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K Kayser

Publications and source records attributed to K Kayser.

At least 37 records · Page 2Linked to original sources

Telepathology overview: from concept to implementation.

Telepathology is the practice of pathology at a distance by using video imaging and telecommunications. Significant progress has been made in telepathology. To date, 12 classes of telepathology systems have been engineered. Rapid and ultrarapid virtual slide processors may further expand the range of telepathology applications. Next-generation digital imaging light microscopes, such as miniaturized microscope arrays (MMA), may make virtual slide processing a routine laboratory tool. Diagnostic accuracy of telepathology is comparable with that of conventional light microscopy for most diagnoses. Current telepathology applications include intraoperative frozen sections services, routine surgical pathology services, second opinions, and subspecialty consultations. Three telepathology practice models are discussed: the subspecialty practice (SSP) model; the case triage practice (CTP) model; and the virtual group practice (VGP) model. Human factors influence performance with telepathology. Experience with 500 telepathology cases from multiple organs significantly reduces the video viewing time per case (P < .01). Many technology innovations can be represented as S-curves. After long incubation periods, technology use and/or efficiency may accelerate. Telepathology appears to be following an S-curve for a technical innovation.

Diffusion of Innovation↗

Relevance of N-acetyltransferase 1 and 2 (NAT1, NAT2) genetic polymorphisms in non-small cell lung cancer susceptibility.

The highly polymorphic N-acetyltransferases (NAT1 and NAT2) are involved in both activation and inactivation reactions of numerous carcinogens, such as tobacco derived aromatic amines. The potential effect of the NAT genotypes in individual susceptibility to lung cancer was examined in a hospital based case-control study consisting of 392 Caucasian lung cancer patients [152 adenocarcinomas, 173 squamous cell carcinomas (SCC) and 67 other primary lung tumours] and 351 controls. In addition to the wild-type allele NAT1*4, seven variant NAT1 alleles (NAT1*3, *10, *11, *14, *15, *17 and *22) were analysed. A new method based on the LightCycler (Roche Diagnostics Inc.) technology was applied for the detection of the polymorphic NAT1 sites at nt 1088 and nt 1095. The NAT2 polymorphic sites at nt 481, 590, 803 and 857 were detected by polymerase chain reaction-restriction fragment length polymorphism or LightCycler. Multivariate logistic regression analyses were performed taking into account levels of smoking, age, gender and occupational exposure. An increased risk for adenocarcinoma among the NAT1 putative fast acetylators [odds ratio (OR) 1.92 (1.16-3.16)] was found but could not be detected for SCC or the total case group. NAT2 genotypes alone appeared not to modify individual lung cancer risk, however, individuals with combined NAT1 fast and NAT2 slow genotype had significantly elevated adenocarcinoma risk [OR 2.22 (1.03-4.81)] compared to persons with other genotype combinations. These data clearly show the importance of separating different histological lung tumour subtypes in studies on genetic susceptibility factors and implicate the NAT1*10 allele as a risk factor for adenocarcinoma.

Aged↗

Glutathione-S-transferase M1, M3, T1 and P1 polymorphisms and susceptibility to non-small-cell lung cancer subtypes and hamartomas.

Polymorphic glutathione-S-transferase (GST) genes causing variations in enzyme activity may influence individual susceptibility to lung cancer. In this case-control study (consisting of 389 Caucasian lung cancer patients, including 151 adenocarcinomas (ACs) and 172 squamous cell carcinomas (SCCs), and 353 hospital control subjects without malignant disease, genotype frequencies for GSTM1, GSTM3, GSTP1 and GSTT1 were determined by polymerase chain reaction (PCR)/ restriction fragment length polymorphism (RFLP)-based methods. While adjusted odds ratios (ORs) indicated no significantly increased risk for lung cancer overall due to any single GST genotype, the risk alleles for GSTM1, GSTM3 and GSTP1 conferring reduced enzyme activity were present at higher frequency in SCC than in AC patients. This is consistent with a reduced detoxification of carcinogenic polycyclic aromatic hydrocarbons (PAHs) from cigarette smoke that are more important for the development of SCC than for AC. An explorative data analysis also identified statistically significantly increased ORs for the combinations GSTT1 non-null and GSTP1 GG or AG for lung cancer overall (OR 2.23, CI 1.11-4.45), and for SCC (OR 2.69, CI 1.03-6.99). For lung cancer overall, and especially among SCC patients, the GSTT1 null genotype was underrepresented (SCC 11.2% v. control subjects 19%, P = 0.026, OR 0.57, CI 0.30-1.06). Additionally, in 28 patients with hamartomas, the GSTT1 null genotype was also protective (P = 0.013), while GSTP1 variant allele carriers were overrepresented (OR 2.48, CI 1.06-6.51). In conclusion, GST genotypes may act differently, either by detoxifying harmful tobacco carcinogens and/or by eliminating lung cancer chemopreventive agents. The latter role for GSTT1 would explain the observed lower risk of SCC and hamartoma associated with GSTT1 null. Further confirmatory studies are required.

