[Improved patient safety through a clinical decision support system in laboratory medicine]. / Verbesserte Patientensicherheit durch "clinical decision support systems" in der Labormedizin.

BACKGROUND: Laboratory diagnostics are essential for diagnosis, initiation of therapy, and monitoring of patients. Laboratory results that are overlooked or incorrectly interpreted lead to adverse events and endanger patient safety. Clinical decision support systems (CDSSs) may facilitate appropriate interpretation of results and subsequent medical response. OBJECTIVES: The research project on digital laboratory medicine (AMPEL) aims at developing a CDSS based on laboratory diagnostics, which supports practitioners in ensuring the necessary medical consequences. MATERIALS AND METHODS: A literature review of CDSSs describes the current state of research. The research project AMPEL is presented with its objectives, challenges, and first results. Furthermore, the development of a framework and reporting system is illustrated through the clinical example of severe hypokalemia. RESULTS AND CONCLUSION: Through interdisciplinary development and constant optimization, a specific CDSS with high acceptance among clinicians was developed. Initial results in the case of severe hypokalemia show a positive effect on patient care. Thereby, more complex frameworks such as sepsis diagnostics or acute coronary syndrome are implemented. The limited availability of standardized and digital clinical data is challenging. In addition to the application of classic decision trees in CDSS, the use of machine learning offers a promising perspective for future developments.

Recurrent ischaemic cerebrovascular events as presenting manifestations of myeloproliferative neoplasms.

BACKGROUND AND PURPOSE: Myeloproliferative neoplasms (MPNs) - polycythemia vera, essential thrombocythemia and primary myelofibrosis - are associated with increased risk for ischaemic cerebrovascular events (ICVEs). Due to their low prevalence, MPNs often remain undiagnosed as the cause of ICVEs. METHODS: Case records at the University of Tübingen between 2014 and 2017 were screened to identify patients with MPN-related ICVEs. Clinical features, brain imaging, laboratory findings, applied treatments and neurological outcomes were assessed. RESULTS: In all, 3318 patients with ICVEs were identified, and amongst them 17 patients with MPN-related ICVEs were included in a retrospective study. In 58% of these patients, ICVEs were the first manifestation of the underlying MPN; 24% presented with transient ischaemic attack and 76% with ischaemic stroke. Potentially concurrent ICVE etiologies were noted in 70% of the patients. The majority (94%) of patients were positive for the JAK2 V617F mutation, whilst in 29% recurrent ICVEs (range two to three) were noted prior to MPN diagnosis. Early MPN diagnosis and management was the only significant prognostic factor for ICVE recurrence (P < 0.001). DISCUSSION: Evidence is provided that, although rare, MPNs represent an underdiagnosed cause of recurrent ICVEs. High clinical awareness is warranted to identify an underlying MPN in patients presenting with sustained, abnormal blood count findings. Clinical algorithms for prompt MPN diagnosis and initiation of MPN treatment (e.g. cytoreductive therapy, phlebotomy) are required. As MPN management comprises a significant protective factor against ICVE recurrence, induction of MPN treatment should be regarded as an integral component of secondary stroke prevention in MPN-associated ICVEs.

[Follicular penetration of nanocarriers is an important penetration pathway for topically applied drugs]. / Bedeutung des follikulären Penetrationswegs für den Wirkstofftransport mittels Nanocarriern.

BACKGROUND: The hair follicle represents a significant penetration route for topically applied substances. ISSUE: The percutaneous absorption of substances can be significantly increased and accelerated by the involvement of hair follicles. In addition, nanoparticles have the characteristic to penetrate deeply and effectively into the hair follicles. MATERIALS AND METHODS: An optimization of drug delivery for topically applied substances is possible if the nanoparticles act solely as a carrier to transport active ingredients into the hair follicle. Once the nanocarrier has penetrated into the hair follicle, the active substance must be released there. This can be triggered by various mechanisms. RESULTS: The released drug can thus pass into the living tissue surrounding the hair follicle independently. With the help of this innovative strategy, the bioavailability of topically applied substances can be significantly improved. CONCLUSION: The transport of active ingredients into the hair follicles with the help of particles and the release of active substances there is a very effective new method for transporting active substances through the skin barrier.

