Neurobehavioural testing in workers occupationally exposed to lead.
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Humans↗
Biomedical subjects
A Seeber
Publications and source records attributed to A Seeber.
A comparison of psoralen plus ultraviolet A (PUVA) monotherapy, tacalcitol plus PUVA and tazarotene plus PUVA in patients with chronic plaque-type psoriasis.
BACKGROUND: Numerous studies have shown that the additional administration of topical or systemic antipsoriatic agents might serve as an effective means to increase the efficacy of photochemotherapy [psoralen plus ultraviolet (UV) A (PUVA)] for psoriasis. OBJECTIVES: To compare the therapeutic response to tacalcitol plus PUVA, tazarotene plus PUVA and PUVA monotherapy in patients with chronic plaque-type psoriasis. In addition, we also assessed the duration of remission induced by each regimen and the tolerability of the two combination treatments. METHODS: Thirty-one patients with chronic plaque-type psoriasis were included in this observer-blinded, intrapatient comparison trial. PUVA treatment was given four times weekly. Additionally, tacalcitol ointment and 0.1% tazarotene gel were applied separately on two target areas once daily in the evening. At the onset of therapy and every 2 weeks thereafter the response to treatment was determined by the Psoriasis Severity Index score, which assesses the degree of erythema, infiltration and scaling of the psoriatic lesions. After complete or near complete clearing patients were followed-up until relapse. RESULTS: Twenty-four patients completed the study. The treatment requirements to induce complete or near complete clearing were significantly lower for both combination treatments than for PUVA monotherapy (P < 0.01). The median cumulative UVA dose and number of exposures were 30.6 J cm-2 (95% confidence interval, CI 22.5-71.2) and 14 (95% CI 11-16) for tacalcitol plus PUVA, 32.3 J cm-2 (95% CI 22.5-73.8) and 14 (95% CI 11-19) for tazarotene plus PUVA, and 37.0 J cm-2 (95% CI 29.5-83.9) and 16 (95% CI 14-22) for PUVA monotherapy. No difference between the three regimens was observed with regard to duration of remission. Adverse reactions occurred more often with 0.1% tazarotene than with tacalcitol but were in general mild and completely reversible upon using a lower concentration of 0.05% tazarotene. CONCLUSIONS: Tacalcitol ointment and tazarotene gel are both comparably effective in improving the therapeutic result of PUVA therapy in patients with chronic plaque-type psoriasis. Besides accelerating the treatment response, both agents, by virtue of their UVA dose-sparing effect, might also help to reduce possible long-term hazards of PUVA treatment.
Adult↗
Psychomotor performance and subjective symptoms at low level toluene exposure.
OBJECTIVES: Possible effects of long term occupational exposure to toluene below the level of 100 ppm on psychomotor performance and subjective symptoms were investigated in a cross sectional approach. METHODS: From German rotogravure printing plants 278 male workers, mean age 39.8 years, mean duration of employment 14.9 years, were examined. A mean lifetime weighted average exposure (LWAE) of 45.1 ppm toluene in ambient air was found for 154 exposed workers (rotogravure printing area), with a mean current exposure of 24.7 ppm. The corresponding data for a second group of 124 workers with very low exposure (endprocessing area) had LWAE of 9.3 ppm and a current exposure of 3.3 ppm toluene. Psychomotor performance (steadiness, line tracing, aiming, tapping, and peg board) and subjective symptoms were examined. RESULTS: No significant differences between the two exposure groups were found by analysis of variance (ANOVA). By stepwise linear regression analyses there were weak associations of LWAE with one performance variable and two symptoms scales, but the results were not significant after correction for the alpha error. Psychomotor performance was mostly affected by age (maximum explained variance up to 13%), and handedness (up to 9%), whereas subjective symptoms are mostly affected by anxiety (up to 38%). CONCLUSIONS: The weak associations between long term exposure to toluene should be used to indicate further longitudinal investigations. The results of this cross sectional study show no obvious dose response relation for psychomotor functions and subjective symptoms among workers exposed to toluene at a current exposure level of 1-88 ppm.