Adenocarcinoma↗

Stimulus characteristics within directives: effects on accuracy of task completion.

Three experiments were conducted in an outpatient setting with young children who had been referred for treatment of noncompliant behavior and who had coexisting receptive language or receptive vocabulary difficulties. Experiment 1 studied differential responding of the participants to a brief hierarchical directive analysis (least-to-most complex stimulus prompts) to identify directives that functioned as discriminative stimuli for accurate responding. Experiment 1 identified distinct patterns of accurate responding relative to manipulation of directive stimulus characteristics. Experiment 2 demonstrated that directives identified as effective or ineffective in obtaining stimulus control of accurate responding during Experiment 1 continued to control accurate responding across play activities and academic tasks. Experiment 3 probed effects of the interaction between the type of directive (effective vs. ineffective) and the reinforcement contingency (differential reinforcement for attempts vs. differential reinforcement for accurate responses) on accurate task completion and disruptive behavior. Results suggested that behavioral escalation from inaccurate responding to disruptive behavior occurred only when ineffective directives were combined with differential reinforcement for accurate task completion. The overall results are discussed in terms of developing a methodology for identifying stimulus characteristics of directives that affect accurate responding.

Child↗

[Telepathology in diagnostic consultations for controversial neoplastic growths in the lung--personal experience].

The authors assessed the diagnostic accuracy of the static telepathology (sTP) for practical consultations in the controversial pulmonary oncology cases. The short characteristics of the diagnostic cases is included. We reported the results of 6 difficult clinico-pathological cases submitted to Dept Quantitative Pathology [DQP] for consultations (5F and 1M, age: 26-68 yrs). Digital images of histological or cytological samples were captured at DQP and transmitted to telepathologist (TPat) in Thoraxklinik, Heidelberg or AFIP, Washington DC. Simultaneously, the same slides (or with a paraffin block) were mailed to TPats for re-evaluation with the conventional microscope (dgn-zwPat). The controversial cases presented 2 types of diagnostic problems: 1/rare entities, 2/common difficulties in the routine work of pathologist, but with indefinitely proved diagnosis. The first group encounters TPat diagnoses as follows: * case A: pulmonary plasma cell granuloma with lymphoidal interstitial infiltrates [LIP]--preleukemia; * case B: microfoci of early metastases of benign uterine leiomyoma; * case D: small cell carcinoma spreading along pleura. The second group included: * case C: invasive epidermoidal carcinoma in bronchus; *case E: probably metastatic adenocarcinoma of colon; *case F: synchronous or metastasising 2 lung tumours sharing NE morphology or NE immunohistochemical features. There was very high concordance between referring pathologist (ref-Pat) diagnoses and TPat diagnoses as well as a consensus in zw-TPat diagnoses. In 2 cases the conceptual problem was solved by TPat. Telepathology offered a support or improved the quality of the final diagnosis. The implementation of sTP remarkably reduced the time of consultations and allowed to present the diagnostic problems to the international group of experts.

Adenocarcinoma↗

hOGG1 polymorphism and loss of heterozygosity (LOH): significance for lung cancer susceptibility in a caucasian population.

