Search

Dermatoglyphs are epidermal ridge configurations on the fingers, palms and soles that are formed during fetal development, and therefore only the intrauterine environment can have any influence on their formation. This study aims at investigating the genetic and environmental contribution in determining quantitative dermatoglyphic traits in 32 monozygotic (MZ) and 35 dizygotic (DZ) same-sex twins from the Albanian population of Kosovo. All genetic analyses were run in the statistical program Mx. After assumptions testing, based on the pattern of MZ–DZ correlations, univariate models were fitted to the data in order to estimate additive genetic (A), common (C) and individual (E) environmental influences for all variables. The exception was the atd-angle for which a model with nonadditive genetic (D) influences was tested, since DZ correlations were less than half of MZ correlations. Goodness of fit of the full ACE or ADE model was compared to the saturated model. The fit of nested models (AE, CE, DE or E) was compared to the full models (ACE or ADE). Our results indicate that additive genetic component strongly contributes to individual differences in finger ridge counts (49−81%), and weakly (0−50%) on the formation of the palmar ridge counts between the palmar triradii a, b, c, and d. The specific pattern found for the atd-angle implies the impact of a nonadditive genetic component, possibly the effect of a major gene. Further, more powered studies are needed to confirm this pattern, especially for resolving the issue of the huge difference in MZ and DZ twin similarity for the atd-angle palmar trait.

Using near-infrared spectroscopy (NIRS) mixed tissue saturation can be calculated by measuring the oxygen saturation of oxygenated and deoxygenated erythrocytes in the tissue. Quality of the calculated value is not only dependent on the exposure of the measured values in the calculation, but also on external factors such as artifacts. Main object of this study was to determine whether and how the measurement quality of different devices varies in their long-term use in premature infants.In 54 measurements, each lasting 2 hours, 4 NIRS devices were attached in pairs on the forehead of 9 cardio-respiratory stable, spontaneous breathing premature infants. Pooled meta-analysis was used to compare the correlation between regional tissue saturation to the pulse oximetry saturation per device.The pooled random effect of all Pearson's correlation coefficients was 0.490 (CI95: 0.403-0.568) with the NIRO 200, 0.575 (CI95: 0.463-0.668) with the INVOS 5100c, 0.712 (CI95: 0.640-0.772) with the Fore-Sight and 0.638 (CI95: 0.554-0.709) with the SenSmart X- 100.In this trial, a significant correlation between the tissue saturation and pulsoxymetry saturation was observed. The tremendous variation range among the measurements showed, however, that the measurement quality can be severely affected by unrecognized artifacts, after excluding other possible causes. None of the devices had reliable artifact detection for long-term measurements in very small premature infants. Key words: Near-Infrared-Spectroscopy, premature infants, Benchmark Test, Long-term measurements.Mittels Nah-Infrarot-Spektroskopie (NIRS) wird durch Messung der Sauerstoffsättigung von oxygenierten und deoxygenierten Erythrozyten im Gewebe eine gemischte Gewebesättigung berechnet. Die Qualität dieses Rechenwerts ist nicht nur von der Gewichtung der Messwerte in der Berechnung, sondern auch von äußeren Einflüssen, wie Artefakten abhängig. Die vorliegende Studie soll untersuchen, ob und wie sich die Messqualität unterschiedlicher Geräte in der Langzeitanwendung bei Frühgeborenen unterscheidet.In 54 jeweils 2 Stunden dauernden Messungen wurden vier NIRS Geräte jeweils paarweise an der Stirn von 9 kardiorespiratorisch stabilen, spontan atmenden Frühgeborenen angebracht. Mittels gepoolten Metaanalysen wurde verglichen, wie sehr die Gewebesättigung der Einzelgeräte mit der pulsoxymetrischen Sauerstoffsättigung korreliert.Der gepoolte random Effekt des Pearson-Korrelationskoeffizienten über alle Messungen betrug 0,490 (KI95: 0,403–0,568) bei NIRO 200, 0,575 (KI95: 0,463–0,668) bei INVOS 5100c, 0,712 (KI95: 0,640–0,772) bei Fore-Sight und 0,638 (KI95: 0,554–0,709) bei SenSmart X-100.Grundsätzlich herrscht eine signifikante Korrelation zwischen Gewebesättigung und pulsoxymetrischer Sättigung. Die enorme Schwankungsbreite zwischen den Messungen zeigt jedoch, dass die Messqualität, nach Ausschluss anderer potentiellen Ursachen, stark von nicht erkannten Artefakten beeinträchtigt werden kann. Keines der Geräte verfügt über eine zuverlässige Artefakterkennung für Langzeitmessungen bei kleinen Frühgeborenen.

