[Autopsy rates in Germany]. / Obduktionszahlen in Deutschland.

BACKGROUND: In 2015 the German professional Association of Pathologists conducted a survey to establish a baseline for an autopsy rate in Germany and to collect data from 2005-2014, as hospitals must meet a fixed autopsy quota to receive the supplementary payment for autopsies as stated in the law for hospital structure (KHSG 10.12.2015). MATERIAL AND METHODS: The survey comprised 12 questions and was sent to 450 institutes of pathology. The overall return rate was 38%. The data of the different institutional types was grouped and statistically analyzed. RESULTS: Of 86.416 reported autopsies on deceased adults in Germany from 2005-2014, 47% took place in university hospitals, 36% in local hospitals and 17% in privately run practices. Out of 4320 autopsies on deceased children and adolescents, the majority (83%) were performed at university hospitals, 8%, and 9%, respectively, at the other two entity types. Of the 14.047 fetal autopsies, 55% were done at university hospitals, 25% at other hospitals and 20% at private practices. From 2005 to 2014 the overall number of autopsies decreased by 30%, independently of the institute type. Within each group of institution types there was a wide range in numbers and rate of autopsies done per year: university hospitals total 0­428, quota of 3,4-19,4%; local hospitals 0­324, quota of 1,1-30,8%; private practices 0­268, quota 0,4-5,2%. CONCLUSION: To this day, there is no universal system to document and register hospital autopsy rates in Germany. Due to the high range of yearly autopsy rates even within the different groups of institute types, the threshold for the autopsy rate that must be met to obtain the supplementary payment should be low in the beginning.

[Clinical autopsies. Practical approach, legal foundations and ethical considerations]. / Klinische Obduktionen. Praktisches Vorgehen, rechtliche Grundlagen und ethische Uberlegungen.

Only an autopsy can demonstrate topographical and morphological circumstances in detail and correlate the clinical and autopsy findings based on the examination of all organs. The practical approach in a fatality is described based on the example of the Lüdenscheid Hospital. A uniform legal regulation for dealing with corpses does not exist in Germany. There are two approaches to the question under which circumstances a clinical autopsy is allowed: the extended permission solution and the objection solution. Whether a clinical autopsy can be carried out is decided by the medical specialist selected on application. Autopsies can be necessary from insurance or administrative legal grounds or in the case of an anatomical autopsy is decided by the persons themselves. In order to guarantee the quality of an autopsy it is necessary to use a standardized approach with evaluation and assessment of the results, for example using a quality assurance protocol and the production of an autopsy report. Using this approach important information can be gained not only on the accuracy of the main diagnosis and cause of death but also on additional diseases, response to therapy and the course of the disease and under circumstances can lead to modifications in the approach.

Prevention of high- and low-dose STZ-induced diabetes with D-glucose and 5-thio-D-glucose.

To induce hyperglycemia in mice by administration of STZ, two experimental protocols that involve different pathogenic pathways are being used. First, the intraperitoneal injection of a single high dose (HD-STZ) exerts direct toxicity on beta-cells, which results in necrosis within 48-72 h and overt permanent hyperglycemia. Second, injections of multiple low doses of STZ (LD-STZ), administered intraperitoneally on 5 consecutive days, induce both beta-cytotoxic effects and STZ-specific T-cell-dependent immune reactions. In LD-STZ models, only a combination of toxic and immunological effects result in gradually increasing hyperglycemia, provided male mice of susceptible strains are being used. In this study, we found that 5-T-G, a glucose analogue that has sulfur for oxygen in the pyranose ring, prevented, in a dose-dependent way, both HD-STZ- and LD-STZ-induced hyperglycemia and that D-G, which was only tested in the LD-STZ system, was also protective, albeit somewhat less so than 5-T-G. This protective effect was achieved by intraperitoneally injecting 5-T-G and D-G, respectively, right before each STZ injection. Protection against hyperglycemia was already achieved with a total of 3 injections of 5-T-G, 1 injection each given before the first 3 of 5 LD-STZ injections. By means of OGTT, it was determined that pretreatment with 5-T-G afforded protection from substantial beta-cell damage in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Silicotic lymph node reactions in mice: genetic differences, correlation with macrophage markers, and independence from T lymphocytes.

