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PubMed2000

Comparison of patient age with MR imaging features of gangliogliomas.

OBJECTIVE: The purpose of this study was to compare MR imaging features of gangliogliomas in children less than 10 years old with those seen in patients at least 10 years old. MATERIALS AND METHODS: Our study population consisted of 15 female patients and 10 male patients with a mean age of 20 years. The early childhood group was composed of six children with a mean age of 5.5 years. The older group was composed of 19 patients with a mean age of 25.6 years. We assessed tumor volume, tumor location, percentage of tumor that was cystic, pattern of contrast enhancement, and degree of edema. RESULTS: The temporal lobe was the most common tumor location in both groups. Mean tumor volume in the early childhood group was 83 cm3, which was significantly larger than the mean tumor volume (9.78 cm3) for the older group (p = 0.001). Cystic tumors were more common in the early childhood group (83%) than in the older group (63%), and the average percentage of cysts in the cystic tumors was much higher in the early childhood group (67%) than in the older group (30%). Contrast enhancement was seen in five of six early childhood tumors and 13 of 16 tumors in older patients. Four of six tumors in the early childhood group and five of 19 tumors in the older patient group had associated edema. CONCLUSION: The mean tumor volume of gangliogliomas in the early childhood group was significantly larger than that of the older patient group. This finding may be indicative of differences in tumor growth patterns in the two groups, ability of the hemicranium to adjust to mass effect in childhood, or sampling error as a result of a relatively small sample size.

Adolescent↗

PubMed2006

[Medical research using Internet questionnaire in Japan].

As the method for questionnaire studies, mail survey and interview survey are frequently used. The utility and validity of applying the Internet method to medical studies have yet to be fully evaluated. For the present investigation, we reviewed 36 Japanese original articles using Internet questionnaire reported through to April 2005. Although original papers using the Internet method have been increasing in recent years, they are still limited in number. There is comparatively much research on disease with many patients in youth and early manhood, such as allergic ailments (allergic rhinitis, atopic dermatitis, and hives). As compared with conventional methods, the advantages of the Internet approach are convenience for both investigators and respondents and the ability to quickly collect data. The disadvantage is that the user's age range is more concentrated. Since samples are extracted from individuals who are registered as monitors, a greater sampling error may occur as compared with a random sampling method. However, it is to be expected that continued explosive growth of the Internet would decrease the limitation in user's age. If more elderly people participate in questionnaire studies using the web, research into more illnesses should be facilitated. Considering the inherent advantage, it is thought that Internet method can become the leading tool for sociomedical and clinical research in the near future.

Adolescent↗

PubMed1989

Use of a laser diffraction particle sizer for the measurement of mean diameter of multicellular tumor spheroids.

Increasing use is being made of tumor cell lines cultured as cell aggregates (generally referred to as multicellular spheroids) in in vitro radiosensitivity and/or chemosensitivity tests. Conventional procedures for the determination of mean spheroid diameters for the construction of growth delay curves employ a microscope-image analyzer. However, this approach can prove excessively time consuming when large numbers of samples have to be measured. We have, therefore, been exploring the use of a Laser Diffraction Particle Sizer, the Malvern 2600 long bench model, for the measurement of mean spheroid diameter and size distribution. We report here a direct comparison between measurements carried out by the instrument and under the microscope. Also a comparison of growth curves for six cell lines constructed from measurements by the microscope and by the instrument. A number of factors that might affect the accuracy of spheroid diameter measurement by the instrument have been investigated: The effect of stirring to maintain the spheroids in suspension during measurement. Sampling error due to removal of a series of spheroid samples from culture flasks for measurement. Optimum numbers of scans to be carried out by the instrument to reach a constant value for mean diameter, and minimum SE of the mean.

Animals↗

PubMed2000

Comparison between anopheline mosquitoes (Diptera: Culicidae) caught using different methods in a malaria endemic area of Papua New Guinea.

