Gadolinium distribution in kidney tissue determined and quantified by micro synchrotron X-ray fluorescence.

Aims of this study were to investigate gadolinium (Gd) in kidney tissue from a female patient with severe renal failure, who had a magnetic resonance imaging (MRI) with Gd-based contrast agent (GBCA) three times prior to kidney transplantation. Secondly to assess (semi-)quantitatively the Gd concentration in renal tissue and the spatial distribution of Gd in association to suspected co-elements such as calcium (Ca) and zinc (Zn). Archival paraffin embedded kidney tissue was investigated by micro Synchrotron X-ray fluorescence (µSRXRF) at the DORIS III storage ring at beamline L, HASYLAB/DESY(Hamburg, Germany). Elementary gadolinium (Gd) could be demonstrated in a near histological resolution in areas of about 2 × 1.5 mm2 of size. Mean Gd resulted in 200 ppm with a huge width of distribution (Gd-max: 2000 ppm). In kidney cortex Gd was in-homogeneously, but not randomly, distributed. Gd was verified throughout the investigated tissue. Low Gd was predominately concentrated either in areas with focally atrophic tubules or in areas with totally preserved uriniferous tubes. Moreover, strong correlations existed between Gd and calcium (Ca) or Gd and zinc (Zn) or Gd and strontium (Sr) distribution. Throughout our analysed areas copper (Cu) was nearly homogeneously distributed and Cu association to Gd could not be established, and also not for Gd to Fe. Gd in glomeruli was relatively reduced compared with mean Gd-values, while iron (Fe) distribution clearly demarks glomeruli mostly due to red blood cell iron in these capillary convolutes. Quantitative µSRXRF analysis provided an insight in element spatial distribution of Gd in the renal cortex. The strong correlation of the spatial distribution and associations between elements like Ca, Zn and Sr let us suspect that these elements are involved in the cell metabolism of GBCA. Low Gd in areas with extreme fibrosis and tubule atrophy or in areas with histologically intact tubes, let us suspect that on the one side Gd cannot be transported and deposited into these tissue areas and on the other side we assume that intact renal tubes do not reabsorb and store excreted Gd.

Gadolinium and Bio-Metal Association: A Concentration Dependency Tested in a Renal Allograft and Investigated by Micro-Synchrotron XRF.

AIMS: This study aimed to investigate gadolinium (Gd) and bio-metals in a renal allograft of a patient who was shortly after transplantation repeatedly exposed to a Gd-based contrast agent (GBCA), with the purpose of determining whether Gd can be proven and spatially and quantitatively imaged. Further elemental associations between Gd and bio-metals were also investigated. MATERIALS AND METHODS: Archival paraffin-embedded kidney tissue (eight weeks after transplantation) was investigated by microscopic synchrotron X-ray fluorescence (µSRXRF) at the DORIS III storage ring, beamline L, at HASYLAB/DESY (Hamburg, Germany). For the quantification of elements, X-ray spectra were peak-fitted, and the net peak intensities were normalized to the intensity of the incoming monochromatic beam intensity. Concentrations were calculated by fundamental parameter-based program quant and external standardization. RESULTS: Analysis of about 15,000 µSRXRF spectra (comprising allograft tissue of four cm2) Gd distribution could be quantitatively demonstrated in a near histological resolution. Mean Gd resulted in 24 ± 55 ppm with a maximum of 2363 ppm. The standard deviation of ±55 ppm characterized the huge differences in Gd and not in detection accuracy. Gd was heterogeneously but not randomly distributed and was mostly found in areas with interstitial fibrosis and tubular atrophy. Concentrations of all other investigated elements in the allograft resembled those found in normal kidney tissue. No correlations between Gd and bio-metals such as calcium, strontium or zinc below ~40 ppm Gd existed. In areas with extremely high Gd, Gd was associated with iron and zinc. CONCLUSIONS: We could show that no dose-dependent association between Gd and bio-metals exists-least in renal tissue-at Gd concentrations below ~40 ppm Gd. This was proven compared with a GBCA-exposed end-stage renal failure in which the mean Gd was ten-fold higher. Our results could shed additional light on Gd metabolism.

Copper and Trace Elements in Gallbladder form Patients with Wilson's Disease Imaged and Determined by Synchrotron X-ray Fluorescence.