Oxidative damage is implicated in several chronic diseases including cancer. 8-Hydroxyguanine (8-oxoG) is one of the major promutagenic DNA lesions, which is produced by reactive oxygen species, causes G:C to T:A transversions and is excised by OGG1, an 8-oxoG specific DNA glycosylase/AP-Lyase. In a nested case-control study, gDNA from 105 Caucasian primary non-small cell lung cancer cases and 105 matched controls was screened for 6 possible new polymorphic sites in the human OGG1 gene, detected previously mainly in tumour tissue. The previously described Ser(326)Cys polymorphism was found to be common (allele frequency 0.22) in Caucasians. However, no major difference in Ser(326)Cys genotype distribution could be detected between cases and controls. Two 5;-end polymorphisms previously found in Japanese as well as Arg(131)Gln could not be detected in this population. An Ala(85)Ser polymorphism was found in 2 controls, whereas Arg(46)Gln was detected in only 1 case. As the hOGG1 gene is mapped (3p26.2) to a region frequently lost in primary lung tumours, the frequency of loss of heterozygosity (LOH) was investigated. Forty-three percent of the studied lung tumours exhibited loss of one of the hOGG1 alleles. The wt Ser(326) allele was not predominantly lost in our sample set, which suggests a minor role of this polymorphism in tumourgenesis. Our results show that LOH at the hOGG1 gene locus is a very common occurrence in lung tumourgenesis, possibly leading to increased mutational damage due to ROS in smokers. However, the hOGG1 polymorphisms studied are probably not major contributors to individual lung cancer susceptibility in Caucasians.

Adenocarcinoma↗

Cathepsin B in infiltrated lymph nodes is of prognostic significance for patients with nonsmall cell lung carcinoma.

BACKGROUND: Tumor cells require specific proteolytic enzymes for invasion and metastasis, including lysosomal peptidases--cathepsins. Cathepsin B is a lysosomal cysteine peptidase, which appears to play a major role in invasion and metastasis of human tumors. In this study, the authors focused on the possible role of cathepsin B in lymphogenic metastasis by investigating the enzyme localization and its activity in lung tumors and corresponding tumor-infiltrated lymph nodes. METHODS: Cathepsin B activity was determined in lung tumors, lung parenchyma, and tumor cell-infiltrated and noninfiltrated regional lymph nodes of the same patient. The authors investigated 35 cancer patients suffering from nonsmall cell lung carcinoma. Cathepsin B throughout activity was measured by cleavage of the fluorogenic substrate Z-Arg-Arg-AMC at pH 6.0. RESULTS: The median specific cathepsin B activity was highest in tumors, followed by the infiltrated lymph nodes, noninfiltrated lymph nodes, and lung parenchyma. The authors showed a significant 1.8-fold increase in cathepsin B activity in tumor-infiltrated lymph nodes compared with noninfiltrated regional lymph nodes and a 4.5-fold increase in lung tumor tissue compared with lung parenchyma. High cathepsin B activity, both in tumors and tumor cell-infiltrated lymph nodes, indicated poor prognosis for overall survival. Immunohistochemical analysis showed the presence of cathepsin B in histiocytes and tumor cells but not in lymphocytes of lymph node tissue. CONCLUSIONS: The authors' findings on higher cathepsin B levels in tumor cell-infiltrated lymph nodes show that increased level of cathepsin B activity is characteristic of the invasive tumor cell phenotype. This corroborates the hypothesis, that tumor cell associated cathepsin B may play a role in lymphogenic metastasis. The authors' results support the use of lymph node associated cathepsin B as a prognostic factor for survival of patients with lung carcinoma.

Adult↗

Benign metastasizing leiomyoma of the uterus: documentation of clinical, immunohistochemical and lectin-histochemical data of ten cases.

