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PubMed2002

Teledermatology and teledermatopathology.

Teledermatology is in essence an application of clinical telemedicine that deals with the practice of dermatology via the latest communication and information technology. As with other telemedicine applications, the goal is to provide the highest quality of dermatologic care more efficiently by moving patient information rather than the patient. Teledermatopathology, on the other hand, is a nonclinical telemedicine application specifically relating to diagnosis of cutaneous histologic specimens. There are numerous articles evaluating diagnostic concordance of teledermatology. However, because of a lack of a "true" gold standard, most published studies have compared diagnostic capabilities of teledermatology to our traditional face-to-face evaluations. Although the diagnostic correlation varies from study to study, most experts agree that Store and Forward and real-time video teleconferencing teledermatology is as clinically effective as a face-to-face consultation, which is less than 100% accurate. Teledermatopathology is showing similar potential, but because of the limitations on sampling error and the high cost of the alternative, robotic remote telepathology units, its acceptance into our daily practice has been delayed. This article focuses mainly on Store and Forward Teledermatology given its significant advantage and reviews the literature on teledermatology and teledermatopathology's diagnostic concordance and acceptance.

Attitude of Health Personnel↗
PubMed2006

[Diagnosis of myocarditis: description and assessment of available methods].

Myocarditis is a common disease in all age groups. Correct diagnosis of myocarditis is difficult, but of clinical and scientific importance. It is the aim of this review to describe and evaluate diagnostic possibilities. It is not possible to make a definitive diagnosis of myocarditis by electrocardiography, laboratory tests or echocardiography. Nor can techniques of nuclear medicine or coronary angiography provide an unequivocal diagnosis of myocarditis. Myocarditis can be diagnosed with certainty only by endomyocardial biopsy, which must be examined by histological, immunohistological and molecular techniques to obtain maximal sensitivity. But optimal diagnosis of a biopsy is subject to the problem of sampling error. Furthermore, myocardial biopsy is in practice used only rarely, despite a low complication rate. Thus the diagnosis of myocarditis is often based merely on suspicion. The limitations of standard methods employed so far have made cardiac magnetic resonance imaging (CMR) a valuable new additional test when there is the clinical suspicion of myocarditis. A myocardial biopsy will often reveal myocarditis in patients with cardiac symptoms and CMRI findings typical of myocarditis, especially if the biopsy was obtained near the area of contrast enhancement in the CMRI. CMRI can also be used for noninvasive and low-risk follow-up of functional parameters and tissue damage.

Biopsy↗
PubMed2005

Weak intermolecular interactions calculated with diffusion Monte Carlo.

The performance of fixed node diffusion Monte Carlo (FNDMC) for weakly interacting molecules is investigated. The effect of Gaussian basis sets on the asymptotic description of the molecular orbitals which is crucial for a successful importance sampling is analyzed for the example of the hydrogen atom. We find that accurate reference binding energies of the water, the ammonia, and the T-shaped as well as the parallel-displaced benzene dimer are correctly reproduced by FNDMC. The binding energies for the benzene dimers are -3.00(0.38) and -3.58(0.38) kcal/mol, respectively. The description of the methane dimer which has the smallest binding energy and a quite large intermolecular distance requires a more flexible basis set of diffuse quadruple-zeta quality in order to prevent sampling errors.

Journal Article↗
PubMed2003

Adequacy of mucosal sampling with the "two-bite" forceps technique: a prospective, randomized, blinded study.

