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Biomedical subjects

R Kiss

Publications and source records attributed to R Kiss.

At least 199 records · Page 11Linked to original sources

Mineralocorticoid production of adrenal cortical adenomas.

We studied in vitro and in vivo corticosteroid production as well as the presence of symptoms of an increased mineralocorticoid effect in patients with 'silent' adrenal cortical adenomas, and compared these results to those found in patients with classical mineralocorticoid excess syndromes. We found that under in vitro conditions, cells from 'silent' adrenal cortical adenomas (n = 19) produced substantial amounts of both zona glomerulosa and fasciculata steroids, although the production of steroids in these cells was lower compared to that in mineralocorticoid-producing adenoma cells (n = 26). Patients with aldosterone-producing and 'silent' adenomas had significantly increased plasma atrial natriuretic peptide levels, which remained non-suppressible after upright posture and furosemide administration. Of the 25 patients with 'silent' adenomas, 11 had low and non-stimulable plasma renin activity (PRA) before but, in most cases, not after adrenal surgery. When compared to those with normal PRA (n = 14), patients with low PRA 'silent' adenomas (n = 11) had higher blood pressure which was significantly reduced after surgery, and a mild hypokalemia before but not after surgery. Although basal plasma concentrations of aldosterone, 18-hydroxy-corticosterone, corticosterone, deoxycorticosterone, 18-hydroxy-DOC, cortisol,11-deoxycortisol and 17-hydroxy-progesterone (17-OH-P) were not increased in either groups of 'silent' adenomas, ACTH stimulation produced a hyperreactive response for all measured steroids, of which an extremely high 17-OH-P seemed to be one of the most intriguing findings. We consider that these observations in 'silent' adrenal cortical adenomas may justify surgical intervention, irrespective of the size and potential malignancy of these adenomas.

Adenoma↗

Use of cell image analysis in the detection of cancer from specimens obtained during endoscopic retrograde cholangiopancreatography.

The authors report a scoring system based on cell image analysis of specimens obtained during endoscopic retrograde cholangiopancreatography from either the biliary or pancreatic duct epithelium. Nine normal, 20 inflammatory, and 19 malignant epithelia were assessed using a cell-image processor that permits determination of morphometric (nuclear area), densitometric (nuclear DNA content), and textural (chromatin distribution) parameters on Feulgen-stained nuclei. The score is based on three densitometric parameters: the DNA histogram type, the nuclear DNA content, and the percent proliferating cell population. These parameters permit distinction of normal and inflammatory from malignant epithelium with 95% sensitivity and 100% specificity. Cell-image analysis of specimens obtained during endoscopic retrograde cholangiopancreatography is a useful clinical tool in the detection of malignant lesions of the pancreas and biliary epithelia.

Bile Duct Diseases↗

Nuclear DNA content, proliferation index, and nuclear size determination in normal and cirrhotic liver, and in benign and malignant primary and metastatic hepatic tumors.

The distribution values of ploidy, of the proliferation index, of the percentages of diploid cells/case, of nuclear size, and DNA histogram type are described in a series of 92 liver samples from 87 patients. The 92 samples include normal (31 cases) and cirrhotic (14 cases) tissues, benign tumors (7 cases), well-differentiated hepatocellular carcinomas (HCCs, 13 cases), moderately and poorly differentiated HCCs (8 cases), and colorectal glandular metastatic tissues (19 cases). The samples are from either fine-needle aspiration biopsy (FNAB) or histologic imprint smears (HIS). Nuclear assessments were computed on Feulgen-stained nuclei by means of a cell image processor. The results show that the mean DNA index value, the mean nuclear area (NA) value, and the mean percentages of diploid cells per sample are significantly different in the three benign groups under study (normal and cirrhotic tissues and benign tumors) as compared with the mean parameter values from the three neoplastic liver groups (well-differentiated and poorly differentiated HCCs and colorectal metastases). None of these three parameters, however, makes it possible to discriminate clearly between these six histopathologic groups at the individual case level. The mean proliferation index values were significantly lower in the normal tissues and the benign tumors than in the four other histopathologic groups. Recognizing six DNA histogram types, ie, diploid, hyperdiploid, triploid, hypertriploid, tetraploid, and polymorphic, we observed that all the benign samples (the normal and cirrhotic tissues and the benign tumors) exhibited a diploid and/or tetraploid DNA histogram pattern, whereas the neoplastic samples exhibited the six DNA histogram patterns. The combination of the five computerized parameters into a cytologic score (CS) ranging from 5 to 15 permits clear-cut discrimination between nonneoplastic and neoplastic liver cases. The specificity and sensitivity, and the positive and negative predictive values relating to this score were as high as 100%, 95%, 100%, and 96%, respectively.

