Dynamics of fertility impairment and recovery after allogeneic haematopoietic stem cell transplantation in childhood and adolescence: results from a longitudinal study.

PURPOSE: Fertility impairment and recovery after haematopoietic stem cell transplantation (HSCT) have been reported in both sexes, but little is known about how they develop over time. Our aim was to describe the dynamics of fertility impairment and recovery after HSCT. METHODS: We retrieved treatment and fertility data for up to 12 years of 361 paediatric patients with malignant and non-malignant diseases from seven European centres. The patients had been treated with allogeneic HSCT between 2000 and 2005. RESULTS: Development of fertility impairment was observed in males (123/217, 56%) after a median time of 2.6 years (range 0.1-11.4) and in females (82/144, 57%) after 2.3 years (range 0.1-12.0) after HSCT. Different busulfan dosages had only a slight impact on the onset of fertility impairment (busulfan ≥ 16 mg/kg with a median time to fertility impairment of 2.9 vs. 3.9 years after busulfan <14 mg/kg). Recovery from fertility impairment was observed in 17 participants after a median time of 4.1 years (range 1-10.6) in females (10/144, 7%) and 2.0 years (range 1-6.3) in males (7/217, 3 %) after fertility impairment first appeared. CONCLUSIONS: In the light of the dynamics of fertility impairment and recovery in the HSCT patients reviewed, these patients should be counselled comprehensively regarding fertility preservation measures.

Efficacy of systemic therapies for moderate-to-severe psoriasis: a systematic review and meta-analysis of long-term treatment.

BACKGROUND: Despite the chronicity of psoriasis, most systematic reviews focus on short-term treatment. METHODS: The systematic search strategy and results from the German Psoriasis Guidelines were adapted. To update the data a literature search in Medline, Embase and the Cochrane Library was conducted. The proportion of participants achieving ≥75% decrease in Psoriasis Area and Severity Index (PASI) as well as Dermatology Life Quality Index (DLQI) reduction at different time points were assessed. Trials were summarized with respect to time periods and study designs. Suitable trials were included in a meta-analysis. Particular attention was paid to statistical approaches of handling dropouts. RESULTS: A total of 33 articles including 27 trials totaling 6575 patients with active treatment were included in the systematic review. Seven randomized controlled trials were eligible for the meta-analysis. Over a 24 week treatment period infliximab [risk difference (RD) 78%, 95% confidence interval (CI) 72-83%] and ustekinumab 90 mg every 12 weeks (RD 77%, 95% CI 71-83%) were the most efficacious treatments. Adalimumab (RD: 60%, 95% CI 45-74%) showed results within the range of different etanercept dosages (etanercept 50 mg once weekly: RD 62%, 95% CI, 52-72%), (etanercept 25 mg twice weekly: RD 45%, 95% CI 34-56%), (etanercept 50 mg twice weekly: RD 56%, 95% CI 49-62%) and (etanercept 50 mg twice weekly until week 12, then 25 mg twice weekly: RD 50%, 95% CI 42-57%). After 24 weeks a decrease in efficacy for inflximab, adalimumab and etanercept was observed. CONCLUSIONS: More sufficient data is required to draw reliable conclusions in extended long-term treatment and head-to-head comparisons are necessary.

Do guidelines change the way we treat? Studying prescription behaviour among private practitioners before and after the publication of the German Psoriasis Guidelines.

Evidence-based psoriasis treatment guidelines may help physicians overcome uncertainties in initiating and monitoring systemic treatment and have thus been suggested as a tool for improving the care provided to psoriasis patients. A prospective cohort study of dermatologists' prescription behaviour was performed with two consecutive documentation periods (before and after the publication of the guidelines). 49 dermatologists were asked to provide continuous documentation of their treatment choices for patients with psoriasis by filling in a standardised documentation form. In addition, a questionnaire consisting of eight items was used to assess familiarity with, attitudes towards, and the impact of the psoriasis guidelines on the participating dermatologists. 49 dermatologists documented their treatment choices during 4,491 patient visits before and 4,120 visits after the publication of the German national psoriasis treatment guidelines. The average proportion of prescribed systemic treatments for patients with moderate to severe psoriasis increased from 31 to 35% after the guidelines were published. 80% of the participants stated that the guidelines had led to changes in their treatment decisions, whereas only 20% stated that the guidelines had had no impact in this regard. All but one participant considered the guidelines "useful" or "very useful". The results of the study show that guidelines can be an important tool for improving the quality of care provided to patients with psoriasis.

[Influence of different head-trunk positions to the upbeat-nystagmus]. / Einfluss der Kopf-Rumpf-Positionsänderung auf den Upbeat-Nystagmus.

