Antifungal prophylaxis with posaconazole vs. fluconazole or itraconazole in pediatric patients with neutropenia.

Pediatric patients with hemato-oncological malignancies and neutropenia resulting from chemotherapy have a high risk of acquiring invasive fungal infections. Oral antifungal prophylaxis with azoles, such as fluconazole or itraconazole, is preferentially used in pediatric patients after chemotherapy. During this retrospective analysis, posaconazole was administered based on favorable results from studies in adult patients with neutropenia and after allogeneic hematopoietic stem cell transplantation. Retrospectively, safety, feasibility, and initial data on the efficacy of posaconazole were compared to fluconazole and itraconazole in pediatric and adolescent patients during neutropenia. Ninety-three pediatric patients with hemato-oncological malignancies with a median age of 12 years (range 9 months to 17.7 years) that had prolonged neutropenia (>5 days) after chemotherapy or due to their underlying disease, and who received fluconazole, itraconazole, or posaconazole as antifungal prophylaxis, were analyzed in this retrospective single-center survey. The incidence of invasive fungal infections in pediatric patients was low under each of the azoles. One case of proven aspergillosis occurred in each group. In addition, there were a few cases of possible invasive fungal infection under fluconazole (n = 1) and itraconazole (n = 2). However, no such cases were observed under posaconazole. The rates of potentially clinical drug-related adverse events were higher in the fluconazole (n = 4) and itraconazole (n = 5) groups compared to patients receiving posaconazole (n = 3). Posaconazole, fluconazole, and itraconazole are comparably effective in preventing invasive fungal infections in pediatric patients. Defining dose recommendations in these patients requires larger studies.

Overestimate of relative aerobic contribution with maximal accumulated oxygen deficit: a review.

Maximal accumulated oxygen deficit (MAOD) is widely utilized in calculating energy production during supra-maximal exercises. Since its introduction by Medbo et al. in 1988, debate on MAOD existed. The purpose of this review was to summarize the development and description of MAOD and another method of calculating energy production (Pcr-La-O2). We reviewed similar studies on relative aerobic contribution (O2%) and analyzed various results of O2% calculated using MAOD or Pcr-La-O2. An overestimate of O2% was found when using MAOD compared to Pcr-La-O2. The overestimate when using MAOD is likely due to the linear extrapolation of oxygen uptake at supra-maximal intensity, the neglect of anaerobic energy release and the reduced duration of each step in sub-maximal incremental test. Since it is unknown which method provides a more reliable estimation of O2%, an exponential regression function (y=22.404 * ex + 45.176, where y=O2% in percentage, x=duration of the supra-maximal exercise in minute) was drawn from the existing data using both methods.

Comparison of itraconazole, voriconazole, and posaconazole as oral antifungal prophylaxis in pediatric patients following allogeneic hematopoietic stem cell transplantation.

Oral antifungal prophylaxis with extended-spectra azoles is widely used in pediatric patients after allogeneic hematopoietic stem cell transplantation (HSCT), while controlled studies for oral antifungal prophylaxis after bone marrow transplantation in children are not available. This survey analyzed patients who had received either itraconazole, voriconazole, or posaconazole. We focused on the safety, feasibility, and initial data of efficacy in a cohort of pediatric patients and adolescents after high-dose chemotherapy and HSCT. Fifty consecutive pediatric patients received itraconazole, 50 received voriconazole, and 50 pediatric patients received posaconazole after HSCT as oral antifungal prophylaxis. The observation period lasted from the start of oral prophylactic treatment with itraconazole, voriconazole, or posaconazole until two weeks after terminating the oral antifungal prophylaxis. No incidences of proven or probable invasive mycosis were observed during itraconazole, voriconazole, or posaconazole treatment. A total of five possible invasive fungal infections occurred, two in the itraconazole group (4%) and three in the voriconazole group (6%). The percentage of patients with adverse events potentially related to clinical drugs were 14% in the voriconazole group, 12% in the itraconazole group, and 8% in the posaconazole group. Itraconazole, voriconazole, and posaconazole showed comparable efficacy as antifungal prophylaxis in pediatric patients after allogeneic HSCT.

Maximal lactate steady state in kayaking.

