CONTEXT:Radioactive contamination from the Chernobyl nuclear accident that happened on the morning of 26th April 1986 had a major impact on thyroid health in the Belarus region.OBJECTIVE:Observational study of a cohort of 99 adults, most strongly exposed to ionizing radioactivity.DESIGN, SETTING AND PATIENTS:Observational study performed between 1998 and 2000. The cohort comprised 99 workers (92 male) of the Chernobyl nuclear power plant. Examination including physical examination, ultrasonography of the thyroid gland and measurement of serum free thyroxin (fT(4)), free triiodothyronine (fT(3)) and TSH. Anti-thyroperoxidase (anti-TPO), antithyroglobulin (anti-Tg) antibodies and thyroid stimulating immunoglobulin were also determined.MAIN OUTCOME MEASURES:The impact of exposure to high-dose radiation, including radioactive iodine, on the thyroid gland was examined.RESULTS:Levels of fT(4) in all probands were within the normal World Health Organization-defined range. Elevated levels of fT(3) were found in two workers (2%), high titres of anti-TPO and anti-Tg antibodies were present in four subjects (4%). Mild hypothyroidism was present in one patient. Enlargement of the thyroid gland was observed in 17 workers (17%). There was no evidence of clinically overt thyroid cancer.CONCLUSIONS:The Chernobyl accident showed surprisingly little impact on the thyroid in a cohort of workers strongly exposed to radiation. Our data suggest an age-dependent heterogeneity in response to the short-lived radioiodine isotopes and favours long-term follow-up analysis.

Abstract Scherthan, H., Abend, M., Müller, K., Beinke, C., Braselmann, H., Zitzelsberger, H., Köhn, F. M., Pillekamp, H., Schiener, R., Das, O., Peter, R. U., Herzog, G., Tzschach, A., Dörr, H. D., Fliedner, T. M. and Meineke, V. Radiation-Induced Late Effects in Two Affected Individuals of the Lilo Radiation Accident. Radiat. Res. 167, 615–623 (2007). Radiation exposure leads to a risk for long-term deterministic and stochastic late effects. Two individuals exposed to protracted photon radiation in the radiological accident at the Lilo Military site in Georgia in 1997 received follow-up treatment and resection of several chronic radiation ulcers in the Bundeswehr Hospital Ulm, Germany, in 2003. Multi-parameter analysis revealed that spermatogenetic arrest and serum hormone levels in both patients had recovered compared to the status in 1997. However, we observed a persistence of altered T-cell ratios, increased ICAM1 and β1-integrin expression, and aberrant bone marrow cells and lymphocytes with significantly increased translocations 6 years after the accident. This investigation thus identified altered end points still detectable years after the accident that suggest persistent genomic damage as well as epigenetic effects in these individuals, which may be associated with an elevated risk for the development of further late effects. Our observations further suggest the development of a chronic radiation syndrome and indicate follow-up parameters in radiation victims.

Objective To evaluate the efficacy of psoralens dissolved in a warm-water bath followed by exposure to UV-A irradiation (bath PUVA) or saltwater phototherapy (SW UV-B) compared with tap-water phototherapy (TW UV-B) or UV-B irradiation alone in psoriasis. Design Multisite, prospective, randomized, controlled trial with 4 parallel groups. Setting Total of 102 dermatologic outpatient clinics. Patients Total of 1241 patients with stable psoriasis vulgaris and a Psoriasis Area and Severity Index score of 7 or greater. Interventions Four-times-weekly UV-B, TW UV-B, SW UV-B, or bath-PUVA with baths preceding UV irradiation over a maximum of 8 weeks. The UV dose was adapted to erythemal response. Main Outcome Measures Incidence of therapeutic success, defined as a reduction of the Psoriasis Area and Severity Index or affected body surface area of 50% or more. Results Patients who received TW UV-B had a significantly higher incidence of therapeutic success than did patients treated with UV-B alone (60.7% vs 43.3%;P<.001; number needed to treat, 5.8; 95% confidence interval [CI], 3.9-10.9). Patients who received SW UV-B or bath PUVA had a significantly higher incidence of therapeutic success than did patients treated with TW UV-B (74.9% vs 60.7%;P<.001; number needed to treat, 7.0; 95% CI, 4.6-14.9; and 78.4% vs 60.7%;P<.001; number needed to treat, 5.7; 95% CI, 4.0-9.7, respectively). Bath PUVA was not superior to SW UV-B (78.4% vs 74.9%;P = .34). Conclusion Bath PUVA and SW UV-B are comparably effective treatments in psoriasis and superior to UV-B and TW UV-B.

