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Applications of exfoliative cytology in the diagnosis of oral cancer.

Exfoliative cytology is a simple non-aggressive technique that is well accepted by the patient, and that is therefore an attractive option for the early diagnosis of oral cancer, including epithelial atypias and especially squamous cell carcinoma. However, traditional exfoliative cytology methods show low sensitivity (i.e. a high proportion of false negatives) in the diagnosis of these pathologies. This low sensitivity is attributable to various factors, including inadequate sampling, procedural errors, and the need for subjective interpretation of the findings. More recently, the continuing development of automated cytomorphometric methods, DNA content determination, tumour marker detection, and diverse molecular-level analyses has contributed to renewed interest in exfoliative cytology procedures for the diagnosis of oral cancer. The present study briefly reviews developments in these areas.

Cytological Techniques↗
PubMed2005

Unexpected estimates of variance components with a true model containing genetic competition effects.

Simulation of a model containing genetic competition effects was initiated to determine how well REML could untangle variances due to direct and competition genetic effects and pen effects. A two-generation data set was generated with six unrelated males that were each mated to five unrelated females to produce 300 progeny, from which 30 females (one per mating in previous generation) were mated to six unrelated males to produce 300 more progeny. Progeny were randomly assigned, six per pen, to 50 pens per generation. Parameters were V(g), V(c), C(gc), V(p), and V(e), representing direct and competition genetic variance with covariance, and pen and residual variance. Eight statistical models were used to analyze each of 400 replicates of 16 sets of parameters. Both V(g) and V(e) were fixed at 16.0. Values of C(gc) were -2.0, -1.0, 0.1, 1.0, and 2.0. Values of V(c) were 1.0 and 4.0, and values of V(p) were 0.1, 1.0, and 10.0. With the full model, average estimates resembled true parameters, except that V(p) was consistently overestimated when small (0.1 and 1.0), which in turn slightly changed other estimates. The most unexpected result was overestimation of V(p) when V(c) and Cgc were ignored. Overestimation depended on V(c) and the number of competitors in common between records in a pen. Upward bias was somewhat greater when Cg(c) was positive than when it was negative. For example, with C(gc) = 2, V(c) = 4, and V(p) = 0.1, the mean estimate of V(p) was 20.4 when C(gc) and V(c) were dropped from the model and 15.3 when C(gc) = -2.0. When V(p) was ignored, estimates of both C(gc) and V(c) increased in proportion with V(p). Also V(g) increased more with greater V(p). Another unexpected result occurred when pen was considered fixed. Empirical sampling standard errors of estimates of C(gc) and V(c) were decreased generally by factors of 2 to 30. Based on these results, we conclude a high estimate of pen variance may indicate genetic competition effects are important, and ignoring either the pen or competition effects will bias estimates of other components.

Algorithms↗
PubMed1987

Responses to a dry eye questionnaire from a normal population.

A dry eye questionnaire was completed by 500 patients who presented for the correction of refractive error. A sample of non-contact lens wearers was extracted (N = 177) and responses were compared between males and females, and between three subgroups according to age. Females responded at a significantly higher rate in regard to 4 of 24 questionnaire segments. Differences according to age were found for 5 of 24 questionnaire segments. Except for the question concerning arthritis, increased prevalence of dry eye findings in over-45-year-old females was not found in this normal population. These results, combined with those reported previously, validate the use of the questionnaire as a screening instrument that will enable ocular sicca cases to be identified.

Adult↗
PubMed1985

Six methods for isolating high-density lipoprotein compared, with use of the reference method for quantifying cholesterol in serum.

