[Un- and dedifferentiated endometrial carcinoma : A rare entity with a wide range of differential diagnosis]. / Das un- und dedifferenzierte Endometriumkarzinom : Eine seltene Entität mit breitem differenzialdiagnostischem Spektrum.

Dedifferentiated endometrial carcinomas (ECs) are composed of undifferentiated EC and a FIGO grade 1 or 2 endometrioid carcinoma. The undifferentiated component represents a malignant epithelial neoplasm with no obvious differentiation and immunohistochemical loss of PAX8, E­cadherin and focal expression of EMA and/or CK18 and the predominant presence of nuclear staining for INI1 (SMARCB1) and BRG1 (SMARCA4). The main differential diagnoses include poorly differentiated endometrioid EC, neuroendocrine carcinoma, lymphoma, plasmocytoma, high-grade endometrial stromal sarcomas, undifferentiated uterine sarcomas (UUS), carcinosarcomas, and metastases to the endometrium. The histogenesis is not yet fully understood and molecular data are still limited. Some tumors represent a loss of MHL1 and PMS2 staining due to MLH1-promotor methylation. Rare cases are associated with Lynch syndrome or POLE mutation. The un- or dedifferentiated EC represents a high-grade endometrial carcinoma that requires extended surgery and indicates a poor prognosis. In cases with mismatch repair protein deficiency or POLE mutation, immuno-oncological treatment with checkpoint inhibitors are a therapeutic option.

[The 2019 FIGO classification for cervical carcinoma-what's new?] / FIGO-Klassifikation für das Zervixkarzinom 2019 ­ was ist neu?

Numerous therapeutic and prognostic studies of cervical carcinoma have necessitated a revision of the FIGO classification.For microinvasive carcinomas, the horizontal dimension is no longer considered and diagnosis and staging will solely be made by the depth of cervical stromal invasion. Lymphovascular invasion beyond the deepest point of stromal infiltration by tumor cells does not alter the stage.There will be a new subclassification of macroinvasive carcinoma confined to the uterine cervix, which will be made by largest tumor extension as follows: FIGO IB1/T1b1 - invasive carcinoma >0.5 cm depth of stromal invasion and ≤2 cm in largest dimension, FIGO IBII/T1b2: - invasive carcinoma >2 cm and ≤4 cm, FIGO IBII/T1b3 - invasive carcinoma >4 cm. Pelvic as well as para-aortic lymph nodes will be defined as regional nodes. Pelvic lymph node metastases only will be categorised as FIGO IIIC1/pN1a and para-aortic lymph node involvement with or without concomitant pelvic involvement will be FIGO IIIC2/pN1b. Uterine corpus as well as adnexal involvement are not relevant for staging purpose.

[TNM classification of gynecologic malignancies : What remains to be done beyond 2017?] / TNM-Klassifikation gynäkologischer Tumoren : Was bleibt über 2017 hinaus zu tun?

For some gynecologic malignancies, there are disagreements between the most recent WHO and TNM classifications and the recommendations of the International Collaboration of Cancer Reporting. These discrepancies are addressed and discussed in this paper. The WHO definition for primary vaginal cancer does not match the TNM definition. The paper also discusses and provides TNM classifications for rare gynecologic tumors like primary malignant vulvar melanomas, sarcomas of the vulva, perivascular epithelioid cell tumor (PECom) of the uterus, undifferentiated uterine sarcomas, and extra-intestinal gastrointestinal stromal tumors (GIST), and provides some recommendations for the reporting and categorization of regional lymph nodes in nonuterine serous pelvic cancer.

[Histopathology and clinical aspects of extrauterine pregnancy]. / Histopathologie und Klinik der Extrauteringravidität.

Ectopic pregnancies are the main sources of pregnancy-related morbidity and mortality in the first trimester. They are usually located in the ampullary part of the fallopian tube and the incidence increases in the setting of assisted reproductive techniques, older age at the time of the first pregnancy, and prior adnexal procedures. The clinical aspects and diagnostic challenges of an ectopic pregnancy for the pathologist are to be outlined. A review of the relevant literature was performed. Proof of gestational tissue is of utmost importance in the pathological-anatomical evaluation of an ectopic pregnancy. A complete evaluation of the specimen of a presumed tubal abruption or after milking out should be performed. Abnormal placentations (blighted ovum, embryonal molar pregnancy) as well as gestational trophoblastic disease (GTD, e.g., partial/complete molar pregnancy, choriocarcinoma) can occur in the setting of an ectopic pregnancy. Caution must be taken to differentiate a trophoblast hyperplasia secondary to the tubal microenvironment from GTD. p57 immunohistochemistry can help exclude a molar pregnancy. Only 50% of ectopic pregnancies are associated with tubal pathologies (e. g. inflammation, tubal adhesions). Chorionic villi and trophoblast epithelia can demonstrate regressive changes after prior methotrexate treatment. Rarely, immunohistochemistry with GATA-3, p63, ß­HCG, PAX-8, and WT-1 can be used in the differential diagnosis of trophoblastic epithelium. Ectopic pregnancies are associated with significant morbidity and mortality. A thorough evaluation of the specimen can help guide management and follow-up.