BACKGROUND: Although the "two-bite" technique (obtaining 2 mucosal biopsy specimens with a single passage of the forceps) is used routinely, the adequacy of the second biopsy for histopathologic examination has not been evaluated. Our hypothesis was that the second sample will be inadequate for this purpose. The aim of this study was to prospectively assess the adequacy of mucosal biopsy specimens obtained with 3 different types of forceps with the two-bite technique. METHODS: Patients undergoing diagnostic EGD were prospectively enrolled in the study. In each patient, mucosal biopsy specimens were obtained as follows: 4 specimens with the two-bite technique in 2 separate passages of the forceps (one from the esophagus followed by one from the stomach, and one from the stomach followed by one from the esophagus, the order being chosen randomly) and 2 single-bite specimens from the same anatomic locations (esophagus and stomach). Each patient underwent the same biopsy sampling sequence with 3 different forceps. An experienced pathologist blinded to the sequence and technique of obtaining the samples and the forceps used evaluated the specimens for number submitted, integrity, and adequacy for histopathologic diagnosis and depth of the sample as assessed by the presence or absence of muscularis mucosae. RESULTS: A total of 288 mucosal samples were obtained from 16 patients. Of these, 192 were taken by using the two-bite technique. Thirty-five (18.2%) samples were missing when the two-bite technique was used compared with only 2 (2.1%) when the single bite technique was used (p < 0.05). Irrespective of the location from which the first mucosal sample was taken, a significantly greater number of first samples were lost (25%) compared with second samples (11.5%) (p < 0.05). The forceps without a spike was associated with significantly more missing samples than the spiked forceps (28.1% vs. 13.3%; p = 0.01). At histopathologic evaluation, there were no significant differences between first and second samples nor differences between samples taken with the two-bite and the single-bite techniques with regard to adequacy, integrity, and depth. With respect to histopathologic evaluation, there were no differences among the 3 types of forceps used in the study. CONCLUSIONS: Although the second mucosal sample obtained with the two-bite technique is adequate for histopathologic purposes, there is a significant risk of losing samples (the first one in particular) with this technique, and thus an increase in the probability of sampling error. This may be particularly true for forceps without a spike.

Adult↗
PubMed2006

In situ labeling of immune cells with iron oxide particles: an approach to detect organ rejection by cellular MRI.

In vivo cell tracking by MRI can provide means to observe biological processes and monitor cell therapy directly. Immune cells, e.g., macrophages, play crucial roles in many pathophysiological processes, including organ rejection, inflammation, autoimmune diseases, cancer, atherosclerotic plaque formation, numerous neurological disorders, etc. The current gold standard for diagnosing and staging rejection after organ transplantation is biopsy, which is not only invasive, but also prone to sampling errors. Here, we report a noninvasive approach using MRI to detect graft rejection after solid organ transplantation. In addition, we present the feasibility of imaging individual macrophages in vivo by MRI in a rodent heterotopic working-heart transplantation model using a more sensitive contrast agent, the micrometer-sized paramagnetic iron oxide particle, as a methodology to detect acute cardiac rejection.

Animals↗
PubMed1990

Genetic variation in clonal vertebrates detected by simple-sequence DNA fingerprinting.

The measurement of clonal heterogeneity is central to understanding the evolutionary and population genetics of the roughly 50 species of vertebrates that lack effective genetic recombination. Simple-sequence DNA fingerprinting with oligonucleotide probes (CAC)5 and (GACA)4 is a sensitive and efficient means of detecting this heterogeneity in natural populations of two clonal fishes, Poecilia formosa, an apomictic unisexual, and Rivulus marmoratus, a selfing hermaphrodite. The fingerprints are clonally stable for at least three generations. The technique clearly differentiates allozymically identical laboratory lines of R. marmoratus that were previously distinguishable only by histocompatibility analysis. The technique also reveals apparent cases of shifts in clonal composition of a natural population of each species. Clonal variation in most natural populations is quite high. For example, a sample of 19 specimens of P. formosa from one station on the Rio Soto la Marina contained 16 clones (average clonal frequency = 0.07). This level of clonal diversity implies that mutation, subsequent to the founding of clonal lineages, is an important source of variation in these populations. It also suggests that chance (sampling error) has a previously unappreciated role in determining the clonal composition of populations even though some of the clones may be divergent in biologically significant features.

Animals↗
PubMed1999

Merkel cell tumour: case reports and review.