BACKGROUND:The importance of changes in the supporting tumor stroma for cancer initiation and progression is well established. The characteristics of an activated tumor stroma, however, are not completely understood. In an effort to better characterize the desmoplastic response to human skin tumors, we evaluated the expression pattern of three stromal cell markers, fibroblast-activation protein (FAP), endoglyx-1, and endosialin, in a series of melanocytic and epithelial skin tumors. METHODS:Immunohistochemistry using antibodies against FAP, endoglyx-1, and endosialin was carried out in skin samples obtained from 43 patients. Furthermore, microarray data from an independent set of human skin cancers were analyzed. RESULTS:FAP-positive fibroblasts were detected in all tumor tissues tested, including cases of melanocytic nevi, melanoma metastases, basal cell carcinomas, and squamous cell carcinomas. In cutaneous melanoma metastases, we identified different compartments within the stromal response on the basis of the regions of FAP expression. Endoglyx-1 expression was confined to normal and tumor blood vessel endothelium including 'hot spots' of neoangiogenesis within the cutaneous melanoma metastases. Endosialin was selectively induced in subsets of small- and medium-sized tumor blood vessels in melanoma metastases and squamous cell carcinomas. CONCLUSIONS:These data describe novel aspects of stromal marker expression in distinct compartments of human skin tumors and may point to potential targets for novel therapeutic strategies aimed at the tumor stroma.

The hazards of acute radiation exposure are commonly addressed with respect to total body gamma or neutron irradiation, resulting primarily in bone marrow failure as the main clinically relevant aspect of the acute radiation disease. Under conditions of inhomogeneous exposure, as they are characteristic for many accident scenarios, other organ systems, such as the skin may become more important in determining clinical prognosis. This became especially obvious in the two worst radiation accidents since 1945, the Chernobyl accident in April 1986 and the Goiania accident in September 1987. The characteristic chronic sequelae of accidental cutaneous radiation exposure and therapeutic results have been described based on own clinical experience with treating patients with acute and late cutaneous effects after therapeutic irradiation, and a distinct group of patients having survived the Chernobyl nuclear power plant accident of April 26, 1986. Apart from clinical examination, histological analysis and high-frequency (20MHz) ultrasound as well as a variety of functional tests have been used to determine the extent of radiation fibrosis and to exclude malignant transformation of keratoses and ulcers. Treatment included, apart from dermatosurgical procedures and plastic surgery for disabling contractures or ulcers, argon laser treatment of telangiectasias, topical tretinoin 0,005% (Epi-Aberel, Cilag, Frankfurt), etretinate and acitretin (Tigason, Neotigason, Hoffmann LaRoche, Grenzach) for radiation keratoses, partly combined with a novel, nonatrophogenic steroid, Mometasonefiiroate (Elocon, Schering-Plough, New Jersey) to antagonize inflammatory reactions, and low-dose interferon-gamma (Polyferon, Rentschler, Laupheim) for extensive radiation fibrosis. Basic dermatotherapy was performed with an ointment containing linoleic acid (Linola, Wolff, Bielefeld). With this combination treatment, transepidermal water loss could be sustained, progression of keratoses and inflammation were stopped. The most remarkable result was the reduction of radiaton fibrosis: sonographically determined skin thickness partly returned to normal levels after treatment of 18 months with Interferon gamma 50ug s.c. 3x/week. Based upon therapeutic experience with patients undergoing radiation therapy, symptomatic relief of pruritus can be achieved by administration of nonsedating antihistamines, such as Loratadine. In the chronic stage of the CRS after radiation therapy, where interferon gamma cannot be used, reduction of radiation-induced cutaneous fibrosis can be reached by a combination of Vitamin E and pentoxyfiline even two decades after radiation exposure. It is concluded that under accidental partial body exposure with high doses of beta and gamma irradiation, the predominant involvement of the skin, described as the cutaneous radiation syndrome, may become the characteristic trait of this increasingly probable accident pattern. Though treatment is complex and requires dermatologic and radiobiological expertise, it results in marked clinical improvement of the affected patients. These results demonstrate that considerable progress has been achieved during the last years regarding diagnosis and treatment of cutaneous radiation sequelae. Surgery has to be considered the treatment of choice for radiation carcinoma, but is no longer the only available therapeutic option. However, systematic controlled clinical trials are still missing for these options.

Tumor necrosis factor (TNF)-α-induced phosphorylation of the IκB proteins by the IκB kinase (IKK) complex containing IKK-2 and subsequent degradation of the IκB proteins are prerequisites for NF-κB activation, resulting in the stimulation of a variety of pro-inflammatory target genes. The C-C chemokine eotaxin-1 is a potent chemoattractant for eosinophils and Th2 lymphocytes, may play an important role in the pathogenesis of atopic dermatitis, and acts via binding to its receptor CCR3. To investigate the role of NF-κB signaling in the regulation of these genes, we stably expressed a transdominant mutant of IκBα and a constitutively active mutant of IKK-2 in mouse NIH3T3 fibroblasts. The transdominant IκBα mutant completely inhibited TNF-α-mediated induction of botheotaxin-1 and CCR3, whereas expression of constitutively active IKK-2 was sufficient to drive almost full expression of these two genes in the absence of TNF-α. Moreover, we observed elevated expression levels of CCR3 and eotaxin-1 protein levels in the skin of IκBα-deficient mice characterized by a widespread dermatitis. Finally, using dermal fibroblasts derived from IκBα-deficient mice, we observed elevated basal expression, enhanced inducibility by TNF-α, and attenuated down-regulation upon TNF-α withdrawal of both CCR3 and eotaxin-1mRNA levels. These results demonstrate that the IKK-2/IκBα/NF-κB pathway plays a critical role forCCR3 and eotaxin-1 expression in fibroblasts and suggests a critical link to the pathogenesis of atopic dermatitis.