Item does not contain fulltext Aim: Clinical research in pediatrics is progressively initiated by academia. As the reliability of pharmacodynamic measures is closely linked to the quality of bioanalytical data, bioanalytical quality assurance is crucial. However, clear guidance on comprehensive bioanalytical quality monitoring in the academic environment is lacking. Methods & results: By applying regulatory guidelines, international recommendations and scientific discussions, a five-step quality control system for monitoring the bioanalysis of aldosterone by immunoassay was developed. It comprised performance qualification, calibration curve evaluation, analysis of the intra- and inter-run performance via quality control samples, incurred sample reanalysis and external quality assessment by interlaboratory testing. A total of 55 out of 70 runs were qualified for the quantification of aldosterone in the study sample enabling the evaluation of 954 pediatric samples and demonstrating reliability over the 29-month bioanalysis period. Conclusion: The bioanalytical quality control system successfully monitored the aldosterone assay performance and proved its applicability in the academic environment.

Contains fulltext : 220641.pdf (Publisher’s version ) (Closed access) While the role of plasma renin activity (PRA) in heart failure has been widely studied in adults, comprehensive data on pediatric heart failure remain lacking. This drawback is increasingly being addressed by academic research. Nevertheless, such pediatric investigations are commonly conducted only once due to ethical constraints. Therefore, the quality of bioanalytical data must be ensured to acquire meaningful insights into maturing humoral parameters. However, appropriate post-validation assessment of bioanalytical runs is currently underrepresented by regulatory guidance. Thus, for applications in an academic environment, an easy-to-handle six-step bioanalytical quality control system was designed based on regulatory guidelines (e.g. U.S. Food and Drug Administration) combined with international recommendations (e.g. Clinical and Laboratory Standards Institute) and current scientific discussion. Its applicability to an enzyme-linked immunosorbent assay for determination of PRA was investigated within three pediatric trials of the EU-funded "Labeling of Enalapril in Neonates up to Adolescents" project. This quality control system identified 15 % bioanalytical runs as non-compliant to the predefined specifications and ensured the reliable quantification of 940 pharmacodynamic samples. The inter-run assessment of quality controls was able to demonstrate the comparability of the study results. Furthermore, 86 % of incurred sample reanalysis pairs complied with regulatory requirements (>67 %), thus underlining the long-term reproducibility of the utilized ligand-binding assay. Successful participation in interlaboratory testing confirmed the accuracy of the applied method throughout the entire study period. Further investigations showed no notable differences between the five applied lots of the PRA assay. The applicability of this quality control system was proven in an academic environment and ensured reliable results for PRA over the entire 24-month study period.