Using 90 serum specimens, we compared six routine procedures for high-density lipoprotein (HDL) isolation to determine the biases, if any, of each. Use of the Reference Method for cholesterol (Duncan et al., Centers for Disease Control, Atlanta, GA) and automated dispensing equipment helped ensure the accuracy of the cholesterol measurements and minimized errors from sample and reagent manipulations. Regression analysis of the results showed significant differences between most HDL isolation methods, except for those involving precipitation with heparin-MnCl2 (1.0 mol/L) or polyethylene glycol 6000, which yielded comparable results with a slope close to one and a zero intercept. The dextran sulfate (Mr 500 000)-MgCl2 method had the largest proportional and constant bias with respect to those two methods. All the methods produced comparable results in the clinically important low HDL-cholesterol range (250 to 350 mg/L), but biases were significant at high concentrations. We conclude that these increased biases in the upper ranges of HDL-cholesterol concentrations are the result of increased heterogeneity of HDL and the different mechanisms involved in forming the insoluble complexes between lipoproteins and the various precipitation reagents.

Analysis of Variance↗
PubMed1979

Sequential analysis of spontaneous abortion. II. Collaborative study data show that gravidity determines a very substantial rise in risk.

Evidence from more than 14,000 reproductive histories in the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke indicates that the risk of spontaneous abortion increases considerably with gravidity. Maternal age, memory errors, and sampling bias related to recurrence risk do not account for the trend. Clustering, or tendency for abortions to follow one another, occurs in histories which include live births.

Abortion, Spontaneous↗
PubMed1983

Computer analysis of changes in pulmonary resistance induced by nasal stimulation in man.

Changes in pulmonary resistance induced by various nasal stimuli were recorded in 16 subjects with nasal allergy and 16 laryngectomized subjects. To avoid human errors in sampling respiratory curves, computer analysis was performed breath by breath, automatically and continuously. In the subjects with nasal allergy the nasal mucosa was stimulated with pressure using a nasal balloon, and by a paper patch with 0.1 ml of 5% histamine hydrochloride. Laryngectomized subjects were stimulated with pressure and by pepper powder. Nasal pressure stimulation up to 50 cm H2O did not cause a statistically significant change in the pulmonary resistance of both groups of subjects. Pepper stimulation caused a statistically significant increase of the pulmonary resistance amounting to 40.4 +/- 28.2% of the prestimulatory level. Histamine stimulation caused a statistically significant change of the pulmonary resistance, but it was difficult to discern whether it caused an increase or a decrease of the resistance. Maximum efforts were used to control the respiratory pattern using the metronome and by visual monitoring of the peak flow rate on the cathode ray oscilloscope, but pepper and histamine stimulation caused a statistically significant increase, although slight, of tidal volume. The effect of slight changes of respiratory patterns induced by nasorespiratory reflex on the observed change of pulmonary resistance could not be ruled out in this human study.

Adult↗
PubMed1981

The frozen-section autopsy.

A protocol for the rapid completion of autopsies using frozen sections was studied. The protocol was tested on 50 autopsy subjects, and the results compared with those from the standard autopsy protocol used on the same 50 cases. Cost, speed with which the reports could be completed, teaching value, and accuracy were compared; autopsy completed by frozen sections was superior in all four areas. There were 47 errors, none of which involved major disease processes. All but nine were errors of sampling and could be remedied by the more liberal sampling of tissues and the occasional supplementation with paraffin sections. The frozen-section autopsy protocol can replace the standard autopsy protocol in most cases. The rapid completion of the autopsy invites participation of the clinician and stimulates cooperation that benefits both the clinician and the pathologist.

Autopsy↗
PubMed1981

Direct assessment of effective renal plasma flow from renoscintigraphy with a gamma camera and an on-line computer.

A concept of a kidney uptake coefficient (UC) of 131I-o-hippurate was developed by analogy from the corresponding kidney clearance of blood plasma in the early period after injection of the hippurate. The UC for each kidney was defined as the count-rate over its ROI at a time shorter than the peak in the renoscintigraphic curve divided by the integral of the count-rate curve over the "blood"-ROI. A procedure for normalization of both curves against each other was also developed. The total kidney clearance of the hippurate was determined from the function of plasma activity concentration vs. time after a single injection; the determinations were made at 5, 10, 15, 20, 30, 45, 60, 75 and 90 min after intravenous administration of 131I-o-hippurate and the best-fit curve was obtained by means of the least-square method. When the UC was related to the absolute value of the clearance a positive linear correlation was found (r = 0.922, p greater than 0.99). Using this regression equation the clearance could be estimated in reverse from the uptake coefficient calculated solely on the basis of the renoscintigraphic curves without blood sampling. The errors of the estimate are compatible with the requirement of a fast appraisal of renal function for purpose of clinical diagnosis.

