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At least 253 records · Page 14Linked to original sources

Limitations with light microscopy in the detection of colorectal cancer cells.

PURPOSE: The failure of light microscopy to predict individual patient survival accurately in pStage I and II colorectal carcinoma can hinder planning postoperative therapy and follow-up. This study was designed and conducted in two parts to assess the influence of relative sensitivity of the light microscope on the pathologist's ability to detect malignant cells in lymph nodes. METHODS: The first part of the study examined the issue of sampling error as a fraction of the number of lymph node sections examined by asking the question, "Does increasing the number of sections (sampling) taken from the block increase tumor cell detection in a lymph node?" Three levels of five sections 4 to 5 microm thick separated by 15 to 20 microm were obtained from each of 494 blocks from 173 cases of pStage I and II colorectal carcinoma. A total of 1,721 lymph nodes were examined. Sections from each level were stained with hematoxylin and eosin and for the expression of cytokeratin. The second part of the study examined the relative sensitivity of the light microscope to detect tumor cells in a lymph node. To simulate lymph nodes, cell blocks were made that contained 10(6) or 10(7) mononuclear cells admixed with increasing numbers of SW480 tumor cells (0, 50, 10(2), 5 x 10(2), 10(3), and 5 x 10(3)). Three pathologists independently examined sections from ten control and ten experimental blocks. RESULTS: Results from the first part of the study demonstrated cytokeratin-positive cells in 278 lymph nodes from 102 of 172 (59 percent) cases. These cells were identified in the first level in 177 (64 percent) as compared with the second or third level or both in 101 (36 percent) of the lymph nodes. Results from the second part of the study demonstrated an overall sensitivity of light microscopic examination of hematoxylin and eosin-stained sections to be approximately 23 percent, representing tumor cells correctly detected in 7 sections of the 30 sections containing tumor cells. The overall specificity was 87 percent or 26 sections correctly classified as lacking tumor cells of a possible 30. Immunohistochemical staining for cytokeratin expression improved sensitivity of the light microscope to detect tumor cells to 18 of 30 (60 percent) and the specificity to 30 of 30 (100 percent). CONCLUSION: This study demonstrates several sources of variability that can induce errors in pathologic staging. These include 1) inadequate section, i.e., sampling, of lymph nodes, 2) use of only hematoxylin and eosin-stained sections, 3) samples with tumor cells below the level of detection sensitivity of the light microscope, and 4) observer variability.

Colorectal Neoplasms↗

Telemedicine: application of telepathology-remote microscopy for intraoperative diagnoses on frozen sections.

Due to the time delay, intraoperative consultations result in an extension of operation times, leading to prolonged anesthesia and idle time during surgery. Using a remote controlled microscope for telepathology, transfer times between hospital and pathologist can be eliminated and pathological expertise obtained independently of the geographic location of the hospital. In cooperation with a community hospital located 100 km apart from the Institute of Pathology of the Justus Liebig University Giessen, telepathological intraoperative consultations have been performed since 1999. After preparation and staining of the cryosection in the hospital, the slide was examined in our institute using a remote-controlled microscope (Leica DMRXA) and a special telepathological software (Leica TPS1). Data were transferred via two ISDN connections in parallel. The telepathology system contains an additional macroscopic examination equipment. Up to now more than 40 telepathological consultations have been done. Time required for the microscopic diagnosis ranged between 4 and 25 minutes. The amount of time saved, compared to the transfer to the next available pathologist, was approximately 45 minutes. In our experience, telepathological diagnoses were fully in accordance with conventional diagnoses routinely performed afterwards. The application of telepathology can lead to a significant shortening of surgery time if a pathologist is locally not available. In the study presented, no diagnostic errors occurred. The additional application of a macroscopic equipment allows inspection and interactive guidance for sampling, thus preventing sampling errors.

Efficiency↗

Comparison of semi-automated image analysis and manual methods for tissue quantification in pancreatic carcinoma.

