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Biomedical subjects

M Petein

Publications and source records attributed to M Petein.

At least 19 recordsLinked to original sources

Laryngeal aspergillosis in an acquired immunodeficiency syndrome patient.

Aspergillosis is a rare infection. It varies considerably in its virulence depending on whether or not the patient affected is immunodepressed. The serious form is characterized by vascular invasion with haematogenic dissemination, tissue infarction and necrosis. The most often affected site is the lung. A laryngeal localization is exceptional and usually results from dissemination from a lower airways portal of entry. Diagnosis is difficult: cultures are only positive in 50 per cent of cases, while in 60 per cent of cases the characteristic histological features reminiscent of sprigs of mistletoe are only found on postmortem examination. In view of the high morbidity and mortality in acquired immunodeficiency syndrome (AIDS) sufferers, this condition must be treated early and aggressively. Treatment is based essentially on amphotericin B and itraconazole.

AIDS-Related Opportunistic Infections

The chromatin pattern of cell nuclei is of prognostic value for renal cell carcinomas.

Using a series of 105 renal cell carcinomas (RCCs) we investigated whether features quantitatively describing the appearance of Feulgen-stained nuclei and, more particularly, of their chromatin (on the basis of computer-assisted microscopy) can contribute any significant prognostic information. Thirty morphonuclear and 8 nuclear DNA content-related variables were thus generated. The actual prognostic values of this set of cytometric variables was compared (by means of discriminant statistical analysis) to conventional diagnostic and/or prognostic markers including histopathological grades, tumour invasion levels and the presence or absence of metastases. We obtained complete clinical follow-ups for 49 of the 105 RCC patients under study, making it possible to define a subset of patients with a bad prognosis (i.e., who died in the 12 months following nephrectomy) and a subset of patients with a good prognosis (i.e., who survived at least 24 months following nephrectomy). An original method of data analysis related to artificial intelligence (decision tree induction) enabled a strong prognostic model to be set up. In the case of 10 new patients, this model identified all the dead patients as having a bad survival status, with a total of 8 correct predictions. Another prognostic model similarly generated enabled the correct predictions to be confirmed.

Adult

Coregulatory effects of epidermal growth factor, dihydrotestosterone, and prolactin on benign human prostatic hyperplasia tissue culture proliferation.

BACKGROUND: A variety of hormones have demonstrated effects on prostatic tissue growth dynamics. Our goal was to define the effect of dihydrotestosterone (DHT), epidermal growth factor (EGF), and prolactin (PRL) on prostate cellular proliferation. METHODS: Thirty benign human prostatic hyperplasias (BPH) were maintained 48 hr as in vitro cultures. Culture media were supplemented with EGF, DHT, and PRL alone and in combinations. Proliferation was assessed by labeling with tritiated thymidine. RESULTS: The proliferative response of individual BPH cultures was heterogeneous. DHT and EGF tended to have a greater proliferative effect than PRL, both in terms of the percent cultures responding and the magnitude of the response. PRL antagonized EGF-induced proliferative effects. EGF- and PRL-mediated effects correlated with each other, while DHT-mediated effects did not correlate with either those of PRL or EGF. CONCLUSIONS: The proliferative response of individual BPH to DHT, EGF, and PRL, alone or in combination, is too variable to define a predictable response to their influence. Our methodology represents a technique with the capacity to define therapeutic potential for individual cases.

Aged

Classification strategies for the grading of renal cell carcinomas, based on nuclear morphometry and densitometry.

The various grading systems proposed for renal cell carcinomas all suffer from problems related to inter-observer variability. Some of these grading systems are based, either partially or wholly, on morphonuclear criteria, such as nuclear size and shape, anisonucleosis, and chromatin pattern. These criteria can be quantitatively (and thus objectively) evaluated by means of the computer-assisted microscopic analysis of Feulgen-stained nuclei. In the present work, 39 quantitative variables, including two morphometric, 28 chromatin pattern-related, and nine DNA ploidy level-related, were computed for 65 renal cell carcinomas. The actual diagnostic information contributed by each variable was determined by means of multifactorial statistical analysis (discriminant analysis) and two artificial intelligence-related methods of data classification (the decision tree and production rule methods). The results show that quantitative information, as provided by the computer-assisted microscopy of Feulgen-stained nuclei and analysed by means of artificial intelligence-related methods of data classification, contributes significant diagnostic information for the grading of renal cell carcinoma, thus reducing the problem of inter-observer reproducibility.

