Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine via the Group C protocol mechanism of the National Cancer Institute: a report of 979 patients

PURPOSE: To provide cladribine (CdA) to physicians for the treatment of patients with previously treated or untreated hairy cell leukemia (HCL), and to determine the response rate, response duration, survival, and toxicity with this agent. PATIENTS AND METHODS: This Group C phase II study was open to all eligible patients whose primary physician obtained written permission from the National Cancer Institute (NCI) to register patients onto this protocol. Of 979 patients registered, 861 were assessable for response and 895 for toxicity. RESULTS: The complete remission (CR) rate was 50% and the partial remission (PR) rate was 37%. At a median follow-up of 52 months, 12% of patients were reported to have progressed and 62 (7%) have died of disease. CONCLUSION: This large experience confirms the excellent response rates and remission duration of CdA in patients with HCL. Nevertheless, the response rates in this setting, which approximates general clinical practice, were lower than in other series. In general, CdA was well tolerated, but the potential increased risk for secondary malignancies requires additional follow-up evaluation. CdA can now be considered as one of the best agents for the treatment of HCL.     

Report of the elections supervisor.

Presents a report from the elections supervisor concerning 1992 nominations for the office of President-elect of the Society. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acoustic emission from a defective C/Mn steel pressure vessel

Location analysis has been used to examine acoustic emission from a partial thickness slit in a test vessel under pressurisation. Pulse arrival times at three sensors were used to locate emission sources. The requirement for near-coincidence in arrival times at all sensors reduced spurious background events to very low levels. In spite of high background count rates at each individual sensor, the slit was clearly delineated by its emissions. Emission activity moved from the centre to the ends of the slit as the stress on the slit increased. Significantly, the emission count appeared to be directly proportional to the volume of plastically yielded material associated with the defect, based on a simple model for the increase in plastic zone size with pressure. Application of acoustic emission techniques to structural validation is discussed in terms of the measured amplitude spectrum of the detected acoustic emissions. A relationship is derived between the detected emission count, the threshold amplitude for detection, the sensor spacing and the created plastic volume for the steel studied.     

Hemodynamic assessment in managing the critically ill: is physician confidence warranted?

Our current knowledge of risk factors for Alzheimer's disease is limited and primarily addresses early-onset disease. This study aimed to determine the risk factors for late-onset Alzheimer's disease using a case-control approach. Ninety-eight cases and 216 controls were gathered from an ongoing population survey on aging and dementia in Stockholm (the Kungsholmen Project). We found a high relative risk (3.2; 95% confidence interval, 1.8-5.7) with the presence of at least one first-degree relative affected by dementia. Among all the other risk factors, alcohol abuse (relative risk, 4.4; 95% confidence interval, 1.4-13.8) and manual work (relative risk for men of 5.3; 95% confidence interval, 1.1-25.5) emerged as positively associated. No clear association was found with a family history of Parkinson disease, advanced parental age at index delivery, season of birth, or previous head trauma. In conclusion, our data suggest that the main risk factor for late-onset Alzheimer's disease is a family history of dementia, as has been previously reported for early-onset disease. Moreover, alcohol abuse and occupational exposure might play a specific role for this form of the disease.     

Wind/diesel energy systems: Review of design options and recent developments

The combination of wind turbine generators with diesel engine-generator sets offers a potentially cost effective hybrid electric system that has many stand-alone and small girl-connected applications. This article reviews wind/diesel systems and the current status of worldwide research and development on such systems. Included is a detailed summary of the modes of operation and types of wind/diesel systems, as well as a review of recent improvements in system components and analysis. Included with a discussion of general applications is a case study summary of a village-scale wind/diesel systems' generating and economic performance. A design methodology for these types of systems is presented.     

Updating outdated predictive accident models

Reliable predictive accident models (PAMs) (also referred to as safety performance functions (SPFs)) are essential to design and maintain safe road networks however, ongoing changes in road and vehicle design coupled with road safety initiatives, mean that these models can quickly become dated. Unfortunately, because the fitting of sophisticated PAMs including a wide range of explanatory variables is not a trivial task, available models tend to be based on data collected many years ago and seem unlikely to give reliable estimates of current accidents. Large, expensive studies to produce new models are likely to be, at best, only a temporary solution. This paper thus seeks to develop a practical and efficient methodology to allow currently available PAMs to be updated to give unbiased estimates of accident frequencies at any point in time. Two principal issues are examined: the extent to which the temporal transferability of predictive accident models varies with model complexity; and the practicality and efficiency of two alternative updating strategies. The models used to illustrate these issues are the suites of models developed for rural dual and single carriageway roads in the UK. These are widely used in several software packages in spite of being based on data collected during the 1980s and early 1990s. It was found that increased model complexity by no means ensures better temporal transferability and that calibration of the models using a scale factor can be a practical alternative to fitting new models.     

Human therapeutic plasma levels of the selective serotonin reuptake inhibitor (SSRI) sertraline decrease serotonin reuptake transporter binding and shelter-seeking behavior in adult male fathead minnows

Selective serotonin reuptake inhibitors (SSRIs) represent a class of pharmaceuticals previously reported in aquatic ecosystems. SSRIs are designed to treat depression and other disorders in humans, but are recognized to elicit a variety of effects on aquatic organisms, ranging from neuroendocrine disruption to behavioral perturbations. However, an understanding of the relationships among mechanistic responses associated with SSRI targets and ecologically important behavioral responses of fish remains elusive. Herein, linking Adverse Outcomes Pathways (AOP) models with internal dosimetry represent potential approaches for developing an understanding of pharmaceutical risks to aquatic life. We selected sertraline as a model SSRI for a 28-d study with adult male fathead minnows. Binding activity of the serotonin reuptake transporter (SERT), previously demonstrated in mammals and fish models to respond to sertraline exposure, was selected as an endpoint associated with therapeutic activity. Shelter-seeking behavior was monitored using digital tracking software to diagnose behavioral abnormalities. Fish plasma levels of sertraline exceeding human therapeutic doses were accurately modeled from external exposure concentrations when pH influences on ionization and log D were considered. We observed statistically significant decreases in binding at the therapeutic target (SERT) and shelter-seeking behavior when fish plasma levels exceeded human therapeutic thresholds. Such observations highlights the strengths of coupling physiologically based pharmacokinetic modeling and AOP approaches and suggest that internal dosimetry should be monitored to advance an understanding of the ecological consequences of SSRI exposure to aquatic vertebrates.     

Treatment of follicular lymphoma

Follicular lymphoma is one of the most common neoplastic lymphoproliferative diseases encountered in the western world. Intensive scientific scrutiny has led to detailed understanding of the nature of the malignant cell and the specific genetic abnormalities which are frequently encountered and likely to be etiologic. Clinical research focusing on the treatment of follicular lymphoma continues to reveal new insights into the natural history of the disease. Investigations reported during the past year have focused on a number of important issues with regard to the management of patients with the diseases.