ICRP Publication 111 - Application of the Commission's recommendations to the protection of people living in long-term contaminated areas after a nuclear accident or a radiation emergency.

In this report, the Commission provides guidance for the protection of people living in long-term contaminated areas resulting from either a nuclear accident or a radiation emergency. The report considers the effects of such events on the affected population. This includes the pathways of human exposure, the types of exposed populations, and the characteristics of exposures. Although the focus is on radiation protection considerations, the report also recognises the complexity of post-accident situations, which cannot be managed without addressing all the affected domains of daily life, i.e. environmental, health, economic, social, psychological, cultural, ethical, political, etc. The report explains how the 2007 Recommendations apply to this type of existing exposure situation, including consideration of the justification and optimisation of protection strategies, and the introduction and application of a reference level to drive the optimisation process. The report also considers practical aspects of the implementation of protection strategies, both by authorities and the affected population. It emphasises the effectiveness of directly involving the affected population and local professionals in the management of the situation, and the responsibility of authorities at both national and local levels to create the conditions and provide the means favouring the involvement and empowerment of the population. The role of radiation monitoring, health surveillance, and the management of contaminated foodstuffs and other commodities is described in this perspective. The Annex summarises past experience of longterm contaminated areas resulting from radiation emergencies and nuclear accidents, including radiological criteria followed in carrying out remediation measures.

Model testing using data on 137Cs from Chernobyl fallout in the Iput River catchment area of Russia.

Data collected for 10 years following the Chernobyl accident in 1986 have provided a unique opportunity to test the reliability of computer models for contamination of terrestrial and aquatic environments. The Iput River scenario was used by the Dose Reconstruction Working Group of the BIOMASS (Biosphere Modelling and Assessment Methods) programme. The test area was one of the most highly contaminated areas in Russia following the accident, with an average contamination density of 137Cs of 800,000 Bq m-2 and localized contamination up to 1,500,000 Bq m-2, and a variety of countermeasures that were implemented in the test area had to be considered in the modelling exercise. Difficulties encountered during the exercise included averaging of data to account for uneven contamination of the test area, simulating the downward migration and changes in bioavailability of 137Cs in soil, and modelling the effectiveness of countermeasures. The accuracy of model predictions is dependent at least in part on the experience and judgment of the participant in interpretation of input information, selection of parameter values, and treatment of uncertainties.

Model testing using data on 131I released from Hanford.

The Hanford test scenario described an accidental release of 131I to the environment from the Hanford Purex Chemical Separations Plant in September 1963. Based on monitoring data collected after the release, this scenario was used by the Dose Reconstruction Working Group of BIOMASS to test models typically used in dose reconstructions. The primary exposure pathway in terms of contribution to human doses was ingestion of contaminated milk and vegetables. Predicted mean doses to the thyroid of reference individuals from ingestion of 131I ranged from 0.0001 to 0.8 mSv. For one location, predicted doses to the thyroids of two children with high milk consumption ranged from 0.006 to 2 mSv. The predicted deposition at any given location varied among participants by a factor of 5-80. The exercise provided an opportunity for comparison of assessment methods and conceptual approaches, testing model predictions against measurements, and identifying the most important contributors to uncertainty in the assessment result. Key factors affecting predictions included the approach to handling incomplete data, interpretation of input information, selection of parameter values, adjustment of models for site-specific conditions, and treatment of uncertainties.

Structure of the PPARalpha and -gamma ligand binding domain in complex with AZ 242; ligand selectivity and agonist activation in the PPAR family.

BACKGROUND: The peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors belonging to the nuclear receptor family. The roles of PPARalpha in fatty acid oxidation and PPARgamma in adipocyte differentiation and lipid storage have been characterized extensively. PPARs are activated by fatty acids and eicosanoids and are also targets for antidyslipidemic drugs, but the molecular interactions governing ligand selectivity for specific subtypes are unclear due to the lack of a PPARalpha ligand binding domain structure. RESULTS: We have solved the crystal structure of the PPARalpha ligand binding domain (LBD) in complex with the combined PPARalpha and -gamma agonist AZ 242, a novel dihydro cinnamate derivative that is structurally different from thiazolidinediones. In addition, we present the crystal structure of the PPARgamma_LBD/AZ 242 complex and provide a rationale for ligand selectivity toward the PPARalpha and -gamma subtypes. Heteronuclear NMR data on PPARalpha in both the apo form and in complex with AZ 242 shows an overall stabilization of the LBD upon agonist binding. A comparison of the novel PPARalpha/AZ 242 complex with the PPARgamma/AZ 242 complex and previously solved PPARgamma structures reveals a conserved hydrogen bonding network between agonists and the AF2 helix. CONCLUSIONS: The complex of PPARalpha and PPARgamma with the dual specificity agonist AZ 242 highlights the conserved interactions required for receptor activation. Together with the NMR data, this suggests a general model for ligand activation in the PPAR family. A comparison of the ligand binding sites reveals a molecular explanation for subtype selectivity and provides a basis for rational drug design.

International Arctic Seas Assessment Project.

