Hugo W. Rüdiger

Radiofrequency electromagnetic fields (UMTS, 1,950 MHz) induce genotoxic effects in vitro in human fibroblasts but not in lymphocytes

ObjectiveUniversal Mobile Telecommunication System (UMTS) was recently introduced as the third generation mobile communication standard in Europe. This was done without any information on biological effects and genotoxic properties of these particular high-frequency electromagnetic fields. This is discomforting, because genotoxic effects of the second generation standard Global System for Mobile Communication have been reported after exposure of human cells in vitro.MethodsHuman cultured fibroblasts of three different donors and three different short-term human lymphocyte cultures were exposed to 1,950xa0MHz UMTS below the specific absorption rate (SAR) safety limit of 2xa0W/kg. The alkaline comet assay and the micronucleus assay were used to ascertain dose and time-dependent genotoxic effects. Five hundred cells per slide were visually evaluated in the comet assay and comet tail factor (CTF) was calculated. In the micronucleus assay 1,000 binucleated cells were evaluated per assay. The origin of the micronuclei was determined by fluorescence labeled anticentromere antibodies. All evaluations were performed under blinded conditions.ResultsUMTS exposure increased the CTF and induced centromere-negative micronuclei (MN) in human cultured fibroblasts in a dose and time-dependent way. Incubation for 24xa0h at a SAR of 0.05xa0W/kg generated a statistically significant rise in both CTF and MN (Pxa0=xa00.02). At a SAR of 0.1xa0W/kg the CTF was significantly increased after 8xa0h of incubation (Pxa0=xa00.02), the number of MN after 12xa0h (Pxa0=xa00.02). No UMTS effect was obtained with lymphocytes, either unstimulated or stimulated with Phytohemagglutinin.ConclusionUMTS exposure may cause genetic alterations in some but not in all human cells in vitro.

Schellong test in orthostatic dysregulation: a comparison with tilt-table testing

SummaryOBJECTIVE: To evaluate the role of the Schellong test (ST) in forms of orthostatic dysregulation in comparison with the tilt-table test (TT). METHODS: 67 young males (mean age, 22 ± 4xa0years) from the military service, representing two different cohorts, were examined by ST and TT, which served as gold standard. 32 of the 67 subjects were asymptomatic while 35 had sought medical advice because of orthostatic complaints. The subjects subsequently were classified into four categories according to the TT: normal TT, orthostatic hypotension (OH), postural orthostatic tachycardia syndrome (POTS), and neurocardiogenic syncope (NCS). Chi-square test was used to calculate the sensitivity and specificity of ST in detecting forms of orthostatic dysregulation (OH, POTS and NCS). RESULTS: In total, TT detected 23 recruits with POTS, 16 with NCS and 2 with OH. Out of the 32 asymptomatic subjects only one was diagnosed having POTS by TT and ST, the rest had a normal ST and TT. For detecting POTS, ST sensitivity was 61% and specificity was 100% compared with TT. For detecting NCS, ST sensitivity was 31% and specificity 100% compared with the reference test, the TT. The data concerning OH could not be analyzed because of the small number of cases. CONCLUSIONS: In conclusion the results of our study indicate that ST can be used in first line in the diagnosis of patients with orthostatic symptoms by the medical practitioner. If the ST is normal, further examination by TT is indispensable, because sensitivity of ST concerning POTS and NCS is relatively low.ZusammenfassungZIEL: Diese Studie untersucht die Rolle des Schellong-Tests (ST) im Vergleich zur Kipptischuntersuchung (KT) in der Evaluierung von Formen orthostatischer Dysregulation. METHODE: Wir untersuchten 67 Soldaten (mittleres Alter, 22 ± 4xa0Jahre) zweier unterschiedlicher Gruppen mittels ST und KT auf das Vorliegen orthostatischer Dysregulation. 32 Soldaten waren asymptomatisch; 35 hatten zuvor den Arzt wegen orthostatischer Beschwerden aufgesucht. Nach KT wurden die Probanden in folgende Kategorien eingeteilt: normale KT, orthostatische Hypotension (OH), posturales orthostatisches Tachycardia syndrome (POTS) und neurokardiogene Synkope (NKS). ERGEBNISSE: Mittels KT wurden bei 23 Soldaten POTS (11 von den 23 hatten zusätzlich eine NKS) diagnostiziert, bei 16 eine NKS und bei 2 eine OH. Von den 32 asymptomatischen Probanden wurde lediglich bei einem ein POTS mittels ST und KT diagnostiziert, der Rest wies bei beiden Tests normale Ergebnisse auf. Für die Diagnose POTS erreichte der Schellongtest eine Sensitivität von 61% und eine Spezifität von 100%, für die Diagnose NKS eine Sensitivität von 31% und eine Spezifität von 100%, jeweils bezogen auf den Referenztest, die KT. SCHLUSSFOLGERUNGEN: Da alle Probanden mit pathologischem ST auch bei der KT auffällig waren, ist der ST zwar für das Vorliegen einer orthostatischen Dysregulation beweisend, schließt aber bei normalem Ergebnis eine solche nicht aus. Aufgrund der niedrigen Sensitivität des ST bezüglich NCS und POTS ist daher auch bei normalen ST und klinischen Symptomen die Durchführung eines KT unverzichtbar.