Investigations about suspected tissue alterations and the role of gallbladder in Wilson's disease (WD)-an inherited genetic disease with impaired copper metabolism-are rare. Therefore, tissue from patients with genetically characterised WD was investigated by microscopic synchrotron X-ray fluorescence (µSRXRF). For two-dimensional imaging and quantification of elements, X-ray spectra were peak-fitted, and the net peak intensities were normalised to the intensity of the incoming monochromatic beam intensity. Concentrations were calculated by fundamental parameter-based program quant and external standardisation. Copper (Cu), zinc (Zn) and iron (Fe) along with sulphur (S) and phosphorus (P) mappings could be demonstrated in a near histological resolution. All these elements were increased compared to gallbladder tissue from controls. Cu and Zn and Fe in WD-GB were mostly found to be enhanced in the epithelium. We documented a significant linear relationship with Cu, Zn and sulphur. Concentrations of Cu/Zn were roughly 1:1 while S/Cu was about 100:1, depending on the selected areas for investigation. The significant linear relationship with Cu, Zn and sulphur let us assume that metallothioneins, which are sulphur-rich proteins, are increased too. Our data let us suggest that the WD gallbladder is the first in the gastrointestinal tract to reabsorb metals to prevent oxidative damage caused by metal toxicity.

[Training effects in computer-assisted psychological performance tests]. / Ubungseffekte bei computergestützten psychologischen Leistungstests.

OBJECTIVES: Reproducibility of results achieved by psychological performance tests is a precondition to quantify reliable cognitive and psychomotoric behaviour alterations after interventions. However, evidence exists that repeated processing leads to training effects which influence results. Therefore it is essential to elucidate these training effects. METHODS: Ten subjects (6 men and 4 women, 42 +/- 12, 5 years) carried out two computer based performance tests of the "Wiener Testsystem" (WTS), the Determinationstest (DT) and the Arbeitsleistungsserie (ALS). Both tests were performed five times by each test person. Training effects and contrasts were analyzed with one-way analysis of variance (ANOVA) for repeated measures. RESULTS: A significant "training" effect (p

Effects of night shift on the cognitive load of physicians and urinary steroid hormone profiles - a randomized crossover trial.

Mental and physical stress is common in physicians during night shifts. Neurocognitive effects of sleep deprivation as well as alterations in hormonal and metabolic parameters have previously been described. The aim of this crossover study was to evaluate the effects of night-shift work with partial sleep deprivation on steroid hormone excretion and possible associations with mood, sleep characteristics and cognitive functions in physicians. In total, 34 physicians (mean age 42 ± 8.5 years, 76.5% male) from different departments of the General Hospital of Vienna, Austria, were randomly assigned to two conditions: a regular day shift (8 h on duty, condition 1) and a continuous day-night shift (24 h on duty, condition 2). In both conditions, physicians collected a 24 h urine sample for steroid hormone concentration analysis and further completed psychological tests, including the sleep questionnaire (SF-A), the questionnaire for mental state (MDBF) and the computer-assisted visual memory test (FVW) before and at the end of their shifts, respectively. Although mean sleep deprivation during night shift was relatively small (~1.5 h) the impairment in participants' mental state was high in all three dimensions (mood, vigilance and agitation, p ≤ 0.001). Sleep quality (SQ), feeling of being recovered after sleep and mental balance decreased (p ≤ 0.001), whereas mental exhaustion increased (p < 0.05). Moreover, we could show a nearly linear relationship between most of these self-rating items. Testing visual memory participants made significantly more mistakes after night shift (p = 0.011), however, mostly in incorrectly identified items and not in correctly identified ones (FVW). SQ and false identified items were negatively correlated, whereas SQ and time of reaction were positively associated. It is assumed that after night shift, a tendency exists to make faster wrong decisions. SQ did not influence correctly identified items in FVW. In contrast to previous investigations, we found that only excretion rates for pregnanetriol and androsterone/etiocholanolone ratios (p < 0.05, respectively) were slightly reduced in 24-h urine samples after night shift. A considerable stimulation of the adrenocortical axis could not be affirmed. In general, dehydroepiandrosteron (DHEA) was negatively associated with the sense of recreation after sleep and with the time of reaction and positively correlated with correctly identified items in the FVW test. These results, on the one hand, are in line with previous findings indicating that stress and sleep deprivation suppress gonadal steroids, but, on the other hand, do not imply significant adrenocortical-axis stimulation (e.g. an increase of cortisol) during the day-night shift.

