AIM--To investigate the prevalence and amount of polyploidy in fine needle aspiration specimens o... more AIM--To investigate the prevalence and amount of polyploidy in fine needle aspiration specimens of the liver, urinary cytospin preparations, and cytospin preparations from pleural and peritoneal fluid. METHODS--Cells from 44 liver smears, 48 urine specimens, and 46 pleural and peritoneal aspirations were examined. After Feulgen restaining the DNA content of 100 randomly selected nuclei was determined using a TAS-plus image
OBJECTIVE: To reach consensus on the application of quantitative cytochemical analysis of chromos... more OBJECTIVE: To reach consensus on the application of quantitative cytochemical analysis of chromosomal and DNA aneuploidy in cervical cytopathology. CONCLUSION: The current Pap test has limited specificity to predict cancer and its truly progressive pre-malignant lesions. Infection with human papillomavirus may trigger genetic instability, hyperproliferation and immortalization of the cervical mucosa and cause cervical cancer. Several related molecular markers have been shown to be informative about this neoplastic process. Quantitative analysis of chromosomal and DNA aneuploidy has been shown to be an important tool for identifying (progression to) high grade squamous intraepithelial lesions. A high degree of standardization (material handling, calibration and quality control, measurement and interpretation of results) is required for accurate and reproducible measurements. Areas for further study are presented.
Analytical cellular pathology: the journal of the European Society for Analytical Cellular Pathology
A task force of invited experts in the field of diagnostic DNA image cytometry, especially consis... more A task force of invited experts in the field of diagnostic DNA image cytometry, especially consisting of participants from the PRESS (Prototype Reference Standard Slides) and EUROPATH (European Pathology Assisted by Telematics for Healthcare) projects, but open to any other scientist or physician revealing experience in that new diagnostic procedure (names are given in the Annex A) agreed upon the following updated consensus report during the 5th International Congress of the ESACP 1997 in Oslo. This report is based on the preceeding one [9] and on results of the above mentioned European research projects. It deals with the following items: Biological background and aims of DNA image cytometry, Principles of the method, Basic performance standards, Diagnostic interpretation of DNA measurements, Recommendations for practical use.
Verhandlungen der Deutschen Gesellschaft für Pathologie
Carcinogenesis of lung cancer proceeds via a complex process that involves multiple genetic abnor... more Carcinogenesis of lung cancer proceeds via a complex process that involves multiple genetic abnormalities, which do not necessarily have a linear progression. Genetic alterations include aneuploidy, deletions and amplifications of chromosomal regions, loss of heterozygosity (LOH), microsatellite alterations, point mutations and aberrant promoter methylation. There is considerable effort to use these genetic alterations as molecular biomarkers for early cancer diagnosis applying different approaches. An ideal tumor marker should be highly sensitive, tumor specific, easily to handle and non-cost intensive. While previous studies used screening for mutations, LOH and microsatellite alterations, more recent strategies concentrate on multicolor fluorescence in situ hybridization (FISH) and aberrant promoter methylation. Since in general the genetic alterations are prone to be more extensive in tumor cells as compared to non-tumor cells, methods that provide quantitative data (e.g., methy...