No cognitive deficits in men formerly exposed to lead.

SummaryOBJECTIVES: The objective of the study was to investigate long-term cognitive effects resulting from low to moderate lead exposure below current threshold values. Executive functions, attention, visuospatial and visuomotor functioning in workers formerly exposed to lead were investigated. METHODS: 48 men formerly exposed to lead and with a mean current blood level (PbB) of 5.4xa0μg Pb/100xa0ml were investigated, together with 48 matched controls (PbB, 4.7xa0μg Pb/100xa0ml) out of a pool of 61 males. The two groups were matched for age, years spent in education, verbal intelligence and gram alcohol consumption per week. The following neuropsychological tests were used: modified Wisconsin card sorting test, block design test, visual recognition test, simple reaction time, choice reaction and digit–symbol substitution. Lead exposure was assessed using both current and cumulative measurements. RESULTS: There were no significant differences in cognitive parameters between the two groups. When analyzing dose–response relationships, negative correlations were found between PbB and performance in the block design test, and between PbB and scores in the visual recognition and digit–symbol substitution tests. High cumulative exposure (IBL, >5000; duration of exposure, >5xa0years) correlated only with wrong reactions in the choice reaction test. CONCLUSIONS: The results of our study indicate that cognitive deficits resulting from low-level exposure to lead are reversible. The study was limited to low-level long-term exposure (all PbB values were always below 55xa0μg Pb/100xa0ml), and extrapolation of these results to persons heavily exposed to lead is not possible.ZusammenfassungZIEL: Das Ziel der gegenwärtigen Studie war es, kognitive Langzeitfolgen von Bleiexposition innerhalb gültiger Grenzwerte nach Expositionsende zu untersuchen. Deshalb wurden exekutive Funktionen, Aufmerksamkeit, visuelles räumliches Denken, einfache und komplexe Reaktionszeit in früher exponierten Bleiarbeitern untersucht. METHODIK: Die Studiengruppe umfasste 48 männliche Arbeiter, die früher berufsbedingt bleiexponiert waren, mit einem mittleren aktuellen Blutblei von 5,4xa0μg/100xa0ml, sowie 48 gematchte Kontrollen (PbB, 4,7xa0μg/100xa0ml), welche aus einem Pool von 61 männlichen Stahlarbeitern gebildet wurden. Die Kontroll- und Studiengruppe wurden hinsichtlich Alter, Bildungsjahre, verbaler Intelligenz und der Einnahme alkoholischer Getränke parallelisiert. Folgende neuropsychologische Tests wurden durchgeführt: Modified Wisconsin Card Sorting Test, Block Design Test, visuelles räumliches Denken, einfache Reaktionszeit, komplexe Reaktion und der Zahl-Symbol-Substitutionstest. Die Bleibelastung wurde anhand von aktuellen und kumulativen Parametern beurteilt. RESULTATE: Bei allen neurobiologischen Parametern zeigten sich keine signifikanten Unterschiede zwischen den Gruppen. Negative Korrelationen wurden zwischen aktuellen Blutblei und Block Design Test, visuell-räumlichen Denkens und Zahl-Symbol-Substitutionstest gefunden. Hohe kumulative Exposition (IBL, >5000; Dauer der Exposition länger als 5xa0Jahre) korrelierte nur mit falschen Reaktionen beim komplexen Reaktionstest. SCHLUSSFOLGERUNGEN: Die Ergebnisse unserer Studie weisen darauf hin, dass kognitive Defizite von niedriger Bleiexposition reversibel sind. Unsere Ergebnisse sind auf langjährige niedrige Bleiexposition limitiert (alle aktuellen Blutblei-Werte waren immer unter 55xa0μg/100xa0ml). Eine Extrapolation der Ergebnisse auf höher exponierte Arbeiter ist daher nicht möglich.