The mosquito sampling efficiency of CDC (Centers for Disease Control) miniature light traps hung adjacent to mosquito nets, was compared with that of both indoor and outdoor human-bait collections in ten villages in the Wosera area of Papua New Guinea. The most frequently collected anopheline in the matched indoor and light trap samples was Anopheles koliensis Owen, followed by A. punctulatus Dönitz, A. karwari (James), A. farauti Laveran (sensu lato), A. longirostris Brug and A. bancroftii Giles. All species were much less frequent in the light traps than in landing catches. The hypothesis that the numbers of mosquitoes in light traps are proportional to human landing catches was examined using regression models that allowed for sampling error in both entomological measurements. Light traps under-sampled A. punctulatus and A. farauti s.l. at high densities. The models indicated that the ratio of light trap to landing catch females of A. koliensis and A. karwari increased with increasing mosquito density. Light trap catches of A. longirostris were proportional to indoor landing rates but when outdoor landing rates were high this species was under-sampled by light traps. Numbers of A. bancroftii in light traps were found to be proportional to those in outdoor landing catches, but were negatively related to those attempting to bite indoors. Circumsporozoite positivity rates for both Plasmodium falciparum Welch and P. vivax (Grassi & Feletti) in A. punctulatus and A. farauti s.l. were significantly higher in light trap collections than in either indoor or outdoor landing catches, suggesting that light traps may selectively sample older mosquitoes of these species.

Animals↗

PubMed1988

Estimation of allele frequencies at isoloci.

In some polyploid animals and plants, pairs of duplicated loci occur that share alleles encoding proteins with identical electrophoretic mobilities. Except in cases where these "isoloci" are known to be inherited tetrasomically, individual genotypes cannot be determined unambiguously, and there is no direct way to assign observed variation to a particular locus of the pair. For a pair of diallelic isoloci, nine genotypes are possible but only five phenotypes can be identified, corresponding to individuals with 0-4 doses of the variant allele. A maximum likelihood (ML) approach is used here to identify the set of allele frequencies (p, q) at the individual gene loci with the highest probability of producing the observed phenotypic distribution. A likelihood ratio test is used to generate the asymmetrical confidence intervals around ML estimates. Simulations indicate that the standard error of p is typically about twice the binomial sampling error associated with single locus allele frequency estimates. ML estimates can be used in standard indices of genetic diversity and differentiation and in goodness-of-fit tests of genetic hypotheses. The noncentral chi 2 distribution is used to evaluate the power of a test of apparent heterozygote deficiency that results from attributing all variation to one locus when both loci are polymorphic.

Alleles↗

PubMed1998

The uncertainty associated with the predictive value of test results.

The uncertainty associated with predictive value of test results was taken into consideration, as concerns both sampling error (related to the size of the statistical reference samples) and analytical imprecision (unavoidably involved by the measurement itself). A software package, developed for the statistical calculations, was used for the treatment of the results obtained for serum free thyroxin in euthyroid and dysthyroid subjects, assumed as an experimental model. Examples are shown for the obtainable functions predictive value vs. estimate and the related uncertainty regions. These data could help in comparing test results and, in particular, in preparing fully informative laboratory reports. The difficulties involved by an extensive application of the procedure are discussed.

Humans↗

PubMedDate not supplied

Platinum levels and clinical responses of tumours treated by cisplatin with and without concurrent hyperthermia: a case study.

The heterogeneity of platinum distributed within tissue after clinical administration of cisplatin was evaluated for the first time. Platinum levels were correlated with the observed clinical responses of separate superficial histiocytic sarcomas located in the forearm of a 74-year-old male patient. One of four lesions received four weekly treatments with hyperthermia administered concurrently with 30 mg/m2 cisplatin, while three lesions were treated with cisplatin alone. The lesion receiving hyperthermia concurrently with cisplatin had a solid partial response during a 6-week period following this therapy, whereas two other tumours receiving cisplatin alone progressed. One lesion could not be clinically evaluated. Platinum levels were determined in multiple samplings from three of the four lesions and normal tissue in order to evaluate the validity of taking a single tumour sample of 100 mg or less for the analysis of platinum content. Such a small single sample might provide a value significantly different from the true average because of sampling error. The range in platinum distribution encompassed an average of three-fold difference within eight separate sample groups, with a factor of six being the greatest difference in a single sample group. This degree of heterogeneity is great enough to suggest that conclusions made from the analysis of small and single random tissue samples could be sufficiently in error to misdirect investigative or medical decisions.

