PubMed Health⌕ Search

Biomedical subjects

Robert Winker

Publications and source records attributed to Robert Winker.

13 recordsLinked to original sources

Why life oscillates--from a topographical towards a functional chronobiology.

Chronobiology has identified a multitude of rhythms within our body as well as within each living cell. Some of these rhythms, such as the circadian and circannual, interact with our environment, while others run on their own, but are often coupled to the circadian or to other body rhythms. Recent evidence shows that these rhythms might be more important for our health than expected: Disturbance of the circadian rhythms by jet lag or shift work not only evokes autonomic disturbances but also increases the incidence of cancer, as shown in this issue of Cancer Causes and Control. The occurrence of rhythms in the organism obviously bears several advantages: (1) It increases organismic stability by calibrating the system's characteristics: Regulation curves in time and space are crucial for controlling physiological long-term stability. To determine its properties continuously the system varies its parameters slightly over several time scales at different frequencies-akin to what our body does, e.g. in heart-rate variability. (2) Tuning and synchronization of rhythms saves energy: It was Huygens who observed that clocks on a wall tend to synchronize their beats. It turned out later that synchronisation is a very common phenomenon observed in bodies' rhythms and can be found, for example, when we relax or sleep. At such times energy consumption is minimal, our body working most efficiently. (3) Temporal compartmentalization allows polar events to occur in the same space unit: there are polarities in the universe of our body, which cannot happen simultaneously. Systole and diastole, inspiration and expiration, work and relaxation, wakefulness and sleep, reductive and oxidative states cannot be performed efficiently at the same time and place. Temporal compartmentalization is probably the most efficient way to mediate between these polarities. Chronobiology and chronomedicine are opening a new and very exciting understanding of our bodies' regulation. The biological time and its oscillations gain more attention and importance as these interrelations are understood.

Activity Cycles↗

Effects of short- and long-term unemployment on physical work capacity and on serum cortisol.

AIM: To investigate whether a decrease in physical working capacity occurs during the first year of unemployment and if this is accompanied by a deterioration in mental health. METHODS: In a longitudinal study, 71 unemployed individuals were investigated for 1, 6 months and 1 year after becoming unemployed. An additional 102 individuals who have been unemployed for more than 1 year were included in the cross-sectional part of the study. Possible decrease of physical working capacity was tested by bicycle ergometry. Psycho-emotional stress was tested by serum cortisol concentrations and by the Giessen symptom questionnaire. RESULTS: In short-term unemployed (STU) individuals, a significant decrease (P=0.001) of physical working capacity (16.3%) and a significant increase (P=0.004) of cortisol levels (17.6 microg/dl) was found. The Giessen symptom questionnaire score showed an increased emotional disturbance (P=0.035) during unemployment. The comparison of long-term unemployed and STU revealed a significant decrease (P=0.012) in physical working capacity (18.2%), a significant increase in cortisol levels (P=0.001) and a significant worsening of the Giessen symptom questionnaire score (P=0.001). CONCLUSION: Unemployment has a negative effect on physical working capacity and mental health, depending on the duration of unemployment. Factors that facilitate or impede physical and mental health during unemployment should be identified in future studies.

Adult↗

Welder's maculopathy?

OBJECTIVE: The aim of this study was to verify or to disprove whether the term 'Welder's maculopathy' or 'Welding arc maculopathy' has to be considered being a justifiable occupational hazard and is to be annexed to the list of occupational diseases. METHODS: Multifocal electroretinography (MERG) and thorough ophthalmologic examinations were performed in a group of 89 welders. The matched control group comprised 81 subjects who had never been exposed to welding. All participants of this study were examined by a specialist of occupational medicine prior to the MERG. RESULTS: Multifocal electroretinography as well as ophthalmological tests did not reveal a significant morphological or functional differences between the welders and the control group. On an average, the welders' visual acuity appeared to be better than that of the control group. This phenomenon could be attributed to the so-called healthy worker effect. CONCLUSION: Welding arc maculopathy seems to be rather a sequel of occupational accidents and negligence of safety regulations. The results of this study indicate that the usual protective measures in professional welding appears to be sufficient in order to prevent an occupational risk of welding arc maculopathy.

