[Reproducibility of cytologic diagnosis: study of CRISAP Ile-de-France]. / Reproductibilité du diagnostic cytologique: étude du CRISAP Ile-de-France.

The cervical Pap smear is the method of choice for early detection of precancerous cervical lesions. However, the sensitivity of the Pap smear is not perfect, nor is the specificity, in particular for minor atypia; quality control is the best method to improve the efficiency of the test. The "Centre de regroupement informatique et statistique des données en anatomie pathologique" (CRISAP) Ile-de-France has initiated an external quality control with a protocol aimed at assessing diagnosis reproducibility among observers. Thirteen pathologists agreed to participate on a voluntary basis fur this protocol, which consisted of the rereading of 650 slides chosen at random. Each participant reread 50 cases and sent 50 cases to be reread anonymously. The diagnosis was given according to the Bethesda classification. The reproducibility was assessed using the percentage of agreement and kappa statistics. The percentage of agreement for the whole group was 65% and the weighted kappa 0.66. When normal and unsatisfactory cases were combined as negative and atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LGSIL) and high-grade squamous intraepithelial lesion (HGSIL) as positive, the percentage of agreement was 83% and Kappa 0.66. When normal, unsatisfactory and ASCUS were combined as negative and LGSIL and HGSIL as positive, the percentage agreement raised to 90% and kappa to 0.76. This attempt at assessing the reproducibility of cytologic diagnosis using an informal method had led to good participation among participants. A fairly good agreement for overall cytologic diagnosis was found, though some variability remained concerning the diagnosis of unsatisfactory and those labelled as ASCUS. These results should lead the participants to reflect upon and eventually reassess their criteria on these specific cases.

Suicide by nitrous oxide poisoning.

Fatal nitrous oxide poisoning usually occurs accidentally during the administration of general anesthesia. It seldom occurs during autoerotic behavior or in acute drug abuse. We report an unusual case of a health professional who committed suicide by inhaling nitrous oxide.

Age estimation from quantitation of features of "chest plate" X-rays.

This study presents a method for estimating the age at death from the quantitation of roentgenologic features of X-ray films of chest plates obtained during routine autopsies. Multiple linear regression analysis allows estimation of coefficients of regression of features on known age-at-death individuals. The regression equation can be used in turn for age estimation of an unknown age-at-death individual. The accuracy of age estimation is about +/- 8.4 years (standard error) which is in the range of previously published macroscopic methods, though the present method is much faster and simpler.

Postmortem interval estimation by biochemical determination in birds muscle.

Experimental postmortem interval estimation was assayed by various biochemical components of hens pectoral muscle. Among them, only percentage of non-protein nitrogen on total soluble protein, asparatic amino transferase activity and creatinine concentration showed significant correlation with time after death. Asparatic amino transferase was negatively correlated and non-protein nitrogen percentage and creatinine were positively correlated to postmortem interval. The stronger correlation (0.925) was found for creatinine.

Histological assessment of gestational age in human embryos and fetuses.

A light microscopic study performed on 760 human fetuses allows us to define several stages in their visceral development and to relate these to gestational age. The histological examination of most viscera, such as the central nervous system, is useless when the tissue preservation is poor. Nevertheless, three organs may still be studied in macerated fetuses: the lungs (where different glandular, canalar, and alveolar stages of development are evident), the kidneys (where the respective numbers of rows of primitive glomeruli and of generations of mature glomeruli vary after week 22), and the adrenal glands (where neuroblastic nests are normally found between weeks 7 and 26 of gestation). It is important to compare the degree of histological maturation with the clinical, macroscopic, and radiologic data in order to define the profile of maturation proper to each human fetus.

Automated image analysis of myocardial collagen pattern in pressure and volume overload in rat cardiac hypertrophy.

An automated image analysis system was used to analyze the collagen pattern in picrosirius-stained sections of the left ventricular myocardium from 27 rats: 9 sham-operated animals (controls), 9 animals with one-clip, two-kidney Goldblatt renovascular hypertension (RVH) and 9 animals with an aortocaval fistula (ACF) model of volume overload hypertrophy. The collagen content and fiber thickness were significantly increased in the RVH group as compared to the ACF and sham-operated groups (P less than .001). These parameters were correlated to the left ventricular wall thickness (R = .66; P less than .01). On the other hand, form factors were significantly increased in both treated groups as compared to the controls. These findings indicate that increased collagen formation and increased left ventricular wall thickness probably depend on the type of load and were particularly important when afterload is increased.

Correlation between intracavernous pressure and contraction of the ischiocavernosus muscle in man.

An artificial erection was induced in nine patients consulting for erectile dysfunction. Changes in the intracavernous pressure (ICP) and in the integrated EMG of the ischiocavernosus muscle were recorded during voluntary muscular contractions. During such contractions elevations in ICP, varying between 100 and 525 mm. Hg, were recorded. Changes in ICP were always in phase with changes in the integrated electromyogram (EMG) of the ischiocavernosus muscle, and correlations between the duration of changes showed an almost perfect linear relationship between both physiological events. Correlations between maximum changes in ICP and integrated EMG generally showed a positive relationship between both measures. Results are interpreted to suggest involvement of the ischiocavernosus muscle in the process of penile rigidity.