Biopsy, Needle↗

Characterization of nuclear DNA content, proliferation index, and nuclear size in a series of 181 meningiomas, including benign primary, recurrent, and malignant tumors.

The characterization of nuclear area, the proliferation index, and nuclear DNA content was carried out by means of digital cell image analysis, which makes it possible to compute morphometric and densitometric features on Feulgen-stained nuclei from archival, that is, formalin-fixed, paraffin-embedded materials. The 181 meningiomas studied included 173 classic (41 meningotheliomatous, 27 fibroblastic, 82 transitional, nine psammomatous, eight angiomatous and six hemangioblastic tumors) and eight malignant meningiomas (three hemangiopericytomas and five tumors that we labeled HFM, that is, tumors exhibiting evidence of histological features of malignancy). The results reveal a strong relationship between incomplete surgical resection and recurrence on the one hand and between the probability of recurrence and histopathological type on the other. Whereas neither nuclear area nor nuclear DNA content assessments were helpful in distinguishing the six classic and the two malignant meningioma subgroups, a statistically significant increase in proliferative activity was observed in the malignant meningiomas as compared with classic ones, excepting hemangioblastomas that proliferate at the same rate as the malignant meningiomas. Furthermore, the multiple meningiomas definitely proliferated more actively than the single ones, but a similar proliferative activity was observed in the nonrecurrent and recurrent meningiomas. Proliferation analyses might be therefore helpful for determining aggressive meningiomas and for planning adjuvant therapy in these cases.

Adult↗

DNA histogram typing in a series of 707 tumors of the central and peripheral nervous system.

The diagnostic value of ploidy level was investigated in a series of 707 tumors (from 707 patients) of the central and peripheral nervous system. The series contained 91 nerve sheath tumors (NSTs), 222 meningiomas (MNGs), 37 primitive neuroectodermal tumors (PNETs), 293 glial tumors of the adult (ATTs), and 64 brain metastases (MTTs). The ploidy level of each tumor was obtained by means of its DNA histogram type (DHT), which was computed (digital cell image analysis) on Feulgen-stained nuclei from archival formalin-fixed paraffin-embedded materials. The data reveal that the measurement of the ploidy level showed a diagnostic value in some of these tumor cases. Indeed, the proportion of highly aneuploid cases significantly (p < 0.05-0.01) decreased according to the sequence PNETs (72%)-->MTTs (64%)-->ATTs (40%)-->NSTs (23%)-->MNGs (9%). Nevertheless, this significant diagnostic value in terms of a distinction between benignity and malignancy only appears when all the tumors are taken into consideration. Indeed, at the level of one individual patient, our study shows that, like traumatic neuromas, schwannomas, or classical meningiomas, completely benign tumors can exhibit a high aneuploidy level. In contrast, some tumors from histopathological groups like brain metastases or PNETs, which are known to be clinically aggressive, could be completely diploid.

Astrocytoma↗

Assessment of nuclear size, nuclear DNA content and proliferation index in stereotaxic biopsies from brain tumours.

In this paper we study the feasibility of measuring the diverse biological parameters in stereotaxic biopsies from human brain lesions. These biological parameters are the nuclear area (NA), the proliferation index (PI) and the ploidy level, the latter of which was evaluated by means of the DNA index (DI) and histogram type (DHT). These parameters were assessed by means of the digital cell image analysis of Feulgen-stained nuclei. This analysis was performed on 124 samples from 22 computed tomography (CT)-guided stereotaxic biopsies. The data show that the methodology used here enables the above parameters to be assessed on small samples without limiting the classical anatomopathological diagnosis. The data also reveal that the DHT corresponded more accurately to the ploidy level in the sample analysed than the DI. Lastly, it appears that supratentorial astrocytic tumours of the adult, which constituted the majority of the cases analysed here, are strongly heterogeneous at a biological level.

Biopsy↗

Characterization of factors in routine laboratory protocols that significantly influence the Feulgen reaction.