The clinical histories of 10 women suffering from benign metastasizing leiomyoma (BML) after hysterectomy and information on lung lesions detected in these women are presented, together with corresponding data for 2 women with metastasizing leiomyosarcoma of the uterus for comparison: gross appearance, survival, and light microscopical, immunohistochemical and lectin-histochemical findings are reported. All patients with BML had undergone hysterectomy for uterus leiomyomatosus without any detection of sarcomatous lesions in the uterus wall. After a median period of 14.9 years intrapulmonary masses were detected by imaging techniques. On average, six nodules with a mean diameter of 1.8 cm were seen. Resection of the lesions was performed in all cases. The immunohistochemical and lectin-histochemical examination of the tumors included analysis of the proliferation-associated protein Ki-67, the p53 protein, estrogen and progesterone receptor, sarcolectin as an indicator of the presence of lymphokine macrophage migration inhibitory factor, antibodies and the labeled protein to assess galectin (galactoside-binding animal lectin)-dependent parameters, analysis of tumor vascularization (CD-34), and expression of bcl-2, vimentin, smooth muscle actin, desmin, and keratin. The lesions were characterized by low proliferation activity of 2.9% (measured with Ki-67), frequent hormone receptor expression (8 of the 10 cases presented hormone-specific receptors), low to moderate vascularization compared with metastases from the two uterine sarcomas, remarkable p53 overexpression and frequent expression of the lymphokine, the galectins and accessible binding sites. The median survival of the BML patients was 94 months after excision of the intrapulmonary lesions, and the maximum survival of the two sarcoma patients was 22 months. The results recorded in this patient sample with the methodology applied suggest that benign metastasizing leiomyomas are a slow-growing variant of leiomyosarcoma of the uterus, which becomes clinically apparent at a young age and progresses with low velocity.

Adult↗

Association of concentration of asbestos and asbestos-like fibers with the patient's survival and the binding capacity of lung parenchyma to galectin-1 and natural alpha-galactoside- and alpha-mannoside-binding immunoglobulin G subfractions from human serum.

Our aim in this study was to search for lung parenchyma alterations associated with asbestos and/or asbestos-like fiber concentration. This was done by means of immuno- or glycohistochemistry. The hot-ashing technique determined the asbestos and asbestos-like fiber concentrations in the lung tissues of 100 patients of whom 52 were treated for primary lung and 25 for secondary lung tumors; fiber concentration was also measured for 23 patients whose disease was benign. The results were correlated to smoking habits, survival of the patients, and expression of binding capacities for endogenous lectins, natural carbohydrate-binding and lectin-specific antibodies. The cohort with proven asbestos exposure revealed a mean fiber concentration 114 f/g compared to 95 f/g in the non-exposed group. An increased asbestos fiber concentration was correlated to galectin-1-binding and the presence of epitopes for natural immunoglobulin G subfractions with selectivity to alpha-galactosides and alpha-mannosides. The survival of patients with primary and secondary lung tumors was negatively associated with the fiber concentration. The data indicate that increased presence of asbestos is correlated with an alteration of defined glycohistochemical features of alveolar lining cells.

Adult↗

Routine DNA cytometry of benign and malignant pleural effusions by means of the remote quantitation server Euroquant: a prospective study.

AIM: To analyse the practicability and potential assistance of static DNA cytometry performed by means of the remote quantitation server Euroquant and the internet in routine diagnostic analysis of pleural effusions, and to outline the role of DNA cytometry on pleural effusions in distinguishing between benign and malignant (and herein primary versus metastatic) effusions. MATERIALS AND METHODS: Cytological smears of 294 pleural effusions were stained with the Feulgen method. The DNA content of a minimum of 300 randomly chosen analysis nuclei and 30 reference nuclei (lymphocytes) was measured by internet connection to the remote quantitation server Euroquant. Cytometric features were derived from the histograms, and the time needed for case evaluation, the reliability of staining and measurement procedures, and the contribution to the final diagnosis were evaluated. RESULTS: Only 120 of 294 pleural effusions could be measured. The total measurement time for each specimen was 60 minutes. The guidelines of the consensus report on DNA measurements were fulfilled. Seventy eight malignant (18 mesotheliomas, 60 metastatic tumours) and 42 benign effusions were measured. Seven of 78 malignant effusions were euploid and none of 42 benign effusions were aneuploid. The sensitivity and specificity were 91% and 100%, respectively, for distinguishing benign from malignant effusions, and 95% and 100%, respectively, for discriminating between benign and malignant effusions caused by metastatic malignant tumours. CONCLUSIONS: Static DNA cytometry using the remote quantitation server Euroquant can be performed reliably in the routine diagnosis of pleural effusions; however, only 40% of effusions meet the technical requirements for static DNA cytometry. Within the measurable cases, static DNA cytometry made an important contribution to the confirmation/exclusion of malignancy.

Aged↗

Telediagnosis of transbronchial fine needle aspirations--a feasibility study.

