PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Endpoint Determination”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources
PubMed2001

COX-2 expression in dysplasia of the head and neck: correlation with elF4E.

BACKGROUND: COX-2 inhibitors have shown promise in chemoprevention of epithelial tumors. eIF4E is a biomarker that has identified individuals at high risk for relapse after definitive treatment for head and neck squamous cell cancer (HNSCC). Hence, the authors wanted to determine if COX-2 is expressed in dysplasia of the head and neck and to study the correlation of expression of COX-2 with eIF4E as a potential surrogate endpoint for determining response to COX-2 inhibitors. METHODS: The authors studied the expression of COX-2 and eIF4E in normal epithelium (n = 8), dysplasia (n = 51), mucosa adjacent to tumors (n = 11), and cancer of the head and neck (n = 19) using immunohistochemistry. In addition, Western blot analysis was performed on a subset of the above patient samples and HNSCC cell lines. RESULTS: Immunohistochemical analysis showed expression of COX-2 and eIF4E in all cancers and no expression in normal tissues. In dysplastic epithelium, there was a significant correlation between the expression of eIF4E and COX-2 for all groups of dysplasia combined (chi-square = 40.3, P < 0.001). A Cochran-Armitage trend test showed a significant increase in the proportion of cases that expressed both molecular markers with increasing grades of dysplasia (P = 0.001). Western blot analysis showed increased expression of COX-2 and eIF4E in tumors compared with adjacent mucosa. All three HNSCC cell lines analyzed had increased expression of eIF4E, although only two had increased COX-2 expression. CONCLUSIONS: Expression of COX-2 in dysplasia suggested that COX-2 inhibitors may play a role in chemoprevention of head and neck cancers and that the correlation of Cox-2 with eIF4E indicates that eIF4E can be a potential surrogate marker in chemoprevention trials.

Anticarcinogenic Agents↗
PubMed2005

Application of frog embryo teratogenesis assay-Xenopus to ecological risk assessment.

An expert workshop recently was convened to consider the frog embryo teratogenesis assay-Xenopus (FETAX) as a screening method for identifying the potential developmental toxicity of single chemicals and chemical mixtures. One recommendation from the workshop was that, in order to determine the utility of FETAX for ecological risk assessments, additional consideration of how the assay is conducted is necessary. In addition, a comparative evaluation would be useful of FETAX endpoints (i.e., survival, malformations, growth) versus each other, endpoints from aquatic toxicity tests using more commonly tested species of cladocerans and fish, and tests with other amphibian species. This review provides an evaluation and critique of the current FETAX protocol from two perspectives: Practical considerations relative to conducting the test and sensitivity of the assay (and associated endpoints) compared to tests with other species. Several aspects of the current standard protocol, including test temperature, diet, loading rates, and chemical exposure options, need to be modified to ensure that the assay is robust technically. Evaluation of FETAX data from the open literature indicates that growth is the most sensitive endpoint in the assay, followed by malformations and then survival; unfortunately, the growth endpoint often is not considered or reported in the assay. Comparison of FETAX data with acute toxicity data from tests with other amphibians or traditional aquatic test species indicates FETAX is relatively insensitive. This suggests that environmental risk assessments using acute hazard data from tests with traditional aquatic test species usually would be more protective of native amphibian species than risk assessments that use hazard data from FETAX.

Animals↗
PubMed2005

Male-mediated developmental toxicity.

In recent years, the public has become more aware that exposure of males to certain agents can adversely affect their offspring and cause infertility and cancer. The hazards associated with exposure to ionising radiation have been recognised for nearly a century, but interest was aroused when a cluster of leukaemia cases was identified in young children living in Seascale, close to the nuclear processing plant at Sellafield in West Cumbria. There was a civil court case on behalf of two of the alleged victims of paternal irradiation at Seascale against British Nuclear Fuels. The case foundered on "the balance of probabilities". Nevertheless, there was support for paternal exposure from Japanese experimental X-ray studies in mice. The tumours were clearly heritable as shown by F2 transmission. Also, effects of a relatively non-toxic dose of radiation (1Gy) on cell proliferation transmitted to the embryo were manifested in the germ line of adult male mice even after two generations. In addition in humans, smoking fathers appear to give rise to tumours in the F(1) generation. Using rodent models, developmental abnormalities/congenital malformations and tumours can be studied after exposure of males in an extended dominant lethal assay and congenital malformations can be determined which have similar manifestations in humans. The foetuses can also be investigated for skeletal malformations and litters can be allowed to develop to adulthood when tumours, if present, can be observed. Karyotype analysis can be performed on foetuses and adult offspring to determine if induced genetic damage can be transmitted. Using this study design, cyclophosphamide, 1,3-butadiene and urethane have been examined and each compound produced positive responses: cyclophosphamide in all endpoints examined, 1,3-butadiene in some and urethane only produced liver tumours in F(1) male offspring. This suggests the endpoints are determined by independent genetic events. The results from heritable studies with 1,3-butadiene have been used in the parallelogram approach to determine a risk assessment for the germ cells in man.

