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Results for “Endpoint Determination”

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PubMed1995

Initial use of a broth microdilution method suitable for in vitro testing of fungal isolates in a clinical microbiology laboratory.

Antifungal susceptibility testing methods currently lack a standardized procedure. Many factors, such as inoculum preparation, inoculum density, medium selection, pH, incubation time and temperature, and endpoint determination, affect results. We developed a workable procedure for fungal susceptibility testing, with a microtiter method based upon modifications of the proposed guidelines from the National Committee for Clinical Laboratory Standards, using two different growth media. For this procedure, the microtiter tray is prepared as a panel of 6 drugs (amphotericin B, flucytosine, fluconazole, ketoconazole, miconazole, and itraconazole) alone and in combination with amphotericin B. Eagle's minimal essential medium and RPMI 1640 are the two growth media. Two separate susceptibility trays are inoculated for each sensitivity test, with one tray incubated at 30 degrees C and the other incubated at 35 degrees C. After 48 h of growth, results for both temperatures and both media are recorded and interpreted. The four test environments (two media each at two temperatures) provided growth for 100 of the first 104 organisms that were submitted for testing. This approach provides a workable methodology for routine antifungal susceptibility testing in a clinical microbiology laboratory setting.

Antifungal Agents↗

PubMed1999

Highly reproducible bactericidal activity test results by using a modified National Committee for Clinical Laboratory Standards broth macrodilution technique.

Bactericidal testing historically has exhibited variable reproducibility, even when prior standardized methods were employed. Several modifications to the National Committee for Clinical Laboratory Standards (NCCLS) broth macrodilution method are proposed to improve reproducibility. Recommended changes from the approved NCCLS guidelines (M21-A and M26-A) include omitting serum supplementation of Mueller-Hinton broth, incubating tubes at 35 degrees C for 24 h with no agitation until they are sampled, running all tests in duplicate with six dilutions instead of nine, reincubating the test for an additional 24 h to resolve discrepant bactericidal activity test results, using a single 0.1-ml sample from each clear tube for subculture, and adopting an alternate method for calculating endpoint determination. In order to test these recommendations in a clinical laboratory setting, we used the modified methodology on 224 separate tests for bactericidal activity. There were 102 serum bactericidal titer (SBT) and 122 minimum bactericidal concentration (MBC) assays performed. By defining reproducibility as agreement between duplicate tests +/- 1 dilution, we found 207 of 224 tests (92%) were reproducible at the 24-h subculture point (94% for the SBT assay and 91% for the MBC assay). When the 17 assays with discrepant results were incubated an additional 24 h for a second subculture, only 1 of 224 tests (0.4%) remained discrepant. The method used is practical for a clinical laboratory that chooses to perform bactericidal activity testing and assures a high level of reproducibility between duplicate assays. The total cost of a test was approximately $25.00.

Anti-Bacterial Agents↗

PubMed1979

Modified metabolic inhibition test for serotyping strains of Ureaplasma urealyticum (T-strain Mycoplasma).

Antisera prepared against the eight recognized serotypes of Ureaplasma urealyticum were tested against the homologous and heterologous antigens by a modified metabolic inhibition test that used bromothymol blue broth in microtiter plates. The method gives clear endpoint determinations which are usually maintained on continued incubation. Antisera against serotype 8 showed cross-reactions with types 2 and 4. The ninth strain, Vancouver, when tested by this method did not fit the recognized serotyping scheme and may represent a new serotype.

Antigens, Bacterial↗

PubMed1996

Syphilis seroprevalence among pregnant women and its role as a risk factor for stillbirth in Maputo, Mozambique.

OBJECTIVE: To elucidate the role of current syphilis as a risk factor for foetal death. METHODS: Sera were obtained from 57 women with third trimester foetal death (cases) and 58 women with foetus alive (controls) matched for age and parity. All sera reactive in qualitative Rapid Plasma Reagin (RPR) analyses were tested with serial twofold dilutions to determine endpoint flocculation titres and tested with the micro-haemagglutination assay for Treponema pallidum (MHA-TP). Placental biopsies were sectioned and stained by haematoxylin-eosin and Warthin-Starry for light microscopy. SETTING: Central Hospital, in Maputo, Mozambique, from January 1990 to June 1991. RESULTS: The MHA-TP was reactive in 42% of cases and in 12% of controls (OR = 5.3; 95% CI: 1.9-15.4). The RPR card test was reactive at the dilution of 1.32 or greater in 28% of cases and in 7% of controls. All these results were confirmed by MHA-TP (OR = 5.3; 95% CI: 1.5-15.4). In 9/28 (32%) MHA-TP seroreactive women (7 cases and 2 controls) placental morphological changes indicated syphilitic infection. CONCLUSION: MHA-TP seroreactivity and high titre RPR were associated with stillbirth. Morphological changes presumptive of syphilis infection were found in 32% placentas histologically studied. Syphilis is a risk factor for foetal death in Maputo, Mozambique.