Assessment of validity of DNA measurement in tissue sections by model simulation.

Computer modelling is used to simulate nuclear segments obtained by random sectioning through tissue. A few more computations lead to DNA measurement simulation. Two methods of DNA measurement (a direct one and a variant of the "plug" method) are tested on simulated diploid, tetraploid and octaploid cell populations. The two methods result in negatively skewed DNA frequency distributions. Both the right skewness and the coefficient of variation of measurements are increasing with the ploidy level because nuclear DNA content is assumed to be related to nuclear size in the chosen model. Observed mean values are biased underestimates of expected values but are strongly correlated to the degree of ploidy. The variant of the "plug" method gives rise to smaller coefficients of variation. Finally, the bias introduced by measuring nuclear segments instead of whole nuclei increases the variance of measurements but contributes to less than half the experimentally observed variance. Our conclusion is that microspectrophotometry on tissue sections is a valuable method for DNA content evaluation of small clusters of pathological cells as one may find in endoscopic biopsies.

Morphometric analysis of collagen network and plasma perfused capillary bed in the myocardium of rats during evolution of cardiac hypertrophy.

In order to investigate the consequences of different types of cardiac hypertrophy on myocardial capillary and fibrosis density in rats we describe here, in the same hearts, the pattern of capillary bed density visualized by fluorescein isothiocyanate dextran (FITC-dextran) and the pattern of fibrosis density as determined by automated image analysis. Pressure overload was induced by clipping one renal artery in rats (one-clip, two-kidney Goldblatt hypertension, RHV). Volume overload was induced by creation of an arteriovenous shunt between the abdominal aorta and the vena cava (aorto-caval fistula model ACF). Animals were sacrified at 1, 3 and 6 months following surgical procedure. Immediately prior to sacrifice, FITC-dextran (MW 150,000) was injected with the animal under ether anesthesia. Five minutes later, cardiac diastolic arrest was induced by the i.v. injection of potassium chloride. The heart was rapidly excised and placed in a formaldehyde solution. The degree of cardiac hypertrophy was calculated after measurement of cardiac weight. Left ventricular wall thickness and cavity area were measured by microscopic methods. Capillary density and geometry were determined by morphometric methods, under ultraviolet light microscopy, using a graphic tablet connected to a microcomputer. The degree of myocardial fibrosis, visualized with Sirius Red, was estimated by the use of automated image analysis using light microscopy. In renovascular hypertension, cardiac hypertrophy was maximum at one month (36%) and persisted through the six months of the study. This increase in cardiac mass was concentric, due to a significant increase in ventricular wall thickness and was associated with a marked increase in fibrosis and a significant decrease in subendocardial capillary density. These effects existed already one month and did not change with time. In the aorto-caval fistula model, cardiac hypertrophy was also maximum at one month (+56%), but this eccentric increase in cardiac mass was associated with no significant change in left ventricular wall thickness, but rather with a significant increase in the surface area of the left ventricular cavity. This volume overload hypertrophy was associated with a decrease in subendocardial capillary density which was negatively correlated with time. In contrast to concentric hypertrophy there was no increase in the fibrosis density compared to the sham-operated groups. Despite the identical degrees of hypertrophy, pressure and volume cardiac overload differed in a significant manner in both left ventricular wall thickness and cavity surface area.(ABSTRACT TRUNCATED AT 400 WORDS)

Discrimination between precancerous and cancerous lesions of the uterine cervix by DNA measurements on tissue sections.

Morphologically typical uterine cervical biopsies were separated into normal cervices, condylomas and cervical intraepithelial neoplasias (CIN) grades I, II and III. At least 100 nuclei per lesion were measured on 4 micron Feulgen-stained sections using a Zeiss microspectrophotometer, with a variant of the plug method used to compute the nuclear DNA content. DNA distribution histograms were then decomposed into subsets of diploid, tetraploid, octoploid and aneuploid cells. The decomposition, which assumed a log-normal model of polydiploidy distribution, led to the identification of six indices: (1) the percentage of diploid cells, (2) the percentage of tetraploid cells, (3) the percentage of octoploid cells, (4) the percentage of aneuploid cells with DNA contents less than tetraploidy, (5) the percentage of aneuploid cells with DNA contents between tetraploidy and octaploidy and (6) the percentage of aneuploid cells with DNA contents greater than octoploidy. These indices, along with the mean nuclear radius, the 5c exceeding rate and the 2c deviation index, generated a nine-dimensional space. Two methods of discriminant analysis on this space showed discriminating powers of 78.22% and 87.13%, respectively, as compared to the original diagnoses. The most discriminating variable in both analyses appeared to be the percentage of octoploid cells.