ZusammenfassungFragestellung Ziel dieser Arbeit war es, die Treffsicherheit der nichtinvasiven B... more ZusammenfassungFragestellung Ziel dieser Arbeit war es, die Treffsicherheit der nichtinvasiven Bürstenbiopsie einschließlich DNA-Bildzytometrie in der Routinediagnostik zu bestimmen.Material und Methode In unserer Untersuchung wurden prospektiv 1328 Mundschleimhautabstriche von 205 Patienten mit insgesamt 92 histologisch gesicherten Plattenepithelkarzinomen und 240 benignen Mundschleimhautläsionen zytologisch begutachtet und anschließend mithilfe der DNA-Bildzytometrie geprüft. Dabei wurden 47 Patienten mehrfach aufgrund rezidivierender Läsionen untersucht, 80 Patienten wiesen multiple Veränderungen der Mundhöhle auf.Ergebnisse Die zytologische Begutachtung der Präparate erzielte eine Sensitivität von 91,3% und eine Spezifität von 95,1%. Die nachfolgenden DNA-Messungen aller Präparate erreichten eine Sensitivität von 95,5% und eine Spezifität von 100%. Durch die kombinierte Auswertung der Zytologie und der DNA-Bildzytometrie konnte eine Steigerung der diagnostischen Treffsicherheit erreicht werden; die Sensitivität betrug dann 97,8% bei einer Spezifität von 100%. Der positive Vorhersagewert lag bei 100% und der negative Vorhersagewert erreichte 98,1%.Schlussfolgerung Die Anwendung der DNA-Bildzytometrie mit DNA-Aneuploidie als Marker für neoplastische Transformation in Mundschleimhautabstrichen sicherte die zytologische Diagnose von Mundkrebs. Zudem ermöglicht sie, die Dignität von morphologisch zweifelhaften Epithelveränderungen wie Dysplasien oder regenerativen Epithelien zu klären, indem sie die obligaten Präkanzerosen und die voraussichtlich bösartig verlaufenden Läsionen erkennt und eine frühzeitige effektive Therapie zulässt. Der Nachweis von DNA-Aneuploidie stellt somit die Indikation zur vollständigen chirurgischen Entfernung der Läsion mit histologischer Nachuntersuchung dar. Die DNA-Bildzytometrie als adjuvantes zytopathologisches Verfahren ist in der Lage, sowohl die Sensitivität als auch die Spezifität der nichtinvasiven Bürstenbiopsie der Mundschleimhaut zu erhöhen und die Rate von zytologisch falschnegativen und falschpositiven Diagnosen zu senken.
Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology, 2003
To date, there are only few systematic reports on the quality of DNA extracted from routine diagn... more To date, there are only few systematic reports on the quality of DNA extracted from routine diagnostic cytologic specimens. It was the aim of the present study to evaluate the ability of 50% ethanol/2% carbowax (Saccomanno fixative) to preserve bronchial secretions with high quality genomic DNA as well as to compare different DNA extraction methods. DNA was extracted from 45 bronchial aspirates by four different extraction protocols. Beside DNA yield, DNA quality with regard to purity, integrity, and PCR success rate were investigated. No fragmentation of sample DNA due to the fixative was detected. It was preserved as high molecular weight DNA. DNA yield, purity, and integrity were dependent on the DNA extraction method to some extend. Irrespective of the DNA extraction method the PCR success rate for amplification of beta-globin gene fragments (268, 536, and 989 bp) was 100%. A fixative containing 50% ethanol/2% carbowax preserves high quality DNA which is well suited for PCR-base...
Late diagnosis resulting in late treatment and locoregional failure after surgery are the main ca... more Late diagnosis resulting in late treatment and locoregional failure after surgery are the main causes of death in patients with oral squamous cell carcinomas (SCCs). Actually, exfoliative cytology is increasingly used for early detection of oral cancer and has been the subject of intense research over the last five years. Significant advances have been made both in relation to screening and evaluation of precursor lesions. As this noninvasive procedure is well tolerated by patients, more lesions may be screened and thus more oral cancers may be found in early, curable stages. Moreover, the additional use of DNA image cytometry is a reasonable tool for the assessment of the resection margins of SCC. DNA image cytometry could help to find the appropriate treatment option for the patients. Finally, diagnostic DNA image cytometry is an accurate method and has internationally been standardized. In conclusion, DNA image cytometry has increasing impact on the prevention, diagnostic, and th...