Adult↗
Correlation between 8-methoxypsoralen bath-water concentration and photosensitivity in bath-PUVA treatment.
BACKGROUND: Bath-PUVA treatment, originally established in Scandinavia, offers several advantages over oral PUVA and has become increasingly popular in recent years. Outside Scandinavia 8-methoxypsoralen (8-MOP) is the prevailing photosensitizer for this PUVA modality and is used arbitrarily in a wide range of concentrations. Up to the present, data are lacking on the impact of 8-MOP bath-water concentration on UVA dosimetry. OBJECTIVE: We investigated the influence of increasing 8-MOP bath-water concentrations on photosensitivity in bath-PUVA treatment. METHODS: Fifteen healthy volunteers without abnormal photosensitivity or recent exposure to ultraviolet radiation were included in an intraindividually controlled comparison study. In all volunteers the minimal phototoxic dose (MPD) was determined on the volar side of their forearms after immersion for 20 minutes in 4 different 8-MOP bath-water concentrations (0.5, 1, 2.5, and 5 mg/L). The correlation between 8-MOP concentration and photosensitivity (defined as the reciprocal value of the MPD) was analyzed by linear regression analysis. In addition, the time course of erythema formation and the UVA dose-erythema response curve was assessed for each psoralen concentration. RESULTS: The median MPD and the 25%-75% interquartile were 5.7 J/cm(2) (5.7-8), 4 J/cm(2) (4-5.7), 2.8 J/cm(2) (2.8-5.7), and 2 J/cm(2) (2-2.8) at an 8-MOP concentration of 0.5, 1, 2.5, and 5 mg/L, respectively. Linear regression analysis revealed a significant correlation between 8-MOP bath-water concentration and photosensitivity (r = 0.98; P =.019). Bath-PUVA-induced erythema peaked after a median time interval of 3 days, with a range of 2 to 4 days. The slope of the UVA dose-erythema response curve was similar for all psoralen concentrations. CONCLUSION: UVA dose requirements in bath-PUVA treatment decrease linearly with increasing 8-MOP concentrations. A single MPD assessment at 72 hours after the UVA exposure is inappropriate for accurate determination of the patients' photosensitivity. The hazard of wrong UVA dosimetry is comparable at all psoralen concentrations.
Adult↗
High-dose versus medium-dose UVA1 phototherapy for patients with severe generalized atopic dermatitis.
BACKGROUND: Several studies have demonstrated the efficacy of UVA1 (340-400 nm) phototherapy for patients with severe atopic dermatitis. However, the optimum treatment dose has yet to be determined. Although in seminal investigations high UVA1 doses were used, comparable results were reported in recent studies with a medium-dose regimen. OBJECTIVE: Our purpose was to compare the efficacy of high-dose with medium-dose UVA1 phototherapy for patients with severe generalized atopic dermatitis. METHODS: Ten adult patients with a median baseline SCORAD score of 67 were enrolled in an investigator-blinded, bilateral comparison study. Treatment was given 5 times weekly over a period of 3 weeks on an outpatient basis. Irradiation was performed by exposing one half of the patient's body to high-dose UVA1 (< or =130 J/cm(2)), and the contralateral body side received only half that dose. The clinical response was assessed after 5, 10, and 15 treatments. After completion of the study, patients were followed up for 6 months to evaluate the duration of clinical improvement. RESULTS: All but one patient responded favorably to treatment. High-dose UVA1 led to a decrease of the median SCORAD score by 33.4% after 1 week, 38.4% after 2 weeks, and 34.7% after 3 weeks. The respective values for the medium-dose regimen were 29.7%, 36.4%, and 28.2%. The difference in efficacy between the two dosages remained below the level of significance at all time points. Relapses occurred after a median of 4 weeks. Time of onset and severity of relapse were the same for both doses. CONCLUSION: Our data support previous uncontrolled observations that medium-dose UVA1 is comparably as effective as high-dose treatment for patients with severe generalized atopic dermatitis. Irrespective of the dose regimen, follow-up examinations revealed early relapse in the majority of patients.
