[Validation of medical ethical decisions at the bedside by the autopsy : Experience of the ethics committee at the Stuttgart Clinic]. / Validierung medizinethischer Entscheidung am Krankenbett durch die Obduktion : Erfahrung des Ethikkomitees am Klinikum Stuttgart.

BACKGROUND: Ethics consultations in a clinical setting can be challenging, specifically with respect to limiting therapeutic interventions in terminally ill patients. Some decisions will even be controversial. OBJECTIVE: Can a clinical autopsy be used to confirm the recommendations given by the ethics committee, i. e. limitation of therapy to palliative care? MATERIAL AND METHODS: We report an exemplary case of a patient with endocarditis and subsequent septic cerebral infarction. During treatment in the intensive care unit (ICU) two ethics consultations were held. Both times the patient' s clinical condition and prognosis were controversially discussed. The patient died after a recommendation had been given for supportive care. The subsequent autopsy, which is described in detail, confirmed a fatal set of symptoms with extensive destruction of the heart and disseminated brain infarcts. CONCLUSION: Clinical autopsies are crucial for an objective description of diseases and can corroborate the decision to limit therapeutic intervention in end of life care. It is a valuable tool in evaluating the quality of decision making in ethics counseling.

[The change of pathology in the era of personalized medicine using the example of discordant KRAS mutational status in metastasized colorectal carcinoma]. / Der Wandel der Pathologie in der Ära der personalisierten Medizin. Eine Übersicht am Beispiel des diskordanten KRAS-Mutationsstatusbeim metastasierten kolorektalen Karzinom.

Modern pathology has developed from "omega" to "alpha" and is vital for therapy and follow-up of tumor treatment today. Pathology has a key role as part of personalized medicine. It is possible to intervene therapeutically into the molecular genetic intricacy of tumors by establishing predictive biomarkers with corresponding tumor therapeutic agents.By identifying the KRAS mutational status at the metastasized colorectal carcinoma, a statement about the benefit of an anti-EGFR-therapy can be given, which is nowadays the basis of diagnostic and therapy of this cancer.For a long period of time a high concordance between primary and metastases inside the KRAS status was taken for granted. Meanwhile, there are many studies demonstrating a possibly underestimated high degree of discordance. The identification of discordances might gather a subcollective, which partially holds a KRAS wild type tissue and thereby might respond with a partial remission. Thus, the survival time of these patients and their quality of living could be successfully improved.

[Renal cell carcinoma: unusual late metastases 14 and 23 years after kidney transplantation]. / Nierenzellkarzinom: Ungewöhnliche Spätmetastasierung 14 und 23 Jahre nach allogener Nierentransplantation.

HISTORY AND FINDINGS: An asymptomatic 70-year-old man was found to have a tumor in the region of the left adrenal gland, having undergone cadaveric kidney transplantation 23 years ago. Two years before this a right nephrectomy had been performed for a renal cell carcinoma. There was no left kidney because of agenesis. 14 years after the kidney transplantation a metastasis of the renal cell carcinoma was identified in the thyroid gland. After its resection no further metastases had been discovered. INVESTIGATIONS: Laboratory tests were unremarkable. But a tumor was detected in the left adrenal gland by computed tomography. DIAGNOSIS, TREATMENT AND COURSE: The left adrenal gland was successfully resected. Its histology confirmed a second metastasis of the renal cell carcinoma 23 years after renal transplantation, but no other metastases were found. CONCLUSIONS: Kidney transplantation can be successfully performed even in patients with pre-existing carcinoma. A late metastasis of a renal carcinoma may occur. Close long-term follow-up of the patients is therefore essential.

Selenium requirement of growing male turkeys.