Adult↗

Endothelial NO synthase polymorphisms and postural tachycardia syndrome.

Postural tachycardia syndrome (POTS) is a heterogeneous disorder characterized by an excessive rise in heart rate and symptoms consistent with cerebral hypoperfusion in the upright position. NO produced by endothelial NO synthase is a significant factor in the regulation of blood flow. Genetic polymorphisms in the promoter region (T-786C) and exon 7 (E298D) of the NO synthase isoform 3 gene affect enzyme activity and have been associated with a number of cardiovascular diseases. Because some findings in POTS suggest aberrant NO-mediated functions, we postulated that the variant genotypes of these polymorphisms may increase the risk of developing POTS and correlate with more severe symptoms. We genotyped 136 patients with POTS (mean age 32.2+/-9.9 years; 46 men and 90 women) from Nashville, Tenn, and Vienna, Austria, and compared them with 191 healthy volunteers (mean age 29.1+/-8.0 years; 127 men and 64 women). Participants also underwent orthostatic testing with blood pressure, heart rate, and plasma norepinephrine measurements while supine and upright. The frequencies of the -786CC and 298DD genotypes were significantly lower in patients with POTS than in control subjects (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.14 to 0.57; P=0.001 for -786CC; and OR, 0.44; 95% CI, 0.21 to 0.91; P=0.033 for 298DD). According to 2-locus genotype analyses, patients with -786CC and 298EE or 298ED experienced the largest changes in heart rate and plasma norepinephrine with standing. These results indicate that NO may influence the development of POTS and the severity of POTS symptoms.

Adolescent↗

Chromosomal damage in human diploid fibroblasts by intermittent exposure to extremely low-frequency electromagnetic fields.

Environmental exposure to extremely low-frequency electromagnetic fields (ELF-EMFs) has been implicated in the development of cancer in humans. An important basis for assessing a potential cancer risk due to ELF-EMF exposure is knowledge of biological effects on human cells at the chromosomal level. Therefore, we investigated in the present study the effect of intermittent ELF electromagnetic fields (50 Hz, sinusoidal, 5'field-on/10'field-off, 2-24 h, 1 mT) on the induction of micronuclei (MN) and chromosomal aberrations in cultured human fibroblasts. ELF-EMF radiation resulted in a time-dependent increase of micronuclei, which became significant after 10 h of intermittent exposure at a flux density of 1 mT. After approximately 15 h a constant level of micronuclei of about three times the basal level was reached. In addition, chromosomal aberrations were increased up to 10-fold above basal levels. Our data strongly indicate a clastogenic potential of intermittent low-frequency electromagnetic fields, which may lead to considerable chromosomal damage in dividing cells.

Cells, Cultured↗

Endurance exercise training in orthostatic intolerance: a randomized, controlled trial.

Orthostatic intolerance is a syndrome characterized by chronic orthostatic symptoms of light-headedness, fatigue, nausea, orthostatic tachycardia, and aggravated norepinephrine levels while standing. The aim of this study was to assess the protective effect of exercise endurance training on orthostatic symptoms and to examine its usefulness in the treatment of orthostatic intolerance. 2768 military recruits were screened for orthostatic intolerance by questionnaire. Tilt-table testing identified 36 cases of orthostatic intolerance out of the 2768 soldiers. Subsequently, 31 of these subjects with orthostatic intolerance entered a randomized, controlled trial. The patients were allocated randomly to either a "training" (3 months jogging) or a "control" group. The influence of exercise training on orthostatic intolerance was assessed by determination of questionnaire scores and tilt-table testing before and after intervention. After training, only 6 individuals of 16 still had orthostatic intolerance compared with 10 of 11 in the control group. The Fisher exact test showed a highly significant difference in diagnosis between the 2 groups (P=0.008) at the end of the study. Analysis of the questionnaire-score showed significant interaction between time and group (P=0.001). The trained subjects showed an improvement in the average symptom score from 1.79+/-0.4 to 1.04+/-0.4, whereas the control subjects showed no significant change in average symptom score (2.09+/-0.6 and 2.14+/-0.5, respectively). Our data demonstrate that endurance exercise training leads to an improvement of symptoms in the majority of patients with orthostatic intolerance. Therefore, we suggest that endurance training should be considered in the treatment of orthostatic intolerance patients.

