PubMed Health⌕ Search

Biomedical subjects

P Whitehouse

Publications and source records attributed to P Whitehouse.

At least 19 recordsLinked to original sources
PubMed2003

Incorporation of in situ and biomarker assays in higher-tier assessment of the aquatic toxicity of insecticides.

This study was designed to test the feasibility of integrating in situ, single species exposures and biomarker analysis into microcosm studies. Experimental ponds were dosed with pirimiphos methyl (PM) and lindane. C. riparius fourth instar larvae were deployed for 48h on nine separate occasions during the study period before and after treatment. Surviving larvae were analysed for acetylcholinesterase activity (AChE). Survival and biomarker data were compared to chironomid assemblage analysis by monitoring insects emerging from the microcosms. Survival of chironomids within the in situ systems commenced on day +16 after treatment with 31.6% and 53.3% survival in the lindane and PM treated ponds, respectively. In contrast, the first emergence from the microcosms occurred on days +27, in respect to lindane, and +59 for the PM treated ponds. Thus the in situ bioassay was able to demonstrate gradual reduction in toxicity within the sediment before this was evident from macroinvertebrate monitoring. Significant AChE inhibition was only detected on exposure to PM. Levels decreased from 75% on day +16 to 26% by day +29. The biomarker analysis confirmed that, by the end of the study, the insecticide was no longer exerting an effect. We discuss how the use of in situ bioassays could also aid comparison of microcosm studies by adding a standardized dimension.

Acetylcholinesterase↗
PubMed2001

Measures for protecting water quality: current approaches and future developments.

An important component in protecting the ecological quality of watercourses is the regulation of point source discharges. These are usually expressed in terms of "end of pipe" limits on certain physical parameters or on the concentrations of specific chemicals. Sometimes discharge licences take the form of Emission Limit Values (ELVs) which are based on Best Available Technology with respect to emissions and apply to all discharges (usually for a specified industry sector) irrespective of the dilution capacity of the receiving watercourse. Alternatively, they may be based on water quality standards (e.g., EQSs) for specific chemicals which describe thresholds below which no adverse impact on the receiving water is predicted and which take explicit account of available dilution at different discharge locations. The strengths and limitations of these approaches are reviewed, along with a consideration of new approaches that address some of the limitations associated with control measures based on ELVs or EQSs. These include approaches for controlling well-defined mixtures by a "Toxic Equivalent" approach, exemplified here for discharges containing alkylphenol ethoxylate surfactants, and a fundamentally different approach for regulating complex effluents based on Direct Toxicity Assessment of whole effluents. Circumstances under which these different approaches to controlling point source emissions to surface waters might be appropriate are discussed.

Conservation of Natural Resources↗
PubMed2001

Can saltwater toxicity be predicted from freshwater data?

The regulation of substances discharged to estuarine and coastal environments relies upon data derived from ecotoxicity tests. Most such data are generated for freshwater rather than saltwater species. If freshwater toxicity data are related to saltwater toxic effects in a systematic and predictable way, the former can be used to predict the latter. This would have economic advantages due to a reduction in toxicity testing of saltwater species. If toxicity data are plotted as species sensitivity distributions, four theoretical relationships between freshwater and saltwater can be envisaged. Examples show that each one of these relationships is supported by empirical data. These examples show that although there is considerable potential for freshwater to saltwater prediction, species parity and representativeness need to be examined for each chemical substance to avoid bias.

Animals↗
PubMed2000

Treatment of agitation in AD: a randomized, placebo-controlled clinical trial.

BACKGROUND: Treatment of agitation is a crucial problem in the care of patients with AD. Although antipsychotic and antidepressant medications and behavior management techniques (BMT) have each been used to treat agitation, clinical trials of these treatments have been characterized by small sample sizes and uncontrolled treatment designs. OBJECTIVE: To compare haloperidol, trazodone, and BMT with placebo in the treatment of agitation in AD outpatients. METHODS: A total of 149 patients with AD and their caregivers participated in a randomized, placebo-controlled, multicenter trial. Blind assessment was conducted at baseline and after 16 weeks of treatment. The three active treatments were haloperidol, trazodone, and BMT. The Alzheimer's Disease Cooperative Study Clinical Global Impression of Change was the primary outcome measure. Secondary outcomes included patient agitation, cognition, and function, and caregiver burden. RESULTS: Thirty-four percent of subjects improved relative to baseline. No significant differences on outcome were obtained between haloperidol (mean dose, 1.8 mg/d), trazodone (mean dose, 200 mg/d), BMT, or placebo. Significantly fewer adverse events of bradykinesia and parkinsonian gait were evident in the BMT arm. No other significant difference in adverse events was seen. Symptoms did not respond differentially to the different treatments. CONCLUSIONS: Comparable modest reductions in agitation occurred in patients receiving haloperidol, trazodone, BMT, and placebo. More effective pharmacologic, nonpharmacologic, and combination treatments are needed.