A fixed blood lactate value of 4 mM was commonly used to calculate workload at maximal lactate steady state (MLSS) in kayaking. Our purpose was to measure the actual blood lactate value at MLSS and workload at MLSS in kayaking and assess the validity of using a fixed blood lactate value to calculate the workload at MLSS. 8 junior kayakers (15.1±1.2 years; 179.9±7.3 cm; 72.3±4.9 kg) participated in an incremental workload test and 4-6 sub-maximal constant workload tests (duration of 30 min) on a kayaking ergometer. Blood lactate was measured to calculate the blood lactate value and workload at MLSS. The blood lactate value at MLSS in kayaking was 5.4±0.7 mM. The measured workload at MLSS (112±22 watts) was significantly greater than the calculated workload using a lactate value of 4 mM (104±18 watts, p=0.016). The measured MLSS workload was not significantly different from the calculated workload using a fixed lactate value of 5.4 mM (115±19 watts, p=0.16) or 5.0 mM (113±19 watts, p=0.78) in the incremental tests. A fixed blood lactate value of 5 mM instead of 4 mM might be a better estimate in kayaking given the incremental workload test used in this study.

Alterations in basement membrane immunoreactivity of the diabetic retina in three diabetic mouse models.

BACKGROUND: The mouse retina contains three kinds of basement membrane (BM) structures; the inner limiting membrane (ILM), Bruch's membrane (BrM), and the BM surrounding the capillaries. We aimed to investigate possible variations of individual BM components and to detect effects caused by diabetes in three different diabetic mouse models. METHODS: After 4 and 6 months of diabetes (defined by blood glucose > 250 mg/dl), we analyzed by immunohistochemistry the laminin, collagen IV, and nidogen-1 and nidogen-2 protein composition of the BMs obtained from diabetic and non-diabetic Leptin-receptor deficient (db/db) mice and insulin receptor (IR)/insulin receptor substrate-1 (IRS-1) double heterozygous knockout mice. In addition, C57BL/6 J mice were rendered diabetic by intraperitoneal injections of streptozotocin (STZ). RESULTS: All analyzed BM proteins were detected in all of the three BMs with the exception of collagen IV, which was not detectable in the ILM of db/db mice and IR/IRS-1 mice. We present the first analysis of nidogen expression in diabetic BM. The staining patterns did not differ between the type-1 diabetic model (STZ) or the type-2 diabetic models (db/db and IR/IRS-1) and the wild-type controls, with only one exception: both the db/db mice and the IR/IRS-1 mice but not the STZ mice showed a decreased nidogen-1 immunoreactivity in the BrM after 4 months of diabetes, but not after 6 months. CONCLUSIONS: The BMs in the three mouse strains differ with regard to protein immunoreactivity in the inner limiting membrane. Changes in BM composition may affect both the assembly and the function of the retinal BM. However, there are no marked differences in the BM composition between type-1 and type-2 diabetes. These results provide evidence for BM remodelling during diabetic retinopathy.

Enhancement of awareness through feedback does not lead to interlimb transfer of obstacle crossing in virtual reality.

Locomotor skill transfer is an essential feature of motor adaptation and represents the generalization of learned skills. We previously showed that gait adaptation after crossing virtual obstacles did not transfer to the untrained limb and suggested it may be due to missing feedback of performance. This study investigated whether providing feedback and an explicit goal during training would lead to transfer of adaptive skills to the untrained limb. Thirteen young adults crossed 50 virtual obstacles with one (trained) leg. Subsequently, they performed 50 trials with their other (transfer) leg upon notice about the side change. Visual feedback about crossing performance (toe clearance) was provided using a color scale. In addition, joint angles of the ankle, knee, and hip were calculated for the crossing legs. Toe clearance decreased with repeated obstacle crossing from 7.8 ± 2.7 cm to 4.6 ± 1.7 cm for the trained leg and from 6.8 ± 3.0 cm to 4.4 ± 2.0 cm (p < 0.05) for the transfer leg with similar adaptation rates between limbs. Toe clearance was significantly higher for the first trials of the transfer leg compared to the last trials of the training leg (p < 0.05). Furthermore, statistical parametric mapping revealed similar joint kinematics for trained and transfer legs in the initial training trials but differed in knee and hip joints when comparing the last trials of the trained leg with the first trials of the transfer leg. We concluded that locomotor skills acquired during a virtual obstacle crossing task are limb-specific and that enhanced awareness does not seem to improve interlimb transfer.