Quartz was injected into a hind food of BALB/c and DBA/2 mice and on days 40, 90, and 180 the progressive response ensuing in the draining popliteal lymph node (PLN) was investigated by histopathology and immunohistopathology. The area of silicotic nodules (ASN) was measured by morphometry, and, by this parameter, strain BALB/c proved to be a high responder to quartz, and strain DBA/2 a low responder, albeit both strains showed a similar degree of reactive lymphoid hyperplasia in the draining PLN. Both strains also showed a similar quartz content in the draining PLN but in BALB/c mice quartz particles were concentrated in the ASN, whereas in DBA/2 mice they were evenly dispersed over the PLN. Because the silicotic response of athymic BALB/c nu/nu mice was even stronger than that of euthymic BALB/c mice, T cells are not required for the development of silicotic nodules. This fits the notion that quartz is not an antigen and that high and low responder strains are MHC-identical. Because quartz-treated BALB/c, but not DBA/2 mice, showed a persistent expression of the macrophage differentiation markers MRP8 and MRP14, phenotypically the observed strain difference in silicotic responsiveness seems to be expressed at the level of macrophages.

Fiber-specific molecular features of tumors induced in rat peritoneum.

Molecular markers such as mutational spectra or mRNA expression patterns may give some indication of the mechanisms of carcinogenesis induced by fibers and other carcinogens. In our study, tumors were induced by application of crocidolite asbestos or benzo[a]pyrene (B[a]P) to rat peritoneum. DNA and RNA of these tumors were subjected to analysis of point mutations and to investigation of mRNA expression patterns. With both assays we found typical features depending on the type of carcinogen applied. The analysis of point mutations in the tumor suppressor gene p53 revealed mutations in the B[a]P-induced tumors. However, in the tumors induced by crocidolite asbestos that were of the same tumor type as those induced by B[a]P, mutations in p53 were not detectable. Every mutation detected on the DNA level causes an amino acid substitution within one of the functional domains of the tumor suppressor protein. Therefore, these mutations seem to be of biological relevance for tumor progression and indicate a difference in the carcinogenesis regarding the type of the carcinogenic substance. An additional specificity of crocidolite-induced tumors was detectable by analyzing the mRNA expression of the tumor suppressor gene WT1, which is known to be expressed in human mesothelial and mesothelioma cells. A relatively high amount of WT1 mRNA was measured by quantitative competitive reverse transcription-polymerase using RNA extracted from crocidolite-induced tumors. However, WT1 seems to be expressed on a rather low level in tumors induced by B[a]P.

Pulmonary alveolar proteinosis in rats after administration of quartz: its possible role in morphogenesis of lung cancer.