Gestational chronodisruption leads to persistent changes in the rat fetal and adult adrenal clock and function.

KEY POINTS: Light at night is essential to a 24/7 society, but it has negative consequences on health. Basically, light at night induces an alteration of our biological clocks, known as chronodisruption, with effects even when this occurs during pregnancy. Here we explored the developmental impact of gestational chronodisruption (chronic photoperiod shift, CPS) on adult and fetal adrenal biorhythms and function. We found that gestational chronodisruption altered fetal and adult adrenal function, at the molecular, morphological and physiological levels. The differences between control and CPS offspring suggest desynchronization of the adrenal circadian clock and steroidogenic pathway, leading to abnormal stress responses and metabolic adaptation, potentially increasing the risk of developing chronic diseases. ABSTRACT: Light at night is essential to a 24/7 society, but it has negative consequences on health. Basically, light at night induces an alteration of our biological clocks, known as chronodisruption, with effects even when this occurs during pregnancy. Indeed, an abnormal photoperiod during gestation alters fetal development, inducing long-term effects on the offspring. Accordingly, we carried out a longitudinal study in rats, exploring the impact of gestational chronodisruption on the adrenal biorhythms and function of the offspring. Adult rats (90 days old) gestated under chronic photoperiod shift (CPS) decrease the time spent in the open arm zone of an elevated plus maze to 62% and increase the rearing time to 170%. CPS adults maintained individual daily changes in corticosterone, but their acrophases were distributed from 12.00 h to 06.00 h. CPS offspring maintained clock gene expression and oscillation, nevertheless no daily rhythm was observed in genes involved in the regulation and synthesis of steroids. Consistent with adult adrenal gland being programmed during fetal life, blunted daily rhythms of corticosterone, core clock gene machinery, and steroidogenic genes were observed in CPS fetal adrenal glands. Comparisons of the global transcriptome of CPS versus control fetal adrenal gland revealed that 1078 genes were differentially expressed (641 down-regulated and 437 up-regulated). In silico analysis revealed significant changes in Lipid Metabolism, Small Molecule Biochemistry, Cellular Development and the Inflammatory Response pathway (z score: 48-20). Altogether, the present results demonstrate that gestational chronodisruption changed fetal and adult adrenal function. This could translate to long-term abnormal stress responses and metabolic adaptation, increasing the risk of developing chronic diseases.

TDM-controlled ring resonator arrays for fast, fixed-wavelength optical biosensing.

A novel control concept for serial ring resonator arrays based on a time-division multiplex (TDM) approach is presented. It allows fast sampling rates in terms of biological kinetics. The novelty consists of using both thermal tuning of the effective refractive index and thermo-optical multiplexing for the silicon-on-insulator (SOI) ring resonator arrays, without the need for a tunable laser source. Using a fixed wavelength, fast read-out rates of 100 Hz are demonstrated for each ring.

Sublingual immunotherapy provides long-term relief in allergic rhinitis and reduces the risk of asthma: A retrospective, real-world database analysis.