Primitive neuroectodermal tumors (PNETs) of the kidney, a rare neoplastic disease of high maligna... more Primitive neuroectodermal tumors (PNETs) of the kidney, a rare neoplastic disease of high malignancy with a tendency towards early metastasis, affect young adults (26-30 years) irrespective of the gender. Differential diagnosis from other renal tumors is very important for an effective therapy. Herein, we report on a 24-year-old male patient with a renal tumor consisting of small, round cells, and summarize the diagnostic procedures that establish the diagnosis of PNET. Light microscopy revealed not only areas containing small, round cells forming rosettes and pseudorosettes, but also areas containing spindle cells. Expression of CD 99 in combination with neural markers, such as NSE, was detected by immunohistochemistry, and further evidence of neural differentiation was provided by electron microscopy. Image cytometry revealed a peridiploid DNA-stemline. A reciprocal translocation of the chromosomes 11 and 22 [t(11;22)(q24;q12)] with expression of a EWS/FLI-1 fusion transcript was ...
Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology, 2001
To assess the prognostic value of DNA-image cytometry in cervical carcinoma of the uterus and its... more To assess the prognostic value of DNA-image cytometry in cervical carcinoma of the uterus and its relation to other established prognostic factors. The study included 116 cases of cervical carcinoma FIGO stages IB and II which were treated with radical abdominal hysterectomy. The median follow-up was 55 months (range 1-162 months). DNA image cytometry was performed on cytologic specimens prepared by enzymatic cell separation from formalin-fixed, paraffin-embedded tissues. DNA stemline ploidy, DNA stemline aneuploidy, 5c exceeding rate, 9c exceeding rate, 2c deviation index, and DNA malignancy grade were computed. DNA-variables as well as various clinical and histological variables were related to survival rates. In multivariate statistical analysis DNA stemline ploidy using 2.2c as a cut-off value and FIGO stage showed to be statistically significant available presurgery predictors of survival, whereas the postsurgical parameters lymphonodal status, tumor size and parametrial involv...
Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology, 2000
Heterogeneity of prostate carcinoma is one of the reasons for pretreatment underestimation of tum... more Heterogeneity of prostate carcinoma is one of the reasons for pretreatment underestimation of tumor aggressiveness. We studied tumor heterogeneity and the probability of finding the highest tumor grade and DNA aneuploidy with relation to the number of biopsies. Specimens simulating core biopsies from five randomly selected tumor areas from each of 16 Böcking's grade II and 23 grade III prostate carcinomas were analyzed for tumor grade and DNA ploidy by flow- and fluorescence image cytometry (FCM, FICM). Cell cycle composition was measured by FCM. By determination of ploidy and cell cycle composition, morphologically defined tumors can further be subdivided. Heterogeneity of tumor grade and DNA ploidy (FCM) was 54% and 50%. Coexistence of diploid tumor cells in aneuploid specimens represents another form of tumor heterogeneity. The proportion of diploid tumor cells decreased significantly with tumor grade and with increase in the fraction of proliferating cell of the aneuploid tu...
American journal of obstetrics and gynecology, Jan 15, 1982
Fetal breathing movements and gross fetal body movements were studied subsequent to the intraveno... more Fetal breathing movements and gross fetal body movements were studied subsequent to the intravenous injection of either 25 gm of glucose or an equal volume of normal saline solution in 10 healthy women with uncomplicated pregnancies at 38 to 40 weeks' gestation. The incidence of fetal breathing increased from 17.5% during the control period to 54.9% after glucose injection. Neither glucose nor saline solution had any effect on the incidence of gross fetal body movements. All fetuses made some breathing movements during any 15-minute interval between 30 and 75 minutes after glucose injection. These data suggest a useful strategy for clinical measurement of fetal breathing activity near term.