Merkel cell carcinoma, a small-cell undifferentiated/neuroendocrine carcinoma, is a highly invasive primary malignant neoplasm of the skin that may arise from Merkel cells or an epithelial precursor cell. One tenth of all cases affect the eyelids and periocular region, typically in the elderly population. The presentation is generally as a painless erythematous nodule with telangiectatic blood vessels and often intact overlying skin. The rarity of Merkel cell carcinoma of the eyelid can lead to delay in diagnosis and treatment of this tumour. In the present paper, the authors illustrate the aggressive nature of Merkel cell carcinoma, and the importance of early and wide surgical treatment and close follow-up. They discuss the role of rapid paraffin histology compared to frozen section. METHODS: Three cases are described, discussing the clinical presentation, diagnosis and treatment, with a review of the pathology. RESULTS: All three patients were female, presenting with rapidly growing upper eyelid tumours 20 mm in size; one case had paraffin sections suggesting incomplete clearance when frozen section had appeared clear; exenteration was required. The other two cases had lymph node involvement at one and two months post wide local excision. All patients remain alive at follow-up of 6, 4.6, and 2 years, respectively. DISCUSSION: The cases illustrate the aggressive nature of the tumour, the unusual tarsal involvement and the typical pathology. Sampling errors associated with limited frozen section control of excision may be avoidable by the use of rapid paraffin histology. The highly invasive nature of this tumour requires close follow-up following resection.

Journal Article↗
PubMed2001

Can phyllodes tumours of the breast be distinguished from fibroadenomas using fine needle aspiration cytology?

In an attempt to determine whether it is possible to distinguish phyllodes tumours (PTs) of the breast from fibroadenomas (FAs) using fine needle aspiration cytology (FNAC), we reviewed the cytological slides of eight histopathologically confirmed PTs (six benign and two malignant) and compared them with cytological features of 13 histopathologically confirmed FAs. Each author independently, "blindly" assessed architectural and cytological features of the stromal (six features) and epithelial (seven features) components and the cytological background (three features) and gave a favoured diagnosis for each case. Four of six benign PTs, one of two malignant PTs and 11 of 13 FAs were correctly diagnosed cytopathologically by at least three of the authors. The presence of hypercellular stromal fragments was the most useful feature in distinguishing PTs from FAs, and the presence of cytological atypia of the stromal cells was the most important feature in distinguishing malignant from benign PTs. Sampling error was the most common reason for cytological misdiagnosis of PTs. The two FAs misdiagnosed as PTs were each of cellular type. The results of this study suggest that it is possible to distinguish PTs from FAs using FNAC in most cases. We recommend that if hypercellular stromal fragments are identified in a FNAC specimen of a fibroepithelial lesion, the cytopathologist should raise the possibility of a PT and the surgeon treat the patient accordingly.

Biopsy, Needle↗
PubMed1994

Southern blot analysis of lymphoproliferative disorders: use and limitations in routine surgical pathology.

Antigen receptor gene rearrangement studies are a sensitive means of determining lineage and clonality in lymphoproliferative disorders (LPDs) which remain difficult to classify after assessment of morphology and immunohistochemistry (IHC). This study investigates the utility of genotyping LPDs in a surgical pathology laboratory servicing a large teaching hospital. Ninety-eight specimens with detailed frozen (FS) and/or paraffin section IHC were studied, including 65 B-cell lymphomas, 14 T-cell lymphomas, 2 biopsies of T-zone dysplasia, one unclassifiable lymphoma, 8 Hodgkin's disease (HD) and 8 reactive nodes. Southern blotting (SB) was performed on tumor and control DNA cleaved with restriction enzymes EcoR1, Hind III and BamH1, using radiolabelled probes for the immunoglobulin heavy chain joining region, constant regions of kappa and lambda light chains, and the constant region of the T-cell receptor beta chain. All reactive nodes and those harbouring HD and DNA in the germline configuration, apart from JH rearrangement in one case each of HD and florid reactive hyperplasia. Of the non-Hodgkin's lymphomas (NHL), 17% did not reveal clonal rearrangements (11% B-NHL; 44% T-NHL). Most of the negative results could be explained by sampling error in partially involved nodes, highly polymorphous infiltrates where the neoplastic population may have been below the 1% threshold detectable by SB, and instances of anaplastic large cell lymphoma. After accounting for these cases, a 5% negative rate of genoclonality remained (3% B-NHL; 13% T-NHL). In the majority of NHL (95%), the diagnosis could be established on the basis of morphology and/or IHC alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Southern↗
PubMed1991

The effects of census undercount adjustment on congressional apportionment.