BACKGROUND: Allergy immunotherapy (AIT) is the only treatment for allergic rhinitis (AR) and/or allergic asthma (AA) with long-term efficacy. However, there are few real-life data on the progression of AR and/or AA in patients receiving AIT. OBJECTIVES: To assess the real-world, long-term efficacy of grass pollen sublingual immunotherapy (SLIT) tablets in AR and their impact on asthma onset and progression. METHODS: In a retrospective analysis of a German longitudinal prescription database, AR patients treated with grass pollen SLIT tablets were compared with a control group not having received AIT. Multiple regression analysis was used to compare changes over time in rescue symptomatic AR medication use after treatment cessation, asthma medication use, and the time to asthma onset in the two groups. RESULTS: After applying all selection criteria, 2851 SLIT and 71 275 control patients were selected for the study. After treatment cessation, AR medication use was 18.8 percentage points lower (after adjustment for covariates, and relative to the pretreatment period) in SLIT tablet group than in the non-AIT group (P<.001). Asthma onset was less frequent in SLIT tablet group than in non-AIT group (odds ratio: 0.696, P=.002), and time to asthma was significantly longer (hazard ratio: 0.523; P=.003). After SLIT cessation, asthma medication use fell by an additional 16.7 percentage points (relative to the pretreatment period) in the SLIT tablet group vs the non-AIT group (P=.004). CONCLUSIONS: Real-world treatment of AR patients with grass pollen SLIT tablets was associated with slower AR progression, less frequent asthma onset, and slower asthma progression.

Whole-heart 4D flow cardiac magnetic resonance in healthy dogs.

INTRODUCTION: In cardiac magnetic resonance imaging (CMR), accurate flow measurements rely on perpendicular plane-alignment with flow direction. For 2D phase contrast (PC) cardiac magnetic resonance measurements, planes have to be defined during the examination of the heart, which is time consuming and error-prone. Collection of flow information of the entire volume of the heart by a 4D flow CMR postpones plane alignment to post-processing. Sampling of such a large amount of data requires acceleration of data acquisition with techniques such as SENSitivity Encoding (k-t SENSE) or Broad-use Linear Acquisition Speed-up Technique (k-t BLAST). Objectives of the study were to compare 4D flow CMR, accelerated with two different acceleration methods with the established 2D PC CMR based on assessment of stroke volume at all four cardiac valves. The values of stroke volume acquired with the 4D flow CMR SENSE did not differ significantly when compared to the 2D PC CMR SENSE at the left side of the heart (aortic and mitral valve). Significant differences between the techniques were seen at the pulmonic and tricuspid valves. Acceleration with k-t BLAST revealed significantly lower values of stroke volume at all cardiac valves, except at the mitral valve.

INTRODUCTION: Lors d'examens cardiaques par résonnance magnétique (CMR), le plan pour des mesures de flux précises doit être défini perpendiculairement à la direction de flux sanguin. Dans la CMR en contraste de phases 2D (PC), le choix de ce plan se fait durant l'examen, ce qui prend du temps et peut être sujet à des problèmes. Avec la mesure de toutes les données relatives au flux sanguin dans l'ensemble du coeur au moyen d'un 4D flow CMR, on déplace le moment de ce choix dans la phase de traitement des données. La collecte d'une quantité aussi élevée de données nécessite une accélération de la technique de mesures comme par exemple SENSitivity Encoding (k-t SENSE) ou Broad-use Linear Acquisition Speed-up Technique (k-t BLAST). Le but de cette étude était de comparer la CMR 4D, accélérée avec deux méthodes différentes avec la CMR 2D bien établie, ceci sur la base de la détermination du volume d'éjection systolique au niveau des quatre valvules cardiaques. Les valeurs du volume d'éjection pour le coeur gauche (valvules aortiques et mitrales) obtenues par 4D flow CMR k-t SENSE n'étaient pas significativement différentes de celles obtenues par 2D PC CMR k-t SENSE. Par contre, des différences significatives entre les deux techniques étaient constatées au niveau des valvules pulmonaires et tricuspid. L'accélération par k-t-BLAST donnait de façon générale des valeurs du volume d'élection plus basses au niveau de toutes les valvules, à l'exception de la valvule mitrale.

Femtosecond laser cutting of human corneas for the subbasal nerve plexus evaluation.