Attached and Suspended Denitrifier Communities in Pristine Limestone Aquifers Harbor High Fractions of Potential Autotrophs Oxidizing Reduced Iron and Sulfur Compounds.

Oxygen and nitrate availability as well as the presence of suitable organic or inorganic electron donors are strong drivers of denitrification; however, the factors influencing denitrifier abundance and community composition in pristine aquifers are not well understood. We explored the denitrifier community structure of suspended and attached groundwater microorganisms in two superimposed limestone aquifer assemblages with contrasting oxygen regime in the Hainich Critical Zone Exploratory (Germany). Attached communities were retrieved from freshly crushed parent rock material which had been exposed for colonization in two groundwater wells (12.7 and 48 m depth). Quantitative PCR and amplicon pyrosequencing of nirK and nirS genes encoding copper-containing or cytochrome cd1 heme-type nitrite reductase, respectively, and of bacterial 16S ribosomal RNA genes showed a numerical predominance of nirS-type denitrifiers in both attached and suspended groundwater communities and a dominance of nirS-type denitrifiers closely related to the autotrophic thiosulfate- and hydrogen-oxidizing Sulfuritalea hydrogenivorans and the iron- and sulfide-oxidizing Sideroxydans lithotrophicus ES-1. Potential rates of nitrate reduction in association with exposed crushed rock material were higher with an inorganic electron donor (thiosulfate) compared to an organic electron donor (fumarate/acetate) in the upper aquifer assemblage but similar in the lower, oxic aquifer. Our results have clearly demonstrated that groundwater from pristine limestone aquifers harbors diverse denitrifier communities which appear to selectively attach to rock surfaces and harbor a high potential for nitrate reduction. Our findings suggest that the availability of suitable inorganic versus organic electron donors rather than oxygen availability shapes denitrifier communities and their potential activity in these limestone aquifers.

Proteomic biomarkers for psoriasis and psoriasis arthritis.

UNLABELLED: Although several new biomarkers have been recently proposed for psoriasis (Ps) and psoriasis arthritis (PsA), nothing is known about their diagnostic sensitivity and specificity, and their routine use. We therefore searched in-depth for new biomarker candidates using a biobank with EDTA-plasma from 158 individuals, patients and healthy controls. Samples from 6 selected pairs (patients against healthy controls) were searched proteomically using a workflow of extensive and precise design that is highly comprehensive. Subsequent verification was performed using ELISA and the entire biobank. By proteomic methods, 208 altered proteins were identified. Of these, 15 biomarker candidates were selected for verification. Of these 15, 4 individual parameters and 11 combinations significantly discriminated between patient and control groups. These individual parameters were Zn-α2-glycoprotein, complement C3, polymeric immunoglobulin receptor, and plasma kallikrein. Significant discrimination was obtained by combinations of 2 or 3 parameters. One combination seemed suitable for diagnosing PsA. Moreover, several candidates desmoplakin, complement C3, polymeric immunoglobulin receptor, and cytokeratin 17, correlated with PASI in all patients. This first comprehensive proteomic study on non-depleted plasma identified several biomarker candidates that have not been described before as well as some known from previous studies. BIOLOGICAL SIGNIFICANCE: Our non-gel proteomic analysis is based on the highly comprehensive and significantly optimized chromatographic protein pre-fractionation. The method allows a biomarker search in non-depleted plasma. The subsequent verification by ELISA identifies several biomarker-candidates for the unbiased diagnosis of psoriasis and psoriasis arthritis. Four of the identified candidate markers might be used individually. Combinations of several parameters improve the diagnostic sensitivity and specificity. The still not validated candidates form a reserve for further evaluation. Moreover, mass spectrometric data uncover several biomarker-candidates which show diverse protein species of the same protein with opposing changes in the same sample.