Case-Control Studies↗

PubMed2005

Prostate cancer clinical trial end points: "RECIST"ing a step backwards.

PURPOSE: To relate clinical issues to the clinical manifestations of prostate cancers across disease states using the eligibility and outcome criteria defined by Response Evaluation Criteria in Solid Tumors (RECIST). EXPERIMENTAL DESIGN: The manifestations of prostate cancer that characterize localized, recurrent, and metastatic disease were considered using the eligibility criteria for trials defined by RECIST. To do so, we analyzed the sites, size, and distribution of lesions in patients enrolled on contemporary Institutional Review Board-approved trials for progressive castrate and noncastrate metastatic disease. Prostate-specific antigen (PSA) levels were also assessed. RECIST-defined outcome measures for tumor regression were then applied to the metastatic patient cohorts, and separately to the states of a rising PSA (noncastrate and castrate) and localized disease. RESULTS: Only 43.5% of men with castrate metastatic and 16% of noncastrate metastatic disease had measurable target lesions > 2 cm in size. Overall, 84.4% of the target lesions were lymph nodes, of which 67.7% were > or = 2 cm in the long axis. There are no target lesions in patients in the states of a rising PSA and localized disease, making them ineligible for trials under these criteria. PSA-based eligibility and outcomes under RECIST conflict with established reporting standards for the states of a rising PSA and castrate metastatic disease. The clinical manifestations of prostate cancer across multiple disease states are not addressed adequately using the eligibility criteria and outcomes measures defined by RECIST. Important treatment effects are not described. CONCLUSIONS: Trial eligibility and end points based solely on tumor regression are not applicable to the majority of the clinical manifestations of prostate cancers representing all clinical states. Treatment effects can be described more precisely if eligibility criteria are adapted to the clinical question being addressed and clinical state under study, focusing on the duration of benefit defined biochemically, radiographically, and/or clinically.

Clinical Trials, Phase II as Topic↗

PubMed2005

Study design issues and early stage non-small cell lung cancer.

The most common type of clinical trial in oncology enrolls patients with advanced disease. End points for phase II trials in advanced disease typically include response rate or time to progression, based upon the presumption that these may serve as surrogates for the ultimate end point of improved survival. Unique problems arise with the design of adjuvant trials, for which response rates clearly are not appropriate end points. In addition, survival is much longer, making rapid completion of phase III trials difficult. For lung cancer, the proportion of patients with stage I and II disease is much lower than with other types of cancer, and the absolute number of these patients is relatively low. To conduct large adjuvant trials in lung cancer more efficiently, we need to optimize our trials as much as possible. "Targeted therapies," by definition, inhibit a specific target, thus offering the theoretical advantage of enriching the patient population by restricting enrollment to patients whose tumor expresses the target of interest. Education of health care professionals regarding the benefits of adjuvant therapies, to decrease a sense of nihilism and to increase referrals, and international collaborations may also be necessary to increase accrual.

Carcinoma, Non-Small-Cell Lung↗

PubMed2001

Gene transfer as an approach to treating hemophilia.

Hemophilia is an X-linked bleeding diathesis caused by a deficiency of either factor VIII or factor IX. Present treatment for hemophilia involves intravenous infusion of either recombinant or plasma-derived clotting factor concentrates. Problems with this treatment method, including the expense, need for intravenous access, and risks of blood-borne disease transmission, have fueled an interest in developing a gene-transfer approach to treatment. On the basis of experience with protein concentrate therapy, it seems likely that even modest elevations in circulating levels of factor VIII or factor IX can prevent most of the mortality and much of the morbidity associated with the disease. Hemophilia has a number of advantages as a model system for working out strategies for gene transfer as an approach to the treatment of genetic diseases; these include wide latitude in choice of target tissue, a wide therapeutic window for levels of circulating factor, ease of determining therapeutic endpoints, and existence of excellent animal models of the disease. Preclinical studies over the last decade have recently culminated in the initiation of clinical trials of gene transfer for hemophilia A and B. Three trials, each using different vectors and target tissues, are presently underway, and two additional trials are in late planning stages. This report reviews the preclinical data underlying these strategies and the design of the ongoing and proposed clinical trials.

Animals↗

PubMed2001

Cytomegalovirus infectivity in whole blood following leukocyte reduction by filtration.