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.

Urinary 8-hydroxydeoxyguanosine and sister chromatid exchanges in patients with total hip replacements.

Ion release from metal implants has been suspected to increase the risk of genotoxic effects in patients wearing orthopedic metal devices. In this study we used urinary 8-hydroxydeoxyguanosine (8-OHdG) as marker of oxidative DNA damage and the frequency of sister chromatid exchanges in lymphocytes to test a possible relationship between the concentrations of chromium or cobalt and the induction of cytogenetic modifications in 46 patients with total hip replacements. A broad range of individual levels of metals has been observed in these patients: chromium in blood, 1.59-14.11 microg/L; chromium in urine, 0.79-93.80 microg/24 h; cobalt in blood, 0.77-37.80 microg/L; cobalt in urine, 2.59-166.94 microg/24 h. By linear regression analysis, no significant correlation between urinary 8OHdG or sister chromatid exchange (SCE) and the concentrations of metals was found. However, cobalt in blood as well as 8-OHdG in urine were higher in patients with implants 3-4 yr old as compared to patients with implants 1-2 yr old. Smoking significantly increased the frequency of SCE. Our data do not indicate a dependence of 8-OHdG in urine or SCE on the levels of chromium or cobalt in patients with total hip replacements.

Tissue factor exposing microparticles in inflammatory bowel disease.

BACKGROUND: Circulating procoagulant microparticles (MPs) are thought to be involved in the pathogenesis of venous thromboembolism in patients with inflammatory bowel disease (IBD). However, the exposure of tissue factor, the primary initiator of coagulation activation, on microparticles (TF(+)MPs) and its association with hemostasis activation has not yet been studied in IBD patients. METHODS: In this case-control study 49 IBD patients (28 Crohn's disease, 21 ulcerative colitis) and 49 sex- and age-matched, healthy controls were included. Clinical disease activity (Crohn's Disease Activity Index and Clinical Activity Index, respectively) was assessed and IBD-related data were determined by chart review. Numbers, cellular origin and procoagulant activity of TF(+)MPs in plasma were determined using flow cytometry and a chromogenic activity assay. D-dimer and high-sensitive C-reactive protein (CRP) served as markers for coagulation activation and inflammation, respectively. The primary endpoint was the number of TF(+)MPs in IBD patients compared to controls. RESULTS: Median number (interquartile range) of TF(+)MPs was higher in IBD patients than in controls (14.0 (11.9-22.8)×10(3)/mL vs. 11.9 (11.9-19.1)×10(3)/mL plasma, P=0.029). This finding was due to generally higher plasma levels of MPs from platelets and leukocytes in IBD patients. However, the number of TF(+)MPs was neither correlated with their procoagulant activity and D-dimer nor with disease activity and CRP. CONCLUSIONS: Increased numbers of circulating TF(+)MPs represent a new facet of hemostatic abnormalities in IBD. However, the lack of association with activation of the coagulation system and disease activity questions their pathogenetic role for venous thromboembolism in this patient group.

Physiotherapy-based rehabilitation following disc herniation operation: results of a randomized clinical trial.