Adult↗

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

OBJECTIVE: 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 +/- 4 years) 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.

Adolescent↗

No cognitive deficits in men formerly exposed to lead.

OBJECTIVES: 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 5.4 microg Pb/100 ml were investigated, together with 48 matched controls (PbB, 4.7 microg Pb/100 ml) 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, >5 years) 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 55 microg Pb/100 ml), and extrapolation of these results to persons heavily exposed to lead is not possible.

Adult↗

Influence of an insertion variant in the 5'UTR 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. Chi 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.

5' Untranslated Regions↗

Transient increase in micronucleus frequency and DNA effects in the comet assay in two patients after intoxication with 2,3,7,8-tetrachlorodibenzo- p-dioxin.

BACKGROUND: The genotoxic effects in two patients with 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) intoxication were measured; an association with the workplace was suspected. METHODS: We determined sister chromatid exchange (SCE), micronuclei (MN) and comet assay tail factor in peripheral lymphocytes of the patients and of control persons. RESULTS: A determination of polychlorinated dibenzo- p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) revealed almost pure TCDD at a concentration of 144,000 pg/g blood lipids in patient 1 and 26,000 pg/g blood lipids in patient 2, the first value being the highest level ever reported in humans. The source of TCDD ingestion remains unclear, since TCDD blood levels in 30 employees from the same workplace were in the normal range (1.2-8.6 pg/g blood lipids, average 3.0 pg/g), with the exception of three employees with moderately increased TCDD levels of 93, 149 and 856 pg/g blood lipids, who, however, did not show any clinical symptoms. Systematic measurements of air and equipment did not identify the source of TCDD. We determined SCE and MN in the peripheral lymphocytes of the patients and of control persons. A first determination, a few months after the manifestation of chloracne, showed normal values (2.4 and 2.5 MN/500 binucleated cells; 6.7 +/- 2.2 and 6.0 +/- 2.5 SCEs/metaphase) in both patients. Two months later, when TCDD levels were 85,600 pg/g blood lipids and 17,700 pg/g blood lipids, respectively, MN had increased enormously to 16 and 21.8/500 binucleated cells, SCE remained within normal range. One employee had a TCDD level of 856 pg/g blood lipids but did not develop any clinical symptoms or genotoxic effects, nor did three healthy employees with TCDD levels within background range (1.5-2.9 pg/g blood lipids). Within a period of 13 months, MN had returned to a nearly normal range in both patients. SCE had been within normal ranges all the time. We also determined the comet assay tail factor (DNA damage level) in peripheral lymphocytes of the patients. A first determination, when the TCDD level was 85,600 pg/g blood lipids (proband 1), showed an enormously high value of 33.5%. Nine months later, when the TCDD level was at 73,900 pg/g blood lipids, we found only a moderately increased value of 6.9%. Proband 2 did not have a significantly elevated comet assay tail factor, neither at the TCDD level of 17,700 pg/g blood lipids nor at the level of 15,700 pg/g blood lipids. CONCLUSIONS: This delayed and transient effect seems to indicate some kind of "indirect" or "secondary" genotoxic effect of TCDD. However, DNA damaging effects, caused directly or indirectly, could be an indicator for a possible carcinogenic risk of TCDD.

Benzofurans↗

[Orthostatic intolerance--prevalence, diagnostic management and its significance for occupational medicine].