"This article shows that undercount adjustment [of the 1990 U.S. census] will probably reallocate one [in] three House seats across the states. The adjustment's impact may depend on the method used and the assumptions underlying undercount estimates. Using regression analysis to reduce sampling error in undercount estimates from dual-systems analysis, however, eliminates sensitivity to all but the most extreme changes in assumptions. Generally, adjustment will more likely affect large states than small ones, and large states with proportionately many urban Black and Hispanic residents will likely gain seats at the expense of large states with few such residents."

Americas↗
PubMed1998

Phylogenetic congruence and discordance among one morphological and three molecular data sets from Pontederiaceae.

A morphological data set and three sources of data from the chloroplast genome (two genes and a restriction site survey) were used to reconstruct the phylogenetic history of the pickerelweed family Pontederiaceae. The chloroplast data converged towards a single tree, presumably the true chloroplast phylogeny of the family. Unrooted trees estimated from each of the three chloroplast data sets were identical or extremely similar in shape to each other and mostly robustly supported. There was no evidence of significant heterogeneity among the data sets, and the few topological differences seen among unrooted trees from each chloroplast data set are probably artifacts of sampling error on short branches. Despite well-documented differences in rates of evolution for different characters in individual data sets, equally weighted parsimony permits accurate reconstructions of chloroplast relationships in Pontederiaceae. A separate morphology-based data set yielded trees that were very different from the chloroplast trees. Although there was substantial support from the morphological evidence for several major clades supported by chloroplast trees, most of the conflicting phylogenetic structure on the morphology trees was not robust. Nonetheless, several statistical tests of incongruence indicate significant heterogeneity between molecules and morphology. The source of this apparent incongruence appears to be a low ratio of phylogenetic signal to noise in the morphological data.

Base Sequence↗
PubMed1998

Theoretical evaluation of measurements used to assess the growth of colorectal hepatic metastases.

The measurement of the growth of colorectal hepatic metastases growth provides useful information for the management of patients, and can be used both as a prognostic variable and as an objective assessment of treatment efficacy. A number of techniques have been used to quantify such growth, including measuring the change of an anatomical measure such as tumour size or the percentage hepatic replacement. Cell kinetic studies and analysis of the changes in serum tumour markers such as carcinoembryonic antigen (CEA) are other methods. Anatomical measures are unlikely to be reliable because within the liver a metastasis may change in volume as a consequence of non-neoplastic factors outside the liver. It may also be incorrect to assume that the changes observed in an abnormality identified by radiological methods are the direct result of a change in the neoplastic burden. Measurements of cell kinetics and serum tumour markers are complicated by neoplastic cell heterogeneity across the tumour and are subject to sampling errors. All techniques presently available therefore can be considered to be indirect measures and may not be truly representative of tumour growth. These limitations of growth measurements have to be recognised when applied to the assessment of tumour response.

Biomarkers, Tumor↗
PubMed1998

Field performance measurements of half-facepiece respirators: developing probability estimates to evaluate the adequacy of an APF of 10.

To evaluate the protection provided by negative-pressure, half-facepiece respirators, ambient and in-facepiece samples were collected on workers in foundry, aircraft-painting, and steel-manufacturing operations. Protection was assessed by workplace protection factors (WPF). The appropriateness of the assigned protection factor (APF) for half-facepiece respirators was evaluated with a new approach using the WPF data from these and other studies previously published. The new approach utilizes binomial statistics based on the number of successes (no overexposure) and failures (overexposure) and is illustrated with a graphical representation of WPF data. With this consideration of the data, the probability of overexposure occurring during a wearing period for workers wearing the half-facepiece respirators represented by the studies referenced here was 0.5%, with a 95% confidence interval of 0.01 to 2.7%. If 50% in-facepiece sampling errors are considered, the probability of overexposure was 2.9%, with a 95% confidence interval of 1.1 to 6.3%. The authors believe the current APF of 10 for half-facepiece respirators is appropriate.