STUDY DESIGN: Three-group, randomized, single blinded, controlled trial. OBJECTIVE: To test the effectiveness of physiotherapy-based rehabilitation starting 1 week after lumbar disc surgery. In addition, we tried to estimate the contribution of specific effects to the observed outcome (efficacy). SUMMARY OF BACKGROUND DATA: Physiotherapy-based rehabilitation is usually recommended for patients following lumbar disc surgery. Few and conflicting data exist for the relative effectiveness of this intervention. METHODS: A total of 120 patients following first-time, uncomplicated lumbar disc surgery were randomly assigned to "comprehensive" physiotherapy, "sham" neck massage, or no therapy. Before enrollment, all subjects completed a minimal physiotherapeutic intervention. Physiotherapy was administered by experienced physiotherapists and consisted of 20 sessions per patient over 12 weeks. Masseurs administered "sham massage" to the neck. The amount of treatment time was equal to that of physiotherapy. The main outcome measure was the Low Back Pain Rating Score (LBPRS) at 6 and 12 weeks, and 1.5 years after randomization. Secondary parameters were patients' overall satisfaction with treatment outcome and socioeconomic and psychologic measures. RESULTS: At the end of therapy (12 weeks), the LBPRS revealed a significantly better improvement in the physiotherapy group than in the untreated group. LBPRS outcome, however, did not significantly differ between physiotherapy and "sham" therapy. There was a tendency toward significance between the sham therapy and no therapy. Within the 1.5-year follow-up, LBP rating scales remained significantly improved compared with baseline, but there were no significant outcome differences. No statistically significant between-group differences were found for the secondary outcome parameters. CONCLUSION: As compared with no therapy, physiotherapy following first-time disc herniation operation is effective in the short-term. Because of the limited benefits of physiotherapy relative to "sham" therapy, it is open to question whether this treatment acts primarily physiologically in patients following first-time lumbar disc surgery, but psychological factors may contribute substantially to the benefits observed.

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.

Thermoregulation and rheological properties of blood in primary Raynaud's phenomenon and the vibration-induced white-finger syndrome.

OBJECTIVE: Frequent use of vibrating tools may lead to typical attacks of Raynaud's phenomenon (RP). The present study assesses the feasibility of the use of thermographic measurements of blood rheometry in the diagnosis of vibration-induced white-finger (VWF) syndrome. SUBJECTS AND METHODS: We studied 38 patients that were suffering from RP (primary RP, n=29; VWF, n=9) and 13 controls (six men and 45 women; mean age 49.1+/-11.6 years). Superficial finger skin blood flow was assessed with an infrared thermocamera before and after exposure to heat and cold. Fibrinogen, whole-blood viscosity and erythrocyte aggregation at different shear rates and plasma viscosity were measured. MAIN RESULTS: In patients with RP finger temperatures after re-warming were lower than those in controls [right hand digit (DIG) I P<0.02; DIG II-V P<0.01; left hand DIG I P<0.01; DIG II-V p<0.02], male patients with primary RP had higher Fg-values (P<0.02) and a trend to higher plasma viscosity. Patients with VWF had a trend to lower plasma viscosity than controls. Whole-blood viscosity at each shear rate was highest in patients with VWF. CONCLUSION: Provocation manoeuvres are essential in the diagnosis of RP. We speculate that the decreased plasma viscosity in VWF is a compensatory physiological mechanism, probably counteracting the chronic effects of vasospasm. The rise in whole-blood viscosity could be due to endothelial injury or to a reduction in the venous blood pH level. The abnormal cold reactivity of patients with RP may be partly related to rheological factors.

Laser Doppler anemometry distinguishes primary Raynaud phenomenon from VWF syndrome.

OBJECTIVES: We evaluated two microcirculatory function-tests, the Laser Doppler (LD)-Anemometry and the Laser Doppler Imager (LDI)-Flowmetry in their value to further elucidate functional behavior of the "Vibration-induced white finger syndrome" (VWF) and to distinguish between Raynaud's phenomenon (RP) of idiopathic or vibration origin. PARTICIPANTS AND METHODS: Ninety-four patients, suffering from RP were studied (78 patients with primary RP and 16 patients with VWF). Measurement of blood cell velocity (BCV) before and after provocation was obtained by nailfold capillary microscopy and an included Laser detector ("Anemometry"). Digital blood flux was recorded by LDI-Flowmetry during a standardized cooling and rewarming thermal challenge. RESULTS: "Time to peak" of BCV, a measure of maximal reactive hyperemia was longer in VWF in comparison to primary RP (30.37 versus 19.29 sec P < 0.02), respectively. CONCLUSION: Based on the fact, that prolongation of reactive hyperemia, an indicator of impaired endothelium-dependent vasodilation is also frequently found in peripheral arterial occlusive disease, it is hypothesized that VWF is not only a microcirculatory vasospastic disorder, but may also be related to atherosclerosis. Anemometry, in association with an appropriate provocation-test, could represent a useful non-invasive method for objectifying diagnosis of VWF in patients with RP.

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.