The purpose of this work was to retrospectively evaluate survival and local control rates of triple-negative breast cancer subtypes classified as five marker negative (5NP) and core basal (CB), respectively, after breast-conserving surgery and intraoperative boost radiotherapy with electrons (IOERT) followed by whole breast irradiation. A total of 71 patients with triple-negative breast cancer were enrolled, who were treated with lumpectomy, axillary lymph node dissection, and IOERT with 9.6 Gy (median Dmax) followed by normofractionated whole breast irradiation to median total doses of 54 Gy. Chemotherapy was applied in a neoadjuvant (12 %), adjuvant (75 %), or combinational setting (7 %). After a median follow-up of 97 months (range 4–170 months), 5 in-breast recurrences were detected (7.0 %). For all patients, 8-year actuarial rates for local control, metastases-free survival, disease-specific survival, and overall survival amounted to 89, 75, 80, and 69 %, respectively. All local recurrences occurred in grade 3 (G3) tumors irrespective of their specific immunohistochemical phenotype; thus, the local control rate for grades 1/2 (G1/2) was 100 % for both 5NP and CB, while for G3 it was 88 % for 5NP and 90 % for CB (p = 0.65 and 0.82, respectively, n.s.). For disease-specific survival, only the difference of the best-prognosis group 5-NP/G3 vs. the worst-prognosis cohort CB/G1/2 was statistically significant: 90 % vs. 54 % (p = 0.03). Boost-IOERT provides acceptable long-term in-breast control in triple negative breast cancer. The best subgroup in terms of disease-specific survival was represented by 5NP in combination with tumor grading G3.

To assess retrospectively the role of an anticipated intraoperative tumor electron radiation therapy (IOERT) as a bed boost during breast-conserving surgery followed by conventional whole breast irradiation (WBI).An unselected cohort of 770 breast cancer patients of all risk types was analyzed in terms of local control (LC) and survival outcome. Patients were treated by breast-conserving surgery, IOERT of 10 Gy, and WBI to total median doses of 54 Gy (range, 1.6-2). Patients were retrospectively analyzed for LC, locoregional control, metastasis-free survival (MFS), overall survival (OS), and breast cancer-specific survival (BCSS).After a median follow-up of 121 months (range, 4-200), 21 (2.7%) in-breast recurrences (IBRs) were observed, 107 patients (14%) died and 106 (14%) developed metastases. Ten-year rates of LC, locoregional control, MFS, OS, and BCSS amounted to 97.2%, 96.5%, 86%, 85.7%, and 93.2 %, respectively. In multivariate analysis, HER2+ and triple-negative breast cancer subtype (TN) turned out to be significant negative predictors for IBRs (hazard ratios, 15.02 and 12.87, respectively; P.05). Sorted by subtypes, 10-year LC rates were observed in 98.7% (range, 96.7%-99.5%) (luminal A), 98% (range, 94%-99.3%) (luminal B), 87.9% (range, 66.2%-96%) (HER2+), and 89% (range, 76.9%-94.9%) (TN), respectively.After 10 years, boost IOERT maintains high LC rates in any risk setting.

Combined low-dose radon/hyperthermia therapy has been reported to improve pain and mobility in patients with rheumatic disorders. The key feature of inflammatory rheumatic diseases is the induction of autoimmune processes via the production of autoantibodies. As reducing the autoantibody level through administration of biologicals is described to correlate with delay of disease progression, we investigated the impact of combined low-dose radon/hyperthermia therapy on the serum levels of antibodies directed against cyclic citrullinated peptides in patients with ankylosing spondylitis. We found that levels of circulating anti-CCP antibodies is significantly reduced immediately after a 3 weeks of radon therapy regimen.

© 2013 Ritter et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Effects of Low-Dose Radon Therapy Applied Under Hyperthermic Conditions (RnHT) on Inflammatory and Non-Inflammatory Degenerative Disease Conditions

Background Recent you9ll find more and more sport equipment in the sporting goods industry promising at least to increase the subjective stability of joints, being also called intelligent sportswear. Literature also reports about the influence on the sensorimotor system, not only the mechanical effect. Objective Two different stability devices (knee support, CEP socks) are tested during postural tasks. Design Clinical controlled study. Setting The participant is standing one-legged, hands on hips on the Posturomed® platform running with microswing software (Haider Bioswing GmbH, Germany) in order to stabilize the platform as quickly as possible after slackening a lever over a testing period of 10 seconds. Patients (or Participants) 24 men and women without an injury of the lower extremities during the last 6 months, no artificial limbs, no stiff joints. Interventions (or Assessment of Risk Factors) Three valid measurements are collected (mean was taken for statistical evaluation) on each side for three different test situations (bare, with knee support, with CEP socks) standing on an instable plane (Posturomed®). The order of the test situation is randomized. Main Outcome Measurements Collected points during the 10 second testing period provide information about the ability to stabilize the platform. The more points achieved (0–1000), the better the result. Results Repeated measures and Fisher LSD Test were used for statistical analysis. By using external support postural stability increases significantly, but no significant difference can be found between the two tested devices. Conclusions In accordance with the literature, sensorimotor function can be supported by external devices used in the study. Injury prevention because of an increased postural control, especially during exhausting physical activities, needs some further research.

