[PIMS-a new pediatric challenge]. / PIMS ­ eine neue pädiatrische Herausforderung: 9-Jahre alter Knabe mit SARS-CoV-2 assoziiertem hyperinflammatorischem Schocksyndrom.

The boy of Egyptian origin was previously healthy. After a history of fever for 7 days, abdominal pain, vomiting and dry cough resistant to treatment with oral antibiotics, he was admitted to hospital. The clinical examination showed a slightly red throat, a tense abdomen and erythema. The blood tests revealed leukocytosis and significantly increased inflammatory parameters. The abdominal ultrasound showed thickened intestinal loops in the left lower abdomen and the echocardiography showed minimal mitral regurgitation, a narrow pericardial effusion lamella over both ventricles and normal coronary arteries. Accordingly, cardiac enzymes were elevated. The day after admission, the boy developed an increasing rash and was transferred to the PICU because of septic shock refractory to high volume resuscitation, requiring hemodynamic support with noradrenaline and noninvasive respiratory assistance. The initial testing for SARS-CoV­2 on nasopharyngeal aspirates was negative twice; however, serum IgG antibodies were positive. Other viral and bacterial infections were excluded as the cause of the symptoms.The patient received IVIG, ASS, furosemide and methylprednisolone and the antibiotic treatment was continued. The dosage of the catecholamine could be reduced according to the patient's condition and the serially performed echocardiographic findings. The patient recovered in his general condition and was discharged from the PICU after 8 days. With the help of a detailed family history, we were able to figure out that the whole family, including the patient himself, had symptoms of a cold about 1 month earlier. Hence, SARS-CoV­2 antibody tests carried out showed a positive result for all of them.Pediatric inflammatory multisystem syndrome (PIMS) can quickly lead to manifest shock symptoms, necessitating close monitoring. A PICU background is crucial to treat possibly occurring symptoms and complications. High-dose steroids are used therapeutically alongside supportive therapies.

Advances Using Single-Particle Trajectories to Reconstruct Chromatin Organization and Dynamics.

Chromatin organization remains complex and far from understood. In this article, we review recent statistical methods of extracting biophysical parameters from in vivo single-particle trajectories of loci to reconstruct chromatin reorganization in response to cellular stress such as DNA damage. We look at methods for analyzing both single locus and multiple loci tracked simultaneously and explain how to quantify and describe chromatin motion using a combination of extractable parameters. These parameters can be converted into information about chromatin dynamics and function. Furthermore, we discuss how the timescale of recurrent encounter between loci can be extracted and interpreted. We also discuss the effect of sampling rate on the estimated parameters. Finally, we review a polymer method to reconstruct chromatin structure using crosslinkers between chromatin sites. We list and refer to some software packages that are now publicly available to simulate polymer motion. To conclude, chromatin organization and dynamics can be reconstructed from locus trajectories and predicted based on polymer models.

Towards effective phosphorus recycling from wastewater: quantity and quality.

Precipitation in the Mg-Ca-NH3-PO4 system has been explored to improve understanding of likely phases recoverable from complex wastewaters. Over a range of Mg/Ca combinations (0-100%) and pH 5-11, at least seven identifiable crystalline phases could be precipitated from artificial wastewater including: struvite, hydroxylapatite, newberyite, brushite, merrilite/whitlockite, octocalcium phosphate, and monetite. This experimental study has outlined the physicochemical conditions required to produce various phosphate products from synthetic wastewater, and found that large differences exist between experimentally formed phases and thermodynamical predictions. Struvite formation is the most desirable precipitate for the recovery of phosphate based upon purity, growth characteristics, dewatering properties, phosphate removal efficiency, and its ability to simultaneously remove ammonia. This study has also demonstrated that in specific cases the preliminary precipitation of brushite is a possible means of decreasing calcium content such that subsequent struvite formation could achieve higher-purity. Utilising experimental results and information on current commodity prices, discussion on the choice of Mg and Ca sources for phosphorus recovery provides guidance on appropriate means to optimise the formation and yield of high quality cost-optimised products.