The flow of fluid within the trachea of fetal sheep (121-135 days) has been measured using a newl... more The flow of fluid within the trachea of fetal sheep (121-135 days) has been measured using a newly developed flowmeter. The flowmeter, which is basically a miniature servo-controlled peristaltic pump, is connected in series with an extra-corporeal tracheal loop. Integrated tracheal flow was measured for periods of at least 8 h in 5 control fetuses during which we determined its relationship to fetal breathing movements detected by EMG's of inspiratory muscles or tracheal pressure fluctuations. The overall flow of fluid away from the lungs was 14.4 ml/h; on average outward flow was 5.3 times greater during episodes of breathing movements than during apnea. Interruption of the motor innervation of the larynx in 5 fetuses led to a 25% reduction in mean overall flow and, compared with control fetuses, there was a reduction in net flow associated with breathing movements and an increased flow during apnea. These findings suggest that tracheal flow is normally retarded by a laryngeal ...
Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology, 1991
The DNA distribution was analyzed in 29 cases of oral lichen ruber planus that were negative for ... more The DNA distribution was analyzed in 29 cases of oral lichen ruber planus that were negative for human papillomavirus and not suspected of being precancerous. Monolayer smears prepared from formalin-fixed, paraffin-embedded tissues were automatically Feulgen stained and used for rapid interactive DNA cytometry via a TV-based image analysis system combined with an automated microscope. Nuclei with DNA contents greater than 4c were found in 25 cases (86%). DNA contents greater than 8c were seen in five cases (17%), and small peaks at 8c were found in three cases. These increased DNA values in nonprecancerous lesions must be interpreted as euploid polyploidization and have to be taken into account if DNA measurements are performed for diagnostic purposes in lichen ruber planus lesions that are suspected of having malignant transformation.
The paper describes the key component of the Multimodal Cell Analysis approach, a novel cytologic... more The paper describes the key component of the Multimodal Cell Analysis approach, a novel cytologic evaluation method for early cancer detection. The approach is based on a repeated staining of a cell smear. The correlation of features and data extracted from different stainings, and related to relocated individual cells, will yield a dramatic increase of diagnostic reliability. The necessary fully automatic preprocessing steps are presented: coregistration of multimodal images, segmentation, and classification of cell nuclei. Both efficiency and robustness of all steps reached at the current stage of research, are high regarding medical image material, and strongly support clinical application.
AIM--To investigate the prevalence and amount of polyploidy in fine needle aspiration specimens o... more AIM--To investigate the prevalence and amount of polyploidy in fine needle aspiration specimens of the liver, urinary cytospin preparations, and cytospin preparations from pleural and peritoneal fluid. METHODS--Cells from 44 liver smears, 48 urine specimens, and 46 pleural and peritoneal aspirations were examined. After Feulgen restaining the DNA content of 100 randomly selected nuclei was determined using a TAS-plus image
OBJECTIVE: To reach consensus on the application of quantitative cytochemical analysis of chromos... more OBJECTIVE: To reach consensus on the application of quantitative cytochemical analysis of chromosomal and DNA aneuploidy in cervical cytopathology. CONCLUSION: The current Pap test has limited specificity to predict cancer and its truly progressive pre-malignant lesions. Infection with human papillomavirus may trigger genetic instability, hyperproliferation and immortalization of the cervical mucosa and cause cervical cancer. Several related molecular markers have been shown to be informative about this neoplastic process. Quantitative analysis of chromosomal and DNA aneuploidy has been shown to be an important tool for identifying (progression to) high grade squamous intraepithelial lesions. A high degree of standardization (material handling, calibration and quality control, measurement and interpretation of results) is required for accurate and reproducible measurements. Areas for further study are presented.
Analytical cellular pathology: the journal of the European Society for Analytical Cellular Pathology
A task force of invited experts in the field of diagnostic DNA image cytometry, especially consis... more A task force of invited experts in the field of diagnostic DNA image cytometry, especially consisting of participants from the PRESS (Prototype Reference Standard Slides) and EUROPATH (European Pathology Assisted by Telematics for Healthcare) projects, but open to any other scientist or physician revealing experience in that new diagnostic procedure (names are given in the Annex A) agreed upon the following updated consensus report during the 5th International Congress of the ESACP 1997 in Oslo. This report is based on the preceeding one [9] and on results of the above mentioned European research projects. It deals with the following items: Biological background and aims of DNA image cytometry, Principles of the method, Basic performance standards, Diagnostic interpretation of DNA measurements, Recommendations for practical use.