In rats, primary peripheral lung tumors composed predominantly of alveolar type II cells have been induced by inhalation of alpha quartz. In our retrospective study on proliferation markers we evaluated lung specimens of 140 Wistar rats from larger experiments, which had been exposed to Dörentrup quartz (DQ12) by inhalation (10 mg/m3, 56 Weeks, 5 days/week, 7 h/day: n = 27) or intratracheal instillations (5 mg: n = 38; 20 mg: n = 10; 50 mg: n = 28; 15 x 3 mg: n = 12). In the last group 8/12 animals developed lung tumors. Animals were sacrificed 1-32 months after administration. For identification of an increased proliferation of alveolar type II cells the DNA content was monitored by microscopic (static) cytophotometry in histological slides. The argyrophil (AgNOR) method for the demonstration of nucleolar organizer regions (NOR) was used as second marker of type II cell proliferation. Measurements made 24 months after inhalation of DQ12 showed a slight increase of pneumocytic proliferation with 1.64 +/- 0.14 AgNOR/nucleus compared to the controls (1.23 +/- 0.04 mean AgNOR/nucleus). After intratracheal instillation of DQ12 a significant increase of AgNOR was found, e.g. 5 mg: 1.93 +/- 0.23 AgNOR/nucleus (6 months) and 1.96 +/- 0.19 (12 months); 50 mg: 1.77 +/- 15 (6 months) and 2.18 +/- 0.05 (12 months); 15 x 3 mg (+2 ml 2% polyvinylpyridine N-oxide s.c.): 1.81 +/- 0.13 AgNOR/nucleus (27-32 months). With the aid of the 2 c deviation index, i.e. the mean square deviation from the diploid DNA value, it was possible also to identify the pathologically increased proliferation of type II cells after intratracheal instillation of quartz: 0.02 +/- 0.01-0.06 +/- 0.04 c2 (controls); 0.07 +/- 0.04 c2 (5 mg/12 months); 0.12 +/- 0.08 c2 (15 x 3 mg/>27 months) and 0.68 +/- 0.48 c2 (50 mg/12 months). Only in the last group were nearly triploid values detected. Summarizing our results, intratracheal instillation and inhalation of quartz in rats regularly induces alveolar proteinosis and interstitial fibrosis in combination with a dose- and time-dependent increase of the type II cell proliferation rate. As mitogenesis increases carcinogenesis, alveolar proteinosis with increased pneumocytic proliferative activity might be a prerequisite for enhanced tumor development.

Regeneration of beta-cells in response to islet inflammation.

Subtotal pancreatectomy (90%) in Lewis rats induces chronic islet inflammation and tissue damage in the remaining pancreas 4 months after surgery. Concomitantly, significant enlargement of the islets of Langerhans was observed (90% pancreatectomy: islet/pancreas area: 25.6 +/- 9.6 x 10(-3), beta-cell/pancreas area: 12.4 +/- 4.4 x 10(-3); n = 4; controls without pancreatectomy: islet/pancreas area: 5.5 +/- 1.7 x 10(-3), beta-cell/pancreas area: 4.6 +/- 1.5 x 10(-3); n = 4; p < 0.05, respectively). Islet growth is mainly due to an increase in beta-cell mass. Beta-cell regeneration was not caused by the surgical manipulations or by metabolic stress. The former was ruled out by performing 10% pancreatectomy which did not cause islet enlargement after 4 months (islet/pancreas area: 13.6 +/- 11.3 x 10(-3), beta-cell/pancreas area: 7.1 +/- 2.0 x 10(-3); n = 3). An influence of metabolic stress was excluded by continuous substitution of syngenic islet antigens, which inhibits insulitis. In the absence of islet inflammation, despite persistent metabolic stress, beta-cell regeneration did not occur (islet/pancreas area: 7.0 +/- 5.5 x 10(-3), beta-cell/pancreas area: 5.5 +/- 4.1 x 10(-3); n = 4). Continuous treatment of animals after 90% pancreatectomy by insulin implants (1.5 U/day) avoided insulitis and beta-cell growth (islet/pancreas area: 9.2 +/- 1.1 x 10(-3), beta-cell/pancreas area: 6.8 +/- 1.0 x 10(-3), n = 3): All enlarged islets observed 4 months after 90% pancreatectomy without further treatment were infiltrated. Thus, beta-cell growth appears to be a response to insulitis. The stimulus for beta-cell growth could result from tissue damage caused by infiltrating cells or from cytokines secreted by the infiltrating cells, or both.

Mesothelial proliferation due to asbestos and man-made fibres. Experimental studies on rat omentum.