Animals↗
PubMed2000

The functional observational battery in adult and developing rats.

Neurobehavioral screening methods, such as the functional observational battery (FOB), are now widely used to identify potential neurotoxicity of new and existing chemicals. These methods have been validated and a large database now exists for the effects of a wide range of chemicals. Since most of the observations recorded are subjective, the quality of the test data depends largely on the observer's ability to detect and describe changes in the animal's behavior and neurologic function. Efforts are underway to aid in the training of observers and to achieve consistency across laboratories in the use of these methods. With the increasing concern over potential neurotoxicological consequences of chemical exposure in the developing organism, there is growing interest in testing laboratory animals at very young ages. We present here an initial report of the development of an FOB suitable for young rats, using some modifications of the individual adult FOB test measures to make them age-appropriate. We have evaluated pre- and postweanling rats to determine the range of behaviors (as evaluated with the FOB) displayed at each age, develop appropriate scoring criteria, and collect control data to document the ontogeny of each of the endpoints in the FOB. This revised FOB protocol may be useful for assessing behavioral or neurological changes due to acute chemical exposure in young rats, or following gestational/lactational exposures typical of developmental neurotoxicity studies.

Aging↗
PubMed2002

Integrated condition indices as a measure of whole effluent toxicity in zebrafish (Danio rerio).

Toxic exposure of organisms interferes with organismal integrity at the biochemical level and ultimately gives rise to effects at the individual level. These effects may result in reductions in ecologically relevant characteristics such as growth, reproduction, and survival. A chronic toxicity test with zebrafish (Danio rerio) was conducted where fish were exposed to 50, 75, and 100% effluent for 28 d under flow-through conditions. Effects of effluent exposure were determined using endpoints of physiological (respiration during swimming), growth (condition, length, and weight), and reproductive (spawning and hatching) processes within the same population. Results clearly indicate that the condition and growth of zebrafish is depressed by exposure to the effluent. Also, increased oxygen consumption was found after 14, 21, and 28 d of exposure. Reproduction proved to correlate well with the condition of the motherfish in the control, and spawning and hatching were significantly depressed by effluent exposure. These results indicate that the evaluation of endpoints describing different ecologically relevant processes provides a rational assessment of the cause-effect relationships of effluent toxicity. This approach can quantify effects on different biological processes and can determine the interactions that occur between these different processes.

Animals↗
PubMed2004

Sources of variability in plant toxicity testing.

Published literature is investigated regarding the response of plants to various substances to determine the sensitivity of agricultural plants versus other species, the similarity of effects seen at different taxonomic levels, sensitivity of plants growing outdoors versus in a greenhouse, and the sensitivity of different measurement endpoints. We find that agricultural species are not consistently more or less sensitive to the herbicides tested than non-crop species. Genus and family taxonomic groupings may show similar responses among species, but this similarity quickly decreases as the comparison progress between orders and classes. Results from field and greenhouse studies are less in agreement between studies than data from the other topics. Shoot length will be affected at concentrations lower than for other vegetative endpoints for most species tested for inorganic substances, but for organic substances root and shoot mass were more sensitive. Overall, there is no one species or endpoint that is consistently the most sensitive for all species or all chemicals in all soils, and differences in bioavailability among compounds may confound comparison of test results. Therefore, species sensitivity distributions, adjusted for bioavailability when possible, should be considered in order to better evaluate effects to non-target terrestrial plants.

Biological Availability↗
PubMed2003

Closing the loop: assessing the effectiveness of psychiatric competency measures.