Ionized water aerosols have been suggested to exert beneficial health effects on pediatric allergic asthma. Their effect was evaluated in a randomized controlled clinical trial as part of a summer asthma camp.Asthmatic allergic children (n = 54) spent 3 weeks in an alpine asthma camp; half of the group was exposed to water aerosol of an alpine waterfall for 1 hour per day, whereas the other half spent the same time at a "control site". Immunological analysis, lung function testing, and fractional exhaled nitric oxide (FeNO) testing were performed during the stay, and sustaining effects were evaluated 2 months later. Symptom score testing was done over a period of 140 days.The water aerosol group showed a significant improvement in all lung function parameters, whereas only the peak expiratory flow improved in the control group. All patients showed a significant improvement in symptom score and a significant decrease in FeNO after the camp. Only the water aerosol group exhibited a long-lasting effect on asthma symptoms, lung function, and inflammation in the follow-up examination. Induction of interleukin (IL)-10 and regulatory T (Treg) cells was measured in both groups, with a pronounced increase in the water aerosol group. IL-13 was significantly decreased in both groups, whereas IL-5 and eosinophil cationic protein were decreased only in the water aerosol group.Our findings confirm the induction of Treg cells and reduction in inflammation by climate therapy. They indicate a synergistic effect of water aerosols resulting in a long-lasting beneficial effect on asthma symptoms, lung function, and airway inflammation.

GHRH antagonists have been shown to inhibit growth of various human cancer cell lines xenografted into nude mice including estrogen receptor negative human breast cancers. Previous observations also suggest that GHRH locally produced in diverse neoplasms including breast cancer might directly affect proliferation of tumor cells. In the present study we demonstrate that a novel highly potent GHRH antagonist JMR-132 strongly inhibits the proliferation of both estrogen receptor negative SKBR 3 and estrogen receptor positive ZR 75 human breast cancer cell lines in vitro. The proliferation in vitro of ZR 75 and SKBR 3 was increased after direct stimulation with GHRH(1-29)NH2. The GHRH antagonist JMR-132 had a significant antiproliferative activity in the absence of GHRH and nullified the proliferative effect of GHRH in these cell lines. SKBR 3 and ZR 75 expressed the GHRH ligand as well as the pituitary type of GHRH-receptor, which likely appears to mediate the antiproliferative mechanisms in these cell lines. These in vitro results suggest that JMR-132 is a potent inhibitor of breast cancer growth, independent of the estrogen receptor status. Further investigations on the combination treatment with endocrine agents affecting the estrogen pathway and GRHR antagonists are needed in order to improve the treatment of breast cancer.

Recent evidence indicates that growth hormone-releasing hormone (GHRH) functions as a growth factor for gastrointestinal (GI) tumours. The tumourigenic effects of GHRH appear to be mediated by the splice variant 1 (SV-1) of GHRH receptor as well as the full length pituitary type receptor for GHRH (GHRH-R). We examined the protein and mRNA expression of GHRH-R and SV-1 in normal human tissues and tumours of the gastrointestinal (GI-) tract by immunohistochemical staining and reverse transcriptase (RT)-PCR. Squamous cells and squamous cell carcinoma of the oesophagus were negative for GHRH-R and SV-1, while Barrett's mucosa and adenocarcinomas of the oesophagus showed a strong expression of both receptors. The expression of GHRH-R was absent in normal colonic mucosa other than neuroendocrine cells (NE) and lining epithelium (LE) but strong in tubular adenomas of the colon, while the staining for SV-1 was absent in cells other than NE. However, the expression of both receptors was significantly increased in tubulovillous adenomas and colorectal cancers. No differences were seen in protein levels for both receptors between normal and neoplastic tissues of the stomach, pancreas and liver. Because of low mRNA levels for both receptors in all samples tested, only a qualitative assessment could be made. However, mRNA for GHRH-R and SV-1 showed a near-perfect correlation with the assessment of receptor proteins by immunostaining. Our study shows that in contrast to normal mucosa, transformed mucosa of the oesophagus and the colon expresses GHRH-R and SV-1. This aberrant expression of GHRH-R and SV-1 in oesophageal and colorectal malignancies may provide a molecular target for a therapeutic approach based on GHRH antagonists.