Aged↗
PubMed1997

Multicenter evaluation of new instruments for Alzheimer's disease clinical trials: summary of results. The Alzheimer's Disease Cooperative Study.

The Instrument Development Project of the Alzheimer's Disease Cooperative Study (ADCS) evaluated new assessments in five domains: (a) cognitive function; (b) clinical global change; (c) activities of daily living; (d) behavioral symptoms, and (e) cognition in severely impaired patients. These new instruments demonstrate excellent discrimination between normal controls and patient groups and show adequate validity and reliability. Stability of measurement and sensitivity to longitudinal change were also demonstrated in each of these areas. Examination of several domain-specific questions also contributed new information on the measurement of cognitive function with different subtasks across AD severity levels, the stability of clinical ratings of global change, and the applicability of behavioral assessment across severity levels. The success of this project enhances the state of the art in the measurement of efficacy in AD clinical trials and also provides a basis for future research on improving AD outcome measures.

Activities of Daily Living↗
PubMed1997

Protocols to demonstrate slowing of Alzheimer disease progression. Position paper from the International Working Group on Harmonization of Dementia Drug Guidelines. The Disease Progression Sub-Group.

Two suggested clinical trial designs for assessing progression of Alzheimer disease are the randomized withdrawal design and the randomized start design. The most promising of these, the randomized start design, has the potential to demonstrate a delay in progression, but there remain problematic design, ethical, and statistical issues to be solved before the protocol can be used in a clinical trial. The development of biological markers of the disease process using neuroimaging or other measures also may provide a robust method of measuring disease progression and demonstrating the biological effect of a drug on the disease process.

Aged↗
PubMed1996

The need for anonymous genetic counseling and testing.

Concerns are mounting about the risks of genetic discrimination resulting from the release of predictive and presymptomatic genetic test results to employers, insurers, and others. The ability to keep this information confidential is questionable, particularly in view of the expansion of electronic medical databases. One solution is to afford individuals access to anonymous genetic counseling and testing. Probands would be identified only by a code that would not reveal personal information, and test results would be stored, retrieved, and released solely on the basis of this code. The experience with anonymous HIV testing, while not completely analogous, suggests that such an approach would be both practical and effective.

Anonymous Testing↗
PubMed1996

Measures of psychiatric symptoms in Alzheimer patients: a review.

This review of instruments for the identification and quantification of psychiatric symptoms in Alzheimer disease (AD) is intended as a reference source for clinicians and researchers concerned with evaluating, quantifying, and managing psychiatric symptoms in AD. We review 16 clinician- and caregiver-rated scales selected from >30 scales on the basis of their face validity, their psychometric properties, the frequency of their use, and their promise as assessment instruments. Instruments are described in terms of the population on which they were developed, the symptoms assessed, informant, by whom administered, time to administer, time interval covered, number of items, measurement of frequency and severity, assessment of impact on caregiver, reliability, validity, and scoring. Recommendations are made concerning the best use of each scale. We summarize in table form the sources of information for instruments, characteristics of the instruments by domain, and potential use of instruments for quantification or management of symptoms and for estimation of caregiver burden. There are a number of reliable and valid scales for the assessment of psychiatric symptoms in AD, each with specific assets and liabilities. Knowledge of the specifics of these scales will enable clinicians and researchers to select the best instruments for their particular needs and to design more effective instruments.

Activities of Daily Living↗
PubMed1992

Management of behavior disturbance in Alzheimer disease: current knowledge and future directions.

Assessment and treatment of behavior problems in patients with Alzheimer disease and related disorders is a seriously neglected area of study. Despite the fact that such problems are integral to the disorder, little is known about effective management. This article summarizes the current thinking on five areas of prime importance to patients, care providers, and health care professionals: agitation, assault/aggression, screaming, wandering, and depression/apathy/withdrawal. Methodological guidelines for studying these disorders are provided. Emphasis is on recognizing that behavior problems are important areas of study in their own right as well as in conjunction with studies of cognition.

Activities of Daily Living↗
PubMed1992

Amyloidoma of the CNS. I. Clinical and pathologic study.

We report a 32-year-old man with a 4-year history of headaches, seizures, and dementia secondary to multifocal amyloidomas in the white matter. Immunohistochemical and electron microscopic analyses suggest that the amyloidomas resulted from processing of plasma-cell-derived amyloidogenic protein by microglial cells.

Adult↗
PubMed1992

Selective abortion for familial Alzheimer disease?

Advances in human genetics will soon allow prenatal diagnosis of genetic conditions in the fetus that range from trivial to devastating. This commentary explores the concept of severity in genetic diseases and decisions regarding selective abortion. Familial Alzheimer disease is used as a model for the analysis of ethical issues raised by prenatal diagnosis and the subsequent termination of pregnancy. The genetics of the disease has yet to be elucidated, but this condition may be amenable to prenatal diagnosis in the near future, at least in some families. Abortion is a choice open to women in the United States; however, it is still desirable to discuss on purely ethical grounds pregnancy termination in the case of late-onset but severe diseases.

Abortion, Eugenic↗