Adult

Objective measurement of the different collagen types in the corpus cavernosum of potent and impotent men: an immunohistochemical staining with computerized-image analysis.

Quantitative measurements of the collagen types (I, II, and IV) in the corpora cavernosa of potent and impotent men were carried out to investigate whether quantitative immunohistochemistry might contribute additional information as to the cause of erectile dysfunction. The study group consisted of 22 men with various etiologies of impotence and 4 normal, potent men. The quantitative immunohistochemistry measurements were performed by means of a cell-image processor. Three variables for each of the three types of collagen were studied, namely, the mean optical density (MOD), which relates to histochemical staining intensity; the labeling index (LI), which is positively related to the percentage of immunostaining; and the quick score (QS) index, which takes into account both LI and MOD values. None of the quantitative parameters taken individually (monovariate statistical analyses) made it possible to obtain any statistically significant difference between the types of collagen of the group under study. The mean QS value recorded for collagen type IV was significantly lower than that noted for collagen type I in the psychogenic (P = 0.019), arteriogenic (P = 0.012), and venogenic (P = 0.001) groups, whereas the MOD value was significantly lower in the normal (P = 0.043), arteriogenic (P = 0.013), and venogenic (P = 0.001) groups but not in the psycogenic group. The mean MOD of collagen type III was intermediate between that of the other types. In contrast, the mean LI value recorded for collagen type IV was significantly lower only in the venogenic (P = 0.032) and psychogenic (P = 0.049) groups as compared with the other groups. No objective qualitative change in the collagen types was observed that could be correlated to the etiology of erectile dysfunction. The significant difference seen in the quantitative parameters with regard to collagen type IV and the observed increase in the type I/III collagen ratio might attest to the notion that the response of the erectile tissue to ischemia is similar to that of other organs. The net effect of these changes is a restricted capacity for corporal expansion and alteration of the veno-occlusive mechanism.

Adult

Biochemical alterations of the tunica albuginea in impotence.

PURPOSE: The objectives of this study were to quantify the immunohistochemical stainings of collagen types I, III and IV, and investigate the value of glycohistochemical staining with 3 lectin types specific to a particular glycan structure, Arachis hypogaea, Triticum vulgare and concanavalin A, as a method of defining possible changes in the collagen structure of the tunica albuginea in potent and impotent patients. MATERIALS AND METHODS: The study involved 4 normal men, 4 with pure venous leakage and 4 with pure arterial disease. Collagen types I, III and IV, and lectins Arachis hypogaea, Triticum vulgare and concanavalin A were studied using a cell image processor. The labeling index relates to the percentage of staining and mean optical density relates to the staining intensity. RESULTS: Mean labeling index values for the 3 types of collagen and lectins were similar (p > 0.05). Mean optical density value relating to collagen type I was significantly higher in the arteriogenic group than in the other groups (p < 0.05), while mean optical density value of collagen type IV was significantly higher in the venogenic group than in the 2 other groups (p < 0.05). Mean optical density values relating to the 3 lectin types were similar in the 3 clinical groups (p > 0.05). CONCLUSIONS: An alteration in the distribution and structure of the various collagen types and lectins in the tunica albuginea of impotent patients has been shown that may interfere with normal function and lead to impotence.

Adult

Decision tree induction: a useful tool for assisted diagnosis and prognosis in tumor pathology.