The intraperitoneal test in rats has proven to be an appropriate method controlling fibrogenicity and carcinogenicity of asbestos fibres and other fibrous dusts. We analyzed the reaction patterns of mesothelial cover layer to different natural mineral fibres (crocidolite, chrysotile, actinolite, erionite, wollastonite) and man-made mineral and synthetic fibres (glass fibres 104/475, polypropylene, aramide fibres). The injection of doses between 0.01 and 100 mg dust suspended in saline solution led to a continued repairing proliferation of submesothelial connective tissue cells and focal submesothelial fibrosis. These changes were never observed after application of granular dusts as mine dust and quartz. After 15 to 28 months we often found an association of fibrosis and local reactive hyperplasia of partly atypical proliferation of rat omentum mesothelium. These changes were also demonstrated in cases without macroscopically visible tumors. In later stages the underlying fibrosis was often infiltrated and dissolved by mesotheliomas.

Dendriform pulmonary ossification.

Four cases of dendriform pulmonary ossification are reported from postmortem roentgenography of isolated lungs. All showed pathoanatomical evidence of chronic fibrosing, mostly interstitial, rarely intraalveolar pneumonia, besides the typical manifestations of dendriform pulmonary ossification. Microscopy revealed fluid transition from proliferating, interstitially increased connective tissue to fully developed osseous structures. These dendriform structures can be seen in some analogy to the structural pattern of interstitial, bronchovascular as well as septal connective tissue; however, actual topographical correlation between bone structures and blood or lymph vessels could not be safely determined. Our observations suggest that dendriform pulmonary ossification may be interpreted as a rare complication, or special manifestation, of chronic fibrosing interstitial inflammation of the lung.

Ultrastructure of mesothelial regeneration after intraperitoneal injection of asbestos fibres on rat omentum.

In order to describe the ultrastructural features of the early phases of regenerating mesothelium in rat peritoneum, 69 cases were examined after intraperitoneal injection of 0.05-15 mg crocidolite, chrysotile B and other mineral and synthetic fibers. The findings show the presence of intermediate or transition cells between proliferating submesothelial connective tissue cells bearing the ultrastructural phenotype of myofibroblasts and mature fully regenerated mesothelium. Our results and data accumulated in the literature provide strong support for the hypothesis of submesothelial cells origin for regenerating mesothelium.

[Computer tomographic localisation in primary aldosteronism. Comparison with adrenal scintigraphy (author's transl)]. / Computertomographische Lokalisationsdiagnostik beim primären Aldosteronismus. Vergleich zur Nebennierenszintigraphie.

13 patients with verified primary aldosteronism (unilateral adrenal adenoma = 10, bilateral idiopathic hyperplasia = 3) underwent examination by CT and 131J-cholesterol-scintigraphy. CT-scan can successfully employed for localization of unilateral adenoma exceeding 10 mm in diameter. Small lesions and hyperplasia are rare CT-findings. The value of 131J-cholesterol-scintigraphy for differentiation of the two main subgroups of primary aldosteronism--adenoma and hyperplasia--is limited. In our experience both non-invasive methods are helpful to avoid misleading interpretation. In controversial cases bilateral adrenal venous blood sampling by catheterization is mandatory.

Basement membrane proteins in synovial membrane: distribution in rheumatoid arthritis and synthesis by fibroblast-like cells.

Rheumatoid arthritis is a complex disease of unknown origin. In consequence of some immunological reactions, proliferative invading synovial tissue leads to destruction of normal joint architecture. The aim of this study was to investigate qualitative changes in extracellular matrix distribution of proliferating rheumatoid synovium and their cellular origin. Synovial tissues from 57 clinically indicated arthrotomies were investigated with immunofluorescence, using specific antibodies against extracellular matrix proteins in tissue slides and cultured cells, which were also studied for collagen biosynthesis. Results indicated that synovial fibroblast-like cells synthesize and secrete basement membrane proteins laminin and collagen type IV as e.g. endothelial cells or organogenic fibroblasts. Laminin and collagen type IV were specifically demonstrated pericellularly in the hyperplastic lining layer of active rheumatoid synovitis. These findings are discussed with respect to the possible implication of altered cell-matrix interactions in rheumatoid synovial proliferation.

Differential diagnosis of malignant tumours in the abdominal cavity of rats after intraperitoneal injection of crocidolite or benzo[a]pyrene.