We investigated the parameters that could affect the cytophotometric analysis of cell nuclei stained by the Feulgen reaction. These parameters included: the hydrolysis temperature (in the normal "room temperature" range); the composition of the Schiff's reagent; the speed of centrifugation of the cell suspensions; the mode of preservation [air-drying or ethanol-formalin-acetic acid (EFA) fixation]; the fixation time; the pronase digestion time; and the concentration of pronase used to obtain cell suspensions from archival (formalin-fixed, paraffin-embedded) materials. Relatively homogeneous material was studied: the MXT mouse mammary adenocarcinoma growing in vivo as tumors with both small and hyperchromatic cell nuclei and in vitro as monolayers with larger and less hyperchromatic cell nuclei. The results of these investigations demonstrate the necessity for the precise definition of a protocol for such procedures as sampling, fixation, and staining of cell nuclei if computerized cell image analyses are to be objective and reproducible. For present purposes this protocol differs depending on whether fresh or archival material is studied. For fresh tissue the protocol is immersion of the sample in EFA within 10 sec, fixation for 30 min, and staining by the Feulgen reaction in which hydrolysis is performed with 6 N HCl at 24 degrees C for 60 min. For archival tissue, the protocol becomes fixation in formol (or EFA), embedding, sectioning at 80 microns, digestion with 0.05% pronase for 2 hr, centrifugation at 1200 x g on glass slides, and staining by the Feulgen reaction in which hydrolysis is performed with 6 N HCl for 60 min at 24 degrees C.

Animals↗

The role of Propionibacterium propionicus in chronic canaliculitis.

Delicate branching filaments, and cocci or rods, were seen by microscopic examination in the pus of the canaliculus lacrimalis in patients with chronic canaliculitis. Propionibacterium propionicus and different bacteria were cultivated and identified in the pus. After i.p. inoculation of mice with the Propionibacterium strains, the morphological changes characteristic of this microorganism were observed in the peritoneum, in the spleen and in the lung, giving an adequate explanation of the direct microscopic findings in the pus.

Animals↗

DNA histogram typing in retinoblastomas and neuroblastomas.

The nuclear DNA content characterization was carried out by means of both DNA index and DNA histogram type assessments in a series of 21 retinoblastomas, 11 neuroblastomas, 1 ganglioneuroblastoma, and 4 medulloblastomas. These measurements were performed by means of the cytophotometric digital cell image analyses of Feulgen-stained nuclei. The results indicate that as far as nuclear DNA content is concerned, retinoblastomas seem to be very different from neuroblastomas. In fact, in terms of DNA index, retinoblastomas are significantly more aneuploid than neuroblastomas. The DNA histogram type shows that the high level of aneuploidy found in retinoblastomas corresponds to genotypically polymorphic tumors, and this could reflect a serious degeneration of the genomic material in retinoblastomas. This type of degeneration seems to be much less frequent in neuroblastomas, which basically seem to be either diploid or hypertriploid.

Adolescent↗

Heterogeneity of DNA ploidy, proliferation index and nuclear size in human colorectal carcinomas.

Measurements of DNA ploidy, proliferation index and nuclear area were performed on 210 samples taken from 15 human colorectal tissues. The tissues were divided into four groups labeled G1, G2, G3 and C. For each of the 15 tissues 9 samples were taken from the so-called unaffected--i.e., marginal--mucosa (G1-G3 groups) and 5 from the tumor (C group). The 9 samples from the unaffected mucosa of each tumor were obtained at a distance of 10 cm (3 samples/tissue, G1 group), 5 cm (3 samples/tissue, G2 group) and 1 cm (3 samples/tissue, G3 group) from the tumor. Computerized cell image analysis was carried out on Feulgen-stained cell suspensions obtained from paraffin-embedded, formalin-fixed tissues. The results revealed that four to five analyses are necessary to detect minor aneuploid cell nuclei populations in human colorectal tumors. A definite homogeneous diploid pattern was found in the G1-G3 samples. In contrast, proliferative activity varied widely between the normal and tumor samples, with such variations observed at both the sample-to-sample and tissue-to-tissue level. The nuclear area also varied markedly across the samples from a given tissue--i.e., both marginal and tumoral and across the tissues themselves. Finally, we observed that the diploid tumors, the nuclear sizes of which varied as widely as those of the aneuploid tumors, possessed a higher proportion of highly proliferating samples than did the aneuploid.

Aged↗

Spontaneous evolution of cytoplasmic lectin binding and nuclear size and deoxyribonucleic acid content in human colorectal cancers grafted onto nude mice.