Aged↗

PubMed1998

Estimating sample size for epidemiologic studies: the impact of ignoring exposure measurement uncertainty.

Sample size requirements for epidemiologic studies are usually determined on the basis of the desired level of statistical power. Suppose, however, that one is planning a study in which the participants' true exposure levels are unobservable. Instead, the analysis will be based on an imprecise surrogate measure that differs from true exposure by some non-negligible amount of measurement error. Sample size estimates for tests of association between the surrogate exposure measure and the outcome of interest may be misleading if they are based solely on the anticipated characteristics of the distribution of surrogate measures in the study population. We examine the accuracy of sample size estimates for cohort studies in which a continuous surrogate exposure measure is subject to either classical or Berkson measurement error. In particular, we evaluate the consequences of not adjusting the sample size estimation procedure for tests based on imprecise exposure measurements to account for anticipated differences between the distributions of the true exposure and the surrogate measure in the study population. As expected, failure to adjust for classical measurement error can lead to underestimation of the required sample size. Disregard of Berkson measurement error, however, can result in sample size estimates that exceed the actual number of participants required for tests of association between the outcome and the surrogate exposure measure. We illustrate this Berkson error effect by estimating sample size for a hypothetical cohort study that examines an association between childhood exposure to radioiodine and the development of thyroid neoplasms.

Adolescent↗

PubMedDate not supplied

Immunocytochemical detection of p16INK4a protein in scraped cervical cells.

OBJECTIVE: To develop an immunocytochemical technique for p16INK4a protein detection in scraped cervical cells for cancer screening. STUDY DESIGN: We took duplicate cervical scrapes from each participant, the first for a Pap smear and the second for p16INK4a protein detection. From a 50-microL cell suspension prepared from the scrape rinsing, a 10-microL aliquot was dropped in a 5-mm-diameter circle on a glass slide, air dried and fixed in 0.1% formal saline (1 hour) and in 95% ethanol (10 minutes). Using the immunocytochemical technique, slides from 30 samples of each Pap diagnosis class were stained sequentially with mouse monoclonal anti-p16INK4a (primary antibody), biotinylated goat antimouse IgG (secondary antibody), horse-radish peroxidase-labelled streptavidin and 3,3'-diaminobenzidine and mixed hydrogen peroxide, then counterstained with hematoxylin. A positive sample had to contain > or = 3 immunoreactive cells. Results were confirmed by western blot analysis of lysates from the remaining 40 microL of each cervical cell suspension. RESULTS: Samples were grouped as control (normal cervical cells), mild dysplasia (ASCUS, LSIL) and high abnormality (HSIL, SCC). Using the immunocytochemical technique, > 95% of the positive (SiHa cells) but 0% of the negative controls (human embryonic lung fibroblast cells) showed immunoreactive cells. All slides displayed a clear background without mucus, and positive cells were stained in both the cytoplasm and nucleus. p16INK4a Protein was detected in 17 of 30 (56.67%) ASCUS and 10 of 30 (33.33%) LSIL and increased with the degree of abnormality to 93.33% (28 of 30) and 96.67% (29 of 30) in the HSIL and SCC group, respectively. Normal cervical cells and degenerated malignant cells were nonimmunoreactive. Western blot analysis confirmed similar positive samples in the low-abnormality group, while the whole high-abnormality group was immunoreactive. A sampling error might have caused the 2 HSIL and 1 SCC sample to be negative using our immunocytochemical technique. CONCLUSION: p16INK4a Protein detection in scraped cervical cells using the immunocytochemical technique correlated with western blot analysis and was nontraumatic and precise. It offers a significant diagnostic adjunct to the Pap test for cervical cancer screening.

Biomarkers, Tumor↗

PubMed1989

Sources of diagnostic error in fine needle aspiration of the thyroid.