Objective measurements of tissue area during histological examination of carcinoma can yield valuable prognostic information. However, such measurements are not made routinely because the current manual approach is time consuming and subject to large statistical sampling error. In this paper, a semi-automated image analysis method for measuring tissue area in histological samples is applied to the measurement of stromal tissue, cell cytoplasm and lumen in samples of pancreatic carcinoma and compared with the standard manual point counting method. Histological samples from 26 cases of pancreatic carcinoma were stained using the sirius red, light-green method. Images from each sample were captured using two magnifications. Image segmentation based on colour cluster analysis was used to subdivide each image into representative colours which were classified manually into one of three tissue components. Area measurements made using this technique were compared to corresponding manual measurements and used to establish the comparative accuracy of the semi-automated image analysis technique, with a quality assurance study to measure the repeatability of the new technique. For both magnifications and for each tissue component, the quality assurance study showed that the semi-automated image analysis algorithm had better repeatability than its manual equivalent. No significant bias was detected between the measurement techniques for any of the comparisons made using the 26 cases of pancreatic carcinoma. The ratio of manual to semi-automatic repeatability errors varied from 2.0 to 3.6. Point counting would need to be increased to be between 400 and 1400 points to achieve the same repeatability as for the semi-automated technique. The results demonstrate that semi-automated image analysis is suitable for measuring tissue fractions in histological samples prepared with coloured stains and is a practical alternative to manual point counting.

Algorithms↗

Embryonal adenoma of the kidney: a report of two cases.

Embryonal (metanephric) adenoma of the kidney, like Wilms' tumor, exhibits small monomorphic, blue cells arranged as vague, tubular rosettes. Unlike Wilms' tumor, which requires chemotherapy or multi-modality therapy for optimal management, the available evidence indicates that embryonal adenoma is most likely cured by simple enucleation or nephrectomy. Two women, age 54 (Case 1) and 78 (Case 2), respectively, underwent needle biopsy for a radiologically well circumscribed renal lesion with associated hematuria. The cellular smears contained vague rosette-like arrangement of small, blue cells with scant cytoplasm and evenly distributed, fine, nuclear chromatin. In cell blocks, these cells were arranged as compact, primitive, tubular rosettes or rare, moresolid clusters. Assuming that the absence of undifferentiated blastema and primitive glomeruli represented a sampling error, a diagnosis suggesting of Wilms' tumor was made in Case 1. At nephrectomy, despite extensive sampling, the typical triphasic Wilms' morphology and anaplastic or necrotic areas were not seen. In the presence of architectural monotony, the diagnosis in Case 1 was amended to embryonal adenoma. Case 2 was cytologically diagnosed as embryonal adenoma of the kidney and is being followed conservatively. In our opinion, the presence of monotypic architecture at cytology/histology is very helpful in differentiating renal embryonal (metanephric) adenoma from Wilms' tumor.

Adenoma↗

Information-theoretic dissection of pairwise contact potentials.

Pairwise contact potentials have a long, successful history in protein structure prediction. They provide an easily-estimated representation of many attributes of protein structures, such as the hydrophobic effect. In order to improve on existing potentials, one should develop a clear understanding of precisely what information they convey. Here, using mutual information, we quantified the information in amino acid potentials, and the importance of hydropathy, charge, disulfide bonding, and burial. Sampling error in mutual information was controlled for by estimating how much information cannot be attributed to sampling bias. We found the information in amino acid contacts to be modest: 0.04 bits per contact. Of that, only 0.01 bits of information could not be attributed to hydropathy, charge, disulfide bonding, or burial.

Amino Acids↗

The Assessment of Goal Commitment: A Measurement Model Meta-Analysis.

Goals are central to current treatments of work motivation, and goal commitment is a critical construct in understanding the relationship between goals and performance. Inconsistency in the measurement of goal commitment hindered early research in this area but the nine-item, self-report scale developed by Hollenbeck, Williams, and Klein (1989b), and derivatives of that scale, have become the most commonly used measures of goal commitment. Despite this convergence, a few authors, based on small sample studies, have raised questions about the dimensionality of this measure. To address the conflicting recommendations in the literature regarding what items to use in assessing goal commitment, the current study combines the results of 17 independent samples and 2918 subjects to provide a more conclusive assessment by combining meta-analytic and multisample confirmatory factor analytic techniques. This effort reflects the first combined use of these techniques to test a measurement model and allowed for the creation of a database substantially larger than that of previously factor analyzed samples containing these scale items. By mitigating sampling error, the results clarified a number of debated issues that have arisen out of previous small sample factor analyses and revealed a five-item scale that is unidimensional and equivalent across measurement timing, goal origin, and task complexity. It is recommended that this five-item scale be used in future research assessing goal commitment. Copyright 2001 Academic Press.