1. The aim of the experiment was to estimate the selenium requirement of growing male turkeys using the selenium concentrations in different organs and blood plasma and by fitting a continuous broken line to the activity of glutathione peroxidase in liver and plasma. 2. Newly hatched male BUT BIG 6 turkeys were fed either on the selenium deficient basal soybean-maize diets (selenium <0.010 mg/kg diet) adapted to the NRC (1994) and GfE (2004) recommendations for growing turkeys from 0 to 2 weeks (prestarter diet) and 3 to 5 weeks (starter diet) or the basal diets supplemented with 0.10, 0.15, 0.20, 0.25, 0.30, 0.35 or 0.40 mg selenium/kg diet as sodium selenate. Vitamin E was supplemented adequately in all diets. 3. After 5 weeks the weight in all groups (mean 2568 g) exceeded the expectations for the genotype investigated. Feed consumption and weight gain were however significantly reduced in the group receiving the selenium-deficient diet. 4. After 2 and 5 weeks selenium concentration and activity of glutathione peroxidase in the plasma and the organs examined were greatly influenced by selenium supplementation. 5. Under the conditions investigated, 0.30 mg Se/kg diet was necessary for fast-growing male turkeys to ensure maximum selenium accumulation in the organs examined and maximum glutathione peroxidase activity in plasma and liver.

[Characterization and staging of renal tumors: significance of MRI diagnostics]. / Charakterisierung und Staging von Nierentumoren: Bedeutung der MRT-Diagnostik.

PURPOSE: Retrospective evaluation of MRI in the diagnosis of renal masses and determination of the correlation of MRI with histology or follow-up. MATERIALS AND METHODS: 46 consecutive patients (13 female, 33 male, mean age 64.7 yrs) with suspected renal tumors were examined with a 1.5 T MR scanner using a standardized protocol (TSE T2fs, 2DGRE T1, dynam. ce3DGRE T1fs, ce2DGRE T1fs, ce3DGRE urogram). RESULTS: 142 renal lesions were found with diameters of < 2 cm up to 14 x 18 cm. A primary classification as solid and cystic lesions was performed according to MRI criteria. In 29 cases we found lesions bilaterally, in 17 patients only in one kidney, and in four cases we found multifocal renal tumors unilaterally (n = 3) or bilaterally (n = 1). In 22 patients with renal tumors, cystic lesions could be seen as well. In 19 cases these were uncomplicated cysts, and in 3 cases these were complicated cysts. 35/43 lesions were histologically proven solid vascularized tumors (29 renal cell carcinomas, 6 urothelial carcinomas), five additional masses with tumor signs in MRI appeared to be progressive during follow-up thus suggesting malignancy, and one case was a multifocal bilateral renal tumor. 3/43 lesions were initially reported as being suspected of malignancy but were proven during follow-up or histologically to be benign. Tumor thrombus was depicted in MRI in the renal vein in 5 cases, stretching into the IVC in 4 cases and proven histologically in 4 and 3 cases, respectively. Of these solid masses, 99 cystic lesions could be differentiated clearly in MRI (88 simple cysts, 11 complicated cysts) that remained unchanged during follow-up (6 - 65 months) or were proven to be cysts histologically. In 17 cases these cysts were bilateral, in 19 cases unilateral, and 33 kidneys showed multicystic changes. In characterizing renal masses, MRI showed a positive predictive value of 93 % for the diagnosis of a malignant tumor. The T-stage of histologically proven renal cell carcinomas using MRI was correct in 89 %. CONCLUSIONS: MRI is a valid modality for characterizing and staging renal masses using a suitable sequence protocol that includes dynamic ce studies. Venous tumor invasion can be depicted safely. MRI can be employed alternatively to state-of-the-art ceCT and additionally to CT in unclear cases.

Severe acute cholestatic hepatitis by infiltration of monoclonal plasma cells in multiple myeloma.

BACKGROUND: Plasma cell infiltration of the liver can be detected in 25 to 40% of patients with multiple myeloma. However, there are only rare cases of multiple myeloma clinically presenting as acute liver disease. CASE REPORT: We report an 88-year-old woman with painless jaundice and abnormal liver function tests, resembling acute cholestatic hepatitis. Viral hepatitis as well as autoimmune hepatitis could be excluded. Liver biopsy revealed a diffuse portal and sinusoidal infiltration of plasma cells with lambda light chain restriction. Serological immune fixation disclosed monoclonal gammopathy of IgG lambda with bone marrow infiltration of 25% plasma cells. After administration of 60 mg prednisolone per day, the elevated liver enzymes declined considerably. CONCLUSION: Hepatic plasma cell infiltration of multiple myeloma can, in rare cases, manifest as acute cholestatic hepatitis, which may respond to treatment with corticosteroids.