The aim of the present work is to show that decision tree induction algorithms are a useful tool for extracting reliable information from data series, with the objective of assisting pathologists in identifying specific diagnostic and prognostic markers in various types of tumor pathologies. In terms of accuracy, we show that the decision tree technique exceeds other more sophisticated techniques, such as multilayer neural networks. Furthermore, because of the case with which decision tree results can be interpreted (logical classification rules), new methodologies can be readily developed to further assist in analyzing complex data that mix heterogeneous features. In this paper, we illustrate such capabilities in the context of different complex diagnostic and/or prognostic problems in tumor pathology relating to bladder, astrocytomas, and adipose tissues.

Adult

Contribution of quantitative lectin histochemistry to characterizing well-differentiated, dedifferentiated and poorly differentiated liposarcomas.

OBJECTIVE: To find new diagnostic markers in the group of lipomatous tumors. STUDY DESIGN: The histochemical lectin staining pattern was characterized in a series of 45 lipomatous lesions, including 10 typical lipomas, 6 atypical lipomas, 8 well-differentiated, 6 myxoid, 5 dedifferentiated and 10 pleomorphic liposarcomas. Three lectins were used-peanut (Arachis hypogaea) agglutinin, which binds to terminal Gal(beta 1,3)GalNAc residues; wheat germ (Triticum vulgare) agglutinin (s-WGA, the succinylated form of WGA), which binds to ((1-4)-D-GlcNAc)n and Neu5NAc residues; and jack bean (Concanavalia ensiformis) agglutinin which binds to alpha-D-Man and alpha-D-Glc residues. Histochemical staining was quantitatively measured by means of a cell image processor. RESULTS: In the case of certain carbohydrate residues, typical lipomas closely resemble atypical lipomas, which in turn closely resemble well-differentiated liposarcomas; typical lipomas differ significantly from well-differentiated liposarcomas. This indicates that atypical lipomas, or at least some of them, could represent a biologic link between typical lipomas and well-differentiated liposarcomas. While well-differentiated and pleomorphic liposarcomas differed significantly from each other, the poorly differentiated component of dedifferentiated liposarcomas included histochemical lectin properties, which were common to both well-differentiated and pleomorphic liposarcomas. CONCLUSION: Some atypical lipomas exhibit glycohistochemical characteristics that are common to those of well-differentiated liposarcoma. The poorly differentiated component of dedifferentiated liposarcomas remains more differentiated in terms of glycohistochemical markers than do poorly differentiated pleomorphic liposarcomas.

Adult

Methodological aspects of using decision trees to characterise leiomyomatous tumors.

The aim of the present work is to present the potential uses of a classification technique labeled the "decision tree" for tumor characterisation when faced with a large number of features. The decision tree technique enables multifeature logical classification rules to be produced by determining discriminatory values for each feature selected. In this report, we propose a methodology that used decision trees to compare and evaluate the information contributed by different types of features for tumor characterisation. This methodology is able to produce a set of hypotheses related to a diagnosis and or prognosis problem. For example, hypotheses can be producted (on the basis of a set of descriptive features) to explain why tumor cases belong to a given histopathological group. To illustrate our purpose, this methodology was applied to the difficult problem of leiomyomatous tumour diagnosis. The aim was to illustrate what kind of diagnostic information can be extracted from a sample data set including 23 smooth muscle tumors (14 benign leiomyomas and 9 malignant leiomyosarcomas) described by a large set of computer-assisted, microscope-generated features. Three groups of features were used relating to: (1) ploidy level determination (10 features), (2) quantitative chromatin pattern description (15 features), and (3) immunohistochemically related antigen specificities (6 features). All these features were quantified by digital cell image analysis. The results suggest that an objective distinction between leiomyomas and leiomyosarcomas can be established by means of simple logical rules depending on only a few features among which the immunohistochemically revealed antigen expression of desmin plays a preponderant part. One of the combinations of features proposed by the methodology is interesting for pathologists, because it includes two features describing the appearance of a nucleus in terms of chromatin distribution homogeneity and density, two features widely used by pathologists in tumor-grading systems.