Prevalence of osteoporosis among cancer patients in Germany: prospective data from an oncological rehabilitation clinic.

UNLABELLED: In this prospective study, we measured bone mineral density (BMD) in 1,041 cancer patients undergoing an oncological rehabilitation program in an inpatient rehabilitation clinic. There was an osteoporosis prevalence of approximately 16%, independent of sex, which is considerably higher than in the community-dwelling population. INTRODUCTION: There is evidence that cancer patients are at risk of an increased BMD-loss following the disease and its therapy. Nevertheless, there is only little data available about the prevalence of osteoporosis in German cancer patients. Therefore, we measured BMD in 1,041 oncological inpatients undergoing rehabilitation. METHODS: From February 2006 to September 2009, BMD was measured in oncological patients with dual-energy x-ray absorptiometry (DXA; femur and spine). Statistical analysis for prevalence of osteoporosis was done in descriptive manner calculating means, standard deviation, frequencies, and 95% confidence intervals. To compare the prevalence of osteoporosis in different subgroups, χ (2) tests were done with p < 0.05. To create a risk profile, odds ratios were calculated using uni- and multivariate logistic regression. RESULTS: In 1,041 patients with a mean age of 57.1 years (11.0 years), DXA-measures were performed. Of them, 22% were male and 78% were female. The osteoporosis prevalence was about 16% (13.8, 18.2), independent of sex (p = 0.9722) or cancer type (p = 0.7174). As risk factors influencing the development of osteoporosis, age, weight, menopausal state, and hormone replacement therapy were identified in women and weight only in men. CONCLUSIONS: Compared to the general population, the rate of osteoporosis is distinctly elevated in German cancer patients independent of sex or cancer type. Hence, a general recommendation for a DXA screening in these patients appears to be justified.

[Vocational interventions integrated in inpatient rehabilitation]. / Medizinisch-berufliche Interventionen in der stationären orthopädischen Rehabilitation. Explorative Evaluation eines Pilot-projektes aus Patientensicht.

Orientation on work place associated problems is a typical assignment of medical rehabilitation in Germany. The implementation of special vocational programmes, however, may be associated with several challenges concerning staff and space required, which could be difficult to overcome.

Obstacle avoidance training in virtual environments leads to limb-specific locomotor adaptations but not to interlimb transfer in healthy young adults.

Obstacle avoidance is one of the skills required in coping with challenging situations encountered during walking. This study examined adaptation in gait stability and its interlimb transfer in a virtual obstacle avoidance task. Twelve young adults walked on a treadmill while wearing a virtual reality headset with their body state represented in the virtual environment. At random times, but always at foot touchdown, 50 virtual obstacles of constant size appeared 0.8 m in front of the participant requiring a step over with the right leg. Early, mid and late adaptation phases were investigated by pooling data from trials 1-3, 24-26 and 48-50. One left-leg obstacle appearing after 50 right-leg trials was used to investigate interlimb transfer. Toe clearance and the anteroposterior margin of stability (MoS) at foot touchdown were calculated for the stepping leg. Toe clearance decreased over repeated practice between early and late phases from 0.13 ± 0.05 m to 0.09 ± 0.04 m (mean ± SD, p < 0.05). MoS increased from 0.05 ± 0.02 m to 0.08 ± 0.02 m (p < 0.05) between early and late phases, with no significant differences between mid and late phases. No differences were found in toe clearance and MoS between the practiced right leg for early phase and the single trial of the left leg. Obstacle avoidance during walking in a virtual environment stimulated adaptive gait improvements that were related in a nonlinear manner to practice dose, though such gait adaptations seemed to be limited in their transferability between limbs.

Sexual cues alter working memory performance and brain processing in men with compulsive sexual behavior.