Feasibility of a multdisciplinary lung cancer videoconference between a peripheral hospital and a comprehensive cancer centre.

OBJECTIVE: Treatment of lung cancer patients is changing rapidly and new treatment options have emerged in recent years. In 2007, to guarantee the best treatment procedure for lung cancer patients being treated in our peripheral hospital, we decided to introduce an interdisciplinary tumour videoconference between the Haemato-Oncological Day Hospital in Merano and the Comprehensive Cancer Centre Innsbruck. This retrospective analysis aims to describe the feasibility of such a conference. PATIENTS AND METHODS: Two hundred and three patients with lung cancer treated at the peripheral hospital of Merano between May 2003 until May 2011 were retrospectively analysed. After introduction of the tumour videoconference in 2007, 54% (n = 110) of the patients in this cohort were discussed in the conference. RESULTS: One hundred and four videoconferences were performed. Videoconference was feasible for 110 patients. Radiotherapeutic treatments were prescribed more frequently in patients from the conference group. Overall, major and minor treatment changes were undertaken in 7% (n = 8) and 18% (n = 20), respectively. CONCLUSION: Interdisciplinary tumour videoconference is feasible between a peripheral hospital and a comprehensive cancer centre. Radiotherapeutic treatment was prescribed more frequently, suggesting that such a conference facilitates the access to cancer-centre-specific treatment modalities. Accordingly, tumour videoconference between a peripheral hospital and a cancer centre is to be recommend.

Time course of the induction of homeostatic plasticity generated by repeated transcranial direct current stimulation of the human motor cortex.

Several mechanisms have been proposed that control the amount of plasticity in neuronal circuits and guarantee dynamic stability of neuronal networks. Homeostatic plasticity suggests that the ease with which a synaptic connection is facilitated/suppressed depends on the previous amount of network activity. We describe how such homeostatic-like interactions depend on the time interval between two conditioning protocols and on the duration of the preconditioning protocol. We used transcranial direct current stimulation (tDCS) to produce short-lasting plasticity in the motor cortex of healthy humans. In the main experiment, we compared the aftereffect of a single 5-min session of anodal or cathodal tDCS with the effect of a 5-min tDCS session preceded by an identical 5-min conditioning session administered 30, 3, or 0 min beforehand. Five-minute anodal tDCS increases excitability for about 5 min. The same duration of cathodal tDCS reduces excitability. Increasing the duration of tDCS to 10 min prolongs the duration of the effects. If two 5-min periods of tDCS are applied with a 30-min break between them, the effect of the second period of tDCS is identical to that of 5-min stimulation alone. If the break is only 3 min, then the second session has the opposite effect to 5-min tDCS given alone. Control experiments show that these shifts in the direction of plasticity evolve during the 10 min after the first tDCS session and depend on the duration of the first tDCS but not on intracortical inhibition and facilitation. The results are compatible with a time-dependent "homeostatic-like" rule governing the response of the human motor cortex to plasticity probing protocols.

Temozolomide and interferon alpha 2b in metastatic melanoma stage IV.