Assessment of various morphological parameters of the corneal subbasal nerve plexus is a valuable method of documenting the structural and presumably functional integrity of the corneal innervation in health and disease. The aim of this work is to establish a rapid, reliable and reproducible method for visualization of the human corneal SBP using femtosecond laser cut corneal tissue sections. Trephined healthy corneal buttons were fixed and processed using TissueSurgeon-a femtosecond laser based microtome, to obtain thick tissue sections of the corneal epithelium and anterior stroma cut parallel to the ocular surface within approximately 15 min. A near infrared femtosecond laser was focused on to the cornea approximately 70-90 µm from the anterior surface to induce material separation using TissueSurgeon. The obtained corneal sections were stained following standard immunohistochemical procedures with anti-neuronal ß-III tubulin antibody for visualization of the corneal nerves. Sections that contained the epithelium and approximately 20-30 µm of anterior stroma yielded excellent visualisation of the SBP with minimal optical interference from underlying stromal nerves. In conclusion, the results of this study have demonstrated that femtosecond laser cutting of the human cornea offers greater speed, ease and reliability than standard tissue preparation methods for obtaining high quality thick sections of the anterior cornea cut parallel to the ocular surface.

Meningitis and Bacteremia Due to Neisseria cinerea following a Percutaneous Rhizotomy of the Trigeminal Ganglion.

Neisseria cinerea is a human commensal. The first known case of meningitis and bacteremia due to Neisseria cinerea following percutaneous glycerol instillation of the trigeminal ganglion is reported. Conventional phenotypic methods and complete 16S RNA gene sequencing accurately identified the pathogen. Difficulties in differentiation from pathogenic neisseriae are discussed.

Can Routine Imaging After Neoadjuvant Chemotherapy in Breast Cancer Predict Pathologic Complete Response?

BACKGROUND: This study evaluated breast imaging procedures for predicting pathologic complete response (pCR = ypT0) after neoadjuvant chemotherapy (NACT) for breast cancer to challenge surgery as a diagnostic procedure after NACT. METHODS: This retrospective, exploratory, monocenter study included 150 invasive breast cancers treated by NACT. The patients received magnetic resonance imaging (MRI), mammography (MGR), and ultrasound (US). The results were classified in three response subgroups according to response evaluation criteria in solid tumors. To incorporate specific features of MRI and MGR, an additional category [clinical near complete response (near-cCR)] was defined. Residual cancer in imaging and pathology was defined as a positive result. Negative predictive values (NPVs), false-negative rates (FNRs), and false-positive rates (FPRs) of all imaging procedures were analyzed for the whole cohort and for triple-negative (TN), HER2-positive (HER2+), and HER2-negative/hormone-receptor-positive (HER2-/HR+) cancers, respectively. RESULTS: In 46 cases (31%), pCR (ypT0) was achieved. Clinical complete response (cCR) and near-cCR showed nearly the same NPVs and FNRs. The NPV was highest with 61% for near-cCR in MRI and lowest with 44% for near-cCR in MGR for the whole cohort. The FNRs ranged from 4 to 25% according to different imaging methods. The MRI performance seemed to be superior, especially in TN cancers (NPV 94%; FNR 5%). The lowest FPR was 10 % in MRI, and the highest FPR was 44% in US. CONCLUSION: Neither MRI nor MGR or US can diagnose a pCR (ypT0) with sufficient accuracy to replace pathologic diagnosis of the surgical excision specimen.

Trapezius muscle activity increases during near work activity regardless of accommodation/vergence demand level.

AIM: To investigate if trapezius muscle activity increases over time during visually demanding near work. METHODS: The vision task consisted of sustained focusing on a contrast-varying black and white Gabor grating. Sixty-six participants with a median age of 38 (range 19-47) fixated the grating from a distance of 65 cm (1.5 D) during four counterbalanced 7-min periods: binocularly through -3.5 D lenses, and monocularly through -3.5 D, 0 D and +3.5 D. Accommodation, heart rate variability and trapezius muscle activity were recorded in parallel. RESULTS: General estimating equation analyses showed that trapezius muscle activity increased significantly over time in all four lens conditions. A concurrent effect of accommodation response on trapezius muscle activity was observed with the minus lenses irrespective of whether incongruence between accommodation and convergence was present or not. CONCLUSIONS: Trapezius muscle activity increased significantly over time during the near work task. The increase in muscle activity over time may be caused by an increased need of mental effort and visual attention to maintain performance during the visual tasks to counteract mental fatigue.