Enhanced Dietary Awareness and Lifestyle Changes in First-Year Medical Students Following Exposure to Problem-Based Nutrition Education

Background: The ever-increasing prevalence of chronic lifestyle-associated diseases has resulted in greater awareness of the importance of preventative medicine and its incorporation as an integral component of modern undergraduate medical curricula. As excessive dietary intake and physical inactivity are widely acknowledged as leading risk factors for the onset of chronic lifestyle-associated diseases; the promotion of a healthy lifestyle is regarded as a priority for today's primary care physicians. For this reason; it was deemed appropriate by the designers of the problem-based learning (PBL) curriculum; which was introduced at the Nelson R. Mandela School of Medicine in 2001; to include a six-week Nutrition theme early in the medical students' five-year curriculum. This study set out to determine the impact of this theme; which included a specific focus on the importance of nutrition in avoiding lifestyle-associated disorders; on the dietary awareness and lifestyle of the 2004 intake of medical students.Methods: First-year medical students (n = 213) spent the first six weeks of their curriculum (following an orientation period) engaged in a problem-based learning Nutrition theme; which included active; personalised learning experiences such as analysing their own dietary intakes and recording their personal anthropometric measures. They were questioned two weeks after conclusion of the theme regarding (i) the impact of the theme on their dietary awareness and lifestyles; (ii) whether they had; since the start of the theme; shared their newly acquired insights with others; and (iii) the extent to which they recalled their personal measured anthropometric data and calculated kilojoule (kJ) intakes derived during the practical sessions.Results: Nearly 84 of the students responded to the anonymous survey (n = 178). A greater awareness of their personal dietary intake following the completion of the Nutrition theme was acknowledged by 88.2( n = 157); while 65.1 (n = 116) reported improvements to their general lifestyle. Eighty-five percent reported having counselled family members and friends about diet and lifestyle-related issues in the eight-week period since the start of the theme. While recall of body mass indices was higher (p 0.01) in females (85.8) than in males (61.5 ); recall of daily kJ intakes was independent of gender. Unsolicited mention by the students surveyed in this study of components of the South African Food-based Guidelines and recent alternative food pyramids suggests that these models were recognised as health priority areas by this student cohort.Conclusion: The introduction of a Nutrition theme at the start of the problem-based medical learning curriculum appeared to have impacted significantly on the dietary awareness and lifestyles of the students surveyed; with a tendency among students to share this awareness with others. From the open-ended responses of the students; the findings of this study appear to confirm that medical students appreciated learning about their own health factors; and that personalising the information made the learning experience more valuable to them. Attitudinal changes and apparent internalisation of the newly acquired nutritional awareness were reflected by the high percentage of students who acknowledged that they had advised others within the two-week period following the completion of the theme. This augurs well for the potential preventative counselling practices of these future medical graduates. It will; however; be of interest to survey this student cohort longitudinally to establish whether their changed perceptions have a longer term impact and result in attitudes and practices that support preventative health care

Refinement of the spinocerebellar ataxia type 4 locus in a large German family and exclusion of CAG repeat expansions in this region.

Spinocerebellar ataxia type 4 (SCA4) is an autosomal dominant disorder mapped to chromosome 16q22.1 in a large Utah kindred. The clinical phenotype is characterized by cerebellar ataxia with sensory neuropathy. We describe a five-generation family from northern Germany with similar clinical findings linked to the same locus. Haplotype analyses refined the gene locus to a 3.69 cM interval between D16S3019 and D16S512. Analysis of nine CAG/CTG tracts in this region revealed no evidence for a repeat expansion.

Histochemical analysis of phenylphenalenone-related compounds in Xiphidium caeruleum (Haemodoraceae).

Phenylphenalenones represent a typical group of secondary metabolites of the Haemodoraceae. Some of these phenolic compounds show organ-specific distribution within the plant. However, detailed information on cellular localisation is still lacking. To this end, confocal laser-scanning microscopy, microspectral photometry and high-performance liquid chromatography were used to study the tissue localisation of phenylphenalenone-type compounds in Xiphidium caeruleum Aubl. From the autofluorescence potential of these compounds, specific distribution of allophanylglucosides and non-glucosidic compounds of the phenylphenalenone-type in distinct cells of the roots (apical meristem, cortex, cap, epidermis) and the shoot system was revealed. Fluorescence enhancement using "Naturstoff reagent A" (NA) indicated the occurrence of NA-positive natural products in the vacuoles of leaf epidermal cells. The present results provide new insights into the possible functions of phenylphenalenone-related compounds in the context of their localisation. Additionally, the advantages and limitations of the techniques are discussed.

Over-expression of wild-type Rad51 correlates with histological grading of invasive ductal breast cancer.