Adult↗
Kinetics of two pathways in peroxyoxalate chemiluminescence
It has been shown that 1,1'-oxalyldiimidazole (ODI) is formed as an intermediate in the imidazole-catalyzed reaction of oxalate esters with hydrogen peroxide. Therefore, the kinetics of the chemiluminescence reaction of 1,1'-oxalyldiimidazole (ODI) with hydrogen peroxide in the presence of a fluorophore was investigated in order to further elucidate the mechanism of the peroxyoxalate chemiluminescence reaction. The effects of concentrations of ODI, hydrogen peroxide, imidazole (ImH), the general-base catalysts lutidine and collidine, and temperature on the chemiluminescence profile and relative quantum efficiency in the solvent acetonitrile were determined using the stopped-flow technique. Pseudo-first-order rate constant measurements were made for concentrations of either H2O2 or ODI in large excess. All of the reaction kinetics are consistent with a mechanism in which the reaction is initiated by a base-catalyzed substitution of hydrogen peroxide for imidazole in ODI to form an imidazoyl peracid (Im(CO)2OOH). In the presence of a large excess of H2O2, this intermediate rapidly decays with both a zero- and first-order dependence on the H2O2 concentration. It is proposed that the zero-order process reflects a cyclization of this intermediate to form a species capable of exciting a fluorophore via the "chemically initiated electron exchange mechanism" (CIEEL), while the first-order process results from the substitution of an additional molecule of hydrogen peroxide to the imidazoyl peracid to form dihydroperoxyoxalate, reducing the observed quantum yield. Under conditions of a large excess of ODI, the reaction is more than 1 order of magnitude more efficient at producing light, and the quantum yield increases linearly with increasing ODI concentration. Again, it is proposed that the slow initiating step of the reaction involves the substitution of H2O2 for imidazole to form the imidazoyl peracid. This intermediate may decay by either cyclization or by reaction with another ODI molecule to form a cyclic peroxide that is much more efficient at energy transfer with the fluorophore. The reaction kinetics clearly distinguishes two separate pathways for the chemiluminescent reaction.
Journal Article↗
A meta-analysis for neurobehavioural results due to occupational lead exposure with blood lead concentrations <70 microg/100 ml.
The size of performance effects caused by exposure to inorganic lead was determined by a meta-analytical procedure. Twenty-two studies covering exposure conditions of <70 microg/100 ml blood lead concentration were considered as to whether the methods of recording performance deficits were comparable. As a consequence of different test procedures and insufficient documented test results only 13 tests out of 12 studies could be included in the analysis. For the tests Block Design, Logical Memory and Santa Ana performance deficits were found, which may be interpreted as 'small' effects in accordance with a convention for evaluating effect sizes. For the example of Block Design it could be shown that these effects are nevertheless serious. The extent of the exposure related decrease of performance was comparable with those changes of performance which can be expected during aging of up to 20 years. Subsequently, a blood lead concentration of 70 microg/100 ml cannot be considered as a safe limit against long-term decreases of psychological performance.
Adult↗
Scleroderma-like syndrome in a child: eosinophilic fasciitis or scleredema adultorum?
UNLABELLED: A 6-year-old female patient presented with a rapidly progressive scleroderma-like syndrome involving almost the entire integument. Initially clinical patterns and histopathological data of both eosinophilic fasciitis and scleredema adultorum were present. The course of the disease remained unusual for both conditions but finally argued in favour of the diagnosis of eosinophilic fasciitis. CONCLUSION: Eosinophilic fasciitis and scleredema adultorum might be subtypes of one disease entity.
Child, Preschool↗
Correlation between bathing time and photosensitivity in 8-methoxypsoralen (8-MOP) bath PUVA.
Bath PUVA (psoralen plus ultraviolet A) using 8-methoxypsoralen has become increasingly popular in recent years as an effective treatment option for a continuously expanding range of skin disorders. Among the various variables of bath PUVA treatment, the impact of bathing time on photosensitivity has never been investigated in detail. We therefore determined the threshold UVA dose for erythema induction after different bathing periods. A marked influence of bathing time on photosensitivity was found. Increasing the soaking period from 5 min to 30 min resulted in a greater than 60% reduction of the minimal phototoxic and minimal perceptible phototoxic dose. Our results demonstrate that the duration of the psoralen bath is a critical parameter in bath PUVA treatment and has a major influence on UVA dose requirements.