Smears obtained from 795 patients with suspicious thyroid nodules by fine needle aspiration (FNA) of the thyroid gland were seen over a 5-year period at the UCLA Center for the Health Sciences. From 72 patients who underwent subsequent surgical excision of their nodules, inadequate or discrepant FNA diagnoses were noticed in 20 cases (27.8%). These errors could be attributed to inadequate material for diagnosis (n = 6), sampling errors (n = 2), and cytodiagnostic errors (n = 12). If the diagnosis of follicular neoplasm was treated as indeterminate for malignancy, the overall efficiency of FNA was 88.9%. All false-negative diagnoses were related to procedure (i.e., inadequate smears or missed sampling of the lesion). The frequency of inadequate smears, in turn, was strongly related to the type of physician performing the aspiration. The frequency was highest among community-based clinicians (32.4%) and lowest among hospital-based cytopathologists (6.4%). With adequate sampling, the finding of 100% sensitivity in the diagnosis of malignant neoplasms by FNA cytology reaffirms its role as the procedure of choice in the initial screening of thyroid nodules.

Adolescent↗

PubMed2003

The Effect of altering ADL thresholds on active life expectancy estimates for older persons.

OBJECTIVES: Research on disability and active life expectancy (ALE) has often criticized the measurement of disability but has rarely empirically investigated the effect of changing measurement. The purpose of this study was to determine whether altering the number of activities of daily living (ADLs) required to consider an individual "disabled" affects population-based ALE estimates after considering parametric uncertainty and sampling error. METHODS: The authors develop a Bayesian approach to estimating multistate life tables for a three-dimensional state space, using data on community-dwelling older adults from the 1989 and 1994 National Long Term Care Survey analytic files. Empirical confidence intervals for ALE are compared across 6 models using successively higher ADL cutoffs for defining individuals as being disabled. RESULTS: After considering sampling and other errors in the estimation of transition probabilities, the authors found that altering the threshold for measuring disability has relatively little effect on ALE estimates, especially with higher ADL-level thresholds and at older ages. DISCUSSION: The implications of the results include that disability measurement, including altering the definition of being disabled and possibly expanding the state space of a model, may not affect population-based estimates of ALE.

Activities of Daily Living↗

PubMed2005

Mercapturic acids of styrene in man: comparability of the results obtained by LC/MS/MS and by HPLC-fluorimeter, and stability of samples under different storage conditions.

Two analytical methods (HPLC-fluorimeter [HPLC-FLD] and tandem mass spectrometry LC/MS/MS) are available to assay phenyl-hydroxyethylmercapturic acids (PHEMAs), the mercapturic acids of styrene in humans. In the past, each method was used to check different populations of subjects, but until now no attempt has been made to compare the two methods. This study was designed to verify whether the two methods actually give comparable results. The influence of different conditions of sample storage in altering the concentration of PHEMAs was also investigated. Urine samples were collected at the beginning and at the end of the workshift from 10 workers exposed to different levels of styrene. Each sample was analysed both by LC/MS/MS after storage under different conditions (respectively, at -20 and +4 degrees C, and after repeated freezing-thawing cycles), and by HPLC-FLD (in the same conditions of storage). Strong correlations were found between the two methods both for total PHEMAs and for each of the isomers measured, including the minor (S,R)-M1. Also an alternative approach, the Bland-Altman test, confirmed the agreement between the two methods. The different storage conditions tested did not decrease the concentration of PHEMAs but, surprisingly, a clear trend to increase was shown, particularly for (R,R)-M1, (S,R)-M2 and (R,R)-M2 in samples stored at +4 degrees C for 1 week. In conclusion, the study demonstrates that the methods give comparable results. Indirectly, this confirms also the main characteristics of PHEMAs, showed in the previous experiments: low biotransformation rates of styrene into PHEMAs; large inter-individual variability; and the presence of a clear preference in the excretion of the isomers deriving from (S)-styrene oxide. PHEMAs appear stable under different storage conditions, but further studies are needed to explain the increase of levels that occurs when samples are not kept frozen. To avoid pre-analytical errors, samples collected for biomonitoring or research purposes should be frozen as soon as possible, and thawed only one time just before the analysis.

Acetylcysteine↗

PubMed1998

Fine needle aspiration cytology diagnosis of malignant lymphoma and reactive lymphoid hyperplasia.