BACKGROUND: The development of certain biologic characteristics in human colorectal tumor xenografted onto nude mice are described with respect to their precocious passages, i.e., passaging below 10 onto athymic mice. EXPERIMENTAL DESIGN: The biologic characteristic monitoring involved the determination of modifications occurring in cytoplasmic lectin binding and spontaneous development in nuclear size and DNA content. The lectin immunohistochemistry included the characterization of staining modifications in the glandular parts of the colorectal xenografts of wheat germ, Dolichos biflorus, peanut, Solanum tuberosum and Ulex europaeus I agglutinins. The nuclear modifications were monitored by means of the digital cell image analyses of Feulge-stained nuclei. RESULTS: The results show that although the xenografted human colorectal lines may be relatively stable according to their macroscopic growth over serial passaging, certain of their microscopic characteristics develop markedly. Three lectins, i.e., wheat germ agglutinin, Solanum tuberosum, and Ulex europaeus I, showed a glandular binding which remained relatively stable over serial passaging, whereas the peanut binding exhibited some variations and the DBA binding progressively disappeared. These cytoplasmic modifications occurring over time were less pronounced than those that occurred with respect to nuclear measurements, i.e., size and DNA content. CONCLUSIONS: Nuclear DNA content heterogeneity as revealed by DNA histogram typing rather than by DNA index assessments increased markedly in the colorectal xenografts over their serial passaging on nude mice.

Animals↗

The application of computerized analysis of nuclear images and multivariate analysis to the understanding of the effects of antineoplastic agents and their mechanism of action.

The present work involves the creation of a model that makes the rapid study of anticancer drugs possible. In order to make possible the multilevel study of antineoplastic derivatives (their effects on cell proliferation, their cell kinetics, their chromatin texture and the study of their potential operating mechanisms), the computerized analysis of nuclear images linked to multivariate analysis was chosen, and, in so doing, took into account 15 computer-calculated morphonuclear parameters for Feulgen-stained cell nuclei. In order to validate the method it was subjected to a series of well-known cancer drugs. The present results are in agreement with those obtained by conventional methods similar to those used for the study of the cytotoxicity of anticancer molecules or their effect on cell kinetics. Multivariate analysis applied to the parameters described by image analysis should make possible the rapid study of new anticancer drugs together with the rapid orientation of studies undertaken to ascertain their operating mechanisms.

Animals↗

Histopathologic grading and DNA ploidy in relation to survival among 206 adult astrocytic tumor patients.

BACKGROUND: The authors studied the benefit of performing histopathologic grading and DNA ploidy characterization with respect to patient survival in a series of 206 astrocytomas (AST) for which they obtained 134 complete clinical follow-ups. METHODS: The material analyzed came from archival material, i.e., formalin-fixed paraffin-embedded tissues. DNA ploidy was assessed by means of a cell image processor computing the integrated optical density (IOD) on Feulgen-stained nuclei. RESULTS: Results showed that histopathologic diagnosis in three grades, i.e., AST, anaplastic astrocytoma (ANA), and glioblastoma multiforme (GBM), had a significant prognostic value. Patients with AST showed a mean survival time (between histopathologic diagnosis and death) of more than 36 +/- 6 months (AST versus ANA or GBM) (P less than 0.001). Patients with ANA and GBM showed a mean survival time of 15 +/- 2 and 10 +/- 1 months, respectively, (ANA versus GBM) (P less than 0.05). Patient age strongly correlated with survival. Patients younger than 40 years of age had a mean survival time of 20 +/- 4 months. Patients between 41 and 60 years of age had a mean survival time of 12 +/- 2 months, and patients older than 60 years of age had a mean survival time of 11 +/- 1 months. CONCLUSIONS: Considering DNA ploidy characterization, the authors noticed that aneuploid ANA (DNA index [DI] more than 1.30) were associated with a significantly higher mean patient survival time compared with that associated with euploid ANA. In contrast, the authors did not find this in either of the groups with AST and GBM. Recognizing six DNA histogram types (diploid, triploid, tetraploid, hyperdiploid, hypertriploid, and polymorphic), the authors observed that hypertriploid tumors were associated with greater patient survival compared with what happened in the cases of the five other DNA histogram types. This was true with respect to the three AST histopathologic types. Thus, DNA ploidy determination seemed helpful in characterizing aggressiveness in adult AST.

Adolescent↗

Spontaneous evolution of nuclear size and DNA content of non-small-cell-lung cancers grafted onto nude mice.