Carotenoids are decreased in biopsies from colorectal adenomas.

UNLABELLED: A lower intake of carotenoids is associated with an increased risk of colorectal cancer. In order to take advantage of the chemopreventive properties of carotenoids, it is necessary to determine carotenoid concentration at the target tissue. As early stages in the adenoma-carcinoma sequence of colorectal cancer might be susceptible to chemoprevention, we sought to determine carotenoid concentrations in biopsies from colorectal adenomas. METHODS: Biopsies from colorectal adenomas and non-involved mucosa were taken from seven patients. For controls, biopsies were obtained from the ascending and descending colon of patients without polyps (n = 5). Concentration of carotenoids (alpha-, beta-carotene, lutein, lycopene, zeaxanthin, beta-cryptoxanthin) were determined by optimizing gradient HPLC-analysis. Results are expressed as pmol/microg DNA. RESULTS: Except for alpha-carotene, all carotenoids could reliably be detected in all specimens. In control patients carotenoid concentrations were highest in the ascending colon, being followed by the descending colon and non-involved mucosa from polyp-carriers. In colorectal adenomas all carotenoids were significantly reduced as compared to-non-involved mucosa (beta-carotene: 0.37 vs 0.19, P<0.03; lycopene: 0.34 vs 0.21, P<0.06, beta-cryptoxanthin: 0.14 vs 0.09, P<0.03, zeaxanthin: 0.18 vs 0.09, P<0.02; lutein: 0.18 vs 0.13,P <0.02). CONCLUSION: All carotenoids investigated are reduced in colorectal adenomas, suggesting that mucosal carotenoids could serve as biomarkers for predisposition to colorectal cancer. Moreover, anti-tumor activity exerted by carotenoids is limited due to mucosal depletion. We speculate that supplementation of a larger array of carotenoids might be beneficial for patients with colorectal adenoma.

[Intramedullary bone endoscopy (IBE). First results of experimental intramedullary endoscopy of long bone]. / Intramedulläre Knochenendoskopie (IBE) Erste experimentelle Ergebnisse der Endoskopie des langen Röhrenknochens.

INTRODUCTION: Intramedullary preparation and endoscopy of long bone is not mentioned in literature. We present our first results of experimental intramedullary endoscopy of long bone. METHODS: Experimental tests were performed at 4 corpse bones (twice tibia, twice femur). RESULTS: Intramedullary endoscopy and preparation was possible in all cases. A good view for inspection of the medullary canal was achieved by using the endoscope (Wolf GmbH, Germany). CONCLUSION: Endoscopic preparation and intramedullary endoscopy in the long bone ist possible. By using the endoscopic tools, a "neocavum" for endoscopic manipulation could easily be created.

[Inflammatory myofibroblastic tumor of the pancreas with regional lymph node involvement]. / Inflammatorischer, myofibroblastischer Tumor des Pankreas mit Beteiligung regionärer Lymphknoten.

Inflammatory myofibroblastic tumors (IMT) can be found in virtually any location of the human body. Histologically a mesenchymal aspect predominates and makes these mostly benign tumors apt to be erroneously diagnosed as a soft tissue sarcoma. Cases showing infiltrative growth and local recurrence further complicate the assessment. Localization of an IMT in the pancreas is extremely rare. Clinical investigations regularly lead to the putative diagnosis of a malignant tumor and only subsequent histological examination can establish the correct tumor classification. We present the case of a 62-year-old woman with IMT of the pancreas. Evidence of lymph node involvement has not yet been reported in this setting.

Irx1 and Irx2 expression in early lung development.

We describe a comparative lung expression analysis of the murine Irx1 and Irx2 genes. At embryonic day 8.5 (E8.5), the Irx1 and Irx2 expression starts in the foregut region, where the laryngo-tracheal groove will form. The expression is prominent in the lung epithelium during glandular development. It declines at the end of the canalicular phase. We further compare the Irx1 and Irx2 expression domains to Gli1, 2, 3 and Mash1. Their homologues in Drosophila melanogaster are known as regulative partners of the iroquois complex. The Irx and Gli genes are coexpressed in the developing lungs at the same time. Their transcripts are not localised in the same cells but adjacent to each other in either mesenchymal or epithelial structures. It is thought that the lung development is regulated by the mesenchymal/epithelial interactions.