Breast cancer is a major cause of cancer-related death in women. BRCA1 tumour-suppressor function is abolished in sporadic breast cancer by down-regulation of the protein level. This down-regulation inversely correlates with tumour grading. BRCA1 is part of a multiprotein complex, which also contains the recombination factor Rad51. Here we describe that in contrast to BRCA1, histological grading of sporadic invasive ductal breast cancer significantly correlates with over-expression of wild-type Rad51. These data suggest that in addition to the absence of the tumour-suppressor protein BRCA1, over-expression of wild-type Rad51 also contributes to the pathogenesis of a significant percentage of sporadic breast cancers and that other mechanisms than mutations must be responsible for this altered expression.

DNA repair and recombination factor Rad51 is over-expressed in human pancreatic adenocarcinoma.

Molecular processes that could contribute to differences in chemo- and radioresistance include variations in DNA repair mechanisms. In mammalian cells, the product of the rad51 gene mediates DNA repair via homologous recombination. We describe that in contrast to conventional monolayer cell systems Rad51 protein accumulates to high-levels in three-dimensional cell culture models as well as in orthotopic xeno-transplants of human pancreatic cancer cells. Strikingly, over-expression of wild-type Rad51 was also found in 66% of human pancreatic adenocarcinoma tissue specimens. Functional analysis revealed that Rad51 over-expression enhances survival of cells after induction of DNA double strand breaks. These data suggest that perturbations of Rad51 expression contribute to the malignant phenotype of pancreatic cancer. Oncogene (2000).

Intraarticular, epidural, and intravenous analgesia after total knee arthroplasty.

BACKGROUND: After total knee arthroplasty, patients regularly suffer from severe pain. It is unclear whether epidural or systemic pain therapy is superior in terms of postoperative pain relief, patients' comfort and side effects. A new therapeutic approach, intraarticular opioids, has been suggested with the detection of opioid receptors in inflamed tissue. This method has proven suitable for clinical use in small operations (e.g. knee arthroscopy). In this study, we compared epidural analgesia and intraarticular application of morphine plus "on-demand" intravenous analgesia to "on-demand" intravenous analgesia alone. METHODS: Thirty-seven patients, scheduled for total knee arthroplasty, were randomly assigned to three treatment groups: in group 1 (EPI) patients received bolus doses of morphine via an epidural catheter; in group 2 (IA) an intraarticular bolus of 1 mg of morphine was applied at the end of the operation with subsequent use of a patient-controlled analgesia (PCA) pump; group 3 (Control), in which only PCA was provided, served as control for both analgesic procedures. Main outcome measures included visual analogue pain scales, total morphine consumption, and stress hormones. RESULTS: No statistically significant differences in visual analogue pain scales could be detected between the three groups. Application of intraarticular morphine did not reduce the amount of analgesics required for postoperative analgesia as compared to intravenous analgesia alone. Application of epidural morphine significantly suppressed beta-endorphine release, but did not significantly influence other stress hormones as compared to the control group. CONCLUSION: Epidural and intravenous analgesia after total knee arthroplasty are equivalent methods of pain relief. In major orthopaedic procedures, application of intraarticular morphine does not reduce analgesic requirements.

[Reduction of bacterial contamination during mechanical autotransfusion by uv irradiation--initial results]. / Reduktion von bakteriellen Kontaminationen während maschineller Autotransfusion durch UV-Bestrahlung--Erste Ergebnisse.

OBJECTIVE: To investigate the effects of UV-radiation of autologous blood on bacteria and red blood cells when using intraoperative sampling of autologous blood using a cell separator--an established method for reducing the need for donor blood during surgery--which is reported to have a bacterial contamination rate of 5-75%, due mainly to coagulase-negative staphylococci (CNS). METHODS: Cell-separator blood was diluted to a haematocrit level permitting transmission of 1% of the UV-radiation used in this study (lambda 254 nm, coat thickness 1 mm). CNS samples were irradiated for 2, 4, 10, 20 and 30 seconds. Free haemoglobin and methaemoglobin levels were measured, and erythrocytes examined microscopically at the end of the procedure. RESULTS: Blood samples had to be diluted to a haematocrit of 1% to permit transmission of 1% of the UV light. The optimal irradiation duration was 4 seconds, when bacteria were completely eliminated. Longer irradiation durations were associated with increasing levels of free haemoglobin and methaemoglobin, the levels of which at 4 seconds exposure were 12.5 mg/L and 15.5%, respectively. CONCLUSIONS: It is possible to prevent CNS contamination of cell-separator blood by irradiation with UV light. Prior to clinical application, however, the method will need to be modified to minimize side effects and increase its decontamination efficacy.

The infection characteristics of the antelope schistosomes, Schistosoma margrebowiei and S. leiperi, in inbred BALB/c mice and in Mastomys coucha.