BACKGROUND: During the past several years there has been a growing emphasis on competency assessment in graduate education in all specialties, including psychiatry. Methods of assessment are continuously being devised and refined. OBJECTIVE: To outline principles and methods of assessing the validity of competency measures and their relevance to trainees. METHODS: The authors reviewed the literature relevant to competency assessment and quality improvement in the fields of elementary and secondary education, adult learning, undergraduate medical education, and postgraduate medical training. Three means were used to evaluate the assessment program: 1) The authors surveyed graduates and credentialing agencies for feedback on the relevance of the measures they previously developed for current and envisioned future practice of psychiatry; 2) They measured the completion rates of competency measures by residents in the first 3 years of a program, measuring general psychiatric competencies; and 3) They surveyed residents and faculty regarding satisfaction with the existing process. RESULTS: Despite small numbers, the results indicated that measures devised in 1998 were relevant to the practice of psychiatry in 2001 and envisioned by practitioners for the subsequent 5 to 10 years. Resident completion rates of competency requirements indicated that the structure of the measures was appropriately paced to parallel the learning expectations of the training program. Participant satisfaction with the process of developing and implementing the measures was high. CONCLUSIONS: While devising and implementing competency assessments is critical, the process should not stop with the application of the measures. Ongoing evaluation of these measures for their continued suitability is essential. Training programs can readily determine the effectiveness of competency programs and improve them as necessary.

Education, Medical, Graduate↗
PubMed2006

A nexus of progression of chronic kidney disease: charcoal, tryptophan and profibrotic cytokines.

Fibrosis plays a role in the pathogenesis of progressive chronic kidney disease (CKD). The inhibition of the renin-angiotensin system, which promotes fibrosis, has become the standard of care in the treatment of patients with CKD. A novel charcoal compound, AST-120, has been used for over a decade in Japan to prevent progression of CKD. It is thought that the oral administration of AST-120 blocks the intestinal absorption of tryptophan-derived indole. This prevents the hepatic conversion of indole to indoxyl sulfate (IS). IS has been shown to stimulate the production of profibrotic cytokines such as transforming growth factor-beta. AST-120 lowers IS in a dose dependent fashion and does not change the creatinine appearance rate in the urine. Enteric capsules containing Bifidobacterium longum have been shown to prevent progression of CKD in a preliminary study. These findings suggest that prospective clinical trials be undertaken to determine if these other potential methods of inhibiting fibrosis are useful in slowing progressive CKD.

Administration, Oral↗
PubMed2004

Relationship between blood pressure measurements recorded on patients' charts in family physicians' offices and subsequent 24 hour ambulatory blood pressure monitoring.

BACKGROUND: In most western countries 20% of adults have hypertension. Reports in the literature suggest that from 31 to 86% of treated patients are not at recommended target levels. However it is important to consider how we are determining whether targets are unmet and the degree to which they are unmet. Our underlying hypothesis is that white coat effect is partially responsible for the reported low rates of control of hypertension by primary care practitioners. METHODS: The study population consists of 1142 patients who are being assessed for enrollment in two community-based randomized controlled trials. Patients must have essential hypertension, be on antihypertensive medication, and must not have met their blood pressure targets. We are reporting on the proportion of patients who have not achieved target, and the degree to which they have not achieved their target. We also report on the mean daytime blood pressures on 24 hour ABPM and compare these to mean blood pressures found on the patients' charts. RESULTS: We identified 3284 patient charts of patients with hypertension. Of these, 1142 were determined to be "out of control" (did not achieve target) and 436 agreed to undergo 24 hour ABPM for final determination of eligibility. Overwhelmingly (95.8% of the time) it was the systolic blood pressure that was not under control. However, most of the patients who had not achieved target according to our criteria were within 10 mmHg of the recommended targets. Isolated systolic blood pressure was the best predictor of elevated mean daytime blood pressure on 24 hour ABPM. CONCLUSIONS: At least 35% of patients had not achieved target blood pressure levels and this is primarily due to lack of control of systolic blood pressure. The best predictor of continuing hypertension on 24 hour ABPM was the mean systolic blood pressure on the patients chart. However, only 69% of patients who were uncontrolled according blood pressures recorded in the chart were uncontrolled according to 24 hour ABPM criteria. This suggests that the white coat effect makes blood pressure measurements in the doctor's offices, at least as currently done, not sufficiently accurate for determining treatment endpoint.

Adult↗
PubMed1985

Polymeric dyes: useful nonabsorbable reference markers for intestinal perfusion studies in animals.