Pornography has been repeatedly at the centre of public attention and has been controversially discussed for a long time. However, little is known about the connection between pornographic stimuli and individual (neuronal) processing of attention and memory. Here, the impact and neural underpinnings of pornographic pictures on working memory processes in a sample of subjects with compulsive sexual behaviour was investigated. Therefore, whilst using functional magnetic resonance imaging (fMRI), a letter n-back task with neutral or pornographic pictures in the background was employed in 38 patients and 31 healthy controls. On the behavioural level, patients were slowed down by pornographic material depending on their pornography consumption in the last week, which was reflected by a higher activation in the lingual gyrus. In addition, the lingual gyrus showed a higher functional connectivity to the insula during processing of pornographic stimuli in the patient group. In contrast, healthy subjects showed faster responses when confronted with pornographic pictures only with high cognitive load. Also, patients showed a better memory for pornographic pictures in a surprise recognition task compared to controls, speaking for a higher relevance of pornographic material in the patient group. These findings are in line with the incentive salience theory of addiction, especially the higher functional connectivity to the salience network with the insula as a key hub and the higher lingual activity during processing of pornographic pictures depending on recent pornography consumption.

Advanced cantilevers for magnetic force microscopy and high frequency magnetic force microscopy.

In order to improve the spatial resolution achieved by magnetic force microscopy (MFM) technique and its derivatives, we employ here advanced MFM tips fabricated by means of focused ion beam (FIB) milling. The magnetic coating applied on these tips is a CoCr film of 10 nm thickness. The MFM measurements on hard disk test samples reveal the achieved high resolution, and the measurement on a garnet film demonstrates the low invasiveness. High-frequency MFM (HF-MFM) is a development of the MFM technique to observe the HF stray fields emerging from magnetic recording writer poles at their operating conditions. By means of HF-MFM, magnetic recording writer poles are characterized in the frequency range 100-1,000 MHz. Up to now, all HF-MFM experiments conducted were using standard MFM cantilevers. From the HF-MFM images obtained using the advanced MFM cantilevers, it is clearly seen that the spatial resolution is considerably improved over the images obtained using standard MFM tips. However, the 10 nm thick magnetic coating of the cantilevers is found to work properly only at frequencies of up to about 500 MHz.

[Effect of propriocetiv trainings tools for the muscles in stance stability]. / Auswirkung propriozeptiver Trainingsgeräte auf beteiligte Muskulatur im Einbeinstand.

Today in each therapy and training program proprioceptive exercises are integrated. A lot of equipment you can buy. But for an more effective training exercises and equipment should be select more regarding the aim and the problem of the training. In literature is not much written about the specific way proprioction equipment stimulate different muscles. In this study 15 students of sport sciences (25.7 +/- 2.2 years, 8 male, 7 female) were tested for a period of 15 seconds in a single-leg standing position on a small rocker board, a wobble board, a gym mat and the Posturomed(c). The exercise was done just one time on each tool in a random way. The effect of the exercise was measured by EMG on six main stabilising muscles, m. tibialis ant., m. peroneus long., m. gastrocnemius med. And lat., m. semimembranosus and m. vastus med. At the end of the test series MVC of each muscle was tested. For the analysis we regarded the first, middle and last second of the test. Also the maximum peak over 0.5 sec. and the average of the whole test was integrated into the data base. The statistics was done with the Wilcoxen-Test. The experimental standard deviation was defined of 5 %. The highest EMG activity we noticed on the small rocker board. The activity was over the whole test series significant higher in the muscles m. tibialis ant., m. peroneus long. and m. gastrocnemius. The m. semimebranusus shows in all exercises the slightest EMG activity, the m. peroneus long. shows the highest activity. During the test all muscles decrease in EMG activity except m. peroneus long. on the small rocker board and the Posturomed. With these facts of EMG activity during proprioceptive exercises we are able to advice training more specifically: Because of the decreasing activity we advice doing repeated intervals not longer than 15 seconds. In the aim of ankle stabilisation use the small rocker board and the gym mat. For rehabilitation and prevention on the knee use the Posturomed, the mat or even the small rocker board. The advocacies are given looking to the tested rehab tools.

Randomised trial comparing as-needed versus regular treatment with formoterol in patients with persistent asthma.