AIM: To analyze the diagnostic accuracy of telediagnostic procedures for transbronchial fine needle aspirations. MATERIAL AND METHODS: A double blind study was performed on cytological slides of 54 randomly selected cases with transbronchial fine needle aspirations. The slides were digitized using a Leica digital camera DC100 mounted on a microscope Leica Laborlux S, and analyzed by an experienced pathologist without knowing the definite diagnosis or any additional clinical data. The diagnoses stated by analyzing the digital images were compared to the final conventional diagnoses. In addition, the duration of the digital diagnosis, used magnifications, and difficulties for correct sampling were documented. RESULTS: The "digital" diagnoses of the 54 cases were all in general agreement with the definite diagnoses. No wrong positive or wrong negative case in respect to malignant/non-malignant (31/23) or to small cell/non-small cell (9/22) occurred. The performance of a digital diagnosis lasted for 115 s at average (15-260 s), and is significantly longer compared to that of conventional fine needle aspiration judgement (20 s). The screening magnification was commonly set to x2.5, that for definite diagnostic analysis x40. Benign diseases (2 tuberculosis and 3 sarcoidosis cases) were correctly classified. CONCLUSIONS: Telepathology systems can probably be used for fine needle aspiration analysis without major diagnostic errors. Their use can improve the endoscopic sampling and avoid second anesthesia when missing the lesion of request during the first examination.

Adenocarcinoma, Bronchiolo-Alveolar↗

Diagnostic errors in interactive telepathology.

Telepathology (TP) as a service in pathology at a distance is now widely used. It is integrated in the daily workflow of numerous pathologists. Meanwhile, in Germany 15 departments of pathology are using the telepathology technique for frozen section service; however, a common recognised quality standard in diagnostic accuracy is still missing. In a first step, the working group Aurich uses a TP system for frozen section service in order to analyse the frequency and sources of errors in TP frozen section diagnoses for evaluating the quality of frozen section slides, the important components of image quality and their influences an diagnostic accuracy. The authors point to the necessity of an optimal training program for all participants in this service in order to reduce the risk of diagnostic errors. In addition, there is need for optimal cooperation of all partners involved in TP service.

Breast Neoplasms↗

Recent developments and present status of telepathology.

Telepathology which is the diagnostic work of a pathologist at a distance has been developed to routine application within the last ten years. It can be classified in relation to application, technical solutions, or performance conditions. Diagnostic pathology performance distinguishes primary diagnosis (for example, frozen section statement) from secondary diagnosis (for example, expert consultation) and quality assurance (diagnostic accuracy, continuous education and training). Applications comprise (a) frozen section service; (b) expert consultations; (c) remote control measurements; and (d) education and training. The technical solutions distinguish active (remote control, live imaging) systems from passive (conventional microscope handling, static imaging), and the performance systems with interactive (on-line, live imaging) use from those with passive (offline, static imaging) practice. Intra-operative frozen section service is mainly performed with remote control systems; whereas expert consultations and education/training are commonly based upon Internet connections with static imaging in an off-line mode. The image quality, transfer rates, and screen resolution of active and passive telepathology systems are sufficient for an additional or primary judgment of histological slides and cytological smears. From the technical point of view, remote control telepathology requires a fast transfer and at least near on-line judgement of images, i.e., image acquisition, transfer and presentation can be considered one performance function. Thus, image size, line transfer rate and screen resolution define the practicability of the system. In expert consultation, the pixel resolution of images and natural color presentation are the main factors for diagnostic support, whereas the line transfer rate is of minor importance. These conditions define the technical compartments, especially size and resolution of camera and screen. The performance of commercially available systems has reached a high quality standard. Pathologists can be trained in a short time and use the systems in a routine manner. Several telepathology systems have been implemented in large Institutes of Pathology which serve for frozen section diagnosis in small hospitals located in the local area. In contrast, expert consultation is mainly performed with international connections. There is a remarkable increase of expert consultations by telepathology according to the experiences of the Armed Forces Institute of Pathology or the Department of Pathology, Thoraxklinik, Heidelberg. In expansion of these experiences, a "globalization" of telepathology can be expected. Telepathology can be used to shrink the period necessary for final diagnosis by request for diagnostic assistance to colleagues working in appropriate related time zones. Telepathology is, therefore, not a substitute of conventional diagnostic procedures but a real improvement in the world of pathology.