The properties of two polymeric dyes were examined to determine their suitability as nonabsorbable reference markers for intestinal perfusion studies. The first dye was a violet anthroquinone dye, R-478, named polyporphyre; the second was a blue anthroquinone dye, R-411, named polycyanine. The dyes could be determined spectrophotometrically over a concentration range of 0.03-5 microM (1-200 micrograms/mL) and had no appreciable osmotic effect. They were light stable and their absorption spectra did not change in solution over a pH range of 1-11. The dyes had a molecular weight of approximately 40,000 by gel permeation chromatography; they did not appear to have hydrophobic binding sites because they did not bind added dihydroxy bile acid or fatty acid anions. Determination of the dyes was not influenced by the presence of bilirubin when the latter was present at concentrations reported to occur in small intestinal content during digestion. The dyes did not interfere with an endpoint enzymatic determination of bile acids. The dyes caused little quenching of 3H- or 14C-radioactivity in a toluene-based liquid scintillation cocktail. Dyes were easily removed from aqueous solution by passage over a large-pore anion exchange column or by a BaCl2:ZnSO4 protein precipitation procedure. When tested in a rat jejunal perfusion model, changes in dye concentration evoked by hypotonic or hypertonic perfusates were identical to those of polyethylene glycol 4000, a commonly used reference marker. The dyes did not influence the rate of glucose absorption and did not bind to mucus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Dose-response assessment for developmental toxicity. III. Statistical models.

Although quantitative modeling has been central to cancer risk assessment for years, the concept of dose-response modeling for developmental effects is relatively new. The benchmark dose (BMD) approach has been proposed for use with developmental (as well as other noncancer) endpoints for determining reference doses and reference concentrations. Statistical models appropriate for representing the unique features of developmental toxicity testing have been developed and applied (K. Rai and J. Van Ryzin, 1985, Biometrics 41, 1-9; L. Kupper, C. Portier, M. Hogan, and E. Yamamoto, 1986, Biometrics 42, 85-98; R. Kodell, R. Howe, J. Chen, and D. Gaylor, 1991, Risk Anal. 11, 583-590). Generalizations of those models (designated the RVR, LOG, and NCTR models, respectively) account for the correlations among observations in individual fetuses or implant within litters; the potential for variables other than dose, such as litter size, to affect the probability of adverse outcome; and the possibility of a threshold dose below which background response rates are unaltered. The generalized models were applied to a database of 607 endpoints with significant dose-related increases in response rate. It was determined that the models were generally capable of fitting the observed dose-response patterns, with the LOG model appearing to be superior with respect to fit. A significant contributor to the ability of the LOG model to fit the data was its flexibility with respect to the representation of the dependence of response probability on litter size, a trait not shared by the other two models. Litter size appeared to be a significant covariable for predicting response rates, even when intralitter correlation was accounted for by assuming a beta-binomial distribution for the observations among individual fetuses. In contrast, a threshold dose parameter did not appear to be necessary to adequately describe the observed dose-response patterns. BMD estimates (corresponding to 5% additional risk) from all three models were similar to one another and to BMDs estimated from other, generic dose-response models (not specifically designed for developmental toxicity testing) that modeled average proportion of fetuses affected. The BMDs at the 5% level of risk were similar to no observed adverse effect levels determined by statistical tests of trend. Greater emphasis on and further examination of dose-response modeling for developmental toxicity testing are needed; biologically based approaches that consider the continuum of developmental effects induced in such tests should be encouraged.

Animals↗
PubMed2002

Ecotoxicology and sustainable use of the planet.

The goal of sustainable use is indefinite use of the planet by humankind. This objective, in turn, requires that the planet's ecological life support system, consisting of natural capital and ecosystem services, remains healthy for an indefinite period. Achieving sustainability will require a new view of the responsibilities of professionals, such as ecotoxicologists, to ensure a healthy ecological life support system. Because both human society and natural systems are complex and multivariate, a high degree of uncertainty will remain. Therefore, sound judgment will be needed in determining what, if any, precautionary measures should be taken until more robust information has been gathered. The role of ecotoxicologists in the quest for sustainable use of the planet is quite varied: 1) shifting goals and endpoints from an absence of harm to persuasive evidence of health; 2) increasing both temporal and spatial scales of ecotoxicological studies; 3) achieving a critical mass of qualified personnel; 4) including demographic change in ecotoxicological analysis and judgment; 5) developing new ecological thresholds; 6) being prepared for environmental surprises; 7) focusing on design for a quality environment; 8) developing ecosystem services as endpoints in ecotoxicological studies, and 9) being prepared for climate change and other events that might destabilize the biosphere and require major adjustments in the process of ecotoxicological testing. Both sustainable use of the planet and the field of ecotoxicology are rapidly developing fields that are mostly evolving in isolation from each other. To be successful, they must co-evolve.

Animals↗
PubMed2001

Controlled balloon inflation reduces long-term restenosis after percutaneous transluminal coronary angioplasty.