PURPOSE: The aim of this study was to demonstrate the equivalent efficacy of inhaled formoterol in asthmatic patients, either given as-needed or on a regular twice-daily schedule. METHODS: Randomised, open 12-week study in patients with mild to moderate asthma not adequately controlled with inhaled glucocorticosteroids alone. Patients received inhaled formoterol as needed or on a regular schedule (2x2 puffs/day with 6 microg formoterol per puff). Patients in the twice-daily formoterol group could use salbutamol as a rescue medication. The primary endpoint was the number of patients with asthma exacerbations in each group. RESULTS: Thirty-nine centres randomised 359 patients. The number of patients with asthma exacerbations showed neither a clinically relevant nor a statistically significant difference between groups: formoterol as-needed: 3.95% (7 of 177); twice daily: 3.45% (6 of 174). Patients in the formoterol as-needed group used significantly less formoterol (-1.5 puffs per day; P<0.0001). Including the saved rescue medication (up to one puff per day), total beta-2 agonist use in the formoterol as-needed group decreased by approximately 2-2.5 puffs per day. Both formoterol treatment schedules were well tolerated. Musculoskeletal pain and tremor were less frequent in the formoterol as-needed group: headaches were slightly more frequent. CONCLUSION: Formoterol given as needed and without additional beta-2 agonist, and formoterol given on a regular basis twice daily, supplemented by salbutamol as a rescue medication, appeared equally effective in this clinical study. Drug consumption was markedly lower in the former group.

A convenient method for large-scale STM mapping of freestanding atomically thin conductive membranes.

Two-dimensional atomically flat sheets with a high flexibility are very attractive as ultrathin membranes but are also inherently challenging for microscopic investigations. We report on a method using Scanning Tunneling Microscopy (STM) under ultra-high vacuum conditions for large-scale mapping of several-micrometer-sized freestanding single and multilayer graphene membranes. This is achieved by operating the STM at unusual parameters. We found that large-scale scanning on atomically thin membranes delivers valuable results using very high tip-scan speeds combined with high feedback-loop gain and low tunneling currents. The method ultimately relies on the particular behavior of the freestanding membrane in the STM which is much different from that of a solid substrate.

Presence of 14Hz spindle oscillations in the human EEG during deep anesthesia.

OBJECTIVE: To report on presence of human EEG spindle oscillations on the cortical level within flat periods of the burst-suppression pattern during propofol-induced anesthesia; to search for corresponding oscillations and possible functional connections. METHODS: Artefact-free epochs of spindle activation were selected from the electroencephalograms of opiate-dependent patients undergoing rapid opiate detoxification. Power spectral analysis and source localization using low-resolution-brain-electromagnetic-tomography (LORETA(Key)) were performed. RESULTS: Sinusoidal rhythms with waxing and waning amplitudes appeared after propofol-induced narcosis but no direct correlations could be determined between individual dosage and characteristic spindle attributes. The power maximum stood midline over the cortical areas, especially around C(z). We calculated a peak frequency of 14(+/-1.2) Hz. Motor fields, particularly in the frontal, parietal, and various cingulate areas, were found to be the primary sources of spindle oscillations in the cortex. CONCLUSIONS: The frequent occurrence of these localized spindle sources demonstrates the preference for motor fields. Spindle oscillations observed during propofol-induced narcosis were similar in frequency and shape to those observed in natural sleep. SIGNIFICANCE: The results lend support to models that postulate a close link between the motor system and the organization of behavior. In addition, spindle rhythms under propofol bore some resemblance to spindle types which occur during sleep.

[Strategies for talking to the patient with sexual dysfunction in the doctor's office]. / Tabuthema Sexualstörung: Wie spreche ich den Patienten darauf an? Ein Fragebogen kann den Einstieg erleichtern.

The use of a questionnaire for initiating talks about the topic of sexual disorders and the efficacy and acceptance by the physician and patient of various communication strategies, were investigated. Each of a total of 1191 general practitioners distributed a health questionnaire which contained questions on sexuality to 150 men aged 30 and above. In a total of 10,622 first talks on sexual health, the questionnaire met with a high level of acceptance, and was the trigger for talks in 54% of the cases. More than two-thirds of the patients reacted positively to such talks, speaking freely and readily, and relieved that this aspect of their lives was being addressed. In 75% of the patients an erectile dysfunction was diagnosed, in 27% further diagnostic measures were prescribed, and in 60% treatment was initiated. In the exes of the physician, the clearly signaled readiness to talk and the discussion of treatment options were the most favorable communication strategies.