Recent evidence indicates that growth hormone-releasing hormone (GHRH) functions as a growth factor for gastrointestinal (GI) tumours. The tumourigenic effects of GHRH appear to be mediated by the splice variant 1 (SV-1) of GHRH receptor as well as the full length pituitary type receptor for GHRH (GHRH-R). We examined the protein and mRNA expression of GHRH-R and SV-1 in normal human tissues and tumours of the gastrointestinal (GI-) tract by immunohistochemical staining and reverse transcriptase (RT)-PCR. Squamous cells and squamous cell carcinoma of the oesophagus were negative for GHRH-R and SV-1, while Barrett's mucosa and adenocarcinomas of the oesophagus showed a strong expression of both receptors. The expression of GHRH-R was absent in normal colonic mucosa other than neuroendocrine cells (NE) and lining epithelium (LE) but strong in tubular adenomas of the colon, while the staining for SV-1 was absent in cells other than NE. However, the expression of both receptors was significantly increased in tubulovillous adenomas and colorectal cancers. No differences were seen in protein levels for both receptors between normal and neoplastic tissues of the stomach, pancreas and liver. Because of low mRNA levels for both receptors in all samples tested, only a qualitative assessment could be made. However, mRNA for GHRH-R and SV-1 showed a near-perfect correlation with the assessment of receptor proteins by immunostaining. Our study shows that in contrast to normal mucosa, transformed mucosa of the oesophagus and the colon expresses GHRH-R and SV-1. This aberrant expression of GHRH-R and SV-1 in oesophageal and colorectal malignancies may provide a molecular target for a therapeutic approach based on GHRH antagonists.

Bombesin (BN) or gastrin-releasing peptide (GRP) can stimulate the growth of neoplasms such as breast cancer and small-cell lung carcinoma (SCLC). Antagonists of BN/GRP have been shown to inhibit these cancers. We evaluated whether antagonists of BN/GRP can suppress the growth of human non-SCLC (NSCLC) xenografted into nude mice. The effect of the administration of BN/GRP antagonist RC-3940-II on the growth of H460 and A549 NSCLC cell lines orthotopically xenografted into the intrapulmonary interstitium was examined. Protein levels of K-Ras, COX-2, Akt/pAkt, WT p53, Erk1/2, and lung resistance-related protein (LRP) in tumors were analyzed by Western blot analaysis, and receptors for BN/GRP were investigated by radioligand-binding studies. The effect of RC-3940-II on the proliferation of H460 and A549 cells in vitro was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays. High-affinity receptors for BN/GRP were found on tumors. Treatment with RC-3940-II significantly ( P < 0.001) inhibited growth of H460 and A549 NSCLC xenografts by 30–50% and led to an improved performance status, compared with controls. In H460 NSCLC, the antitumor effect was associated with a significant ( P < 0.001) reduction in protein levels of K-Ras, COX-2, pAkt, and pERK1/2 and with a major augmentation in the expression of WT p53, compared with controls. In A549 NSCLC, pAkt and LRP were significantly down-regulated. Our findings demonstrate the efficacy of BN/GRP antagonist RC-3940-II for the treatment of NSCLC. The suppression of K-Ras, COX-2, pAkt, and LRP, as well as the up-regulation of WT p53 might contribute to the antitumor action of BN/GRP antagonists.