Air Pollutants, Occupational↗
PubMed1973

Qualitative and quantitative morphological changes in subcellular fractions from mouse cerebral cortex during postnatal development.

Discontinuous Ficoll-sucrose gradients were used to prepare subcellular fractions from mouse cerebral cortex at various stages of postnatal development. Representative samples of each subcellular fraction were obtained by sedimentation in an analytical ultracentrifuge and each fraction was examined quantitatively and qualitatively by electron microscopy. The amount of synaptosomal material was determined for each fraction on the basis of volume percentage, obtained from a series of contiguous micrographs, to circumvent any sampling error. This allowed an accurate appraisal of synaptosomal distribution during neural development and a direct comparison of the Ficoll-sucrose gradient fractions to the original crude mitochondrial preparations. The distribution of synaptosomal material was shown to be quantitatively altered during neural development, and maturation-dependent changes, at a qualitative level, were described. In addition, the relationship between neural maturation and the relative proportion and distribution of subcellular particles which contain processes tentatively identified as growth cones were characterized.

Animals↗
PubMed2006

View-independent reconstruction algorithms for cone beam CT with general saddle trajectory.

In Yang et al (2006 Phys. Med. Biol. 51 1157-72), an exact filtered backprojection (FBP) reconstruction algorithm was proposed for cone beam tomography with saddle trajectory based on the seminal works of Pack and Noo (2005a Inverse Problems 21 1105-20; 2005b 8th Int. Meeting on Fully 3D Reconstruction in Radiology and Nuclear Medicine (Salt Lake City) ed F Noo, H Kudo and L G Zeng pp 287-90). However, the artefacts due to discretization and/or sampling errors in the reconstructed images by this method were still visible, especially when the pitch is large. In this paper, two view-independent (VI) algorithms, which are similar to the FDK-type algorithms (Feldkamp et al 1984 J. Opt. Soc. Am. A 1 612-19), are proposed for planar detector geometry. The first VI algorithm involves two filtered projections and a small additional term (two-dimensional (2D) Radon transform term). One of the filtered projections is obtained by ramp filtering (as in the FDK algorithm for circular trajectory) and the other one is obtained by Hilbert transform. The 2D Radon transform term is just like the term which was first derived by Hu (1996 Scanning 18 572-81) for a circular trajectory. The second VI algorithm involves only one filtered projection term, which is obtained by differentiation followed by Hilbert transform and the 2D Radon transform term. Both algorithms involve only one backprojection step with a weighting factor as in the FDK algorithm. The simulation studies show that the pixel values of the reconstructed images by the VI algorithms are more accurate than those by the original view differencing (VD) algorithm, the streak artefacts are also reduced, and their computational times are comparable to that of the original VD algorithm. We also generalize the concept of saddle trajectory and the corresponding reconstruction algorithm. The generalized algorithm is also theoretically exact, has a shift-invariant FBP structure, and does not depend on the concept of pi-line.

Algorithms↗
PubMed1999

Reliability of fine-needle aspiration in patients with familial nonmedullary thyroid cancer.