Computers↗
PubMed1994

The pathophysiology and organ-specific consequences of severe transfusion reactions.

Transfusion of blood components is usually required in the management of critically ill patients. However, pathologic interactions between blood products and organ function may result from transfusion reactions. Emerging understanding of the mediation and interruption of clinical inflammatory responses is applicable to severe transfusion reactions. The pathophysiology of four types of severe transfusion reactions are reviewed: a) acute hemolysis; b) bacterial contamination of blood components; c) transfusion-related acute lung injury (TRALI); and d) anaphylaxis. Acute hemolytic reactions are often caused by preventable errors in sample or patient identification. Renal toxicity, coagulopathy, and hypotension may result from circulating red cell stroma and immune-complex activation of complement and cytokine secretion. Bacterial contamination of blood components has caused patient sepsis in many cases; platelets stored at 20 degrees to 24 degrees C are of particular concern. Careful blood collection and handling is essential for prevention. TRALI is manifested by acute respiratory distress, which is usually caused by infusion of plasma containing antibodies against the patient's leukocytes. Complement activation and cytokine stimulation cause edema and neutrophil accumulation in the lungs. Anaphylactic reactions may result from patient immunoglobulin (Ig)E antibodies against donor plasma constituents. IgA-deficient patients are at risk for anaphylactic reactions if these patients develop anti-IgA antibodies. Vasoactive or complement-activating factors in a blood product may also cause anaphylactoid reactions in some patients.

Acute Disease↗
PubMed1993

Molecular pathology of lung cancer and its clinical relevance.

Evidence indicates that several molecular genetic markers involved in the initiation and progression of lung cancer are useful in predicting prognosis in early stage lung cancer, thus allowing selection of subsets of patients for additional therapy and are likely to be useful in the diagnosis of malignancy in equivocal biopsies and cytology specimens. In the future, these markers may also prove to be useful in the early detection of lung cancer and in predicting response to specific therapies. Most of these markers can already be assessed by routine immunohistochemical techniques on paraffin-embedded tissue and development of antibodies to other markers is currently underway. The use of immunohistochemistry for evaluating these markers permits direct visualization of the tumor to avoid errors of sample size and contamination inherent in traditional molecular techniques and is a rapid, well-established technique familiar and available to surgical pathologists.

Adenocarcinoma↗
PubMed1994

Critical evaluation of endothelins assay.

Endothelin(s) is (are) generally measured by highly-sensitive RIA (radioimmunoassay) or sandwich-EIA (enzyme immunoassay) methods after preliminary extraction and chromatographic purification using Sep-Pak C18 cartridges; however, there is no general consensus about the range of endothelin circulating levels in healthy subjects and patients. We have evaluated the analytical performance of two commercial RIAs for plasma endothelin-1 assay (supplied by Peninsula Laboratories, Belmont, California, and by Biomedica Gruppe, Biomedica Gesellschaft mbH, Vienna, Austria) in order to verify whether differences in extraction procedures, antibody affinities or standard preparations can explain the different results obtained by these two RIAs. The RIA kits tested in the present study showed some differences in the analytical performance; in particular, different antibody specificities have been observed. The concentration range of endothelin(s) assayed with an imprecision better than 15%, which can be considered the working range, was wider for the Peninsula than for the Biomedica kit (i.e. from 1.6 to 50 fmol/tube vs 0.7 to 10 fmol/tube), whereas the two RIA kits showed similar sensitivity (i.e. about 0.2 fmol/tube). Taking into account the working range and sensitivity of the two RIAs to measure with an acceptable error the samples of normal subjects and the most part of patients, > or = 3-ml volumes of plasma must be extracted by Sep-Pak C18 cartridges and then measured by RIA. Owing to the central role played by the endothelin superfamily in several pathophysiological conditions, it is important to have a reliable assay for the measurement of these peptides in biological fluids and tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1996

Coupled error spending functions for parallel bivariate sequential tests.