Journal Article↗

Genetic differentiation between two host "races" and two species of cleptoparasitic bees and between their two hosts.

In this paper we test the following two hypotheses: (1) that apparently conspecific samples of the cleptoparasitic bee Coelioxys funeraria, differing markedly in size and reared from different host species, do indeed represent one panmictic population; (2) that bees that nest in holes in wood or twigs have higher levels of genetic variation than those nesting in the ground. Based upon 41 loci, the genetic differences between the two samples of C. funeraria could be explained entirely in terms of sampling error. In contrast, the sympatric C. moesta showed 16 fixed allelic differences from the C. funeraria samples. Similarly, the two hosts of C. funeraria, Megachile relativa and M. inermis, had 21 fixed allelic differences between them out of 42 presumptive gene loci. Heterozygosities among the wood-nesting bees were not particularly high for Hymenoptera, ranging from 0.045 to 0.054. Comparisons of heterozygosity estimates among bees remain ambiguous as to whether soil nesting confers sufficient environmental buffering effects to reduce possible advantages of heterosis in ground-nesting species.

Alleles↗

The TSH-dependent variation of the essential elements iodine, selenium and zinc within human thyroid tissues.

Instrumental Neutron Activation Analysis was used in order to measure iodine, selenium and zinc concentration in thyroid samples. A pair of samples of normal and nodular tissue were collected from the thyroid gland from 72 patients selected on the basis of pathological criteria (44 cases of multinodular goiter, 12 of chronic lymphocytic thyroiditis (CLT), 6 of thyroid adenoma (TA) and 12 of thyroid cancer (TC)). The check for tissue homogeneity and sampling error was performed by means of the coefficient of variation (CV%) of the elements in replicate samples of normal and altered tissues. High CV% values (> 15%) for iodine reflected a functional variability in thyroid follicles, while low CV% values (< 10%) for selenium and zinc indicated that the composition of selected tissues was rather homogeneous. The variation of the element's concentration was compared in normal and altered tissues. The mean element concentrations had values close to those already reported in the literature; furthermore, our patients had marginal iodine and selenium deficiency. Both normal and nodular tissues in CLT showed statistically significant lower zinc values as compared with the other thyroid diseases. To evaluate the thyroid function, thyroid stimulating hormone (TSH) and thyroxine (T4) levels were measured in the serum of patients. Two arbitrary serum-TSH threshold levels (TSH < 1.0 and > 4.0 mU/L) were introduced in order to classify, respectively, hyperthyroidism and hypothyroidism, as well as euthyroid conditions (1.0 < TSH < 4.0 mU/L), and each patient was assigned to one of these groups. The influence of TSH in the variation of the concentration of iodine, selenium and zinc in normal and altered human thyroid tissues was significant.

Adolescent↗

The potential for increased risk of infection due to the reuse of convective air-warming/cooling coverlets.

BACKGROUND: The use of convective air warming and/or cooling for the prevention of hypothermia or to induce hypothermia is growing rapidly. To date, there is no information available as to the potential risks for infection associated with either the post-surgical reuse or the repositioning of coverlets closer to the wound. We hypothesized that use of coverlets either intra- or postoperatively leads to increased contamination. METHODS: The bacterial contamination of commercially available coverlets before (control group, n = 10) and after patient application (n = 18) was investigated. From 3 predetermined sites, 1 cm x 2 cm pieces of coverlet were removed and analyzed for bacterial contamination. RESULTS: Even prior to use, coverlet samplings provided identifiable contamination (3 out of 30 sites, 10%), but this could be within our study's sampling error. Nevertheless, following clinical use the frequency of contamination was considerably increased; 17 out of 57 sampled sites (31.5%) elicited contamination (P < 0.05, Fisher's exact test). CONCLUSION: This study demonstrates that the use of the coverlets, intra- or postoperatively, can lead to significant bacterial contamination. It is concluded that it is not advisable to reuse coverlets for multiple clinical applications.

Bedding and Linens↗

Detecting failed WBC-reduction processes: computer simulations of intermittent and continuous process failure.

