GHSI EMERGENCY RADIONUCLIDE BIOASSAY LABORATORY NETWORK - SUMMARY OF THE SECOND EXERCISE.

The Global Health Security Initiative (GHSI) established a laboratory network within the GHSI community to develop collective surge capacity for radionuclide bioassay in response to a radiological or nuclear emergency as a means of enhancing response capability, health outcomes and community resilience. GHSI partners conducted an exercise in collaboration with the WHO Radiation Emergency Medical Preparedness and Assistance Network and the IAEA Response and Assistance Network, to test the participating laboratories (18) for their capabilities in in vitro assay of biological samples, using a urine sample spiked with multiple high-risk radionuclides (90Sr, 106Ru, 137Cs, and 239Pu). Laboratories were required to submit their reports within 72 h following receipt of the sample, using a pre-formatted template, on the procedures, methods and techniques used to identify and quantify the radionuclides in the sample, as well as the bioassay results with a 95% confidence interval. All of the participating laboratories identified and measured all or some of the radionuclides in the sample. However, gaps were identified in both the procedures used to assay multiple radionuclides in one sample, as well as in the methods or techniques used to assay specific radionuclides in urine. Two-third of the participating laboratories had difficulties in determining all the radionuclides in the sample. Results from this exercise indicate that challenges remain with respect to ensuring that results are delivered in a timely, consistent and reliable manner to support medical interventions. Laboratories within the networks are encouraged to work together to develop and maintain collective capabilities and capacity for emergency bioassay, which is an important component of radiation emergency response.

A puzzling case of contamination with 241Am.

Two people were exposed to and contaminated with 241Am. In vivo determinations of the incorporated 241Am were performed using a whole-body counter and two partial-body counters for the skull and lung, respectively. Additionally, urine samples were analysed to estimate the systemic activity removed from the body. To improve the geometry of the skull measurements, an optimised detector configuration was used, a calibration with three physical phantoms of the human head was conducted, and the morphological variability between the individuals was also considered. The results of the measurements indicate that activity is not deposited in the deep tissues, rather in the skin tissues close to the body surface. Unfortunately, the many open questions relating to the actual circumstances during and after the incident make the interpretation of this case difficult if at all possible.

GHSI EMERGENCY RADIONUCLIDE BIOASSAY LABORATORY NETWORK: SUMMARY OF A RECENT EXERCISE.

The Global Health Security Initiative (GHSI) established a laboratory network within the GHSI community to develop their collective surge capacity for radionuclide bioassay in response to a radiological or nuclear emergency. A recent exercise was conducted to test the participating laboratories for their capabilities in screening and in vitro assay of biological samples, performing internal dose assessment and providing advice on medical intervention, if necessary, using a urine sample spiked with a single radionuclide, 241Am. The laboratories were required to submit their reports according to the exercise schedule and using pre-formatted templates. Generally, the participating laboratories were found to be capable with respect to rapidly screening samples for radionuclide contamination, measuring the radionuclide in the samples, assessing the intake and radiation dose, and providing advice on medical intervention. However, gaps in bioassay measurement and dose assessment have been identified. The network may take steps to ensure that procedures and practices within this network be harmonised and a follow-up exercise be organised on a larger scale, with potential participation of laboratories from the networks coordinated by the International Atomic Energy Agency and the World Health Organization.

AN INTERLABORATORY COMPARISON ON THE DETERMINATION OF 241Am, 244Cm AND 252Cf IN URINE.

An intercomparison exercise on the determination of (241)Am, (244)Cm and (252)Cf in urine was performed. Since it was designed with regard to emergency preparedness, the detection limit for each nuclide was set to 0.1 Bq per 24-h urine sample. Most of the participating laboratories were established bioassay laboratories. However, some laboratories that routinely determine (241)Am only in environmental samples were also invited in order to explore their potential for emergency bioassay analysis. Another aspect of the intercomparison was to investigate the performance of all laboratories concerning the chemical yields of the (243)Am tracer in comparison with (244)Cm and (252)Cf. In summary, both types of laboratories showed good results. There was a negative bias for the results of (244)Cm and (252)Cf, which can be explained by slightly different radiochemical behaviours of americium, curium and californium and which is in agreement with results reported in the literature.

Chemoprevention by celecoxib and mutagen sensitivity of cyclin d1 in patients with oropharyngeal carcinoma.