PURPOSE: The trauma induced by balloon angioplasty has an impact on the outcome of coronary interventions, such as stent procedures. However, balloon inflation for PTCA is not yet standardized even though procedural and long-term outcomes might be affected. METHODS: During routine PTCA, a total of 454 patients [mean age, 60.9 +/- 9.0 years; 162 (35.7%) with 1-vessel disease; 159 (35%) with 2-vessel disease; 133 (29.3%) with 3-vessel disease] were allotted to computer-assisted dilatation (CAPS) with a pressure slope of 0.2 bar/s (CAPS 0.2; n = 149 patients), 1.0 bar/s (CAPS 1.0; n = 154 patients) or to standard inflation with a hand-driven pump (n = 151 patients). Angiographic follow-up rates after 4.1 +/- 3.2 months were 88.1% for the hand-driven pump, 94% for CAPS 0.2 and 87.7% for CAPS 1.0. RESULTS: Flow reducing (1.3-2.0%) and non-flow reducing (12.6-14.9%) dissections were equally distributed among all groups as were major adverse cardiac events (2.6-4.0%). The stent rate was 1.3% with the hand-driven pump, 0.7% with CAPS 0.2 and 1.3% with CAPS 1.0. Angiographic restenosis rate was 48.9% with the hand-driven pump, 44.3% with CAPS 0.2 and 32.6% with CAPS 1.0. (hand-driven pump versus CAPS 1.0, p < 0.007; CAPS 0.2 versus CAPS 1.0, p < 0.049). CONCLUSIONS: The pressure slope during balloon inflation in PTCA has a significant impact on restenosis. The impact on stent procedures has yet to be determined.

Adult↗
PubMed1988

Distinct domains of recombinant human IFN-gamma responsible for anti-viral effector function.

A panel of 21 independently isolated neutralizing mAb directed against the human rIFN-gamma (rHuIFN-gamma) was used to characterize those epitopes that are involved in the antiviral function of the rHuIFN-gamma. A sandwich competition assay was developed to determine the cross-reactivities between the mAb. The 125I-labeled mAb were allowed to compete with varying amounts of unlabeled mAb for binding to rHuIFN-gamma under Ag-limiting conditions, and the 50% inhibition endpoints were determined for each of the 21 mAb. The competition of each heterologous mAb relative to the competition of the homologous mAb was determined. By grouping the competition patterns of the 21 mAb, it was apparent that at least two epitopes (E1 and E2) were important to the antiviral function of rHuIFN-gamma. The possibility of the separation of the receptor binding site and signal transduction effector site(s) is discussed.

Antibodies, Monoclonal↗
PubMed2005

Determination of fluidized bed granulation end point using near-infrared spectroscopy and phenomenological analysis.

Simultaneous real-time monitoring of particle size and moisture content by near-infrared spectroscopy through a window into the bed of a fluidized bed granulator is used to determine the granulation end point. The moisture content and particle size determined by the near-infrared monitor correlates well with off-line moisture content and particle size measurements. The measured particle size is modeled using a population balance approach, and the moisture content is shown to follow accepted models during drying. Given a known formulation, with predefined parameters for peak moisture content, final moisture content, and final granule size, the near-infrared monitoring system can be used to control a fluidized bed granulation by determining when binder addition should be stopped and when drying of the granules is complete.

Chemistry, Pharmaceutical↗
PubMed2004

Changes in heart rate variability in response to treatment with electroconvulsive therapy.

BACKGROUND: Objective methods are needed to determine when to terminate a course of electroconvulsive therapy (ECT). Heart rate variability (HRV) has proven predictive value for patients with cardiac and neurologic disorders and correlates with depression severity and treatment effects. Variable changes in HRV after ECT have been reported. METHODS: Holter monitoring was performed before and after ECT in 11 patients with depression. Measures of HRV were obtained from these recordings and the relationships between HRV and treatment outcome was analyzed. Response to ECT was measured by the 24-item Hamilton Rating Scale for Depression. RESULTS: Standard deviation of interbeat intervals (SDNN, a measure of HRV) increased in subjects who improved with ECT (P < 0.02) but not in those who became confused and agitated. Among those patients who acutely responded to ECT, SDNN increased (P < 0.05) in subjects with a sustained response but not in subjects who relapsed within 3 weeks. SDNN was significantly lower in the rapid relapse group at baseline (P < 0.05) and after ECT (P < 0.05) compared with the group with a sustained response. CONCLUSIONS: Low baseline HRV is associated with rapid relapse of depression after ECT. Both high baseline HRV and increasing HRV predict a sustained outcome. Further research is necessary to support these findings and to clarify if the serial measurement of HRV during ECT may help to determine the optimal number of treatments for each patient.

Adult↗