Cytomegalovirus (CMV) may be transmitted by transfusion of whole blood and cellular components processed according to standard processing procedures. A need exists to develop new procedures to remove CMV and other leukocyte-borne viruses from donor blood. Ten patients (AIDS/bone marrow transplants) who were CMV antigenemic (virus subsequently confirmed by isolation), donated 50 mL of venous blood within 24 to 72 hours of the initial antigen detection. Twenty-five-milliliter aliquots of each specimen were passed through Purecell Neo Neonatal Leukocyte Reduction Filters (Pall, East Hills, NY). The remaining 25-mL nonfiltered aliquots, as well as the blood filtrates, were subjected to infectivity endpoint determinations. The Purecell Neo filter effected a 3 to 4 log10 leukocyte reduction. CMV input titers ranged from less than 10 to 7.3 x 10(1) median tissue culture infectious dose (TCID50) per milliliter. CMV was not isolated from any postfiltration effluent (i.e., leukocytes, erythrocytes, or plasma). CMV DNA was not detected by nested polymerase chain reaction in 8 of 10 postfiltrate blood specimens. The Purecell Neo filter was efficacious in eliminating or significantly reducing viral (CMV) load in venous blood.

Adult↗

PubMed1986

Thyrotropin enzyme-immunoassay in dried blood spots: a spectrophotometric method for neonatal thyroid screening.

We describe an enzyme-immunoassay with photometric endpoint determination, suitable for the measurement of thyrotropin (TSH) in dried blood spotted on filter paper. Using reagents of a commercially available test kit provided for the measurement of thyrotropin in 200 microliter serum, we have adapted the method to the determination of thyrotropin in blood spots containing ca. 10 microliter blood. This was achieved by prolongation of the assay time from 3 to 20 hours, and by increasing the amount of enzyme-antibody complex. Precision and sensitivity of the blood spot assay are comparable to those of our in-house thyrotropin RIA, and the RIA/EIA correlation coefficient is 0.987 (n = 150). The advantages of EIA are the simplicity of the photometric end point determination (although strict time control has to be observed in order to avoid drifts in results), the long stability of reagents, and the non-isotopic label. The method therefore appears to be a suitable alternative to thyrotropin RIA for the determination of thyrotropin in neonatal thyroid screening.

Humans↗

PubMed1992

Predictors of over- and underachievement of age-predicted maximal heart rate.

The age-predicted maximal heart rate (PMHR) formula, 220--age, is frequently used for identifying exercise training intensity, as well as determining endpoints for submaximal exercise testing. This study was designed to identify variables discriminating those with actual maximal heart rates considerably above or below that predicted from the 220--age equation. Subjects included 2010 men and women ranging in age from 14 to 77 yr. Stepwise discriminant analysis was performed using maximal heart rate error groups as the dependent variable, and selected preexercise test characteristics as predictors. The HR error groups were based on the difference between the measured and PMHR as follows: below (> or = 15 beats.min-1 below PMHR), within (+/- 14 beats.min-1 of PMHR), and above (> or = 15 beats.min-1 above PMHR). A contrast of the below and above groups identified age, resting HR, body weight, and smoking status as predictors of group membership (P < 0.01) for both men and women. The overall canonical correlation was 0.282 and 0.294 for the men and women, respectively. Older age, higher resting HR, lower weight, and non-smoking were related to the above group, while the inverse was related to the below group. Standardized coefficients suggest that age and resting heart rate for the men, and age and smoking status for the women were the most potent variables for discriminating extreme deviations between measured and PMHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1997

The IPCS Collaborative Study on Neurobehavioral Screening Methods: IV. Control data. Steering Group.

The goal of the International Programme on Chemical Safety (IPCS) Collaborative Study on Neurobehavioral Screening Methods was to determine the intra- and inter-laboratory reliability of a functional observational battery (FOB) and an automated assessment of motor activity in eight laboratories worldwide. The control data were crucial to the outcome of the studies in terms of sensitivity and reliability of the test measures, which in turn impact on the between-laboratory comparisons of chemical effects. In addition, analyses of control data can aid in determining endpoints that may require modification to improve their sensitivity and reliability. The control data from the eight laboratories were examined in terms of the following parameters: 1) control variability within studies for each laboratory; 2) within-laboratory replicability of control values across studies; 3) within-laboratory stability of control values over the course of testing for a given study; and 4) between-laboratory comparisons of parameters (1), (2), and (3). The analyses indicated considerable differences across endpoints, wherein some measures showed high variability and little replicability, while others were extremely reproducible. Generally, there were similar ranges of variability and replicability of control data across laboratories, although in some cases one or two laboratories were markedly different from the others. The physiological (weight, body temperature) and neuromuscular (grip strength, landing foot splay) endpoints exhibited the least variability, whereas the subjective assessments of reactivity varied the most. These data indicate a reasonable degree of comparability in the data generated in the participating laboratories.