Influence of an Insertion Variant in the 5ʹUTR of the Endothelin-1 Gene on Orthostatic Intolerance

Background:Orthostatic intolerance is a multifactorial disease in which the genetic contribution is probably the result of a number of genes acting in combination. Recent work has shown that orthostatic intolerance is influenced by endothelial nitric oxide synthase gene polymorphisms. Since endothelin-1 (ET-1) is one of the most important vasoconstrictor peptides, a frequent adenine insertion polymorphism within the 5′-untranslated region (5′UTR), which is of functional importance for ET-1 expression, could influence orthostatic intolerance. The aim of this study was therefore to ascertain whether this frequent variant of the endothelin-1 gene influences the risk for orthostatic intolerance. Methods:We studied 257 white patients (120 cases with orthostatic intolerance and 137 controls) for genotyping of the 5′UTR I variant. From this cohort, 111 patients and 99 control subjects underwent a tilt-table test or an upright posture study, including monitoring of blood pressure, heart rate, and plasma catecholamines, in the supine position and during 30 minutes of standing. Genotyping was performed in all participants. &khgr;2 tests of independence were used to test for associations between orthostatic intolerance and genotype. In addition, an association of the insertion polymorphism with hemodynamic variables (heart rate, supine and upright blood pressure) was ascertained using one-way analysis of variance. Results:The 5′UTR I variant was significantly less common in patients with orthostatic intolerance (allele frequency 0.36 and 0.28, in controls and cases, respectively). Additionally, we found a significant decrease in the risk of orthostatic intolerance among people who were homozygous for the 5′UTR variant (I/I) compared with the wild-type variant (D/D) (odds ratio, 0.41; 95% confidence interval, 0.17 to 0.97; P = 0.04). No association between the 5′UTR variant and heart rate or blood pressure regardless of diagnosis was found. Conclusions:Our current results suggest that the hereditary adenine insertion variant in the 5′-UTR of the endothelin-1 gene is protective for orthostatic intolerance. The increased ET-1 protein expression that has been linked with the I variant might be associated with a more efficient hemodynamic response to standing. This is likely one of several common genetic loci that may represent modifiers of orthostatic intolerance phenotypes.

Answer to comments by A. Lerchl on “Radiofrequency electromagnetic fields (UMTS, 1,950 MHz) induce genotoxic effects in vitro in human fibroblasts but not in lymphocytes” published by C. Schwarz et al. 2008

Genotoxic effects induced in vitro by the third generation mobile communication standard UMTS have recently been described by Schwarz et al. (Int Arch Occup Environ Health 81:755–767, 2008). These findings which may have considerable significance for environmental health have been commented upon by Lerchl (Int Arch Occup Environ Health in press, 2008) (this issue). These comments which are invalid in part have to be set right. Although some of his minor points are correct the objected inconsistencies are largely based on the author′s incomplete and superficial consideration of published data in the field. Moreover, the statistical points being made cannot cast doubts on the validity of the experimental data reported by Schwarz et al. and may not change the principal conclusion of in vitro genotoxic action of UMTS signals.