Background Radon therapy as alternative therapy for rheumatic diseases in curative tunnels such as the Heilstollen Bad Gastein in Austria has been reported to reduce pain and amount of drug usage [1,2]. Inhaled radon remains in the body as decaying radioactive radon progeny, and exhibits analgesic and anti-inflammatory effects [3]. In the Heilstollen the patients usually receive mean radon doses of 44.000 Bq/m 3 air (dependent on the weather conditions). Objectives Placebo effects of radon treatment at a health resort (caused by excitement, caring by the physicians) are discussed to contribute to clinical improvement of rheumatic diseases. To exclude placebo effects we analysed benefits of the radon therapy in an animal experiment performed under controlled conditions. Mice over-expressing human TNF-α that develop poly-arthritis served as animal model for rheumatoid arthritis. Methods Gaseous radon from water of radon galleries of Bad Gastein, Austria, was prepared using an evaporation system. In addition to the breathing air the drinking water of the animals contained radon. The dosimetry was performed by liquid scintillation with radon enrichment on an activated carbon matrix. TNF tg (n=10) and wild type (n=7) mice were 12 x exposed to radon in 3 weeks for 3 hours per day. Mock treated TNF tg (n=11) and wild type mice (n=7) served as controls. The course of the disease was monitored by measurements of body weight, grip strength and mortality. All analyses were performed by two researchers blinded to the treatment conditions the mice had received. Results The mean daily radon doses applied to the mice were 119213±39113 Bq/m 3 by inhalation. The drinking water contained 800-900 Bq/l. TNF tg mice showed severe illness marked by reduced body weight and decreasing grip strength compared to wild type controls. After treatment with radon TNF tg mice showed an improved body constitution and movement activity, measured by body weight and grip strength. Improvements continued until death of the mice. Interestingly, the TNF tg mice treated with radon showed an increased survival compared to mock treated TNF tg control mice. Conclusions Radon therapy ameliorates the inflammatory processes responsible for the arthritogenic activity of human TNF in mice. The overall radon dosis applied to the mice is in the same range as during the treatment of patients in the Heilstollen Bad Gastein/Austria. References Falkenbach A, Kovacs J, Franke A, Jorgens K, Ammer K., Radon therapy for the treatment of rheumatic diseases – review and meta-analysis of controlled clinical trials. Rheumatol Int. 2005; 25:205-10. Franke A, Reiner L, Pratzel HG, Franke T, Resch KL., Long-term efficacy of radon spa therapy in rheumatoid arthritis – a randomized, sham-controlled study and follow-up, Rheumatology (Oxford). 2000; 39:894-902. Shehata M, Schwarzmeier JD, Hilgarth M, Demirtas D, Richter D, Hubmann R, Boeck P, Leiner G, Falkenbach A., Effect of combined spa-exercise therapy on circulating TGF-beta1 levels in patients with ankylosing spondylitis., Wien Klin Wochenschr. 2006;118:266-72. Disclosure of Interest None Declared

Blistering in epidermolysis bullosa simplex type Dowling-Meara (EBS-DM) is associated with an inflammatory phenotype, which can be disrupted by diacerein in vitro. In this pilot study we hypothesized, that a topical formulation of diacerein 1% reduces blistering. Five patients initially applied diacerein underneath both armpits. Then, each participant received 1% diacerein-cream for one armpit, and placebo for the other (randomized withdrawal). The number of blisters was reduced significantly (left: -78%; right: -66% of baseline) within two weeks and remained significantly below the initial level even during withdrawal in four patients. These findings point to a relevant effect of diacerein and provide important information for a confirmative study.