Detailed studies were carried out to assess the infection characteristics of the antelope schistosomes in BALB/c mice and Mastomys coucha. Both schistosome species reached sexual maturity in these hosts. However, they differed markedly in terms of egg production rates and preferred sites of tissue egg deposition. Tissue egg deposition commenced between 4 and 5 weeks in the case of Schistosoma margrebowiei and between 6 and 7 weeks in the case of S. leiperi. Tissue egg accumulation rates of S. leiperi were calculated to be 334 and 311 eggs/gravid worm pair/day in mice and M. coucha, respectively. The fecundity of S. margrebowiei was found to be substantially greater (approximately 5 times; daily output ranging from 1600-1900 eggs/gravid worm pair). While S. leiperi infections remained relatively stable in both hosts during the study period (i.e. up to 15 weeks after onset of egg laying), S. margrebowiei infections were observed to deteriorate rapidly in M. coucha.

Enhancement of HIV-1 gp41 binding to Raji cells by PWM, LPS, interferon-gamma and interleukin-6.

Based on our finding that HIV-1 gp41 independently of CD4 can bind to several proteins (gp41 binding protein: GBP) on the human T-cell line H9, B-cell line Raji and monocyte-cell line U937, we examined the effect of mitogens and cytokines on binding of gp41 to H9, Raji and U937 cells. Flow cytometry (FACS) analysis demonstrated that PWM and LPS, IFN-gamma and IL-6, but not Con A, IFN-alpha, -beta, -omega and IL-2, could increase gp41 binding to Raji cells. In controls, none of the regulators (IFN-alpha, -beta, -gamma, -omega, IL-2, IL-6, Con A, PWM, LPS) could modify the binding potential of H9 and U937 cells. Our data suggest that the expression of HIV-1 binding proteins is subject to regulation by PWM, LPS, IFN-gamma and IL-6 in the case of B-cells, while on T-cells and macrophages, the binding proteins may be constitutively expressed.

The infection characteristics of a South African isolate of Schistosoma mansoni: a comparison with a Puerto Rican isolate in BALB/c mice and Mastomys coucha.

The infection characteristics of a South African (RSA) laboratory isolate of Schistosoma mansoni were compared with those of a widely studied Puerto Rican (PR) isolate in BALB/c mice and Mastomys coucha over the period of 5-12 weeks after infection. The infectivity, maturation and, in particular, the fecundity of the two schistosomes were found to differ markedly. Tissue egg-accumulation rates of the RSA strain were substantially lower than those of the PR strain. Although the maturation of both parasite strains was somewhat delayed in M. coucha, the characteristics of each was essentially consistent in both rodent hosts. Notwithstanding the possible influence of prolonged laboratory passage on the behaviour of schistosome isolates, the results of the present study are nevertheless considered to support the idea that parasite strain differences may, to some extent, account for regional variations in the morbidity of intestinal schistosomiasis. The need to be cognizant of the characteristics of individual host-parasite combinations when comparing different schistosome species and strains, particularly with respect to both their abilities to elicit immunopathology and induce concomitant immunity and their susceptibilities to chemotherapy, is highlighted.

Intestinal parasites of conventionally maintained BALB/c mice and Mastomys coucha and the effects of a concomitant schistosome infection.

A longitudinal study was carried out to identify the spectrum of intestinal parasites present in conventionally maintained BALB/c mice and Mastomys coucha and to determine the effects of concomitant schistosome infections on their parasite status. Six parasites were observed during the course of the study, namely the nematodes Aspiculuris tetraptera and Syphacia obvelata, Entamoeba muris and the flagellates Trichomonas muris, Spironucleus muris and Chilomastix spp. Although the 2 rodents shared common facilities, the overall prevalences of S. obvelata, T. muris and S. muris were significantly higher in M. coucha than BALB/c mice. BALB/c mice with concomitant schistosome infection had increased prevalences of E. muris, T. muris and S. muris. In M. coucha, in contrast, there were no significant increases in parasite prevalences. Infection intensities of T. muris and S. muris were significantly greater in M. coucha than BALB/c mice. Concomitant schistosome infection resulted in increased intensities of T. muris infection in BALB/c mice only. The influence of immune status in determining the susceptibilities of rodents to environmentally transmitted parasites is discussed.

The infectivity of Schistosoma mansoni in mice, following dipping with an acaricide.

The effect of prior treatment of mice with an acaricide (Alugan) on the infectivity of Schistosoma mansoni cercariae via the percutaneous route was assessed. No effects were observed, even in animals dipped only 1 day before exposure to cercariae.