Europe↗

Telecommunication--a new tool for quality assurance and control in diagnostic pathology.

Telepathology is the diagnostic work of a pathologist at a distance. It includes specific application fields which require specific system solutions. These comprise: a. frozen section service; b. expert consultations; c. remote control measurements, and d. education and training. Applications but, in addition, all aspects of diagnosis, especially those involved in the daily work flow of a pathologist. The image quality, transfer rates, and screen resolution of telepathology systems are sufficient for an additional or primary judgment of histological slides and cytological smears. It is, therefore, possible to include this technique into intralaboratory quality control of all steps of diagnostic procedures and to use this technique for quality assurance and control. Diagnostic quality is not a well defined term, and depends, in addition to external circumstances, on the diagnosis itself. The diagnostic quality can be maintained or even improved by use of telepathology systems. They can serve for control of image quality, access to various information sources, simultaneous transfer of images and diagnosis, and continuous education of the involved pathologists. For example, in continuous education and training, as a first step the pathologist should have access to an image data bank storing images related to the specific case, for example images taken from the same organ and from patients of similar age. The final stage would be an intra-diagnostic learning from the specific case; i.e. the time difference between questionnaires for a difficult diagnosis and the final diagnosis will become a minimum. Automated storing of the specific and diagnosis-associated images of the case will permit an open diagnostic system which will itself adjust to the micro-environment of the department of pathology. Although this future scenario has not been implemented to our knowledge, there is little doubt the development in telepathology will promote the technical procedures in the environment of a diagnostic pathologist. Telepathology is, therefore, not a substitute of conventional diagnostic procedures but a real improvement in the world of pathology.

Education, Medical, Continuing↗

Integrated nuclear fluorescence and expression of hormone-binding sites in malignant pleural effusions.

OBJECTIVE: To investigate potential disease- and prognosis-associated nuclear and cellular features from cell properties in a prospective study on malignant pleural effusions. STUDY DESIGN: Integrated nuclear fluorescence and the expression of binding capacities of carrier-immobilized estradiol, progesterone and testosterone; and of labeled sarcolectin; and the presence of calcyclin were measured in 50 cases with proven malignant pleural effusions (10 mesotheliomas, 40 metastasizing tumors). A double fluorescence technique using the fluorochrome DAPI and a Texas Red-based avidin-biotin detection system were applied. Detailed clinical data, including the follow-up for up to 40 months, were included. RESULTS: Pleural effusions in all patients with mesotheliomas occurred prior to (9/10) or at the time of histologic confirmation. Mesotheliomas had the highest tumor cell fraction (12.4%) in S phase and breast carcinomas the lowest (10.7%). More than 80% of malignant cells expressed binding capacities for the applied probes. A statistically significant correlation was noted between the S-phase-related tumor cell fraction and the expression of progesterone receptors. Survival was associated with tumor origin, treatment by pleurodesis, and certain cytometric and histochemical features. CONCLUSION: The immunofluorescence double-staining technique can be applied successfully in malignant effusions to combine DNA measurements with those of immunohistochemical and ligand histochemical reactivity.

Aged↗

The application of thermodynamic principles to histochemical and morphometric tissue research: principles and practical outline with focus on the glycosciences.