OBJECTIVE: Orthostatic intolerance (OI) is a syndrome which is characterised by headache, concentration difficulties, palpitation of the heart, dizziness associated with postural tachycardia and plasma norepinephrine concentrations that are disportionately high in upright posture. OI hitherto can only be diagnosed by a tilt table examination with high expenditure. In this paper we examine the reliability and validity of a questionnaire as a screening instrument for OI. METHODS: We studied 138 young males (mean age 21.6 years) from the military service. After a medical check and filling in the questionnaire, the participants underwent a tilt table test. The questionnaire consisted of 10 items registering presence and frequency of typical OI-symptoms. RESULTS: 104 probands showed a normal tilt table test. OI was diagnosed in 14 probands, orthostatic hypotension (OH) in 6 and postural orthostatic tachycardia syndrome (POTS) in 14. The participants with OI scored significantly higher in the questionnaire than the normal subjects: The mean score of the OI group was 22.6, the normal participants had a mean score of 3.9. Participants with POTS had a mean score of 13.5 and subjects with OH had a mean score of 17.0. CONCLUSIONS: We were able to establish a short questionnaire as a reliable and valid screening instrument for OI. Usage of this questionnaire can simplify enormously the diagnostic management of patients with suspected OI.

Adult↗

Orthostatic intolerance is not necessarily related to a specific mutation (Ala457Pro) in the human norepinephrine transporter gene.

BACKGROUND: Orthostatic intolerance (OI) is a syndrome characterized by lightheadedness, palpitations, fatigue, blurred vision, dizziness, chest discomfort, cognitive impairment, and occasionally syncope. These symptoms usually occur after upright posture and are associated with tachycardia and high plasma concentrations of norepinephrine. It has been proposed that a mutation in exon 9 of the norepinephrine transporter gene (Ala457Pro), resulting in more than 98% loss of function compared with the wild type, might provide a pathogenetic mechanism to explain the clinical symptoms of patients with OI. METHODS: We studied 46 young men from military service who had sought medical advice because of dizziness while standing. Every patient underwent a tilt-table test, with monitoring of blood pressure, heart rate, and plasma catecholamines in supine position and during 30 minutes of standing. Fourteen patients showing the full-blown OI syndrome (30 bpm increase in heart rate and 600 pg/mL plasma norepinephrine levels while standing) underwent direct DNA sequencing of exon 9 of the norepinephrine-transporter gene. RESULTS AND CONCLUSIONS: The specific mutation (Ala457Pro) was not detected in any of the 14 OI patients. Based on these findings, we doubt that this specific genetic transport defect is a frequent cause of the impaired uptake of norepinephrine in OI patients. Its routine determination will therefore not be helpful to establish the clinical diagnosis of OI.

Adolescent↗

Reduced cognitive abilities in lead-exposed men.

OBJECTIVES: Since it is still controversial whether-low-to moderate long-term lead exposure below current threshold values causes neurobehavioural deficits in adults, we investigated executive functions of the prefrontal cortex, attention, and visuospatial and visuomotor functioning in lead-exposed subjects. METHODS: Forty-seven lead-exposed subjects with a mean blood lead (PbB) level of 30.8 microg/100 ml and 53 non-lead-exposed aged-matched subjects (PbB: 4.32 microg/100 ml) with the same socio-economic background were investigated. Both groups were also matched on verbal intelligence. Neuropsychological tests were done by the modified Wisconsin card sorting test, block design test, visual recognition test, simple reaction time, choice reaction and digit symbol substitution. Lead exposure was assessed by current and cumulative measures. RESULTS: While there were significant differences in the results of the Wisconsin, block design and visual recognition tests, no differences were found in simple reaction time, choice reaction and digit symbol substitution. Significant correlations existed between current exposure and cognitive deficits. No correlation was found between cumulative exposure measures and cognitive parameters. CONCLUSIONS: Our results show that PbB below 70 microg/100 ml reduce neurobehavioural abilities, particularly visuospatial abilities and executive functions referring to the prefrontal cortex. As neurobiological substrate of the prefrontal dysfunction, glutamatergic system disturbances are discussed.

Adult↗