[The validity of measuring methods for intranuclear DNA on thin sections. Theoretical and experimental study]. / Validité des méthodes de mesure d'ADN intranucléaire sur coupe fine. Etude théorique et expérimentale.

Computer modelling is used to simulate nuclear segments obtained by random sectioning through tissue. A few more computations lead to DNA measurement simulation. Simulation results in negatively skewed DNA frequency distributions. Both the right skewness and the coefficient of variation of measurements are increasing with the ploidy level because nuclear DNA content is assumed to be related to nuclear size in the chosen model. Observed mean values are biased underestimates of expected values but are strongly correlated to the degree of ploidy. Finally, the bias introduced by measuring nuclear segments instead of whole nuclei increases the variance of measurements but contributes to less than half the experimentally observed variance. Our conclusion is that microspectrophotometry on tissue sections is a valuable method for DNA content evaluation of small clusters of pathological cells as one may find in endoscopic biopsies.

A perimeter algorithm applied to lung pathology.

A new image analyser, the NS 2000, explores the image using 256 photodiodes and, according to an adjustable threshold, converts it into a set of digital points of logical level 0 or 1. The method of fitting squares of increasing size consists of checking the presence of a square of a given size and of a given logical value throughout the image studied and gives the areas of successive erosions of the image. Using the parameters provided by the device one can obtain the total boundary BA per unit area for the phase studied, which is proportional to the number of squares having points of the two logical levels. Errors in length measurement as a function of orientation and for isotropic structures are compared to other automatic perimeter algorithms and to manual square grid measurement. Using the parameters provided by the device for the quantitative evaluation of lesions of elastase induced emphysema in hamster lungs, the values obtained for internal surface area (ISA) of alveoli, are lower by about 40% in elastase treated hamsters when compared to normal controls. This difference is highly significant (P less than 0.001) and the results obtained by the described method are in good agreement with those obtained by the classical manual procedure. Efficiency, defined as the precision of the estimate per unit measurement time on a given set of sample units (pictures in this paper), is given for both NS 2000 and manual procedures. The results obtained show comparable values but the automatic procedure includes a statistical treatment and it is significantly faster on histological sections than on micrographs, which was not the case with the manual method.

[Effect of experimental myocardial hypertrophy on coronary microcirculation in the rat]. / Effets de l'hypertrophie myocardique expérimentale du rat sur la microcirculation coronaire.

Effects of cardiac hypertrophy on coronary capillary density and volume have been studied in two models: systemic hypertension (1c. 2K Goldblatt model, n = 27), and volume overload (aorto-caval fistula, n = 27) compared to a control group (n = 27). Studies have been performed at 1 month, 3 and 6 months. Subendocardial and subepicardial coronary capillaries have been visualized by in injection of fluorescein-labeled dextran (FITC). The body weights were not significantly different in the three groups. The heart weight was the same in hypertensive model and fistula. Goldblatt model was associated with a high blood pressure and an increase in left ventricular wall thickness, whereas fistula was associated with a lower blood pressure and no difference in wall thickness as compared to controls. No difference in subepicardial capillary density was found in the three groups, whereas the subendocardial capillary density was decreased in the two models of cardiac hypertrophy (-25%). Capillary area and mean perimeter, were increased in fistula, due to vasodilatation, and decreased in Goldblatt model in relation to vasoconstriction.

[Right ventricular fibroma. Value of different methods of invasive and noninvasive exploration]. / Fibrome ventriculaire droit. Intérêt des différents modes d'exploration invasifs et non invasifs.

The authors report the case of a 20 year old man with a primary cardiac tumour. The relative usefulness of invasive (catheterisation and angiography), and non-invasive investigations (echocardiography, computerised axial tomography, myocardial scintigraphy and digitalised angiography) in determining operability and the benign or malignant nature of the tumour was evaluated. The patient was admitted to hospital for severe incapacitating effort dyspnoea. Cardiac auscultation was suggestive of pulmonary stenosis associated with tricuspid regurgitation. M mode and 2D echocardiography demonstrated a large mass within the right ventricular cavity and also its size shape, mobility and its relationship to the interventricular septum, tricuspid valve and the main pulmonary artery. Echo contrast studies confirmed tricuspid regurgitation and also demonstrated a patent foramen ovale. The cardiac CAT scan confirmed the preceding data. Myocardial scintigraphy demonstrated the vascular character of the tumour. Digitalised angiography showed the presence of a tumour in the right ventricle and the rest of the morphological information was identical to that obtained by conventional angiography. Cardiac catheterisation demonstrated an obstruction to right ventricular ejection and abnormal filling of both ventricles. It was the association of 2D echocardiography and Technetium 99 myocardial scintigraphy which provided the most information. The results of the other investigations were not essential in deciding the operative indications. A 230 g tumour was excised at surgery and the tricuspid valve replaced by a Hancock n 33 bioprosthesis. Anatomopathological examination showed the tumour to be a fibroma. The finding of a tricuspid diastolic rumble led to control catheter and angiographic studies 13 days after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)