In this case-control study we describe how often thyroid cancers and occult cancers are diagnosed or not diagnosed by fine-needle aspiration (FNA) in patients with thyroid nodules and a family history of nonmedullary thyroid cancers (FNMTC). Our hypothesis is that patients with thyroid nodules and a family history of FNMTC seem to be similar to patients with thyroid nodules and a history of exposure to low-dose therapeutic radiation. Both have been reported to have multifocal thyroid neoplasms and malignant tumors are common. Cytological examination may therefore be less accurate. From 1979 to 1996, 27 patients from 24 families with FNMTC were examined histologically after a preoperative cytological examination in all of them. A positive cytology examination was defined when biopsy documented thyroid cancer. It was interpreted as a false-negative study when a benign diagnosis was made and thyroid cancer was present anywhere within the thyroid, including in areas sampled or not sampled by FNA and not palpable preoperatively. A randomized control group, matched for age and gender, contained 27 patients with papillary thyroid cancer without familial disease. In our study group, 25 patients were treated with total thyroidectomy, including 7 with neck dissection, and 2 by thyroid lobectomy. At final histological examination 17 of 27 patients (63%) in this study group had multiple nodules and 25 of 27 (92.6%) had thyroid cancer. Thyroid cancer was diagnosed by FNA in 22 of 25 patients (88%), with 3 (12%) false-negative biopsies due to sampling errors (thyroid cancer not in the index nodule), versus 1 (3.7%) false-negative biopsy in the control group. Two patients in the study group with benign nodules were accurately diagnosed. In patients with false-negative biopsies and a history of FNMTC, the cancer was situated in one or more small nodules. Only one cancer was occult (< 1.0 cm). One-third of the patients in our study group (33%) had a history of radiation; 44% of the irradiated group had a single nodule; 56% had multiple nodules. In the control group, 9 of 27 patients (33%) also had a history of radiation; 33% of the irradiated group had a single nodule, 67% had multiple nodules. In conclusion, the reliability of FNA in patients with FNMTC appears to be less accurate than it is for other patients because of the high incidence of multifocal thyroid cancer and coexistence of benign nodules. Patients with thyroid nodules and a family history of thyroid cancer are more likely to have thyroid cancer and because they also have more coexistent benign nodules, they must be followed closely or treated with total or near-total thyroidectomy.

Biopsy, Needle↗
PubMed1994

Evaluation of a new slide-based laser scanning cytometer for DNA analysis of tumors. Comparison with flow cytometry and image analysis.

DNA measurements generated by a new automated slide-based cytometer, the laser scanning cytometer (LSC), were compared with those produced by commercial flow cytometry (FCM) and image analysis (IA) devices. Laser scanning-cytometric analysis was performed by scanning alcohol-fixed, propidium iodide-stained tumor imprints with a 5-microns spot laser beam. Fifty-three malignant tumors (51 breast carcinomas and 2 lung carcinomas) were studied. Ploidy concordance rates for FCM versus LSC, IA versus LSC, and FCM versus IA were 96%, 91%, and 91%, respectively. Statistically significant agreement between methods was determined by linear regression analysis of DNA indices. Synthesis-phase fractions generated by FCM and LSC also were comparable, as demonstrated by linear regression (r = .83). Mean coefficients of variation for the LSC compared favorably with those for FCM and IA. The few discrepancies in ploidy status between methods could be explained by sampling error, the presence of possible near-diploid aneuploid populations that could not be effectively resolved by one or another modality, and the visual selection bias with IA when small aneuploid cell populations were present. The LSC shares many useful features with FCM, including automation, accuracy of quantitation, rapidity, and generation of reliable information regarding cell proliferation (synthesis-phase fraction). In addition, it has some of the advantages of IA, such as minimal tissue requirement, no need for special preparation, and the potential for visual selection of the cells measured. The LSC holds great promise for use in the clinical laboratory because of these combined characteristics.

Breast Neoplasms↗
PubMed1995

Cytologic/histologic correlation for quality control in cervicovaginal cytology. Experience with 1,582 paired cases.

For quality-control purposes, federal regulations require cytology laboratories to compare Papanicolaou smear and cervical biopsy reports, if available, and determine the cause of any discrepancies. The authors reviewed 56,497 cervicovaginal smears, of which 1,582 (2.8%) had a subsequent cervical biopsy or endocervical curettage within 2 months. A total of 175 discrepancies (11%) were identifed, and biopsies and smears from these cases were reviewed at a weekly conference. In the majority of cases, the diagnosis of the smear and biopsy was confirmed on review, and the discrepancy was attributed to sampling error (n = 159; 91%). Six cases (3.4% of all discrepant cases) were errors in cytologic diagnosis. Five of these were interpretation errors, and one case was a screening error. There were 10 errors in the evaluation of cervical biopsies (5.7% of all discrepant cases): five biopsies were undercalled, and five were overdiagnosed as a squamous intraepithelial lesion. The results of testing for human papillomavirus DNA by in situ hybridization were helpful in arbitrating some diagnositic disagreements.

Biopsy↗