Sequential procedures are developed to facilitate marginal monitoring of bivariate response vectors in clinical trials. The general approach is based on an extension of the error spending function methodology of Lan and DeMets (1983, Biometrika 70, 659-663) and is sufficiently flexible that one may elect to fix the experimental type I error rate (Cook, 1994, Controlled Clinical Trials 15(3), 187-200) or the marginal type I error rates. Sample size calculations are described to ensure power requirements are satisfied for marginal tests of significance. Reformulating the procedures in terms of repeated confidence intervals (Jennison and Turnbull, 1989, Journal of the Royal Statistical Society, Series B 51, 305-361) lends added flexibility to the monitoring process. The developments are discussed in the context of responses with a bivariate normal distribution. Data from an asthma intervention trial are used for illustrative purposes.

Asthma↗
PubMed1995

Methods used by the United States National Institute for Occupational Safety and Health to monitor crystalline silica.

The National Institute for Occupational Safety and Health (NIOSH) in the United States has four methods for monitoring the concentration of crystalline silica dust. They all employ a cyclone for size-selective sampling in the field, but differ primarily in that the laboratory measurement is based on either infrared spectroscopy, X-ray diffraction, or colorimetry. The limits of detection for these methods are similar, but their accuracy is poor, particularly at low filter loadings near the current recommended exposure limit (50 mu g center dot m-3). Advances in analytical instrumentation have improved measurement precision. Correction techniques to account for X-ray absorption in samples loaded with nonsilica dust have eliminated one source of bias. Direct analysis on collection filters is a convenient technique that should decrease sample manipulation errors, but it has not been shown to improve precision or accuracy significantly.

Crystallization↗
PubMed1977

[Critical observations on the rate of "False Negative" findings in gynecologic cytology (author's transl)].

In order to obtain a resonable approach to the rate of false negative findings in gynecologic cytology, all cases available to the authors for analysis with cervical carcinoma, carcinoma in situ and dysplasia during 1971 to 1973 were examined for any previous history of negative cytologic findings during the years preceding the detection of these pathologic conditions. It was found that negative results had been obtained in 11% of the patients suffering from cervical carcinoma, whereas the corresponding percentage figure was 18% negative results in carcinoma in situ patients. However, in about half of the cases, repetition of the smear had been recommended. Among the possible causes of false negative cytologic findings, the laboratory error (screening and evaluation) is the only one which can be accurately determined; in the present analysis, one-third of the false findings were found to be due to laboratory error. It is probable that the majority of the other false negative cytologic findings are mainly due to errors in sampling. As a matter of fact, rapidly growing carcinomas and carcinomas in situ are probably rare.

Carcinoma in Situ↗
PubMed1976

NMR study of relative oxygen binding to the alpha and beta subunits of human adult hemoglobin.

NMR spectra of the downfield region of normal adult hemoglobin are reported as a function of oxygenation and temperature. Spectra were run in D2O at pD 7.4. A specially made NMR tube insert allowed precise measurement of the degree of oxygenation and of methemoglobin formation before and after taking the NMR spectrum. Plots of the estimated intensity of the most downfield prominent NMR peak, identified as arising from a deoxy-beta subunit by Davis et al. ((1971) J. Mol. Biol. 60, 101-111), versus the average degree of oxygenation y, measured optically, yield a nearly straight line within experimental error, for samples stripped of organic phosphates and for samples containing 2,3-diphosphoglycerate or inositol hexaphosphate. Intensities of peaks further upfield than this peak, previously attributed to deoxy-alpha subunits, are difficult to measure directly especially for samples containing inositol hexaphosphate. The latter samples show broadening in these alpha peaks as the degree of oxygenation increases. This extra broadening appears to increase with temperature. Linearity of the beta peak intensity with oxygenation is expected if there is no large oxygen affinity difference between alpha and beta subunits. However, the cooperativity of binding, and inaccuracy of the data, make it impossible to make accurate estimates of affinity differences.

Adult↗