BACKGROUND: A multicentre, centrally randomized, open-labelled study with temozolomide and interferon (IFN)-alpha 2b was carried out to study the therapeutic effect in patients with metastatic melanoma stage IV. OBJECTIVES: The response rate, efficacy, side-effects, reasons for discontinuation of therapy and survival rate of 47 patients treated with temozolomide in combination with two different dosing regimens of IFN-alpha 2b were documented. PATIENTS/METHODS: Twenty-nine male and 18 female patients (mean age 57.6 years, range 34-74) were centrally randomized to two different arms: 20 patients received a treatment schedule with temozolomide 150 mg m(-2) on days 1-5 orally every 28 days in combination with IFN-alpha 2b 10 MIU m(-2) every other day and 27 patients received temozolomide 150 mg m(-2) on days 1-5 every 28 days in combination with IFN-alpha 2b in a fixed dose of 10 MIU every other day. RESULTS: We observed an overall response rate of 27.6% comprising five complete remissions (10.6%: one patient group A, four patients group B), in two of these five patients at the last follow-up in the study (4.3%, both in group B); and eight partial remissions (17%: six patients in group A, two patients in group B), in three of these eight patients at the last follow-up in the study (6.4%, two patients in group A, one patient in group B). Three patients showed stable disease (6.4%: one patient in group A, two patients in group B). Mean survival was 14.5 months [95% confidence interval (CI) 10-19] with no significant differences between treatment groups. However, there was a significant correlation with response after three cycles (log rank test, P < 0.03). Within the 32 patients who completed at least three cycles of therapy, seven patients (three in group A and four in group B) with a partial or complete response showed a significantly better mean survival of 30.6 months (95% CI 19.1-42) compared with 25 patients who did not respond (13.7 months 95% CI 9.2-18.3). In total, patients with at least one complete remission showed the longest survival (37.1 months 95% CI 26.3-47.9), followed by patients with at least one partial response (17.4 95% CI 10.9-23.9). Major side-effects of the treatment were nausea, vomiting, headache, leucopenia, thrombopenia, elevation of liver function parameters and neurological symptoms. In five patients, the side-effects led to a discontinuation of treatment: neurological symptoms (two patients), sepsis (one patient), brain haemorrhage (one patient) and exanthema (one patient). There were no treatment-related deaths. CONCLUSIONS: The combination of temozolomide and IFN-alpha 2b can easily be administered and shows tolerable toxicity. When an objective response occurs after three cycles, it indicates a significant survival advantage.

Longitudinal study examining the neurotoxicity of occupational exposure to aluminium-containing welding fumes.

OBJECTIVES: The neurotoxicity of occupational exposure to aluminium (Al)-containing welding fumes has been discussed with controversial results. The aim of the longitudinal study was to examine a group of Al welders for significant central nervous changes in comparison with a non-exposed cohort. METHODS: A group of 98 Al welders (mean age 37 years) in the car-body construction industry, with a median of 6 years of occupational exposure to Al welding fumes, and an education-matched, gender-matched, age-matched control group of 50 car-production workers (mean age 36 years) at the same plant, were included in this longitudinal study. Two cross-sectional studies were done in 1999 and 2001. In the second cross-sectional study 97 welders and 50 controls could be examined. The examination programme consisted, for example, of a standardised anamnesis, focussing on occupational history, education, illnesses, medication, accidents and current alcohol consumption, a physical examination that included neurological status, and the assessment of Al concentration in plasma and urine. The neurobehavioral methods included a symptom questionnaire, modified Q16, and computerised and non-computerised tests: psychomotor performance (steadiness, line tracing, aiming, tapping), verbal intelligence (WST), simple reaction time, digit span, block design (HAWIE), symbol-digit substitution, digit span, switching attention (European neurobehavioral evaluation system, EURO-NES), and standard progressive matrices. The data were analysed by multivariate analysis of covariance (MANCOVA) for repeated measurements with covariates age, education, and carbohydrate-deficient transferrin in plasma (CDT). RESULTS. The median Al urine concentration (mean preshift/postshift) was 52.4 microg/g creatinine (2001) and 57.6 microg/g creatinine (1999). Median respirable air dust was 0.67 mg/m(3) (2001) and 0.47 mg/m(3) (1999). Welders and controls did not report significantly more symptoms in the modified Q16. Furthermore, no significant differences in psychomotor performance and other neurobehavioral tasks, except for reaction time, were seen between welders and non-welders. Regression analyses reveal a significant relationship between reaction time and Al excretion in urine that was confounded by other factors. CONCLUSIONS: At present the outcome for reaction time has to be interpreted as a single result. However, as the modified Q16 questionnaire and the rest of the psychomotor performance showed no significant changes, the next cross-sectional study, in 2003, will provide further information on which a final conclusion can be based.