Animals↗

PubMed2004

Performance of four sources of cholesterol oxidase for serum cholesterol determination by the enzymatic endpoint method.

BACKGROUND: Cholesterol oxidase is used for the determination of serum cholesterol. It can be derived from Streptomyces, Pseudomonas fluorescens, Cellulomonas, and Brevibacterium. This study compared the performance characteristics of four enzymes in the endpoint cholesterol determination. METHODS: Using the Mega analyzer, we studied assay optimization, linearity, precision, recovery, interference, stability, and compared 110 patient samples. RESULTS: The linearity for the four enzymes was up to 13.0 mmol/l at the optimal enzyme activity. The average within-run CVs ranged from 1.6% to 1.9% and between-day ranged from 2.8% to 3.0%, within the NCEP analytical criteria. The analytical recoveries obtained from four reagents ( approximately 96.5%) were excellent. The assays using these enzyme sources compared favorably with the commercial method and appeared accurate near the clinical decision cut-points. Hemoglobin concentration at 1.9 g/l interfered with the P. fluorescens cholesterol oxidase. Bilirubin caused a negative interference while lipemia generated a positive interference with all enzyme sources. Reagents were stable up to 6 weeks. CONCLUSIONS: Streptomyces, Cellulomonas, and Brevibacterium were essentially analytically equivalent. Streptomyces and Cellulomonas cholesterol oxidase are one-quarter as expensive Brevibacterium. Cellulomonas is a new source of cholesterol oxidase for determining serum cholesterol by the endpoint method.

Bilirubin↗

PubMed1978

Determination of the endpoints of partial deletion mutants of the attachment site of bacteriophage lambda by DNA sequencing.

The deletion mutants b508 and b522 of bacteriophage lambda both end within the attachment site. The formation of such deletions is dependent upon the presence of intact integrase, and thus the deletion endpoints may be related to the normal crossover site in site-specific recombination. We have determined the DNA sequences of the attachment site regions of these deletions. Comparison of the sequences with lambda wildtype shows that both the deletions end within the central common homology region but at different positions. The consequences of these findings for current models of site-specific recombination are discussed.

Base Sequence↗

PubMed1995

Studies on the establishment of appropriate spermatogenic endpoints for male fertility disturbance in rodent induced by drugs and chemicals. I. Nitrobenzene.

The effect of nitrobenzene on several spermatogenic endpoints was examined to determine which endpoints were affected by chemicals, how changes in spermatogenic endpoints are related to decreases in the rate of male fertility, and how long a treatment period is needed before damage can be detected. An experimental group of male Sprague-Dawley rats was given nitrobenzene (60 mg/kg, per os), a known inhibitor of male fertility, and a control group was given a diet of sesame oil (1 ml/kg, per os) alone. The rats were mated with normal proestrus females on days 7, 14, 21, 28, 42, 56 and 70 of treatment. Male rats were sacrificed on the day after mating, and sperm motility, progressive motility of sperm, sperm count and sperm morphology were examined. After 7 days of treatment, no changes were observed in the endpoints examined. However, the testicular and epididymal weights, sperm count, sperm motility and progressive motility decreased significantly by day 14. By day 21 sperm viability and the fertility index decreased, while increases were observed in the abnormal sperm rate and instances in which no motile sperm existed. However, even after 70 days of treatment, the copulation index was not affected. The most sensitive spermatogenic endpoints were determined to be sperm count and sperm motility, followed by progressive motility, viability, abnormal sperm rate and fertility index. The copulation index is not a meaningful endpoint for male fertility. Furthermore, a period of at least 14 days is necessary for evaluation of the effect of nitrobenzene on male fertility.

Animals↗

PubMed2005

Rapid and reproducible infectivity end-point titration of virulent phage in a microplate system.

The standard method for measuring the number of infectious phages in solution has traditionally been the plaque forming assay. An alternative method is described where the number of lytic, infectious phages is determined in an endpoint titration assay adapted for a microplate system. In this model system, susceptible Escherichia coli B6 at a density of 4 x 10(7) cells/ml, were mixed with an equal volume (100 microl) of PhiX174 diluted serially in a microtest plate. After 3h of incubation on a microplate shaker the endpoint was determined spectrophotometrically and calculated according to the method of Reed and Muench. A well was considered positive for infection if the OD630-value was < or = 10% compared to the OD630-value of the negative control of uninfected cells. ID50-titers were 2.5x higher than the PFU-titers (CV 15%) and the intra assay reproducibility revealed a CV of 9%. The method has several advantages as compared with the conventional PFU-titration. It is less time and material consuming with the possibility to assess several samples at the same time.