BACKGROUND: By regulation, ongoing process control of WBC-reduced processes is performed on 1 percent of WBC-reduced components, typically four to five samples per month. However, prospective study of the power of this small sample has been difficult. Using computer-generated "residual WBC" distributions, sample size sensitivity to continuous or intermittent WBC-reduction failure was examined. STUDY DESIGN AND METHODS: Populations of log-normally distributed values (mean +/- SD, 4.5+/-0.5; n = 10(5)) were generated. Continuous failure (log-normality maintained) was simulated by incrementally increasing the population mean or its SD. Intermittent failure (bimodal distributions with discrete subpopulations of WBCs > the FDA cutoff) was simulated by admixing increasing percentages of secondary outlier populations. Sample sizes of 4 to 60 were examined (500 repetitions each) for their power to detect drift or failure by standard control criteria. RESULTS: Normally distributed low variance failure was easily detected by comparison of the mean of four samples to an upper control limit (95% confidence of detecting 2% failure). However, 40 samples were required to detect > 5 percent intermittent (bimodal) failure or high variance failure with 90-percent confidence, and only if individual WBC values were compared to cutoff. CONCLUSION: Sampling error limits the detection of high variance or bimodal distributions. While the mean of a small sample is highly sensitive to shifts in a low-variance normal distribution, the detection of a high-variance bimodal population requires a large number of individual values compared to cutoff. Therefore, the number of samples required for confident failure detection depends on both the nature of the underlying distribution and the interpretive criteria. Further research is necessary to determine the true distributions of WBC-reduction process failure, as well as clinically relevant quality limits.

Blood Component Removal↗

Estimation of metabolic rate constants in PBPK-models from liver slice experiments: what are the experimental needs?

A mechanistic model is presented describing the clearance of a compound in a precision-cut liver slice that is incubated in a culture medium. The problem of estimating metabolic rate constants in PBPK models from liver slice experiments is discussed using identifiability analysis. From the identifiability problem analysis, it appears that in addition to the clearance, the compound's free fraction in the slice and the diffusion rate of the exchange of the compound between culture medium and liver slice should be identified. In addition, knowledge of the culture medium volume, the slice volume, the compound's free fraction, and octanol-water-based partition between medium and slice is presupposed. The formal solution for identification is discussed from the perspective of experimental practice. A formally necessary condition for identification is the sampling of parent compound in liver slice or culture medium. However, due to experimental limitations and errors, sampling the parent compound in the slice together with additional sampling of metabolite pooled from the medium and the slice is required for identification in practice. Moreover, it appears that identification results are unreliable when the value of the intrinsic clearance exceeds the value of the diffusion coefficient, a condition to be verified a posteriori.

Animals↗

A comparison of exact, mid-P, and score tests for matched case-control studies.

A recently developed algorithm for generating the distribution of sufficient statistics for conditional logistic models can be put to a twofold use. First, it provides an avenue for performing inference for matched case-control studies that does not rely on the assumption of a large sample size. Second, joint distributions generated by this algorithm can be used to make comparisons of various inferential procedures that are free from Monte Carlo sampling errors. In this paper, these two features of the algorithm are utilized to compare small-sample properties of the exact, mid-P value, and score tests for a conditional logistic model with two unmatched binary covariates. Both uniparametric and multiparametric tests, performed at a nominal significance level of .05, were studied. It was found that the actual significance levels of the mid-P test tend to be closer to the nominal level when compared with those of the other two tests.

Algorithms↗

Therapeutic monitoring of cyclosporine following pediatric bone marrow transplantation: problems with sampling from silicone central venous lines.

Blood concentrations are commonly used to guide dosing requirements of cyclosporine, due to large variations in pharmacokinetics both between and within individuals. Bone marrow transplant patients at The Hospital for Sick Children are prescribed intravenous cyclosporine as part of the posttransplant immunosuppression protocol. Sampling for blood concentration measurement is generally done via a single-lumen central venous line (CVL). Cyclosporine concentrations sampled by this route were compared with concentrations in peripheral capillary samples taken concurrently. Results from the CVL blood were substantially higher despite appropriate flushing of the CVL between the end of the infusion and the time of sample collection. This discrepancy disappeared once the patient was converted to oral cyclosporine. We conclude that the sampling error is due to drug adsorbed to the silicone CVL catheters during intravenous administration and displaced during blood sample collection.