Physiological and psychological approaches to chemosensory effects of solvents.

Workplace related standard settings for solvents are based in a remarkable extent on information about sensory irritations. However, data from controlled human exposure studies are seldom available. Therefore, the aim of this study was to present the association of self-reported symptoms and physiological processes leading to sensory irritations. Three series of laboratory experiments each with 24 young male subjects were performed. Ethyl benzene (EB), 2-butanone (methyl ethyl ketone or MEK), isopropyl alcohol (IPA), 1-octanol (OCT), and 2-ethylhexanol (EHEX) were investigated in low and high concentrations. Ratings for sensory irritations (eyes and nose), olfactory symptoms, and annoyance were assessed repeatedly before, during and after the 4-h-exposures. The anterior active rhinomanometry (AAR) was employed measuring the nasal flow. The nasal lavage was used for the analysis of the neuropeptide substance P as indicator of nasal chemosensory irritations. Goodness-of-fit was calculated for non-linear regression analyses by fitting the sine function on the data of the ratings given during the 4-h-exposure. In general, ratings for annoyance and odor symptoms were fitted on a higher level than those for sensory irritations. However, a high fit could be shown for nasal irritations due to EHEX. In these experiments, a significant reduction of the nasal flow and a significant increase of substance P could be proved.

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.

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.

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.

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.

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.

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.

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.

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.

A randomized trial comparing the introduction of ritonavir or indinavir in 1251 nucleoside-experienced patients with advanced HIV infection.

ISS-IP1, a multicenter, randomized, 48-week open trial, was designed to compare the introduction of ritonavir or indinavir in patients with previous nucleoside experience and CD4+ cell counts below 50/mm3. Concomitant antiretroviral treatment with nucleoside analogs was allowed. Primary efficacy measures were survival and time to a new AIDS-defining event or death, analyzed through the whole period of observation by the intention-to-treat approach. Primary toxicity measures were time to treatment discontinuation and adverse events, grade at least 3/serious, analyzed by an on-treatment approach. Evaluation-of efficacy also included CD4+ cell and RNA response. The trial enrolled 1251 patients in 5 months. At baseline, mean CD4+ cell count was about 20 cells/mm3 and mean HIV RNA copy number was 4.9 log10/ml in both groups. Overall, 402 patients in the ritonavir group and 250 patients in the indinavir group permanently discontinued the assigned treatment (relative risk, 1.96; 95% CI, 1.68-2.30; p = 0.0001), with most of this difference dependent on a higher number of discontinuation for adverse events in the ritonavir group. After a mean follow-up of 307 days (ritonavir, 304; indinavir, 309), 124 deaths (ritonavir, 61; indinavir, 63; relative risk, 0.96; 95% CI, 0.67-1.36; p = 0.80) and 330 new AIDS-defining events (ritonavir, 170; indinavir, 160; relative risk, 1.05; 95% CI, 0.85-1.31; p = 0.60) were observed. CD4+ cell counts increased in both groups in patients still receiving treatment, with about 100 cells gained by week 24 and 150 cells gained by week 48. Body weight also increased over time in both groups. Analysis of RNA response showed a decrease of 1.5 log10 or higher in both treatment groups. Overall, 400 patients in the ritonavir group and 338 patients in the indinavir group developed at least one grade 3/serious new adverse event during follow-up (relative risk, 1.48; 95% CI, 1.28-1.72; p = 0.0001). Favorable CD4+ cell and RNA responses at 24 and 48 weeks were observed in both groups of patients remaining on treatment. Indinavir showed slightly better effects in sustaining RNA, CD4+ cell, and body weight responses. Ritonavir and indinavir results were comparable in terms of clinical outcome (survival and AIDS-defining events).

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.