AIMS: To assess the diagnostic accuracy of lymph node fine needle aspiration (FNA) cytology to distinguish reactive lymphoid hyperplasia from malignant lymphoma, and to evaluate the contribution of ancillary techniques applied to cytological material. METHODS: Two hundred and seventy seven consecutive lymph node FNA specimens reported to be consistent with reactive lymphoid hyperplasia (n = 213) or suggestive/diagnostic of malignant lymphoma (n = 64) were reviewed. Follow up data were obtained by case record review or by histological correlation. The value of immunocytochemistry, in situ hybridisation for immunoglobulin light chain mRNA, and polymerase chain reaction (PCR) towards the final clinicopathological diagnosis was assessed in 92, 61, and 45 cases, respectively. RESULTS: Sixty one of 67 lymphomas and 207 of 209 reactive lymph nodes were accurately diagnosed by FNA cytology. There were six false negative aspirates including three cases of follicular lymphoma, two cases of Hodgkin's disease, and one chronic lymphocytic leukaemia. Two FNA specimens considered suspicious of lymphoma proved reactive on histology or clinical follow up. One metastatic small cell carcinoma was wrongly diagnosed as lymphoma. Ancillary studies contributed to the correct diagnosis in most cases although occasional misleading results were obtained, particularly with PCR. CONCLUSIONS: FNA cytology accurately distinguished reactive lymphoid hyperplasia from malignant lymphoma in 97% of cases. However, occasional wrong diagnoses occurred owing to sampling error or misinterpretation. Ancillary studies can be applied to cytological samples and contribute to the diagnosis in most cases.

Adult↗

PubMed1991

Quantifying lung structure. Experimental design and biologic variation in various models of lung injury.

The lung is a complex organ composed of a large number of different cell types of varying size and shape. Quantification of lung structure requires an understanding of how the distribution of specific cells and their characteristics affect the accuracy of measurement made on them and how to optimize experimental design for a morphometric study. We have studied lung structural modifications in a variety of lung injuries over the last decade. Extensive quantitative data from EM morphometric studies of pulmonary tissue have been collected. These data provide a unique opportunity to study the accuracy and efficiency of methods used to quantitate lung structure. We present and discuss novel computation-intensive methods for the estimation of biologic variability, sampling error, and measurement error. A new concept, unnested analysis of variance for stratified sampling and the use of computer-based methods for statistical analysis (the bootstrap method) and optimizing experimental design (nonlinear minimization procedure) are described in this report. Examples of experimental designs with their corresponding levels of accuracy and cost are also provided. The number of samples needed for a given level of precision is affected by the volume density of the structure being measured. The most important determinant for the overall accuracy of a morphometric study is the number of animals studied. Biologic variations between samples within an animal and among animals can vary significantly as a function of the model of injury studied.

Animals↗

PubMed2004

The EDNAP mitochondrial DNA population database (EMPOP) collaborative exercises: organisation, results and perspectives.

This paper presents an overview of the organisation and the results of the collaborative exercises (CE) of the European DNA Profiling (EDNAP) Group's mitochondrial DNA population database project (EMPOP). The aim of the collaborative exercises was to determine whether uniformity of mtDNA sequencing results could be achieved among different laboratories. These were asked to sequence either the complete mtDNA control region or the two hypervariable regions HVI (16024-16365) and HVII (73-340) from DNA extracts, buccal swabs or bloodstains, proceeding in accordance with the protocol and strategies used in each individual laboratory. The results of the collaborative exercises were employed to identify possible sources of errors that could arise during the analysis and interpretation of mtDNA profiles. These findings were taken as a basis to tentatively make suitable arrangements for the construction of a high quality mtDNA database. One hundred fifty mtDNA profiles were submitted to the evaluating laboratory, and disaccording profiles were classified into four groups corresponding to the source of error: clerical errors, sample mix-ups, contaminations and discrepancies with respect to the mtDNA nomenclature. Overall, 14 disaccording haplotypes (16 individual errors) were observed. The errors included 10 clerical errors, 3 interpretation problems, 2 cases of sample mix-up and 1 case of point heteroplasmic mixture, where the 2 sequencing reactions brought inconsistent base calls. This corresponds to an error rate of 10.7% in a virtual mtDNA database consisting of the collaborative exercise results. However, this estimate is still conservative compared to conclusions drawn by authors of meanwhile numerous publications critically reviewing published mtDNA population databases. Our results and earlier published concerns strongly emphasize the need for appropriate safety regulations when mtDNA profiles are compiled for database purposes in order to accomplish the high standard required for mtDNA databases that are used in the forensic context.