Adult↗
Half-side comparison study on the efficacy of 8-methoxypsoralen bath-PUVA versus narrow-band ultraviolet B phototherapy in patients with severe chronic atopic dermatitis.
In patients with severe chronic atopic dermatitis (AD), both photochemotherapy [psoralen ultraviolet A (PUVA)] and narrow-band (TL-01) UV B phototherapy have been reported to be very effective. As no data exist on the relative therapeutic efficacy of these two regimens, we performed a randomized investigator-blinded half-side comparison study on 12 patients with severe chronic AD. Half-side irradiation with threshold erythemogenic doses of 8-methoxypsoralen bath-PUVA and narrow-band UVB was performed three times weekly over a period of 6 weeks. The severity of the disease was assessed separately for the paired halves of the patients' bodies by a modified SCORAD score at baseline and after 2, 4 and 6 weeks of treatment. Ten of the 12 patients completed the trial. All but one showed marked improvement or complete remission with both treatments. The mean baseline SCORAD score decreased by 65.7% by the bath-PUVA treatment and by 64.1% by the narrow-band UVB treatment (P = 0.48). No serious adverse reactions to either of the two regimens were observed. Our data confirm the high efficacy of bath-PUVA and narrow-band UVB phototherapy in the treatment of patients with chronic severe AD. Both regimens appear to be equally effective when administered in equi-erythemogenic doses.
Adult↗
Narrow-band ultraviolet B (ATL-01) phototherapy is an effective and safe treatment option for patients with severe seborrhoeic dermatitis.
BACKGROUND: Seborrhoeic dermatitis is a common papulosquamous dermatosis affecting 2-10% of the adult population. Current treatment options are limited and not always satisfactory. Objectives We aimed to investigate the efficacy of narrow-band ultraviolet (UV) B (TL-01) phototherapy as an alternative treatment for seborrhoeic dermatitis. METHODS: Eighteen patients with severe disease were enrolled in an open prospective study. Treatment was given three times weekly until complete clearing or to a maximum of 8 weeks. A clinical score assessing erythema, scaling, infiltration and pruritus was performed at baseline and every 2 weeks thereafter. Additionally, the patients were asked to rate the intensity of pruritus on a visual analogue scale. After completion of the study the patients were followed up to determine the median time interval until recurrence. RESULTS: All patients responded favourably to treatment, with six showing complete clearance and 12 marked improvement. The median clinical score decreased from 7.5 (range 4-8) at baseline to 0.5 (range 0-3) after 8 weeks of treatment (P = 0.005). The median pruritus score decreased from 4.5 (range 0-8) at baseline to 0 (range 0-3) at week 8 (P = 0.008). Relapses occurred in all patients after a median of 21 days (range 12-40). No side-effects of treatment were observed except occasional episodes of a moderate erythemal response. CONCLUSIONS: Narrow-band UVB phototherapy appears to be a very effective and safe treatment option for patients with severe seborrhoeic dermatitis.
Adolescent↗
Individual toluene exposure in rotary printing: increasing accuracy of estimation by linear models based on protocols of daily activity and other measures.
Industrial exposure varies distinctly both between persons and for each person over time. It is often not possible to measure individual exposure repeatedly due to high costs. Therefore, a method for assessment of exposure is needed that accounts for inter- and intraindividual variability. We consider a strategy suggested by Preller et al. (1995, Scandinavian Journal of Work, Environment, and Health 21, 504-512), the idea of which is to predict exposure on several days via a linear model using additional variables as regressors. Those additional variables are easier to obtain than exposure measurements and are assumed to influence exposure. The paper gives a theoretical proof of the use of this method. An example is given using toluene exposure data from a study in a rotogravure printing plant.
Biometry↗
Subjective symptoms due to solvent mixtures, dioxin, and toluene: impact of exposure versus personality factors.
