Clinical and histopathological aspects of 113 necrotizing malignant melanomas of the choroid. 1. Clinical and histological features of necrotizing choroidal melanomas

BACKGROUND: Tumor necrosis may reflect a destructive immune reaction. Systematic and statistically significant comparative clinico-histopathologic studies have not yet been reported. PATIENTS AND METHODS: 113 necrotizing choroidal melanomas (NCM) recruited from 701 enucleated globes 1967-1988 were resectioned, stained and compared to 100 choroidal melanomas without necrosis (CM), and data of 74 patients with a follow-up of more than 10 years were evaluated. RESULTS: Statistically significant characteristics of NCM were: patient age < 60 yrs. for NCM 27.4%, CM 46%; patient age in men for NCM was 64 yrs on average (CM: 58 yrs.), in women for NCM 67 yrs. (CM: 59 yrs.). Time elapsed between first symptoms and enucleation was < 12 months in 15.9% of NCM (89% for CM), and > 12 months in 23.9% of NCM (11% in CM). Mixed or epitheloid cell tumors was seen in 54.9% of NCM and 49% of CM, spindle cell tumors in 36.3% of NCM and 51% in CM. Advanced tumor stages T3 and T4 were present in 45.1% resp. 36.3% of NCM compared to 37% resp. 16% in CM. Scleral invasion was documented in 67.3% of NCM and 37% of CM, extrascleral dissemination in 43% of NCM and 16% of CM. Secondary glaucomas were seen in 62.2% of NCM and 6% CM, a penetration through Bruch's membrane in 61.0% of NCM and 46% of CM. Intratumoral hemorrhage was noted in 68.14% of NCM and 24% of CM, extratumoral bleeding in 23.9% of NCM and 0% CM. Inflammatory reactions in tumors were observed in 96.7% of NCM harboring > 30% necrosis compared to 5% in CM, and extratumoral in 94.5% of NCM and 0% of CM. Intraocular extratumoral necrosis was seen in 23.9% of NCM and 0% of CM. There were no significant differences in the degree of pigmentation of the 90.3% pigmented NCM or of the 94% pigmented CM, neither in the tumor localization, being constantly behind the equator in 87% of cases. Survival of patients with NCM patients was 5 years and 9 months on average (5-year mortality rate 41.9%), and 74.3% were deceased from metastatic spread. CONCLUSIONS: Significant clinical and histopathological differences between necrotizing and non-necrotizing malignant melanomas of the choroid can be identified. The inflammatory reaction of NCM must be further elucidated, particularly with respect to the nature of tumor-infiltrating lymphocytes.     

Marfan syndrome: diagnosis of cardiovascular manifestations]

BACKGROUND: Despite the availability of several different markers for Epstein--Barr virus (EBV) serology, the EBV status of some patients cannot be resolved from a single serum sample with routine testing. To avoid the requirement of follow-up samples, supplementary tests have to be used in these cases. OBJECTIVE: To evaluate the usefulness of avidity and immunoblot assays as supplementary tests for the diagnosis of acute EBV infections. STUDY DESIGN: Three groups of samples for which a definite diagnosis on the EBV status could not be obtained with the routine serological tests were further examined by an EBV IgG avidity assay, by an immunoblot based on a lysate of EBV infected cells, and by a second immunoblot based on recombinant EBV antigens. The three groups consisted of 38 samples with negative/borderline EB nuclear antigen 1 (EBNA-1) antibodies, negative/borderline EBV IgM and positive EBV IgG; 10 samples with indeterminate EBNA-1 and/or EBV IgM assays because of control antigen reactions; and 4 samples with positive EBV IgM results that were not plausible. RESULTS: The avidity assay differentiated between acute and past infections for all samples. In contrast, some cases remained unresolved with both the recombinant and the lysate immunoblot. Two samples were incorrectly classified with the lysate immunoblot. Interpretation of the lysate immunoblot banding patterns was complicated when anticellular antibodies were present. CONCLUSION: Avidity testing appears to be the confirmatory method of choice to differentiate between acute and past EBV infections.     

Expression of beta 2-integrins and L-selectin on polymorphonuclear leukocytes in septic patients

Adhesion molecules on polymorphonuclear leukocytes (PMNL) play an important role in nonspecific defense mechanisms directed at invading microorganisms. When local infection, however, cannot be controlled, a systemic inflammatory response syndrome (SIRS) ensues which may progress to septic shock and multiple organ failure, these being major determinants of the patient's outcome. In the present study, the expression of beta 2-integrins and L-selectin on blood PMNL was measured on subsequent days in patients with sepsis (n = 17) and in healthy volunteers (n = 15). beta 2-Integrins and L-selectin molecules were detected by flow cytometry, using the monoclonal antibodies IB4 (anti-CD18) and Dreg200 (anti-CD62L), respectively. Adhesion molecules were determined at baseline immediately after blood collection and also 45 min after incubation of cells in vitro at body temperature to allow for spontaneous regulation. In addition, PMNL were activated by receptor-dependent and receptor-independent stimuli to characterize stimulus-specific adhesion molecule expression. In parallel with the measurement of adhesion molecules, severity of sepsis was assessed by the Elebute score. The results demonstrate significant differences in the basal, spontaneous and stimulus-induced expression of adhesion molecules between healthy volunteers, survivors (n = 11) and nonsurvivors (n = 6). Moreover, when survivors and nonsurvivors with severe sepsis (Elebute score > 12) were compared, basal expressions of both beta 2-integrins and L-selectin were significantly lower in patients who did not survive. Thus, measurement of adhesion molecules on circulating PMNL may be useful to identify septic patients at high risk for lethal outcome.     