The International Atomic Energy Agency responded to the news that the former Soviet Union had dumped radioactive wastes in the shallow waters of the Arctic Seas, by launching the International Arctic Seas Assessment Project in 1993. The project had two objectives: to assess the risks to human health and to the environment associated with the radioactive wastes dumped in the Kara and Barents Seas; and to examine possible remedial actions related to the dumped wastes and to advise on whether they are necessary and justified. The current radiological situation in the Arctic waters was examined to assess whether there is any evidence for releases from the dumped waste. Potential future releases from the dumped wastes were predicted, concentrating on the high-level waste objects containing the major part of the radionuclide inventory of the wastes. Environmental transport of released radionuclides was modelled and the associated radiological impact on humans and the biota was assessed. The feasibility, costs and benefits of possible remedial measures applied to a selected high-level waste object were examined. Releases from identified dumped objects were found to be small and localised to the immediate vicinity of the dumping sites. Projected future annual doses to members of the public in typical local population groups were very small, less than 1 microSv--corresponding to a trivial risk. Projected future doses to a hypothetical group of military personnel patrolling the foreshore of the fjords in which wastes have been dumped were higher, up to 4 mSv/year, which still is of the same order as the average annual natural background dose. Moreover, since any of the proposed remedial actions were estimated to cost several million US$ to implement, remediation was not considered justified on the basis of potentially removing a collective dose of 10 man Sv. Doses calculated to marine fauna were insignificant, orders of magnitude below those at which detrimental effects on fauna populations might be expected to occur. Remediation was thus concluded not to be warranted on radiological grounds.

Patient evaluation of a new injection pen for growth hormone treatment in children and adults.

The aim of this study was to evaluate patients' perception and acceptance of a new multi-dose injection device (Genotropin Pen) for recombinant growth hormone (GH) supplied in a two-chamber cartridge. The pen is combined with a very thin needle (B-D Microfine + (29 G) and meets future demands when dosing of GH will be changed from International Units (IU) to milligrams (mg). A total of 39 children receiving GH treatment (East Hospital, Gothenburg and St Bartholomew's Hospital, London), aged between 7 and 17 years, and 39 GH-treated adults (Sahlgrenska Hospital, Gothenburg and Karolinska Hospital, Stockholm), aged between 20 and 68 years, participated in the study. The daily dose ranged from 0.3 mg to 2.6 mg. The injections were given subcutaneously, once daily, and most of the patients used the thigh as an injection site. After a trial period of 2 weeks, injection technique, pain, fear of injection and convenience of the Genotropin Pen were compared with the experience with the prestudy device (Genotropin KabiPen 16, 16(8) or 36) by questionnaire. A total of 95% of the patients preferred the Genotropin Pen to the prestudy device for the following reasons: a greater certainty of correct dosing with the digital display; the possibility of correcting the set dose; the lock function of the injection button when injection is complete; more comfortable to hold due to the design and the plastic material; and reduced pain when injecting due to the thinner needles. Four patients (5%) preferred the prestudy device KabiPen as they considered this to be 'good enough'. Thus, the Genotropin Pen is a convenient injection device and most patients prefer it to the KabiPen.

Radiographic assessment in relation to clinical and biochemical variables in rheumatoid arthritis.

Radiographs of hands and feet were obtained from 125 consecutive patients with rheumatoid arthritis (RA) and the degree of destruction was assessed numerically on a 200-point scale using Larsen's standard radiographs as reference. The method is shown to possess a satisfactory degree of reproducibility. In 96 of these 125 patients, values of another 15 simultaneously determined clinical and biochemical variables were obtained. On applying linear and quadratic multiple regression analysis to this set as well as to the male and female subsets, an 'automatic' selection procedure (stepwise regression) proved duration of disease to be the most important factor relating to the 'Larsen index'. The 96 patients were therefore ranked with respect to duration of disease and divided into 4 subsets of equal magnitude. In the 3 subsets with duration of disease less than 21 years, stepwise regression produced in the final step linear or quadratic combinations not containing duration of disease but correlating quite well with the 'Larsen index' (R = 0.64-0.96). A similar result was obtained upon performing an analogous procedure in the female subset. In all instances, positive contributions of varying degree were obtained from Ritchie's index, ESR, a-antitrypsin (A1-AT), orosomucoid, fibrinogen, and IgM, while negative correlations were associated with ceruloplasmin, IgG, and IgA.

Pharyngeal function in patients with rheumatoid arthritis of the cervical spine and temporomandibular joint.

Pharyngeal function was studied in 31 patients with rheumatoid arthritis. Eighteen of these patients had dysphagia. Cervical spine abnormalities were present in 14. Destruction of the capitulum and/or ramus of the mandible was registered in 9. Pharyngeal dysfunction was revealed in 20. Patients with a vertical dislocation of the C1-C2 in relation to the occipital bone and patients with destruction of the capitulum and/or ramus of the mandible had an increased frequency of pharyngeal dysfunction. Pharyngeal dysfunction is thought to be due to mechanical factors and caused by derangements of muscular attachments and turning points.

Factors related to the progression of joint destruction in rheumatoid arthritis.