In this study, we analyse the impact of personality factors on the frequency of self-reported symptoms for workers under different exposure conditions. Reported symptoms may depend on the level and type of exposure, as well as on personality factors such as trait anxiety of the worker or his general sensitivity with regard to the environment. The employed data stems from three studies: The first study contains information of 60 workers who suspected to be exposed to polychlorined dibenzodioxins and dibenzofuranes (Lifetime Weighted Average Exposure, LWAE, as an index for contact with the substances). The second study concerns 40 workers who are exposed to different concentrations of solvent mixtures in paint manufacturing (LWAE of total hydrocarbons about 10 ppm). The third study includes repeated measurements of two subgroups of workers from rotogravure printing plants who are exposed to different concentrations of toluene: a "high" exposure group (n = 129, LWAE about 46 ppm, current exposure 25 ppm) and a "low" exposure group (n = 96, LWAE for toluene about 9 ppm, current exposure 3 ppm). Trait anxiety, environmental sensitivity, and self-reported symptoms are measured by validated questionnaires and age as well as verbal intelligence are controlled. To determine the effect of the individual characteristics and the different exposures on self-reported symptoms, frequency analyses and variance analyses are conducted and linear models are fitted. For all analyses, trait anxiety explains the highest share of the variance. If there is no effect of the exposure on the reported symptoms (dioxin and low-level toluene study), trait anxiety seems to have a larger explanatory power in comparison with those studies where the exposure has an effect on the reported symptoms (solvent-mixture and high-level toluene study). Neurotoxicological risk analysis has to account for the detected dependence of self-reported symptoms on personality traits: assessments for elevated symptoms should not only be linked to the intensity of exposure but also related to benchmarks derived from the normal variability of personality factors.
Adaptation, Psychological↗
Neurobehavioral study on the interactive effects of age and solvent exposure.
Initial research revealed interaction effects on health measures between exposure to neurotoxicants and age. Symptom reports of workers were conspicuously increased if high-concentration occupational exposure (e.g. to organic solvents, lead) was combined with age above 54 years. The symptom increase in elderly workers was interpreted as a possible indicator of a biological vulnerable phase or delayed response of former high exposure. A second study of the hypothesized age-exposure interaction was performed with a group of workers who had homogenous exposure to a single organic solvent using a neurobehavioral performance evaluation (the EURO-NES). Workers in the rotogravure printing industry who were exposed to toluene were examined two times with an interval of one year (n =333/278). The sample was stratified by workers with significantly different toluene exposure, printers and end-processing operators, and four age classes (< 31, 31-40, 41-50, > 50). The mean lifetime weighted average exposure (LWAE) varied depending on age classes and years of employment with exposure between 7 and 17 ppm in the operators and between 35 to 62 ppm toluene in the printers. Multivariate analyses revealed a significant performance decrease with age (simple reaction time, symbol digit, switching attention, digit span). Again an interaction between age and exposure was found depending on diverging psychometric performance trends with older age. However, contrary to the hypothesis the group with higher exposures (printers) and older age revealed better performance and less symptoms than the group with lower exposure (end-processing operators). The paradoxical results are explained by differences in the intellectual capability in the oldest strata and a possible reversibility of neurobehavioral effects of former high toluene exposure under the condition of later low exposure. There are no hints of adverse delayed effects of former toluene exposure in a possible vulnerable phase in age over 50 years. The different interaction findings of the initial and present study seem to depend mainly on exposure differences in quality and quantity.
Adult↗
Switching attention--additional aspects for the analysis.
Problems related to attentional functions have often been reported within the neurotoxicology of long-term exposure to solvents, but knowledge about neuroanatomical sites involved in this degenerative process is still rare. However, some studies have emphasized the frontal cortex as a region of structural or functional changes in long-term exposed patients or accidental intoxications. Neurobehavioral tests using active switching tasks are widely used to detect frontal lobe dysfunction. Test batteries used in neurotoxicology provide such tasks but standard test interpretations often neglect these aspects. Rotogravure printing workers exclusively exposed to toluene were investigated in a longitudinal study with cross-sectional design. Data from two examination periods are presented. In the first sample 333 male workers were investigated. In the second examination period 278 workers could be retested. The workers differed with respect to level and duration of lifetime exposure to toluene. All subjects completed a neurobehavioral test battery including the task switching attention (EURONES). Different parameters were computed for consecutive trials with constant vs. shifted tasks and repetitions vs. changes of the response direction. In general the expected interaction between the two sequence factors could not be observed. In both examination periods the alternative strategy revealed no marked differences between task/response shifts. Considering the result of previous studies on task/response shifts, the results were highly unexpected. One explanation might be the strong deviations from equality for the relative frequencies of the four sequence conditions, resulting in biased expectancies. These may have superimposed on the basic effects of task shifts. However, in both examination periods weak effects of task shift could be revealed in the subgroup of the long-term exposed workers. In further studies it is necessary to balance conditions more carefully in order to exploit the sensitivity that the measurement of shift costs promises to provide. The exposure-related results of this study support this aspect.