Solidification microstructures in rapidly solidified,gas atomized aluminium-lithium alloy powders

The examination of the solidification behaviour and resultant microstructures in an Al-Li-Cu-Mg-Zr alloy processed by high-pressure inert gas atomization is reported. Using analytical transmission electron microscopy some quantification of the segregation behaviour is possible which allows the comparison with a simple solute redistribution model (Scheil analysis). It is shown that for powder sizes likely to be of commercial interest (10 to 20 m), cellular solidification structures are to be expected on atomization, and methods of utilizing such structures are discussed.     

Out-of-Field Hippocampus from Partial-Body Irradiated Mice Displays Changes in Multi-Omics Profile and Defects in Neurogenesis

The brain undergoes ionizing radiation exposure in many clinical situations, particularly during radiotherapy for brain tumors. The critical role of the hippocampus in the pathogenesis of radiation-induced neurocognitive dysfunction is well recognized. The goal of this study is to test the potential contribution of non-targeted effects in the detrimental response of the hippocampus to irradiation and to elucidate the mechanisms involved. C57Bl/6 mice were whole body (WBI) or partial body (PBI) irradiated with 0.1 or 2.0 Gy of X-rays or sham irradiated. PBI consisted of the exposure of the lower third of the mouse body, whilst the upper two thirds were shielded. Hippocampi were collected 15 days or 6 months post-irradiation and a multi-omics approach was adopted to assess the molecular changes in non-coding RNAs, proteins and metabolic levels, as well as histological changes in the rate of hippocampal neurogenesis. Notably, at 2.0 Gy the pattern of early molecular and histopathological changes induced in the hippocampus at 15 days following PBI were similar in quality and quantity to the effects induced by WBI, thus providing a proof of principle of the existence of out-of-target radiation response in the hippocampus of conventional mice. We detected major alterations in DAG/IP3 and TGF-β signaling pathways as well as in the expression of proteins involved in the regulation of long-term neuronal synaptic plasticity and synapse organization, coupled with defects in neural stem cells self-renewal in the hippocampal dentate gyrus. However, compared to the persistence of the WBI effects, most of the PBI effects were only transient and tended to decrease at 6 months post-irradiation, indicating important mechanistic difference. On the contrary, at low dose we identified a progressive accumulation of molecular defects that tended to manifest at later post-irradiation times. These data, indicating that both targeted and non-targeted radiation effects might contribute to the pathogenesis of hippocampal radiation-damage, have general implications for human health.     

Bioenergetic Alterations of Metabolic Redox Coenzymes as NADH,FAD and FMN by Means of Fluorescence Lifetime Imaging Techniques

Metabolic FLIM (fluorescence lifetime imaging) is used to image bioenergetic status in cells and tissue. Whereas an attribution of the fluorescence lifetime of coenzymes as an indicator for cell metabolism is mainly accepted, it is debated whether this is valid for the redox state of cells. In this regard, an innovative algorithm using the lifetime characteristics of nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD) to calculate the fluorescence lifetime induced redox ratio (FLIRR) has been reported so far. We extended the FLIRR approach and present new results, which includes FLIM data of the various enzymes, such as NAD(P)H, FAD, as well as flavin mononucleotide (FMN). Our algorithm uses a two-exponential fitting procedure for the NAD(P)H autofluorescence and a three-exponential fit of the flavin signal. By extending the FLIRR approach, we introduced FLIRR1 as protein-bound NAD(P)H related to protein-bound FAD, FLIRR2 as protein-bound NAD(P)H related to free (unbound) FAD and FLIRR3 as protein-bound NAD(P)H related to protein-bound FMN. We compared the significance of extended FLIRR to the metabolic index, defined as the ratio of protein-bound NAD(P)H to free NAD(P)H. The statistically significant difference for tumor and normal cells was found to be highest for FLIRR1.     

Regional mass flux balancing for controlling gentle soil remediation operations

Extraction of heavy metals by accumulating plants is a method which is currently in development for the "gentle" remediation of contaminated agricultural soils (phytoremediation, see [2]). Areal contaminant mass flux balances are basic criteria for the design of such remediations and their control. A framework for the integration of contaminant balances relating the field scale of remediation with the regional scale of soil monitoring networks is provided by the recently developed method PROTERRA [3]. The objective of the study presented in this paper was to test the suitability of PROTERRA for planning and monitoring gentle soil remediations. For this purpose we applied the PROTERRA method to the contaminated agricultural land in and around Dornach, Switzerland, to assess copper flux balances.The calculations showed that atmospheric deposition and the application of pesticides and manure are important pathways for the inputs of copper. The copper export with a special maize cultivar accumulating heavy metals would be about three times higher than the average metal export with crops. A moderate increase of sewage sludge application would lead to a substantial increase of the copper input. Decisions to remediate the soil should take the uncertainty of mass flux balances both on field scale as well as on regional scale into account. Therefore, an important need of further development of the PROTERRA method is the integration of uncertainty analysis on both scales.     

The part of the private sector in global water planning: the role of desalination

Water is the key to further development. The private sector is already playing a major role in looking into alternatives for a balanced water supply situation with the help of advanced technologies. We were generously given many Gardens of Eden, but only a few will survive into the next century. A worldwide campaign is necessary to show the scarcity of water. The United Nations Habitat II Conference in Istanbul, June 3–14, 1996, and the preceding IDA World Conference in Abu Dhabi on Desalination and Water Sciences, 18–24 November, 1995, are the immediate platforms on which international institutions and multilateral development banks can discuss this topic and help formulate an agenda for the next century.