We monitored the biological evolution of four human non-small-cell lung cancers labeled KLX6, KLX7, KLX9, and KLX14 that had been grafted onto nude mice. This monitoring was carried out by means of digital cell image analysis which assessed morphometric (nuclear area, NA) and densitometric (nuclear DNA content, DI) features on Feulgen-stained nuclei from imprint smears. In each of the four models, the biological evolution of the NA and DI was characterized through their progression during serial passaging onto nude mice. The results show that of the four lung cancer models analyzed, one (KLX6) remained definitively stable with respect to its DNA content (DI assessments), while the other three, i.e., KLX7, KLX9, and KLX14, varied significantly. As assessed by the morphometric parameter, i.e., the NA, the four xenografted lines also varied significantly over serial passaging. In conclusion, we show that digital cell image analyses of Feulgen-stained cell nuclei including morphometric and densitometric parameters are a powerful tool for monitoring the biological evolution of human lung cancers grafted onto nude mice. We think therefore that the ploidy level of a tumor might be dependent upon its age and/or its related clinical stage.

Animals↗

Remission of Raynaud's phenomenon after L-thyroxine therapy in a patient with hypothyroidism.

A 50-year-old man is described who had a 15-year history of Raynaud's phenomenon with severe and frequent vasospastic attacks in his fingers and toes during the past years. Exacerbation of his digital symptoms, which started about 4 years ago, was accompanied by signs of thyroid deficiency, such as tiredness, memory impairment, decreased libido, constipation, dryness of skin and bradycardia. Hormonal evaluation revealed primary hypothyroidism and the patient began substitution therapy with L-thyroxine. After 2 months of treatment not only did he become euthyroid but the digital symptoms also disappeared. The patient may thus represent one of the very few cases whose thyroid replacement therapy proved to be highly effective in treating both hypothyroidism and Raynaud's phenomenon.

Humans↗

Computerized morphonuclear characteristics and DNA content of adenocarcinoma of the pancreas, chronic pancreatitis, and normal tissues: relationship with histopathologic grading.

We report the morphonuclear characteristics of normal (13 cases), benign (ie, chronic) pancreatitis (six cases), and neoplastic (ie, ductal) adenocarcinoma (22 cases) tissues of the pancreas. This description is based on computerized cell image analysis, which permits the determination of parameters related to the morphometric (nuclear area), densitometric (nuclear DNA content), and chromatin texture features of Feulgen-stained nuclei from paraffin-embedded archival material. We observed that nuclear area discriminates between normal and benign (ie, chronic pancreatitis) as opposed to neoplastic cell nuclei. Morphonuclear parameters describing chromatin pattern characteristics made it possible to discriminate between grade I pancreatic carcinoma and normal and benign cell nuclei on the one hand, and grades I and III carcinoma on the other hand. The nuclear DNA content increased in a continuous manner from normal and benign through low-grade to high-grade neoplastic tissues of the pancreas. Combining the morphometric, densitometric, and textural parameters into one equation, we were able to calculate a score (ie, the malignancy level index) that showed a close relationship to conventional histopathologic grading. Thus, the computer-aided diagnosis of cytologic specimens from pancreatic lesions offers information of the same significance as that obtained by conventional histopathologic grading.

Adenocarcinoma↗

Monitoring of radiotherapy-induced morphonuclear modifications in the MXT mouse mammary carcinoma by means of digital cell image analysis.

The present work deals with the characterization of the morphological changes induced by ionizing radiation on MXT mouse mammary cancer cell nuclei. The monitoring of the radiotherapy-induced morphonuclear modifications was carried out by means of digital cell image analysis, which made it possible to compute morphometric (nuclear area), densitometric (nuclear DNA content) and textural (chromatin pattern characteristics) parameters assessed on Feulgen-stained nuclei. The biological material was obtained from serial fine needle-aspirations performed on control tumors and 2Gy and 8Gy irradiated tumors. Digital cell image analyses were assessed at the 7th, 18th, and 28th days-post irradiation. We showed that radiotherapy induced specific morphonuclear modifications that appeared in a dose-dependent and time-dependent manner. The 2Gy and 8Gy radiotherapy doses led to an increase in the mean nuclear area value, this feature being observed at both the 1st and the 4th week post-irradiation. The resultant effect on the chromatin pattern characteristics corresponded to a decrease in overall condensation level as compared to the control cell nuclei. Finally, the mean nuclear DNA content increased at the 1st week post-irradiation, but decreased at the 4th week post-irradiation as compared to the MXT control tumor. Computerized cell image analysis, therefore, appears to be a useful tool in helping to monitor the radiotherapy-induced effects that occur in neoplastic cell nuclei and which can be observed by means of optical microscopy.

Animals↗