Clinical Laboratory Techniques↗

PubMed2001

The development of a blend-sampling technique to assess the uniformity of a powder mixture.

This article discusses the challenges overcome during the development of a blend-sampling technique and the successful validation of the blending operation for a tablet dosage form containing 2% active ingredient. Content uniformity results are discussedfor three pilot-scale (15-kg) and seven commercial-scale (150-kg) batches of tablets. Blend and core content uniformity data from the pilot-scale batches were acceptable. For the initial commercial-scale batches, although the tablet core content uniformity data were acceptable, the blend uniformity results were poor. The blend data for these batches had very high mean values, but acceptable relative standard deviations (RSDs). This suggested that the drug was being preferentially sampled by the thief but in a consistent, reproducible manner. Extensive testing was performed on a commercial-scale development batch to identify potential causes of sampling error. The results of this testing helped define the blend-sampling technique and strategy used to validate the mixing operation.

Bias↗

PubMed2003

Detection of rare disseminated tumor cells identifies head and neck cancer patients at risk of treatment failure.

PURPOSE: This study was designed to help establish the most appropriate samples and tests to detect disseminated tumor cells (DTCs) for head and neck cancer patients. EXPERIMENTAL DESIGN: Samples of bone marrow (BM) and central venous blood (CVB), collected preoperatively, and BM and peripheral venous blood, collected 3 months transcription postoperatively, were screened for the presence of DTCs using immunocytochemistry (ICC) with a pan-cytokeratin antibody and E48 reverse transcriptase-PCR. The molecular approach was also applied to intraoperative CVB. RESULTS: The concordance between the molecular and ICC tests applied to preoperative samples, measured by Cohen's kappa, was not uniformly good, which likely reflected sampling errors, heterogeneity of E48 antigen expression, or stochastic effects. However, testing samples of BM and CVB preoperatively with the molecular or ICC approaches gave results that predicted disease-free survival and distant-metastases-free survival. Application of a single preoperative test predicted development of distant metastases, and the prediction could be improved by combining information derived from testing both CVB and BM. Applying two tests to the same sample of blood or BM served to validate the findings from a single assay but did not improve the prediction. Testing the intraoperative sample of CVB was also a sensitive predictor of distant metastases, but testing BM or blood 3 months postsurgery was not useful. CONCLUSIONS: These findings suggest that detection of DTCs pre- or intraoperatively indicates a high risk of local and distant recurrence and reduced survival in head and neck cancer.

Bone Marrow↗

PubMed1989

Fine-needle aspiration of the liver: out of the ivory tower and into the community.

This study of 160 consecutive fine-needle aspirates of localized hepatic masses analyzed the efficacy of the technique when extended into a multicenter setting. The aspirates were processed and interpreted by a single cytology service, but they were performed, under radiographic imaging, in eight different hospitals by at least 20 radiologists, few of whom had had the opportunity to acquire long-term experience. Of 108 malignancies, 101 were correctly sampled (sensitivity, 93.5%), including 30 primary hepatocellular carcinomas, 70 metastatic tumors, and 1 lymphoma. Specific benign pathologic lesions in 12 cases were amenable to cytodiagnosis. The problem of the remaining 47 samples, which contained exclusively blood, necrotic material, or normal and reactive hepatic constituents, was addressed at length. These were considered "nondiagnostic" samples in the context of aspirating focal masses. The majority had benign lesions on further study, but tumors were found in seven, all of which had been sampling errors, resulting in a negative predictive value of 82.5%. Fine-needle sampling of localized lesions, particularly neoplasms, can thus perform well in transition from single-center studies to more widespread usage in daily practice. Confident reliance on the procedure can be maintained if appropriate radiologic and cytologic facilities exist, provided that the limitations of nonneoplastic aspirates are fully understood.

Adolescent↗