H&G Zeitschrift für HautkrankheitenVolume 77, Issue 9 p. 439-444 131. Tagung der Vereinigung Südwestdeutscher Dermatologen 20. bis 21. September 2002 Ulm/Donau Ralf U. Peter, Ralf U. PeterSearch for more papers by this author Ralf U. Peter, Ralf U. PeterSearch for more papers by this author First published: 28 June 2008 https://doi.org/10.1046/j.1439-0353.2002.02567.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume77, Issue9September 2002Pages 439-444 RelatedInformation

Tumor necrosis factor (TNF)-alpha-induced phosphorylation of the IkappaB proteins by the IkappaB kinase (IKK) complex containing IKK-2 and subsequent degradation of the IkappaB proteins are prerequisites for NF-kappaB activation, resulting in the stimulation of a variety of pro-inflammatory target genes. The C-C chemokine eotaxin-1 is a potent chemoattractant for eosinophils and Th2 lymphocytes, may play an important role in the pathogenesis of atopic dermatitis, and acts via binding to its receptor CCR3. To investigate the role of NF-kappaB signaling in the regulation of these genes, we stably expressed a transdominant mutant of IkappaBalpha and a constitutively active mutant of IKK-2 in mouse NIH3T3 fibroblasts. The transdominant IkappaBalpha mutant completely inhibited TNF-alpha-mediated induction of both eotaxin-1 and CCR3, whereas expression of constitutively active IKK-2 was sufficient to drive almost full expression of these two genes in the absence of TNF-alpha. Moreover, we observed elevated expression levels of CCR3 and eotaxin-1 protein levels in the skin of IkappaBalpha-deficient mice characterized by a widespread dermatitis. Finally, using dermal fibroblasts derived from IkappaBalpha-deficient mice, we observed elevated basal expression, enhanced inducibility by TNF-alpha, and attenuated down-regulation upon TNF-alpha withdrawal of both CCR3 and eotaxin-1 mRNA levels. These results demonstrate that the IKK-2/IkappaBalpha/NF-kappaB pathway plays a critical role for CCR3 and eotaxin-1 expression in fibroblasts and suggests a critical link to the pathogenesis of atopic dermatitis.

To the Editor: Methylenetetrahydrofolate reductase (MTHFR) catalyzes the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. The C677T in the gene that encodes MTHFR decreases the activity of the enzyme by 35 percent in persons who are heterozygous for the mutation and by 70 percent in those who are homozygous.1 The prevalence of the homozygous form is estimated to be between 5 percent and 10 percent. One study showed an increase in sperm count and motility after three months of treatment with folinic acid.2 By determining the frequency of the MTHFR C677T mutation, it may be possible to identify patients who have a . . .

BACKGROUND:In April 1986, numerous reactor workers and firemen were exposed to high doses of ionizing radiation during the Chernobyl nuclear power plant accident. Apart from high ambient gamma-ray exposures they received inhomogeneous contamination with beta-rays from fission products, resulting in severe skin exposure.PATIENTS AND METHODS:Sixteen of these so called Liquidators were repeatedly examined between 1991 and 1996. Their doses ranged from 0.35 to 9 Gy, partly confirmed by determination of chromosomal aberrations. Ophthalmologic examination included non-subjective assessment of lenticular radiation damage with an electronic Scheimpflug camera system. Digital image analysis allowed the comparison of opacification units to previous and normal findings.RESULTS:Four Liquidators had posterior subcapsular opacifications in different degrees, one presented only after cataract extraction. One patient had dense corticonuclear cataracts and pseudoexfoliation-like changes. Three men had severe dry eye syndrome. Eight men had no ocular complications. Retinal radiation damages were absent. 15 Liquidators suffered from severe chronic cutaneous radiation damage, which led to amputations in 3 cases.CONCLUSIONS:A relation between ocular and dermatological findings was not expected and could, in fact, not be seen. The comparison of posterior subcapsular opacification and doses revealed no distinct relation, although it indicates a correlation that is here not quantified. The doses represent organ doses for the bone marrow which is primarily exposed to deeper penetrating gamma-radiation. Thus they need not be correlated with combined beta- and gamma-doses in organs such as skin and eye because the superficial exposure due to beta-radiation may differ greatly form the whole body exposure as reflected in bone marrow doses.

Melanoma Research Group, Department of Dermatology, Ludwig-Maximillians-University of Munich, Germany

Melanoma Research Group, Department of Dermatology, Ludwig-Maximilans-University of Munich, Germany