[Echinococcus cyst of the right ventricle. Diagnosis and therapy of a rare disease picture]. / Die Echinokokkuszyste des rechten Ventrikels. Diagnostik und Therapie eines seltenen Krankheitsbildes.

Cardiac involvement is only found in less than 2% of all patients with echinococcosis. The case of a 68-year old woman suffering from a hydatid cyst in the wall of the right ventricle is reported. The clinical, radiological, serological, and histological findings are demonstrated. Immediate relief from the symptoms was accomplished by surgical resection of the cyst without the use of a cardio-pulmonary bypass. The problems of correct diagnosis and therapy of this rare disease are discussed with reference to literature.

[Secondary spontaneous pneumothorax in tuberous sclerosis]. / Sekundärer Spontanpneumothorax bei tuberöser Sklerose.

Secondary pneumothorax occurs as a symptom of an underlying pulmonary disease. We report the case of an 18-year-old woman with tuberous sclerosis (Bourneville's disease) and recurrent pneumothoraces. Clinical outcome was favorable 6 months after bilateral videothoracoscopic pleurectomy. The complete triad of tuberous sclerosis (TS) (mental retardation, seizures, adenoma sebacium) is not always present in those who develop pulmonary involvement. When TS involves the lung it is clinically and pathologically indistinguishable from lymphangioleiomyomatosis (LAM). The very rare pulmonary involvement of TS and LAM are problems primarily of women in childbearing age. A pneumothorax can be the first symptom of TS or LAM.

Identification of a novel mouse Iroquois homeobox gene, Irx5, and chromosomal localisation of all members of the mouse Iroquois gene family.

The Drosophila genes of the Iroquois-Complex encode homeodomain containing transcription factors that positively regulate the activity of certain proneural Achaete/Scute-C (AS-C) genes during the formation of external sensory organs (J. L. Gomez-Skarmeta and J. Modolell, EMBO J 17:181-190, 1996). Previously, we have identified three highly-related genes of the mouse Iroquois gene family that exert specific expression patterns in the central nervous system (A. Bosse et al., Mech Dev 69:169-181, 1997). In the present paper, we report the identification of a novel member of the Iroquois gene family, Irx5, that shows a restricted spatio/temporal expression during early mouse embryogenesis, distinct from the expression of Irx1-3. An extensive sequence analysis of 20 Iroquois-like genes from seven organisms reveals a high conservation of the homeodomain. Phylogenetic tree reconstruction showed a clustering of the members of the Iroquois gene family into groups of orthologous genes. Together, with the data obtained from the chromosomal mapping analysis, the results indicate that these genes have appeared in vertebrates during evolution as a result of gene duplication.

[Cerebral and basilar artery thrombosis following cervical spinal injury]. / Thrombose der Vertebral- und Basilararterie nach Verletzung der Halswirbelsäule.

Vertebral artery injury may complicate cervical spine injury and may result in severe neurological impairment. We present a case of a 54 year-old male who sustained a hyperextension injury of the neck during horse-back riding with cervical spine dislocation of C3/4. As a consequence of right-sided traumatic vertebral artery thrombosis and extension of the thrombus into the basilar artery the patient developed a brainstem and bilateral cerebellar infarction with fatal outcome. In a review of the literature the characteristics of 33 cases with vertebral artery injuries following cervical spine trauma and with associated neurological complications are described. The problems of vertebral artery injury are discussed concerning diagnosis and therapy.

MDM2 amplification and loss of heterozygosity at Rb and p53 genes: no simultaneous alterations in the oncogenesis of liposarcomas.

