ (KATP) channel modulators affect α-cell [Ca2+]c

Brain metastases at the time of presentation of non-small cell lung cancer: a multi-centric AERIO analysis of prognostic factors

A multi-centre retrospective study involving 4 French university institutions has been conducted in order to identify routine pre-therapeutic prognostic factors of survival in patients with previously untreated non-small cell lung cancer and brain metastases at the time of presentation. A total of 231 patients were recorded regarding their clinical, radiological and biological characteristics at presentation. The accrual period was January 1991 to December 1998. Prognosis was analysed using both univariate and multivariate (Cox model) statistics. The median survival of the whole population was 28 weeks. Univariate analysis (log-rank), showed that patients affected by one of the following characteristics proved to have a shorter survival in comparison with the opposite status of each variable: male gender, age over 63 years, poor performance status, neurological symptoms, serum neuron-specific enolase (NSE) level higher than 12.5 ng ml−1, high serum alkaline phosphatase level, high serum LDH level and serum sodium level below 132 mmol l−1. In the Cox's model, the following variables were independent determinants of a poor outcome: male gender: hazard ratio (95% confidence interval): 2.29 (1.26–4.16), poor performance status: 1.73 (1.15–2.62), age: 1.02 (1.003–1.043), a high serum NSE level: 1.72 (1.11–2.68), neurological symptoms: 1.63 (1.05–2.54), and a low serum sodium level: 2.99 (1.17–7.62). Apart from 4 prognostic factors shared in common with other stage IV NSCLC patients, whatever the metastatic site (namely sex, age, gender, performance status and serum sodium level) this study discloses 2 determinants specifically resulting from brain metastasis: i.e. the presence of neurological symptoms and a high serum NSE level. The latter factor could be in relationship with the extent of normal brain tissue damage caused by the tumour as has been demonstrated after strokes. Additionally, the observation of a high NSE level as a prognostic determinant in NSCLC might reflect tumour heterogeneity and understimated neuroendocrine differentiation. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Dry Gas Seals

Discussion Grou

High Performance Bearing Comparison

LectureWith the increasing demand for high performance gearboxes, larger, faster, more highly loaded bearings are requiring more oil and creating more heat than ever before. This means the lubrication systems must be larger to handle the increasing heat loads and oil demands. Offshore applications, in particular, are greatly affected due to space constraints and increased lubrication system size and cost. In an effort to reduce the oil flow and heat load requirements for the gearbox, experimental tests and field tests were performed with three different bearing designs. The designs were pressure dam, offset half, and tilting pad journal bearings. Data was acquired using a dedicated test rig that allows operation at and beyond design speeds and loads. Field test data was also collected from a full speed, full load string test of a turbo compressor drivetrain. This paper will present results of the experimental test data from these three bearings to assist in the selection of a design that will provide optimum performance for given operation conditions