Physicochemical terms such as entropy or current of entropy are commonly used to refer solely to the description of reactions in the realm of chemistry and physics. Since these thermodynamic terms have a predictive value for the further course of development of such reactions, e.g., extent of a chemical reaction or affinity of molecular interactions, it is tempting to introduce the respective algorithms to biological problems. By combining quantitative morphology with the histochemical visualization of distinct cellular and textural properties such as nuclear DNA contents or intensity of histochemical staining, equations from the general theory of thermodynamics can be adapted. They permit appropriate calculations to be performed which introduce the entropy concept to the processing of the information collected by analysis of structures formed by histochemically labeling cells. The theory of weighted graphs offers the appropriate mathematical tools. Nuclei are defined as vertices. Their DNA contents measured by the integrated optical density or additional cellular features (for example staining intensity of applied immuno-/ligandohistochemical probes) define the associated weights and the minimum spanning tree as a derivative from Voronoi's theorem for the definition of the geometrical neighborhood. This technique is equivalent to syntactic structure analysis as developed by Lu and Fu (1978), Sanfeliu et al. (1981), Kayser and Schlegel (1982), and Kayser (1988). Assuming that the texture of a healthy tissue is displayed in the energetically most efficient and stable manner to perform the required biological functions, i.e., to maintain the lowest level of entropy, deviations from this level are reflected in differences in distances and weights between neighboring nuclei or cells. The measure of textural differences in relation to the normal appearance of an organ or tissue is denoted as structural entropy. Since organisms or their compartments are thermodynamically open systems, they are insufficiently described by the (structural) entropy. This parameter only provides a snapshot, with no information about the status of entropy changes from a directed exchange with the environment. The current of entropy, which is equivalent to the amount of entropy exported or imported through a boundary, is an appropriate measure of the "thermodynamic distance" of the system under consideration from its environment, as is readily appreciated for tumors. A solid tumor is a biological system embedded in another one (healthy tissue). Its current of entropy can be calculated if its boundary and proliferative activity are known. This parameter can be measured by histochemical methods (Ki-67 antibody) or from the cytometric characteristics (percentage of S-phase-related tumor cells), and the boundary can be measured by the volume fraction of the internal vessels and the size of the external surface of the tumor. Since biochemical factors will contribute to the generation and establishment of these structural and thermodynamic features at the level of tissue organization, histochemical studies can uncover the correlation with these parameter alterations. Taking glycohistochemical determinants as an example for this hypothesis, the potential value of combining the results of immuno-/ligandohistochemistry with the data derived from the cytometric or syntactic structure analysis measurements and from the calculations based on thermodynamic theorems is illustrated.

Animals↗

Quantitation of asbestos and asbestos-like fibers in human lung tissue by hot and wet ashing, and the significance of their presence for survival of lung carcinoma and mesothelioma patients.

Technical standardization on randomly chosen samples of tissue specimen is essential for the validity of interpretations derived from measurements on the presence of asbestos fibers in lung in combination with further features of the patients. Fixed non-tumorous lung tissue (2-3 g) of 150 patients after surgery for various lung diseases were either digested in 45 ml of 13% solution with sodium hypochlorite (NaClO; wet ashing) or heated in an oven at 600 degrees C for 15 min (hot ashing). After tissue disintegration asbestos and asbestos-like fibers were counted by visual inspection, and the fiber concentration in the lung parenchyma was computed. In addition, the patients' survival, and the occupational and social history were analyzed. As a result, the mean concentrations of fibers were found to be 55 f/g (fibers/gram, hot ashing) and 46 f/g (wet ashing). The difference is statistically not significant. Mesotheliomas contributed 49% (73 patients), non-small cell lung carcinomas 32% (59 patients) to the entire cohort. Eighteen patients had a non-malignant lung disease. Analysis of living habits revealed that 73 (49%) patients were heavy smokers, and 99 (66%) patients had a history of occupational asbestos exposure which lasted for 18 years on average. A statistically significant difference of the asbestos fiber concentration between the group with professional exposure and that without detectable asbestos exposure could be obtained in mesothelioma patients and non-malignant lung diseases only, and a tendency for elevated fiber presence was seen in non-small cell lung carcinoma patients. In tissue specimen of patients with non-malignant lung diseases the highest fiber concentration was measured (median 104 f/g) followed by mesothelioma patients (77 f/g), and lung carcinoma patients (62 f/g wet tissue). The difference in the fiber concentration between smokers and ex-smokers versus non-smokers was particularly high in patients with non-malignant lung diseases (103 f/g in smokers versus 33 f/g in non-smokers), still statistically significant in mesothelioma patients (100 f/g smokers versus 61 f/g non smokers), and negligible in lung carcinoma patients (58 f/g smokers versus 62 f/g non-smokers). Only 5/70 mesothelioma patients were not exposed to asbestos at work, and nearly half of the patients (36) were non-smokers. The median survival of mesothelioma patients was significantly shortened for patients with a high intrapulmonal fiber concentration greater than 70 f/g (35 weeks versus 60 weeks). This correlation was also true for lung carcinoma patients (110 weeks versus 230 weeks).

Asbestos↗