PURPOSE: The present study aimed to investigate the status of alterations of the MDM2, Rb and p53 genes in a series of 45 liposarcomas. Furthermore, the possible correlation with histological and clinical parameters was studied. METHODS: MDM2 amplification was examined by non-radioactive Southern blot hybridization with a human MDM2 cDNA probe. Mutations in the p53 gene were screened by polymerase chain reaction/single-strand conformation polymorphism analysis and direct sequencing. To study loss of heterozygosity (LOH) at the tumor-suppressor genes Rb and p53, we used four polymorphic intragenic Rb markers (introns 1, 17, 20, and 25) and two p53 markers (intron 1 and exon 4). RESULTS: MDM2 amplification was found in 19 of 45 liposarcomas (42.2%). The frequency of LOH in Rb and p53 was nearly identical (22%). In 4 of 9 tumors (44.4%) with LOH, allelic loss was a concurrent event in both genes. Of 45 liposarcomas, 6 (13.3%) showed p53 mutations. Overall, alterations of the p53/MDM2/Rb pathway occurred in 30 of 45 liposarcomas (66.6%). In contrast to myxoid and pleomorphic variants, well-differentiated liposarcomas were characterized by a high frequency of MDM2 amplification, a lack of LOH of Rb and p53, and p53 mutations. CONCLUSIONS: Obviously MDM2 amplification and LOH at the Rh and p53 genes do not occur simultaneously in the oncogenesis of liposarcomas, as is the case for MDM2 amplification and p53 gene mutations (with one exception). We suggest that well-differentiated, myxoid and pleomorphic liposarcomas are characterized by a different pattern of molecular alterations.

[Diagnostic and predictive validity of DNA image cytometry in soft tissue tumors]. / Der diagnostische und prädiktive Wert der DNA-Image Zytometrie bei Weichteiltumoren.

Malignant neoplasms are associated with chromosomal aberrations. This phenomenon called aneuploidy can be substantiated by interactive DNA cytometry and is accepted as a major prognostic parameter in tumor biology and oncology. In a retrospective study 114 non-infantile soft tissue tumors were analysed by DNA cytometry. The results were compared with classical morphological parameters. As a marker for malignancy in soft tissue lesions, DNA aneuploidy substantiated by cytometry has a sensitivity of 94% and a specifity of 82%: 50 of 53 malignant soft tissue tumors were DNA aneuploid; from 61 non-sarcomatous soft tissue tumors 11 were found to be aneuploid. These lesions were classified as intermediate dignity. No aneuploid tumor could be found among 30 histologically benign soft tissue tumors. The positive predictive value of DNA cytometry was 82%: of 61 aneuploid soft tissue tumors 11 were non-sarcomatous tumors with intermediate dignity. The negative predictive value of DNA cytometry was 97%: from 53 non-aneuploid soft tissue tumors only three were found to be sarcomas. Malignant soft tissue tumors demonstrate a significantly higher DNA-index (DI) and DNA grade of malignancy (DNA MG) than benign lesions. Our results show that DNA ploidy may serve as an additional parameter in problematic histological dignity assessments of soft tissue tumors. The histopathological grading levels of sarcomas show significantly different DI and DNA MG, so that DNA cytometry enables substantiated grading of soft tissue.

[Clinical aspects, differential diagnosis and histogenesis of heterotopic ossification]. / Klinik, Differentialdiagnose und Histogenese der heterotopen Ossifikation.