In 103 (M = 25, F = 78) of 150 consecutive RA patients, values of the following variables were obtained at the start and end of a 2-year follow-up period: radiographic destruction score of hands and feet according to Larsen (Larsen index), Ritchie index, B-hemoglobin, ESR and plasma proteins (alpha 1-antitrypsin, ceruloplasmin, CRP, fibrinogen, haptoglobin, orosomucoid, IgA, IgG, IgM, C3 and C4). 60% of the values of delta LI (final minus initial value of Larsen index) were significantly larger than zero (11-44 units, p less than 0.05). delta LI was larger in females than in males (p = 0.11). Comparing women with duration of disease (DoD) 1-6 years versus 7-52 years. delta LI was larger in the former group (p = 0.005). Comparing women with the largest delta LI (19-44 units) with the remainder ones (delta LI = -9-18 units), CRP and haptoglobin was higher and IgM lower in the former group (p = 0.03, 0.02 and 0.03 respectively). In women with DoD 1-6 years (and only in this interval) significant linear relationships were found between delta LI and hemoglobin (r = 0.52, p less than 0.01) Ritchie index, haptoglobin, CRP (r = 0.41-0.46, p less than 0.05) and IgM (r = -0.43, p less than 0.05). The mean of repeated hemoglobin values correlated even more strongly with delta LI (r = 0.70, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Protease inhibitors in rheumatoid synovial fluid: a quantitative analysis.

The concentrations of the main endogenous inhibitors of granulocyte proteases (anti-leukoprotease, alpha 1-antitrypsin, alpha 1-antichymotrypsin, and alpha 2-macroglobulin) were estimated in paired samples of synovial fluid and serum/plasma from seropositive rheumatoid arthritics and controls. Rheumatoid synovial fluid contained significantly higher levels of all inhibitors except antileukoprotease. The influence of the synovial membrane on these concentrations was taken into account by comparing the ratio between the observed concentration and that predicted from a certain regression curve fitted to a set of non-inhibitory reference proteins of extra-articular origin (orosomucoid, albumin, and ceruloplasmin). Divergences were interpreted as the net result of intra-articular production or consumption of the inhibitor in question. The results suggested a consumption of antileukoprotease and alpha 1-antitrypsin in the rheumatoid joint, while the increased levels of alpha 1-antichymotrypsin and alpha 2-macroglobulin probably reflected the altered trans-synovial membrane protein flux with some reservation for alpha 2-macroglobulin.

Plasma levels of beta 2-microglobulin in rheumatoid arthritis.

A simple and inexpensive method is described for the determination of beta 2-microglobulin (beta 2-MG) by enzyme-amplified single radial immunodiffusion. The values obtained with this method correlate well with those determined by means of a commerical RIA kit. Using the immunodiffusion method we have measured the plasma levels of beta 2-MG in 135 patients with rheumatoid arthritis (RA) and normal serum creatinine levels. 33% of the patients had increased concentrations of beta 2 MG, but the levels were found to correlate poorly with the values of several variables generally used as indices of the degree inflammatory activity in RA. Furthermore, in contrast to earlier claims to the contrary, beta 2-MG correlated positively with age. The value of beta 2-MG in plasma as an index of inflammatory activity in RA is questioned.

Abnormal axillary lymph nodes in rheumatoid arthritis.

Mammary radiography was performed in 56 patients with arthritis, predominantly rheumatoid arthritis. Definite abnormal axillary lymph nodes were found in 24 and probably abnormal nodes in 8. Abnormal nodes were characterized by increased attenuation, rounded shape and absence of fatty replacement.

Plasma salicylate levels in rheumatoid arthritis: a comparison between micro-encapsulated and conventional aspirin.

Ten patients with rheumatoid arthritis were given identical amounts of conventional aspirin (Magnecyl) tablets and micro-encapsulated aspirin (Reumyl) capsules. Steady-state salicylate levels were determined after 4 days' treatment at 8 a.m., 12 noon, 4 p.m., 10 p.m. and again at 8 a.m. No difference was noted between the levels at 12 noon or 4 p.m. The 10 p.m. levels were slightly though not significantly higher and the last set of 8 a.m. levels were significantly higher during the capsule administration. A criterion for inclusion was good tolerance of Magnecyl. The clinical effectiveness was not evaluated, but the observed good absorption features of Reumyl indicate that this preparation may prove to be of value in long-term treatment.

A comparison of ketoprofen and naproxen in rheumatoid arthritis.

Ketoprofen, 50+50+100 mg, was compared to naproxen, 250+250+250 mg, in a double-blind, cross-over twice 4-weeks' study on patients with RA. There was no significant difference in the effect on morning stiffness, pain at rest, joint count, grip strength or ESR. Among 28 patients 10 preferred ketoprofen and 7 naproxen. Two ketoprofen and 1 naproxen periods were interrupted owing to intolerable side-effects. Twenty of the patients experienced some side-effect from at least one drug. The most common complaints were gastrointestinal, seen in 12 patients on ketoprofen and 9 on naproxen. Most side-effects were mild. No abnormality in blood morphology, liver function tests, serum creatinine or fasting blood glucose was observed. No occult bleeding was detected on routine stool examination.