Combined analysis and single-step detection of GAD65 and IA2 autoantibodies in IDDM can replace the histochemical islet cell antibody test.

Cytoplasmic islet cell antibodies (ICAs) are the classical serological markers for diagnosis and prediction of IDDM, but high technical demands have limited the widespread use of the histochemical ICA test. To investigate whether combined analysis of autoantibodies to two defined islet antigens can replace the histochemical ICA test, we established quantitative radioimmunoassays for autoantibodies to glutamate decarboxylase (GAD65-A), the tyrosine phosphatase IA2/ICA512 (IA2-A), and the cytoplasmic part of IA2 (IA2c-A). The GAD65-A and IA2c-A profiles of 920 sera from healthy individuals and from patients with IDDM, other organ-specific autoimmune diseases, and polyendocrine autoimmune syndrome were compared with the ICA profiles from these same individuals. Combined analysis of GAD65-A and IA2c-A detected 93-100% of the ICA+ sera, and, at equal specificity, improved the diagnostic sensitivity (85%) for IDDM compared with that of ICA (74%). This effect was especially pronounced in children with disease onset before 16 years of age (91% sensitivity). To replace ICA testing in risk assessment for IDDM, we designed a strategy adapted to study groups with low antibody prevalence. A combined radioimmunoassay for single-step detection of GAD65-A and IA2c-A was developed, and positive sera were reanalyzed to define their single autoantibody specificity. We identified 93% of the ICA+ sera from 204 first-degree relatives of IDDM patients. Single-step detection reduced costs and effort by more than 40% compared with separate testing, allowing an efficient large-scale screening of sera for GAD65-A and IA2c-A in IDDM. In sum, GAD65-A and IA2c-A detected much ICA reactivity, and their combined evaluation and detection is suitable to replace the histochemical ICA test.

A population survey of sexual activity, sexual dysfunction and associated help-seeking behavior in middle-aged and older adults in Germany.

The Global Study of Sexual Attitudes and Behaviors was a survey of 27,500 men and women aged 40 to 80 years in 29 countries. Here we report the sexual activity, the prevalence of sexual problems and related help-seeking behaviour among subjects in Germany. A telephone survey was conducted in 2001 and 2002, using a standardised questionnaire covering demographics, general health, relationships, and sexual behaviours, attitudes and beliefs. A total of 1,500 individuals in Germany (750 men and 750 women) completed the survey. Eighty-six percent of men and 66% of women had engaged in sexual intercourse during the year preceding the interview. The most common male sexual problems were early ejaculation (15%), a lack of sexual interest, erectile dysfunction and non-pleasurable sex (each 8%). The most common female sexual problems were a lack of sexual interest (18%), non-pleasurable sex (14%) and lubrication difficulties (13%). Most sexual problems were less common among men and women in Germany than in other European regions. Increasing age was a significant predictor of a lack of sexual interest and erectile difficulties in men. Only 18% of men and 15% of women had talked to a doctor about their sexual problem(s). In conclusion, many middle-aged and older German adults reported continued sexual interest and activity. Overall, sexual problems were less prevalent in Germany compared with other European regions. Of those who experienced sexual problems, however, few had sought medical help. This was often due to a lack of perception of a problem.

Proteoglycans in the nervous system--the quest for functional roles in vivo.

Large numbers of different proteoglycans are expressed in tightly regulated spatio-temporal patterns by both the nerve cells (neurons) and the supporting glial cells of the nervous system. Several of these proteoglycans have been shown by studies in vitro to affect the migration of neural precursor cells, the elongation and pathfinding of neurites and the formation and stabilization of synapses. Such processes are important for the accurate wiring of the nervous system, and so it has been postulated that proteoglycans play an essential role during neural development. However, with few exceptions, the phenotypes of null mutations in mice and some human genetic diseases have provided little support for this view. Here we will review recent data from both in vitro and in vivo studies analyzing the function of proteoglycans in the nervous system in order to provide possible explanations for their apparent lack of function.