Adolescent

In vitro characterization of prolactin-induced effects on proliferation in the neoplastic LNCaP, DU145, and PC3 models of the human prostate.

BACKGROUND: Proliferation of normal and tumoral prostate tissue is regulated by androgens and various growth factors. We characterized the in vitro proliferative influence of prolactin (PRL) in androgen-sensitive and androgen-insensitive human prostate cancers. METHODS: The biologic models employed included the androgen-sensitive LNCaP and the androgen-insensitive DU145 and PC3 cell lines. PRL-induced influences (0.1-10 mIU/ml of medium) on proliferation were assessed using the colorimetric methylthiotetrazole assay. Androgen sensitivity in the three cell lines was determined by assessing the proliferative influence of dihydrotestosterone (DHT) (0.1-10 nM). PRL-induced modifications in PC3 cell kinetics were assessed using Feulgen-stained nuclear image cytometry. RESULTS: Although DHT markedly stimulated LNCaP proliferation, it had no proliferative effect on the DU145 and PC3 cell lines. By contrast, PRL significantly modulated the proliferation of the DU145 and PC3 lines, but exerted weak, if any, effect on the proliferation of the LNCaP cell line. PRL increased the percentage of PC3 proliferating cells (i.e., cells in the S/G2 phases of the cell cycle) at low doses (0.1 mIU/mL) and decreased this percentage at high doses (10 mIU/ml). CONCLUSIONS: Proliferation of androgen-insensitive human prostate cell lines can be significantly modulated by prolactin.

Androgens

The use of the decision tree technique and image cytometry to characterize aggressiveness in World Health Organization (WHO) grade II superficial transitional cell carcinomas of the bladder.

The aggressiveness of human bladder tumours can be assessed by means of various classification systems, including the one proposed by the World Health Organization (WHO). According to the WHO classification, three levels of malignancy are identified as grades I (low), II (intermediate), and III (high). This classification system operates satisfactorily for two of the three grades in forecasting clinical progression, most grade I tumours being associated with good prognoses and most grade III with bad. In contrast, the grade II group is very heterogeneous in terms of their clinical behaviour. The present study used two computer-assisted methods to investigate whether it is possible to sub-classify grade II tumours: computer-assisted microscope analysis (image cytometry) of Feulgen-stained nuclei and the Decision Tree Technique. This latter technique belongs to the Supervised Learning Algorithm and enables an objective assessment to be made of the diagnostic value associated with a given parameter. The combined use of these two methods in a series of 292 superficial transitional cell carcinomas shows that it is possible to identify one subgroup of grade II tumours which behave clinically like grade I tumours and a second subgroup which behaves clinically like grade III tumours. Of the nine ploidy-related parameters computed by means of image cytometry [the DNA index (DI), DNA histogram type (DHT), and the percentages of diploid, hyperdiploid, triploid, hypertriploid, tetraploid, hypertetraploid, and polyploid cell nuclei], it was the percentage of hyperdiploid and hypertetraploid cell nuclei which enabled identification, rather than conventional parameters such as the DI or the DHT.

Adult

Differential histochemical peanut agglutinin stain in benign and malignant human prostate tumors: relationship with prostatic specific antigen immunostain and nuclear DNA content.

The histochemical binding pattern of the peanut (Arachis hypogaea) lectin (PNA) was quantitatively described by means of computer-assisted microscope analysis in 28 benign prostatic hyperplasias (BPH), 15 prostatic intraepithelial neoplasias (PIN), and 119 prostatic adenocarcinomas. PNA exhibits nonimmune but selective binding to glycoproteins with beta-D-galactosyl(1,3)-N-acetyl-D-galactosamine residues. We also investigated whether a relationship existed between the number of histochemical-related PNA acceptors and the histochemical prostate-specific antigen (PSA) stain intensity, and between the number of PNA receptors and DNA ploidy level. The results show that neoplastic prostate tissues and high-grade intraepithelial prostatic neoplasias (PIN2_3) exhibit a significantly higher number of PNA acceptors than benign prostatic hyperplasias and low (PIN1) grade prostatic intraepithelial neoplasias. A statistically significant correlation was observed between the number of histochemically related PNA acceptors and PSA immunostain intensity. Lastly, diploid prostatic tumors, whether benign or malignant, exhibited a significantly higher number of PNA acceptors than aneuploid ones. These results suggest that PNA acceptors play an important role in the biology of prostate tumors.