Bacteriophage phi X 174↗

PubMed2004

Toxicity assessment of sediments associated with various land-uses in coastal South Carolina, USA, using a meiobenthic copepod bioassay.

Coastal urbanization supplies surrounding estuarine environments with urban-related contaminants such as polycyclic aromatic hydrocarbons (PAHs), metals and pesticide mixtures. In our study, adult female and male copepods (Amphiascus tenuiremis) were chronically exposed to 18 sediment samples collected from sites influenced by different land-uses. Sediment samples were collected from three major suburban areas (Hilton Head, Kiawah Island and the Okatee River watershed) and a pristine site (North Inlet) in coastal South Carolina. Three-sediment bioassays (six sites per bioassay) were conducted by culturing copepods for 14 days in quadruplicate test sediments under flow-through conditions at 20 degrees C and 12:12 LD cycles. Adult survival and copepod reproductive output were quantified. Sediment samples were also analyzed by GC-MS for low and high molecular weight PAHs. Minimal adult mortality was observed in most sediment samples. However, sediments from Hilton Head Island and the Okatee River showed significant effects on copepod reproductive output (i.e., nauplii, copepodites and clutch size). Thus, we determined that reproductive endpoints rather than adult copepod survivorship were more sensitive to effects of contaminated sediments on A. tenuiremis. Furthermore, six (33%) of the 18 sites had a >25% reduction in copepod bioassay endpoints relative to controls, suggesting a high risk to long term A. tenuiremis population maintenance.

Animals↗

PubMed2002

Variations in levels of acid phosphatase present in chicken whole leg meat.

Acid phosphatase (ACP) has been identified as a potential biomarker for endpoint temperature determination in further-processed poultry. Multiple analyses of the same sample for ACP have produced consistent results. The degree of variation in ACP levels present in different production lots has not been identified. This study was conducted utilizing a single flock of broilers. Birds were slaughtered on four separate days (replications), and whole leg, without skin, was homogenized. Proximate composition was analyzed for each replication. Water-soluble proteins were extracted from raw meat and assessed for initial ACP levels. Samples of meat were cooked to an internal temperature of 71.1 C. There were differences (P < 0.05) between replications for both moisture and fat content. When dry fat content was analyzed, no significant differences occurred between replicates. Initial ACP levels were different (P < 0.0001) between replicates (500.33 to 348.97 units of activity/kg). Levels of ACP activity after cooking were also different (P < 0.0001) between replicates (17.61 to 10.82 units of activity/kg). Percentage degradation of activity during cooking was similar (96.98 to 95.89%) between replicates. ACP levels were consistently measured within a replicate. Differences between replicates for both initial and cooked levels indicate a threshold level for determination of thermal endpoint would be difficult to establish. ACP may not be a sensitive measure to estimate the degree of doneness of meat samples in which initial ACP concentration is unknown. Identical raw sample required for such a comparison would be difficult for the processing industry to maintain.

Acid Phosphatase↗

PubMed2006

Toxicity benchmarks for antimony, barium, and beryllium determined using reproduction endpoints for Folsomia candida, Eisenia fetida, and Enchytraeus crypticus.

The U.S. Environmental Protection Agency is developing ecological soil screening levels (Eco-SSLs) for the ecological risk assessment of contaminants at Superfund sites. The Eco-SSLs for several soil contaminants have been developed from toxicity benchmarks for soil invertebrates in the existing literature. Insufficient information to generate Eco-SSLs for Sb, Ba, and Be necessitated toxicity testing to fill the data gaps. We used standardized toxicity tests with the earthworm Eiseniafetida, enchytraeid Enchytraeus crypticus, and collembolan Folsomia candida in the present study. These tests were selected on the basis of their ability to measure chemical toxicity to ecologically relevant test species during chronic assays and their inclusion of at least one reproduction component among the measurement endpoints. Tests were conducted in Sassafras Sandy Loam soil, which supports relatively high bioavailability of metals. Weathering and aging procedures for metals in amended soil were incorporated into these studies to better reflect exposure conditions in the field. The relative toxicity of metals to the soil invertebrates tested was Be > Sb > Ba based on the median effective concentration values for reproduction. These studies produced toxicological data that can contribute to the development of Eco-SSLs for Sb, Ba, and Be for soil invertebrates.

Animals↗