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Biomedical subjects

A Clayton

Publications and source records attributed to A Clayton.

26 records · Page 2Linked to original sources

Preparation of human ovarian cancer ascites-derived exosomes for a clinical trial.

Despite initial response to chemotherapy, at least 50% of ovarian cancer patients will relapse within 18 months. Progression-free survival is related to tumour infiltration with cytotoxic T lymphocytes (CTL). We recently demonstrated that CD8+ T cell responses to recall antigens improve following tumour response to chemotherapy. Vaccination designed to expand CTL, specific for tumour-associated antigens, may be a means of improving outcome. We are planning a clinical trial in advanced ovarian cancer patients undergoing chemotherapy using a combination of a Toll-like receptor 3 (TLR3) agonist and tumour-associated ascites-derived exosomes. Tumour-derived exosomes are a potential source of tumour antigens able to induce CD8+ T cell responses when loaded on mature dendritic cells (DC). DC maturation can be achieved with Toll-like receptor (TLR) agonists, such as the GMP-grade synthetic double stranded RNA, poly[I]:poly[C12U] (Ampligen) which is a TLR-3 agonist. Here, we describe the development of a method suitable for the preparation of GMP-grade exosomes from the ascites fluid of ovarian cancer patients, and the methods used for the molecular and immunological characterisation of these exosomes preceding their use in a clinical trial.

Ascites↗

Responses to the region 5 NHEXAS time/activity diary. National Human Exposure Assessment Survey.

The time/activity diary developed for use in the National Human Exposure Assessment Survey (NHEXAS) was completed by 249 participants in the Research Triangle Institute/Environmental and Occupational Health Sciences Institute (RTI/EOHSI) NHEXAS population-based pilot project conducted in the upper Midwest (EPA Region 5). The majority of participants successfully completed the diary during the 6-day study period. Participant responses showed internal consistency between related questions within the diary and between instruments used within the study. Comparison of response rates with the National Human Activity Pattern Survey, a nationwide population-based study, found consistent results when the same questions were used in both studies. Several questions identified age-specific activities. The value of the 6-day diary over 1-day surveys was apparent in discriminating between episodic and regularly conducted activities and in identifying subpopulations whose behavior may contribute to exposure to environmental pollutants.

Adolescent↗

Validation of the Spanish version of the Changes in Sexual Functioning Questionnaire (CSFQ).

The aim of this study is to adapt and validate the Changes in Sexual Functioning Questionnaire (CSFQ) in Spanish. The CSFQ was administered to 206 depressed patients in different Spanish cities, to 326 health sciences students at the University of Oviedo, and to 48 workers undergoing routine health check-ups. The Hamilton Depression Rating Scale (HAM-D) was administered to the depressed patients. The average time spent answering the CSFQ was 15.19 minutes. The CSFQ discriminated the depressed patients from the workers and university students. In the three areas of reliability (internal, test-retest, and inter-rater), the coefficients obtained were greater than 0.80. The factor analysis demonstrated differences in the internal construct of the American CSFQ and its Spanish equivalent. The psychometrc properties of the Spanish version of the CSFQ indicate that it is a valid instrument for clinical use in treating depressed patients.

Adult↗

Evaluating changes in sexual functioning in depressed patients: sensitivity to change of the CSFQ.

Accurately evaluating alterations in sexual functioning requires a validated instrument that measures clinically relevant change over time. One-hundred one depressed patients from 15 Spanish out-patient clinics completed the Changes in Sexual Functioning Questionnaire (CFSQ; Clayton, McGarvey, & Clavet, 1997) at baseline and after 6 months of treatment with fluoxetine, nefazodone, paroxetine, or venlafaxine. Sexual desire/interest showed a nearly substantial floor effect (30% of patients indicated the maximum score) for women in the nefazodone group at baseline and in the paroxetine group at final visit. The percentage of dimensions recording change was greater for women (80%) than for men (20%) in the nefazodone group (improving changes) and greater for men (40%) than for women (20%) in the paroxetine group (worsening changes). Highest effect sizes were found on sexual desire/frequency with improvement in women in the nefazodone group (SES = 0.49), and on orgasm/ejaculation with worsening in men in the paroxetine group (SES = -1.45). In conclusion, the CSFQ is sensitive to bidirectional changes and is appropriate for measuring sexual dysfunction.

Antidepressive Agents↗

Population-based exposure measurements in EPA region 5: a phase I field study in support of the National Human Exposure Assessment Survey.

The National Human Exposure Assessment Survey (NHEXAS) Phase I study is designed to be part of the total NHEXAS framework developed from a series of scientific discussions and workshops conducted by the U.S. Environmental Protection Agency (EPA) during 1992 and 1993. NHEXAS examines total human exposure and is structured to include: Phase I, scoping studies; Phase II, a full national exposure survey; and Phase III, a series of highly focused characterization modules. Our research program examines the scientific issues important to Phase II, including statistical sampling, methods evaluation, media concentration measurements, formulating quality assurance goals, and identification of important pathways leading to exposure. To determine the feasibility of NHEXAS in characterizing human exposure for a representative population, a hypothesis-driven design is used to answer important questions about human exposure to specific environmental contaminants. This paper describes: (1) hypotheses to be tested; (2) contaminants selected for study; (3) strategies for measuring exposure; (4) study area and population; (5) population sampling design; (6) media sampling and analysis procedures; and (7) data analysis. The contaminants of concern in this Phase I study include selected metals and volatile organic compounds. From these classes the first-tier contaminants to be measured are lead, arsenic, benzene, chloroform, perchloroethylene, and trichloroethylene. Contaminants selected for examination may potentially be found in many media (personal-nonoccupational, personal-occupational, indoor, and outdoor residential air; dust; potable water; food/beverages; soil; blood; hair; and urine) and exposures may occur by multiple routes (inhalation, ingestion, dermal). The central hypothesis of our field study is to discover whether individual and population exposures determined by modeled or extant data are/are not significantly different from those determined directly from multipathway and multimedia measurements. In addition, there are a series of subhypotheses ranging from pollutant-specific exposure measurement and body burden hypotheses to the optimization of exposure models. In keeping with the NHEXAS framework, a probability-based population sample for total exposure and the field study will be conducted in counties located throughout EPA Region 5 (Minnesota, Wisconsin, Illinois, Indiana, Ohio, and Michigan). Sampling units will be households and an individual residing within each household. Environmental, exposure, and biological media sample collection will be performed by this consortium. Analyses of the external media and biological media samples will be completed by this consortium or Federal laboratories of the Centers for Disease Control and Prevention (CDC), Food and Drug Administration (FDA), or EPA. The protocols and analytical techniques selected for use represent the best available for total exposure assessment at this time.

Data Interpretation, Statistical↗