Adult↗
Treatment of metastatic malignant melanoma with dacarbazine plus fotemustine.
Despite the poor prognosis of metastatic malignant melanoma, polychemotherapy with dacarbazine and fotemustine has shown promising results in several studies. We report on the clinical efficacy of a new sequential administration regimen with dacarbazine at a dose of 200 mg/m2 followed 24 h later by fotemustine 100 mg/m2 every 4 weeks in 63 patients with metastatic melanoma. A complete response was noted in 3 patients (5%), a partial response in 4 patients (6%), stable disease in 33 patients (5%) and progressive disease in 23 patients (37%). The duration of the 3 complete responses was 5, 14+ and 60+ months, for the 4 partial responses, 3, 4, 6 and 13 months. The median duration for stable disease was 4 months. The best response rates were obtained for lung and lymph node metastases. Toxicity was mild and mainly limited to haematological without pulmonary side-effects. Although there was a relatively low objective response rate, this chemotherapy regimen as a palliative treatment, is potentially valuable for patients with progressive stage IV melanoma.
Adult↗
Benefit of 6 months long-term physical training in polymyositis/dermatomyositis patients.
OBJECTIVE: The benefit of long-term physical training in patients with chronic polymyositis or dermatomyositis (PM/DM) was studied prospectively. METHODS: Eight patients with chronic PM/DM participated in a training programme for 6 months. A group of five PM/DM patients without any physical training was observed for control purposes. RESULTS: While there was no significant change in serum creatine phosphokinase (CPK) levels, the 'activities of daily living (ADL)' score improved significantly (P < 0.03), peak isometric torque (PIT) generated by muscle groups in the lower extremities rose significantly (P < 0.03) and there was a statistically highly significant increase in peak oxygen uptake (VO2max) relative to body weight (P < 0.02) due to the long-term training. The patients improved their aerobic capacity by 28%, which is clinically significant. In the untrained patients, no improvement in these target parameters was observed. CONCLUSION: In clinically stable DM/PM patients, long-term physical training can safely be performed and is recommended as part of a comprehensive rehabilitation management, particularly in view of the cardiopulmonary risk in these patients.
Activities of Daily Living↗
Improvement of physical fitness and muscle strength in polymyositis/dermatomyositis patients by a training programme.
In the present investigation, the benefit of physical training in patients with inflammatory myopathy was studied. In this prospective, randomized, controlled study, 14 patients with polymyositis (PM) or dermatomyositis (DM) were investigated. The training, consisting of bicycle exercise and step aerobics, took place over a 6 week period. Baseline and endpoint measurements included an 'activities of daily living' (ADL) score, peak isometric torque (PIT) generated by muscle groups in the lower extremities, peak oxygen consumption (VO2max), and creatine phosphokinase (CPK) levels. There was no significant rise in disease activity in the training group in comparison to the controls. The ADL score for the treatment group, in comparison to the control group, improved (P < 0.02), PIT rose (P < 0.05) and there was a statistically significant increase in oxygen uptake relative to body weight (P < 0.05). No rise in inflammatory activity, but significant improvement in muscle strength, oxygen uptake and well-being, were found in patients with inflammatory myopathy as a result of physical training. Besides medication, a physical training programme consisting mainly of concentric muscle contractions should therefore be an integral part of therapy, particularly in view of the cardiopulmonary risk of these patients.
Adult↗