Blood Specimen Collection↗

Brush cytology from the uterine cervix.

Invasive carcinoma of the uterine cervix is a common neoplasm even in countries with extensive screening programmes of several years. The incidence rate per 100,000 is still around 18 in Denmark. The reasons for these persistently high rates of incidence despite various prophylactic measures are many and have been thoroughly discussed over recent years. It is imperative, however, to avoid sampling errors in screening procedures for precancerous lesions, especially erroneous interpretations arising from insufficient cytological material. To improve cytological sampling from the uterine cervix we decided to compare a recently introduced brush technique with the routine procedure in our hospital.

Adult↗

Pathologists' attitudes to implementing telepathology.

If pathologists will benefit so much from using telepathology, why is it taking so long to be introduced? This question has been discussed between experts, but the potential users are rarely asked for their opinions. A questionnaire was sent to the 256 members of the Austrian Society of Pathology; this addressed general aspects of telemedicine, telepathology in frozen-section services and expert consultation, videoconferencing technologies, teleteaching and teletraining. The response rate was 46%. In general, the pathologists thought that telemedicine could become valuable in their daily routine. However, pathologists were most afraid of sampling errors in remote diagnosis and would not readily accept an alternative to the conventional method of looking at a sample. This is only possible using realtime, remotely controlled microscopes. Telepathology systems providing only still images would not be acceptable to most respondents. There was interest in the use of videoconferencing for clinicopathological conferences. Teleteaching and teletraining were seen as welcome additional techniques, but were nevertheless judged unable to replace classical methods of teaching and training.

Attitude of Health Personnel↗

Language differences and the family planning survey.

Language is an important but often neglected source of non-sampling error in family planning surveys. This paper examines the problems of language usage and of translation, in KAP surveys in particular, using examples from African and other research experience. The authors emphasize that language pervades all stages of family planning surveys, pointing out that interpretations of survey results should take into account the possibility of the influence of language differences. Various measures are suggested that can contribute to minimizing this source of response error.

Africa↗

Limitations of child injury data from the CPSC's National Electronic Injury Surveillance System: the case of baby walker related data.

OBJECTIVES: The US Consumer Product Safety Commission's National Electronic Injury Surveillance System (NEISS) is a primary source for children's consumer product injury surveillance data in the US. Differing interpretations of the emergency department based NEISS baby walker data by various parties prompted this detailed examination, reclassification, and analysis of the NEISS data to explain these discrepancies. METHODS: Case selection was performed by searching the NEISS 1982-91 database for the baby walker product code and various text strings for children less than 24 months old. False negative and false positive cases were identified and reclassified. Adjusted population rates were computed and the types and locations of hospitals contributing to the sample were examined. RESULTS: One per cent false positive and 4% false negative misclassification rates were observed. In 1991, two children's hospitals reported 14% of the baby walker related injuries, though these hospitals made up just 2% of the sample frame. Through random allocation, one state currently contains four acute care hospitals and the only two children's hospitals reporting to the NEISS system. These six hospitals contributed 18% of the walker cases whereas the state represents only 3% of the US infant population. CONCLUSIONS: Misclassification in NEISS baby walker reports is minimal, with false negatives outweighing false positives. For trend analysis of product related injuries at the frequency of occurrence observed for baby walkers, NEISS suffers from low sensitivity due to sampling error. For children's injuries, NEISS' estimates have been affected by children's hospitals coming in and out of the sample and currently reflects a random geographic imbalance because one state contributes both of the reporting children's hospitals. To overcome these problems improved multiple product coding, a unique baby walker code, and stratification of children's hospitals in an enlarged NEISS sample is recommended.

Accident Prevention↗

Precision and accuracy of foundry dust exposure estimates from air sampling data.

Errors in the sampling methods and in the determination of respirable size quartz in foundry dust have been evaluated and discussed. In general, the total precision of dust sampling and analysis was better than 20%. The term "exposure dose" is introduced and defined. The temporal variation associated with measuring exposure dose is assessed with reference to the use of a log-normal distribution of air sampling results. The logarithmic standard deviations of dust concentrations at fixed sites and jobs are calculated.

Air Pollutants↗