Adenocarcinoma

Image cytometry analysis of Feulgen-stained nuclei in 72 lipomatous lesions including atypical lipomas and well-differentiated liposarcomas.

Well-differentiated lipomatous tumors constitute a histopathologic category whose nomenclature has been controversial, particularly with respect to the distinction between atypical lipomas of the extremities and well-differentiated liposarcomas of the retroperitoneum. To determine whether there were differences in image analytic parameters between these neoplasms, 72 lesions including 21 typical lipomas, 7 atypical lipomas, 16 retroperitoneal and 5 nonretroperitoneal well-differentiated, 9 dedifferentiated, and 14 pleomorphic liposarcomas were submitted to the computer-assisted microscopic analysis of Feulgen-stained nuclei. This methodology enabled four groups of variables to be calculated. These included: (1) quantitative chromatin pattern description (14 variables); (2) the measurement of proliferative activity (1 variable); (3) nuclear DNA content (DNA ploidy level, 5 variables); and (4) the measurement of cell density and topographical cell nuclei organization (2 variables). The results strongly suggest that atypical lipomas, whether superficial or deep, and well-differentiated liposarcomas, whether retroperitoneal or not, belong to the same category in terms of the variables analyzed.

Adult

The additional predictive value contributed by quantitative chromatin pattern description as compared to DNA ploidy level measurement in 257 superficial bladder transitional cell carcinomas.

The results of quantitative chromatin pattern description were compared with the determination of the DNA ploidy level, and the histological grading and clinical staging of superficial transitional cell carcinomas (sTCCs) of the bladder. We investigated whether this quantitative description adds useful information to the one obtained by the other methods used for predicting the biological behavior of sTCCs. The quantitative chromatin pattern description was carried out by means of the digital cell image analysis of Feulgen-stained nuclei in a series of 257 sTCCs. The results show that according to the clinical sequence "remission (134 patients) --> stable recurrence (101 patients) --> progression (13 patients) --> death (9 patients)', quantitative chromatin pattern description shows that certain areas of the nucleus undergo a continual process of condensation and that the distribution and spread of the chromatin becomes more and more heterogeneous. This is accompanied by a more frequent appearance of pale areas in the nucleus and an increase in nuclear size. Of the 257 sTCC patients, 148 had pTa/PpT1 grade I or III tumors. Of these 148, histological grading and clinical staging made it possible to correctly predict the biological behavior of the tumors of 120/148 (81%). DNA ploidy level determination increased this correct prediction from 81 to 84%. When the information contributed by quantitative chromatin pattern description was added to that contributed by the combination of histological grading, clinical staging and DNA ploidy level determination, the prediction level was 93%.

Adult

[Intra-cavernous collagen analysis in impotence].

The role of the different components of the corpus cavernosum is very important in the physiopathology of erectile dysfunction. The precise function of collagen fibers in erectile physiology is controversial. We measured the different types of collagen (I, III, IV) in the corpus cavernosum of 26 impotent and potent men using cell image analysis and immunohistochemistry. We found differences in the distribution of collagen I, III, IV in each pathological group (arterial, caverno-venous, psychogenic). The augmentation of collagen I and the light diminution in collagen III makes the corpus cavernosum less compliant which translates clinically as an alteration in the filling of the vascular spaces and by dysfunction of the veno-occlusive mechanism. The diminution in collagen IV shows an alteration in the function of endothelial cells. The fact that in the psychogenic group we found also a diminution in collagen IV content, makes us infer that psychogenic impotence could be the first stage of an organic impotence.

Adult

The value of nuclear DNA and texture analysis by digital image processing in the diagnosis of lipomatous and leiomyomatous tumours.