The neck torsion test (NTT) can be used to evaluate the cervico-ocular reflex (COR). We think there are two main reasons why NRT has failed to gain general acceptance in clinical practice: the test does not fully exploit the somatosensory examination potential, and electronystagmography has been most commonly used but is inferior to videonystagmography for a very low-amplitude nystagmus. These considerations have led us to develop a modified neck torsion test (mNTT) with three-dimensional video-oculographic (3D-VOG) recording. Sensors on the video glasses enable three-dimensional and continuous registration of the head position. Horizontal, vertical and rotatory eye movements are determined in six different head-body positions (right/left head tilt, ante/retroflexion of the head, and right/left body rotation). The basis for assessing the mNTT is described in detail. We used the mNTT to examine prospectively compensated, vestibularly deficient (n = 52), and cervically deficient (n = 93) patients with vertigo against a control group (n = 22). Our results show that upbeat-nystagmus (UBN) significantly differentiated the groups. This occurs most frequently in the tonic analysis phase of head inclination and reclination. UBN is differential-diagnostically discussed on the basis of these examination findings, and its cervical origin is elucidated with the aid of model conceptions. We conclude that our modified NRT is an improved instrument for COR determination. A suspected cervical somatosensory reduction warrants testing particularly for UBN.

[Cervicoproprioceptive provocation of horizontal and vertical nystagmus in test subjects]. / Zervikopropriozeptive Provokation von horizontalen und vertikalen Nystagmen bei Probanden.

BACKGROUND: The cervico-ocular reflex (COR) has been confirmed in numerous animal experiments. On the other hand, its clinical assessment is disputed. Anteflexion and retroflexion of the head are among the main movements of the atlanto-occipital joint. We investigated whether these head movements produce neck proprioceptive stimulation in the vestibular system. SUBJECTS AND METHOD: We investigated 50 students under the experimental conditions of strictly cervical provocation. The trunk was rotated, anteflexed, and retroflexed into its end positions for 60 s under video-oculographic control without changing the head-space relationship. During the cervical provocation, horizontal, vertical, or rotational nystagmus within a time window of 5-30 s after the start of the provocation was detected as a target parameter. RESULTS: The results showed that, compared to the baseline, there was a significant increase in vertical and horizontal nystagmus after the cervical provocation. The horizontal nystagmus reaction, rather than the vertical, was increased significantly by the maximum trunk rotation. In addition, we found a significant amount of vertical rather than horizontal nystagmus under trunk flexion provocation. CONCLUSION: Under cervical provocation of test subjects, we were able to elicit horizontal and vertical nystagmus (upbeat nystagmus) via cervico-ocular roots. Due to a neck proprioceptive activation of the vestibular system we interpret our result as a "cervico-tonic provocation nystagmus".

Influence of azithromycin and clarithromycin on macrolide susceptibility of viridans streptococci from the oral cavity of healthy volunteers.

Oral viridans streptococci are a reservoir of resistance genes for pathogens. Through prolonged exposure, long-acting macrolides (e.g., azithromycin) may induce the resistance of the commensals to macrolides more frequently than macrolides with a shorter half-life (e.g., clarithromycin). In a prospective, randomized, evaluator-blinded trial in healthy volunteers receiving standard courses of either azithromycin (n = 20) or clarithromycin (n = 20), we compared the susceptibility of oral viridans streptococci to macrolides over a period of 12 weeks. There was a significant temporal increase in the numbers of resistant isolates in both groups (p < 0.0005 at week 1). The proportion of macrolide-resistant isolates over time was significantly higher following azithromycin treatment (p = 0.0005), but returned to baseline values until week 12 in both groups. Temporal differential effects of azithromycin and clarithromycin on the induction of resistance were observed and need to be investigated regarding their effect on co-colonizing pathogens.

Thymic adult T-cell acute lymphoblastic leukemia stratified in standard- and high-risk group by aberrant HOX11L2 expression: experience of the German multicenter ALL study group.

Adult T-cell acute lymphoblastic leukemia (T-ALL) continues to represent an unfavorable disease. Molecularly based treatment stratifications could help improve outcome. The prognostic impact of HOX11 and HOX11L2 expression has been an area of controversy. We have investigated 286 adult T-ALL patients enrolled into the German Multicenter ALL (GMALL) therapy protocols by comparative real-time RT-PCR. High HOX11 expression and HOX11L2 expression were predominantly seen in thymic T-ALL (P

[Investigations concerning the head-trunk-coordination]. / Untersuchungen zur Kopf-Körper-Koordination.

BACKGROUND: In the assessment of vertigo patients with suspected cervicocephalic somatosensory deficit, the studies published thus far have focused on reflectory systems like the cervico-ocular reflex or the postural systems. Our study examines the cervicocephalic kinesthetic sensibility of head and body coordination. We therefore introduce two preliminary test series: the "subjective zero chin-knee-angle of the occipital joints" and the "saccadic repositioning during trunk rotation". METHODS: Subjective recordings of dizziness complaints were done using the Dizziness Handicap Inventory. PATIENTS: The study population consisted of 24 patients with palpatory cervicocephalic somatosensory deficit (group I) and 23 patients with a central vestibular compensated unilateral vestibular deficit (group II). Twenty-two healthy patients served as controls. The aim of the study is to provide a detailed examination of the "subjective zero chin-knee-angle of the occipital joints" as well as a detailed discussion of "saccadic repositioning with trunk rotation" by three-dimensional videooculography (3D-VOG). RESULTS: We were able to separate patients with a cervicocephalic somatosensory deficit with the first test procedure and differentiate them from groups II and III. The second test procedure shows a significant difference between groups I and III. CONCLUSION: We conclude from the group difference that the recording of cervicocephalic kinesthetic sensibility is a further indication of disturbed cervical proprioception.