Backgroundand objectives Radon therapy as alternative therapy for rheumatic diseases in curative tunnels such as the Heilstollen Bad Gastein in Austria has been reported to reduce pain and amount of drug usage. Inhaled radon remains in the body as decaying radioactive radon progeny, and exhibits analgesic, anti-inflammatory and immune stimulating effects. In the Heilstollen the patients usually receive mean radon doses of 44 000 Bq/m3 air (dependent on the weather conditions). Placebo effects (caused by excitement, caring by the physicians, relaxations during treatment) are discussed to contribute to clinical improvement of rheumatic diseases. To exclude placebo effects the authors analysed benefits of the radon therapy in an animal experiment performed under controlled conditions. Mice over-expressing human tumour necrosis factor α (TNFα) that develop polyarthritis served as animal model for rheumatoid arthritis. Materials and methods Gaseous radon from water of radon galleries of Bad Gastein, Austria, was prepared using an evaporation system. In addition to the breathing air the drinking water of the animals contained radon. The dosimetry was performed by liquid scintillation with radon enrichment on an activated carbon matrix. TNF tg (n=10) and wild type (n=7) mice were 12 × exposed to radon in 3 weeks for 3 h per day. Mock treated TNF tg (n=11) and wild type mice (n=7) served as controls. The course of the disease was monitored by measurements of body weight, grip strength and mortality. All analyses were performed by two researchers blinded to the treatment conditions the mice had received. Results The mean daily radon doses applied to the mice were 119213±39113 Bq/m3 by inhalation. The drinking water contained 800–900 Bq/l. TNF tg mice showed severe illness marked by reduced body weight and decreasing grip strength compared to wild type controls. After treatment with radon TNF tg mice showed an improved body constitution and movement activity, measured by body weight and grip strength. Improvements continued until death of the mice. Interestingly, the TNF tg mice treated with radon showed an increased survival compared to mock treated TNF tg control mice. Conclusions Radon therapy ameliorates the inflammatory processes responsible for the arthritogenic activity of human TNF in mice. The overall radon dose applied to the mice is in the same range as during the treatment of patients in the Heilstollen Bad Gastein/Austria.

GHRH antagonists have been shown to inhibit growth of various human cancer cell lines xenogratted into nude mice including estrogen receptor negative human breast cancers. Previous observations also suggest that GHRH locally produced in diverse neoplasms including breast cancer might directly affect proliferation of tumor cells. In the present study we demonstrate that a novel highly potent GHRH antagonist JMR-132 strongly inhibits the proliferation of both estrogen receptor negative SKBR 3 and estrogen receptor positive ZR 75 human breast cancer cell lines in vitro. The proliferation in vitro of ZR 75 and SKBR 3 was increased after direct stimulation with GHRH(1-29)NH 2 . The GHRH antagonist JMR-132 had a significant antiproliferative activity in the absence of GHRH and nullified the proliferative effect of GHRH in these cell lines. SKBR 3 and ZR 75 expressed the GHRH ligand as well as the pituitary type of GHRH-receptor, which likely appears to mediate the antiproliferative mechanisms in these cell lines. These in vitro results suggest that JMR-132 is a potent inhibitor of breast cancer growth, independent of the estrogen receptor status. Further investigations on the combination treatment with endocrine agents affecting the estrogen pathway and GRHR antagonists are needed in order to improve the treatment of breast cancer.

Ankylosing Spondylitis (AS) is a rheumatic disease and almost 50% of the affected patients suffer from osteoporosis. The ratio of Receptor Activator of Nuclear Factor κB Ligand (RANKL) and Osteoprotegerin (OPG) has become an important marker to assess the status of systemic bone metabolism and has been shown to be dysregulated in AS patients. Combined Low-Dose Radon- and Hyperthermia Therapy (LDRnHT) causes pain reduction in patients with AS and induces the cytokine transforming growth factor-β1 (TGF-β1). TGF-β1 acts as an anti-inflammatory cytokine and influences the OPG/RANK/RANKL system. We therefore performed a study on 33 AS patients to investigate the effect of LDRnHT on serum levels of bone metabolism markers and cytokines involved in chronic inflammatory disorders. It is shown that TGF-β1, TNF-α, IL-6, OPG and RANKL levels significantly increased after LDRnHT and that the ratio of OPG over RANKL is significantly elevated.