The present study investigates whether the quantitative chromatin pattern description carried out by means of the digital cell image analysis of Feulgen-stained nuclei can contribute valuable diagnostic information on sarcomas. A series of 77 soft tissue tumours was consequently studied. This series included 9 benign lipomas versus 26 malignant liposarcomas and 26 benign leiomyomas versus 16 malignant leiomyosarcomas. Of the 26 liposarcomas, 14 were primary and 12 recurrent tumours. Of the 16 leiomyosarcomas, 13 were primary and three recurrent tumours. The results show that the combined use of principal-components analysis and the discriminant analyses of digital data obtained by means of the computer-assisted microscope analysis of Feulgen-stained nuclei made it possible to obtain a clear-cut distinction between the three histopathological groups relating to the lipoma/liposarcoma group of soft tumours. In contrast, while a clear-cut distinction could be made between the recurrent leiomyosarcomas and the primary leiomyosarcomas, such a distinction was not possible between the benign leiomyomas and the malignant primary leiomyosarcomas. This feature, along with previous ones obtained through DNA ploidy level determination, suggests to us that leiomyomas, or at least some of them, are in the process of malignant transformation. In other words, leiomyomas might be the pre-malignant counterpart of leiomyosarcomas, a feature that the present results do not suggest for lipomas versus liposarcomas.

Adult

The computer-assisted microscope analysis of Feulgen-stained nuclei linked to a supervised learning algorithm as an aid to prognosis assessment in invasive transitional bladder cell carcinomas.

The aim of the present work is to ascertain whether additional information to grading and staging can be obtained for the prognosis of invasive bladder tumours (T2, T3, T4) by means of two computer-assisted methodologies. The first methodology relates to the digital image analysis of Feulgen-stained nuclei and the second to a supervised learning algorithm named Decision Tree. The digital image analysis of Feulgen-stained nuclei generated 11 variables for nuclear DNA content and 15 for quantitatively describing chromatin pattern. These 26 variables were submitted to a Decision Tree technique which produces multi-attribute logical classification rules by selecting informative variables and determining discriminatory values for each of them. A series of 41 patients for which the majority of the T2 bladder tumours (68%) were associated with a 'good' prognosis (remission) while the majority of the T3-T4 ones (77%) were associated with a 'bad' one (clinical progression or death) were submitted to the proposed approach. The results show that the decision tree was able to characterise the tumours associated with a 'bad' prognosis in the T2 sub-group (32%) and the tumours associated with a 'good' prognosis in the T3-T4 one (23%), by using only few image-generated variables (added to the clinical stage).

Adult

Quantitative measurements of desmin and vimentin immunostains and cell density in leiomyomas and leiomyosarcomas.

The distinction between benign and malignant smooth muscle tumours relying on histological features such as the mitotic index and pleomorphism remains a generally acknowledged difficulty in modern pathology. A cell image processor was therefore used to quantitatively assess the desmin and vimentin immunostain in 39 smooth muscle tumours which included 26 benign (leiomyomas) and 13 malignant (leiomyosarcomas) cases. The 13 leiomyosarcomas were primary (non-recurrent and non-metastatic). Ploidy level and cell density were also assessed on each of these 39 tumours by means of the computer-assisted microscopic analysis of 5-microns thick Feulgen-stained histological sections. The results show that while neither the ploidy level determination nor the quantitative assessment of the vimentin immunostain made it possible to distinguish between leiomyomas and leiomyosarcomas, cell density determination and the quantitative assessment of the desmin immunostain enabled such a distinction to be made. Indeed, the leiomyomas exhibited a much higher level of desmin positivity than the leiomyosarcomas, as did diploid tumours as compared to the aneuploid (benign or malignant) ones. Furthermore, the leiomyoma group exhibited a significantly lower mean cell density value than the leiomyosarcoma group. The present study further confirms the lack of relationship between ploidy level and cytological malignancy in smooth muscle tumours.

Adolescent