Verhandlungen der Deutschen Gesellschaft für Pathologie
Carcinogenesis of lung cancer proceeds via a complex process that involves multiple genetic abnor... more Carcinogenesis of lung cancer proceeds via a complex process that involves multiple genetic abnormalities, which do not necessarily have a linear progression. Genetic alterations include aneuploidy, deletions and amplifications of chromosomal regions, loss of heterozygosity (LOH), microsatellite alterations, point mutations and aberrant promoter methylation. There is considerable effort to use these genetic alterations as molecular biomarkers for early cancer diagnosis applying different approaches. An ideal tumor marker should be highly sensitive, tumor specific, easily to handle and non-cost intensive. While previous studies used screening for mutations, LOH and microsatellite alterations, more recent strategies concentrate on multicolor fluorescence in situ hybridization (FISH) and aberrant promoter methylation. Since in general the genetic alterations are prone to be more extensive in tumor cells as compared to non-tumor cells, methods that provide quantitative data (e.g., methy...
ZusammenfassungFragestellung Ziel dieser Arbeit war es, die Treffsicherheit der nichtinvasiven B... more ZusammenfassungFragestellung Ziel dieser Arbeit war es, die Treffsicherheit der nichtinvasiven Bürstenbiopsie einschließlich DNA-Bildzytometrie in der Routinediagnostik zu bestimmen.Material und Methode In unserer Untersuchung wurden prospektiv 1328 Mundschleimhautabstriche von 205 Patienten mit insgesamt 92 histologisch gesicherten Plattenepithelkarzinomen und 240 benignen Mundschleimhautläsionen zytologisch begutachtet und anschließend mithilfe der DNA-Bildzytometrie geprüft. Dabei wurden 47 Patienten mehrfach aufgrund rezidivierender Läsionen untersucht, 80 Patienten wiesen multiple Veränderungen der Mundhöhle auf.Ergebnisse Die zytologische Begutachtung der Präparate erzielte eine Sensitivität von 91,3% und eine Spezifität von 95,1%. Die nachfolgenden DNA-Messungen aller Präparate erreichten eine Sensitivität von 95,5% und eine Spezifität von 100%. Durch die kombinierte Auswertung der Zytologie und der DNA-Bildzytometrie konnte eine Steigerung der diagnostischen Treffsicherheit erreicht werden; die Sensitivität betrug dann 97,8% bei einer Spezifität von 100%. Der positive Vorhersagewert lag bei 100% und der negative Vorhersagewert erreichte 98,1%.Schlussfolgerung Die Anwendung der DNA-Bildzytometrie mit DNA-Aneuploidie als Marker für neoplastische Transformation in Mundschleimhautabstrichen sicherte die zytologische Diagnose von Mundkrebs. Zudem ermöglicht sie, die Dignität von morphologisch zweifelhaften Epithelveränderungen wie Dysplasien oder regenerativen Epithelien zu klären, indem sie die obligaten Präkanzerosen und die voraussichtlich bösartig verlaufenden Läsionen erkennt und eine frühzeitige effektive Therapie zulässt. Der Nachweis von DNA-Aneuploidie stellt somit die Indikation zur vollständigen chirurgischen Entfernung der Läsion mit histologischer Nachuntersuchung dar. Die DNA-Bildzytometrie als adjuvantes zytopathologisches Verfahren ist in der Lage, sowohl die Sensitivität als auch die Spezifität der nichtinvasiven Bürstenbiopsie der Mundschleimhaut zu erhöhen und die Rate von zytologisch falschnegativen und falschpositiven Diagnosen zu senken.
Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology, 2003
To date, there are only few systematic reports on the quality of DNA extracted from routine diagn... more To date, there are only few systematic reports on the quality of DNA extracted from routine diagnostic cytologic specimens. It was the aim of the present study to evaluate the ability of 50% ethanol/2% carbowax (Saccomanno fixative) to preserve bronchial secretions with high quality genomic DNA as well as to compare different DNA extraction methods. DNA was extracted from 45 bronchial aspirates by four different extraction protocols. Beside DNA yield, DNA quality with regard to purity, integrity, and PCR success rate were investigated. No fragmentation of sample DNA due to the fixative was detected. It was preserved as high molecular weight DNA. DNA yield, purity, and integrity were dependent on the DNA extraction method to some extend. Irrespective of the DNA extraction method the PCR success rate for amplification of beta-globin gene fragments (268, 536, and 989 bp) was 100%. A fixative containing 50% ethanol/2% carbowax preserves high quality DNA which is well suited for PCR-base...
Late diagnosis resulting in late treatment and locoregional failure after surgery are the main ca... more Late diagnosis resulting in late treatment and locoregional failure after surgery are the main causes of death in patients with oral squamous cell carcinomas (SCCs). Actually, exfoliative cytology is increasingly used for early detection of oral cancer and has been the subject of intense research over the last five years. Significant advances have been made both in relation to screening and evaluation of precursor lesions. As this noninvasive procedure is well tolerated by patients, more lesions may be screened and thus more oral cancers may be found in early, curable stages. Moreover, the additional use of DNA image cytometry is a reasonable tool for the assessment of the resection margins of SCC. DNA image cytometry could help to find the appropriate treatment option for the patients. Finally, diagnostic DNA image cytometry is an accurate method and has internationally been standardized. In conclusion, DNA image cytometry has increasing impact on the prevention, diagnostic, and th...
Primitive neuroectodermal tumors (PNETs) of the kidney, a rare neoplastic disease of high maligna... more Primitive neuroectodermal tumors (PNETs) of the kidney, a rare neoplastic disease of high malignancy with a tendency towards early metastasis, affect young adults (26-30 years) irrespective of the gender. Differential diagnosis from other renal tumors is very important for an effective therapy. Herein, we report on a 24-year-old male patient with a renal tumor consisting of small, round cells, and summarize the diagnostic procedures that establish the diagnosis of PNET. Light microscopy revealed not only areas containing small, round cells forming rosettes and pseudorosettes, but also areas containing spindle cells. Expression of CD 99 in combination with neural markers, such as NSE, was detected by immunohistochemistry, and further evidence of neural differentiation was provided by electron microscopy. Image cytometry revealed a peridiploid DNA-stemline. A reciprocal translocation of the chromosomes 11 and 22 [t(11;22)(q24;q12)] with expression of a EWS/FLI-1 fusion transcript was ...
Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology, 2001
To assess the prognostic value of DNA-image cytometry in cervical carcinoma of the uterus and its... more To assess the prognostic value of DNA-image cytometry in cervical carcinoma of the uterus and its relation to other established prognostic factors. The study included 116 cases of cervical carcinoma FIGO stages IB and II which were treated with radical abdominal hysterectomy. The median follow-up was 55 months (range 1-162 months). DNA image cytometry was performed on cytologic specimens prepared by enzymatic cell separation from formalin-fixed, paraffin-embedded tissues. DNA stemline ploidy, DNA stemline aneuploidy, 5c exceeding rate, 9c exceeding rate, 2c deviation index, and DNA malignancy grade were computed. DNA-variables as well as various clinical and histological variables were related to survival rates. In multivariate statistical analysis DNA stemline ploidy using 2.2c as a cut-off value and FIGO stage showed to be statistically significant available presurgery predictors of survival, whereas the postsurgical parameters lymphonodal status, tumor size and parametrial involv...
Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology, 2000
Heterogeneity of prostate carcinoma is one of the reasons for pretreatment underestimation of tum... more Heterogeneity of prostate carcinoma is one of the reasons for pretreatment underestimation of tumor aggressiveness. We studied tumor heterogeneity and the probability of finding the highest tumor grade and DNA aneuploidy with relation to the number of biopsies. Specimens simulating core biopsies from five randomly selected tumor areas from each of 16 Böcking's grade II and 23 grade III prostate carcinomas were analyzed for tumor grade and DNA ploidy by flow- and fluorescence image cytometry (FCM, FICM). Cell cycle composition was measured by FCM. By determination of ploidy and cell cycle composition, morphologically defined tumors can further be subdivided. Heterogeneity of tumor grade and DNA ploidy (FCM) was 54% and 50%. Coexistence of diploid tumor cells in aneuploid specimens represents another form of tumor heterogeneity. The proportion of diploid tumor cells decreased significantly with tumor grade and with increase in the fraction of proliferating cell of the aneuploid tu...
American journal of obstetrics and gynecology, Jan 15, 1982
Fetal breathing movements and gross fetal body movements were studied subsequent to the intraveno... more Fetal breathing movements and gross fetal body movements were studied subsequent to the intravenous injection of either 25 gm of glucose or an equal volume of normal saline solution in 10 healthy women with uncomplicated pregnancies at 38 to 40 weeks' gestation. The incidence of fetal breathing increased from 17.5% during the control period to 54.9% after glucose injection. Neither glucose nor saline solution had any effect on the incidence of gross fetal body movements. All fetuses made some breathing movements during any 15-minute interval between 30 and 75 minutes after glucose injection. These data suggest a useful strategy for clinical measurement of fetal breathing activity near term.
The flow of fluid within the trachea of fetal sheep (121-135 days) has been measured using a newl... more The flow of fluid within the trachea of fetal sheep (121-135 days) has been measured using a newly developed flowmeter. The flowmeter, which is basically a miniature servo-controlled peristaltic pump, is connected in series with an extra-corporeal tracheal loop. Integrated tracheal flow was measured for periods of at least 8 h in 5 control fetuses during which we determined its relationship to fetal breathing movements detected by EMG's of inspiratory muscles or tracheal pressure fluctuations. The overall flow of fluid away from the lungs was 14.4 ml/h; on average outward flow was 5.3 times greater during episodes of breathing movements than during apnea. Interruption of the motor innervation of the larynx in 5 fetuses led to a 25% reduction in mean overall flow and, compared with control fetuses, there was a reduction in net flow associated with breathing movements and an increased flow during apnea. These findings suggest that tracheal flow is normally retarded by a laryngeal ...
Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology, 1991
The DNA distribution was analyzed in 29 cases of oral lichen ruber planus that were negative for ... more The DNA distribution was analyzed in 29 cases of oral lichen ruber planus that were negative for human papillomavirus and not suspected of being precancerous. Monolayer smears prepared from formalin-fixed, paraffin-embedded tissues were automatically Feulgen stained and used for rapid interactive DNA cytometry via a TV-based image analysis system combined with an automated microscope. Nuclei with DNA contents greater than 4c were found in 25 cases (86%). DNA contents greater than 8c were seen in five cases (17%), and small peaks at 8c were found in three cases. These increased DNA values in nonprecancerous lesions must be interpreted as euploid polyploidization and have to be taken into account if DNA measurements are performed for diagnostic purposes in lichen ruber planus lesions that are suspected of having malignant transformation.
The paper describes the key component of the Multimodal Cell Analysis approach, a novel cytologic... more The paper describes the key component of the Multimodal Cell Analysis approach, a novel cytologic evaluation method for early cancer detection. The approach is based on a repeated staining of a cell smear. The correlation of features and data extracted from different stainings, and related to relocated individual cells, will yield a dramatic increase of diagnostic reliability. The necessary fully automatic preprocessing steps are presented: coregistration of multimodal images, segmentation, and classification of cell nuclei. Both efficiency and robustness of all steps reached at the current stage of research, are high regarding medical image material, and strongly support clinical application.
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