In our investigation (i.p. test), crocidolite and benzo[a]pyrene, both caused a progression from initially reactive, then autonomously transformed proliferation of myofibroblasts and undifferentiated mesenchymal cells to malignant, multidirectionally differentiated (desmin and ED-1 positive) fibro-histiocytic tumours. Immunohistochemically these tumours showed no morphological characteristics (for example co-expression of vimentin and keratin in spindle-shaped tumour cells) of human asbestos-associated malignant mesotheliomas. On the other hand many tumour cells induced by crocidolite and benzo[a]pyrene had an ultrastructural appearance resembling fibroblasts and myofibroblasts. These have been demonstrated in only a few desmoplastic and sarcomatous mesotheliomas in human beings. None of the tumours revealed the typical ultrastructural features of epitheloid or transitional mesotheliomas. Apparently, both carcinogenic substances induce the transformation of undifferentiated pluripotent mesenchymal cells in rat peritoneum, regardless of their localization in the submesothelial compartment or perivascular connective tissue (preferentially after crocidolite application) or in the connective tissue pseudocapsule of major benzo[a]pyrene containing beeswax/tricaprylin depots in the mesometrium and mesenterial fatty tissue. In this way asbestos fibres in this animal experiment do not seem to induce an arrest in differentiation of intermediate or immature mesothelial cells as supposed formerly, but rather affect undifferentiated mesenchyme cells and myofibroblasts. This is an explanation for the immunohistochemical expression of markers of muscular differentiation in these tumour cells, which is known to occur in human malignant fibro-histiocytic tumours. If supplementary immunohistochemical investigations with different keratin antibodies also fail to confirm the mesothelial differentiation of the tumours induced in our i.p. test, the decision to call them "mesotheliomas" should be reconsidered. Further immuno-transmission-electron microscopical investigations with intermediate filament or macrophage antibodies are needed to clarify whether the term malignant "fibrohistiocytic sarcoma", "mesenchymoma" or "mesothelioblastoma" would be more correct from the morphological point of view.

P53 mutations in tumours induced by intraperitoneal injection of crocidolite asbestos and benzo[a]pyrene in rats.

Mutation analysis of the tumour suppressor gene p53 in tumours induced in the peritoneal cavity of rats revealed differences in the mutational pattern with regard to the carcinogenic substances applied. In tumours induced by benzo[a]pyrene a considerable amount of p53 mutations resulting in an altered protein structure could be detected. For the development of these tumours an escape from the p53 mediated cell cycle control can be assumed. However, in tumours of the same tumour type induced by crocidolite asbestos no mutations could be observed. Since there were even no spontaneous p53 mutations detectable in this tumour group, it is obvious that in these tumours the escape from cell cycle control does not take place via inactivation of p53. Therefore, it is concluded that the molecular mechanisms of carcinogenesis and tumour development in this tumour type depend on the type of carcinogen applied.

[Significance of sonography of the breast for surgical treatment of breast cancer]. / Bedeutung der Sonographie der Brustdrüse für die operative Therapie des Mammacarcinoms.

In a prospective study of 119 patients with breast carcinoma the value of ultrasonography for surgical therapy was compared with the value of clinical results and mammography. The tumor localization (in 96.8%) and the exact preoperative staging following the pTNM-system (tumor size in 85.8%, lymph node involvement in 77.2%) were better predicted by ultrasonography than by mammography and clinical examination. Especially the multicentric-multifocal carcinomas (20 of 29 cases) were better detected. Preoperative ultrasonography especially improves planning a conservative management of breast cancer.

Role of kidney and adrenals in the humoral pathogenesis of primary hypertension.

In 18 spontaneously hypertensive rats (SHR) of the Münster strain the circulation was connected to that of normotensive animals using the carotid arteries and external jugular veins. The circulations were mixed by a peristaltic pump. In this model the normotensive rats were made hypertensive after a 10-min cross-perfusion cross unidentified humoral factors causing vasoconstriction play an essential role for the development of hypertension in SHRs.