UNLABELLED: The head and neck region is one of the most important locations predisposed for tobacco-associated cancer. Chemoprevention might offer a chance to decrease the risk for this type of disease. MATERIALS AND METHODS: Mini-organ cultures (MOC) of macroscopically-healthy pharyngeal tissues from 20 patients with oropharyngeal squamous cell carcinoma (SCC) and from 20 controls were employed in the study. MOC were firstly incubated with Celecoxib, and DNA damage was induced by incubation with Benz[a]pyren-7,8-diol-9,10-epoxid (BPDE), a major representative of tobacco-associated carcinogens. DNA damage was evaluated with the alkaline single-cell microgel electrophoresis (Comet assay). Furthermore, fragmentation of the cyclin D1 gene, a gene of special importance in head and neck carcinogenesis was examined by the Comet-FISH assay. Finally, the chemoprotective potential of Celecoxib was analyzed after incubation with MOC. RESULTS: As expected, BPDE caused significant DNA fragmentation in tumor compared to negative control tissues. No enhanced damage was observed in the cyclin D1 gene. DNA fragmentation was significantly reduced when MOC were incubated with Celecoxib in the tumor group. Surprisingly, these effects were also observed in the group without cancer of the oropharynx, although COX-2 is not expressed in macroscopically-healthy mucosa. CONCLUSION: Celecoxib showed considerable chemoprotective effeciency against BPDE in both groups and this effect seems to be independent of COX-2 expression. No evidence for higher mutagen sensitivity in the Cyclin D1 gene was observed.

Cortical habituation deficit in tinnitus sufferers: contingent negative variation as an indicator of duration of the disease.

Cortical attention and habituation parameters are altered in patients suffering from tinnitus. The aim of the study was to quantify cortical attention and habituation parameters in tinnitus patients by recording the contingent negative variation (CNV) response and to correlate amplitudes of different CNV parameters with duration of disease. Twenty patients suffering from tinnitus (median: 44 years) and twenty age- and sex-matched healthy controls (median: 41 years) were tested by a CNV paradigm. We recorded overall CNV, initial CNV, and terminal CNV and calculated habituation slopes. All CNV parameters were Spearman-correlated with individual duration of disease. Highly significant between groups differences emerged in total (tinnitus: -8.4 uV vs. controls: -3.8 uV), initial (-11.2 vs. -6.0 uV), and terminal CNV (-11.9 vs. -6.5 uV) demonstrating higher negative amplitudes in tinnitus patients. Habituation differed in total and terminal CNV, indicating missing habituation in tinnitus patients. Overall CNV (ϱ = -.365) and initial CNV (ϱ = -.529) showed a medium Spearman correlation with duration of disease. We conclude that the correlation between duration of tinnitus and the initial CNV amplitudes indicates an altered state of cortical excitability that can also be observed in more negative CNV-amplitudes in tinnitus patients. We assume that this state indicates a chronicity process in tinnitus disease.

Epidermal growth factor receptor in adrenocortical tumors: analysis of gene sequence, protein expression and correlation with clinical outcome.

Adrenocortical carcinoma is a rare but highly malignant neoplasm with still limited treatment options. Epidermal growth factor receptor (EGFR) has been shown to be overexpressed in many solid tumors, but its expression in adrenocortical carcinoma has been studied only in a limited number of cases. Therefore, we analyzed the expression of EGFR in 169 adrenocortical carcinoma samples and compared it with 31 adrenocortical adenomas. Additionally, in 30 cases of adrenocortical carcinoma, exons 18-21 of the EGFR gene were cloned and sequenced. EGFR expression was found in 128 of 169 adrenocortical carcinoma samples (76%), and in 60 of these samples (=36%) strong membrane staining was detected. However, there was no significant correlation with clinical outcome. In addition, all 30 sequenced cases revealed unmutated EGFR genes. In contrast, only 1 out of 31 adrenocortical adenomas weakly expressed the EGFR (3%). In summary, EGFR was overexpressed in more than three-quarters of adrenocortical carcinoma cases of this series. However, no mutations of the EGFR gene were found and EGFR expression was not of prognostic relevance. As EGFR is hardly expressed in adrenocortical adenomas, our results suggest that its expression in adrenocortical tumors indicates a malignant phenotype, which may be used in the differential diagnosis between adrenocortical adenomas and carcinomas.

Rare occurrence of IgVH gene translocations and restricted IgVH gene repertoire in ocular MALT-type lymphoma.

FISH studies on 37 ocular MALT-type lymphomas yielded chromosomal translocations affecting MAL andT1 BCL10 in 1 case each, no evidence for a break in the FOXP1 locus, and trisomy 3 in 14 out of 34 cases (41%). Three out of 8 cases analyzed used the highly mutated VH3-23 gene and showed ongoing somatic hypermutations.