Investigations regarding proliferation behaviour, histogenesis and bone transformation were carried out on soft tissue samples with 133 heterotopic ossifications (HO), collected from the surgical material of the Institute of Pathology, Berufsgenossenschaftliche Kliniken Bergmannsheil, using methods of conventional histology, histochemistry, immunohistochemistry, electron microscopy and molecular biology, yielding the following results: 1. There is only a limited pathognomonic growth pattern for the variant of non-traumatic heterotopic ossification. Basically, the ossification foci may be divided into central, intermediate and peripheral zones. Expression intensities of the proliferation markers PCNA and MIB-1 show the proliferation behaviour in peripheral areas of osteogenesis to be similar to that found in autonomous osseous neoplasias. The phenotypical picture of zonal architecture found in HO can be seen by the simultaneous demonstration of variable image sequences of multifocally arising ectopic formations of new bone with varying degrees of maturation. 2. Vascular endothelium and pericytes are integrated into the formal histogenesis of heterotopic ossification and belong to osteoprogenitor cells as "stem cells" of heterotopic ossification. 3. The histochemically established expression pattern of alkaline phosphatasis is in good correlation with the degree of activity of the step-by-step development of heterotopic ossification. The intracellular demonstration of alkaline phosphatasis is an indicator for the transformation towards an osteogenic direction. In HO, the enzyme is a major characteristic of osteoprogenitor cells. 4. According to our immunohistochemical results, the proteoglycanes Decorin and PG 100-osteogenic matrix proteins-show a phase-like expression and are involved in osteoneogenesis. They are predominantly found in the area of mineralization. The proteoglycane 100 experiences a "modulation" and can be demonstrated almost selectively in osteoclasts in advanced stages of osteodevelopment. 5. Using in situ hybridization-with digoxigenin labeled cDNA probes- and a propidium iodide counterstaining a co-expression of collagene types I, II and III-mRNA could be demonstrated in samples of ossification. The expression pattern is similar to the collagen expression I. in early phases of embryonal bone development II. with callus proliferation and shows III. also similarities to chondral neoplasias. The results underline the reactive-neoplastic character of heterotopic ossification. 6. TGF-beta 1 mRNA shows a polytopic expression pattern with accumulation in areas of osteogenesis. TGF-beta 1 was found mostly in cartilage cells of heterotopic ossifications, as were collagene types I (alpha 1) and III (alpha 1) mRNAs. In sum, our in situ hybridization results underline the central part of cartilage cells in the ossification process in ectopic osteoneogenesis. This is also indicated by a phenotypical alteration of collagen expression as well as by an accumulation of TGF-beta 1 in chondral ossification areas. In situ hybridization propidium iodide counterstaining offers a reproducable image of morphological structures in the histological slide sample by means of fluorescence microscopy. 7. Phenotyping of osteroclasts in HO revealed their derivation from mature local macrophages. The immunohistochemical characterization with the demonstration of the vitronectin receptor classified the multinucleate giant cells of HO as original osteoclasts. Their origin is in accordance with the histogenetical concept of original bone. 8. Summarizing, the results characterize heterotopic ossification as a reactive proliferative and reversible neoplasia in chronically damaged soft tissue. From the formal pathogenetical point of view, relations could be established to orthotopic osteoneogenesis as well as to impaired proliferation kinetics, similar to osseous autonomous neoplastic lesions. (ABSTRACT TRUNCATED)

[Diagnosis and therapy of calcifying intramuscular hemangiomas of the lower extremity]. / Diagnose und Therapie kalzifizierender intramuskulärer Hämangiome der unteren Extremität.

During a 6 year interval from 1990 to 1996 13 patients suffering from calcifying cavernous hemangioma of the lower extremity were treated by surgical resection of the tumor and were followed-up postoperatively for remaining functional loss and recurrence rate. The resection of the medial head of the gastrocnemius muscle was performed seven times, the resection of the lateral head was done in 5 patients. In one patient the soleus muscle was partially resected. Simultaneous lengthening of the Achilles tendon was done in 11 patients for correction of foot drop deformity. The histological examination revealed three cavernous hemangiomas, one arterio-venous angioma racemosum and nine mixed capillary-cavernous hemangiomas. The patients were able to walk at 5.3 weeks following surgery. During the 29 months follow-up period there was no recurrence of symptoms neither of the hemangioma.

[Ossovenography as a diagnostic criterion of post-traumatic femoral head necrosis in internal fixation devices]. / Die ossovenographie als diagnostisches kriterium der posttraumatischen femurkopfnekrose bei liegendem metallimplantat.

Despite advances in the field of orthopedic surgery, necrosis of the femoral head still remains a serious problem. Under normal conditions magnetic resonance tomography (MRT) is the gold standard for early diagnosis. Because of magnetic interference, this technique is not applicable in the diagnosis of posttraumatic necrosis with internal fixation, however. This seems to be an ideal indication for ossovenography: contrast medium is injected into the femoral head under X-ray control and the venous flow is documented. Furthermore, it is possible to get histological samples from suspicious areas. Ossovenography was performed in 12 patients and the results were compared with histological samples. In every patient in whom necrosis of the femoral head was diagnosed by ossovenography (91.6%), we also found necrosis on histological examination. In one patient in whom physiological flow was found, there was a corresponding absence of necrosis in the histological sample. There were no complications during ossovenography. The results suggest that ossovenography is a promising and reliable method for early diagnosis of necrosis of the femoral head in the presence of internal fixation devices.