Clinical use of cold atmospheric pressure argon plasma in chronic leg ulcers: A pilot study.

OBJECTIVE: In the age of multiresistant microbes and the increasing lack of efficient antibiotics, conventional antiseptics play a critical role in the prevention and therapy of wound infections. Recent studies have demonstrated the antiseptic effects of cold atmospheric pressure plasma (APP). In this pilot, study we investigate the overall suitability of one of the first APP sources for wound treatment focusing on its potential antimicrobial effects. METHOD: The wound closure rate and the bacterial colonisation of the wounds were investigated. Patients suffering from chronic leg ulcers were treated in a clinical controlled monocentric trial with either APP or octenidine (OCT). In patients who presented with more than one ulceration in different locations, one was treated with APP and the other one with OCT. Each group was treated three times a week over a period of two weeks. The antimicrobial efficacy was evaluated immediately after and following two weeks of treatment. RESULTS: Wounds treated with OCT showed a significantly higher microbial reduction (64%) compared to wounds treated with APP (47%) immediately after the treatment. Over two weeks of antiseptic treatment the bacterial density was reduced within the OCT group (-35%) compared to a slight increase in bacterial density in the APP-treated group (+12%). Clinically, there were no signs of delayed wound healing observed in either group and both treatments were well tolerated. CONCLUSION: The immediate antimicrobial effects of the APP prototype source were almost comparable to OCT without any signs of cytotoxicity. This pilot study is limited by current configurations of the plasma source, where the narrow plasma beam made it difficult to cover larger wound surface areas and in order to avoid untreated areas of the wound bed, smaller wounds were assigned to the APP-treatment group. This limits the significance of AAP-related effects on the wound healing dynamics, as smaller wounds tend to heal faster than larger wounds. However, clinical wound healing studies on a larger scale now seem justifiable. A more advanced plasma source prototype allowing the treatment of larger wounds will address APP's influence on healing dynamics, synergetic treatment with current antiseptics and effects on multiresistant bacteria.

Effects of grazer presence on genetic structure of a phenotypically diverse diatom population.

Studies of predator-prey systems in both aquatic and terrestrial environments have shown that grazers structure the intraspecific diversity of prey species, given that the prey populations are phenotypically variable. Populations of phytoplankton have traditionally considered comprising only low intraspecific variation, hence selective grazing as a potentially structuring factor of both genetic and phenotypic diversity has not been comprehensively studied. In this study, we compared strain specific growth rates, production of polyunsaturated aldehydes, and chain length of the marine diatom Skeletonema marinoi in both grazer and non-grazer conditions by conducting monoclonal experiments. Additionally, a mesocosm experiment was performed with multiclonal experimental S. marinoi populations exposed to grazers at different levels of copepod concentration to test effects of grazer presence on diatom diversity in close to natural conditions. Our results show that distinct genotypes of a geographically restricted population exhibit variable phenotypic traits relevant to grazing interactions such as chain length and growth rates. Grazer presence affected clonal richness and evenness of multiclonal Skeletonema populations in the mesocosms, likely in conjunction with intrinsic interactions among the diatom strains. Only the production of polyunsaturated aldehydes was not affected by grazer presence. Our findings suggest that grazing can be an important factor structuring diatom population diversity in the sea and emphasize the importance of considering clonal differences when characterizing species and their role in nature.

House dust mite immunotherapy: A real-world, prescription data-based analysis.

BACKGROUND: House dust mite (HDM) sensitisation can contribute to the development of allergic rhinoconjunctivitis (AR) or allergic asthma (AA). As treatment, allergen immunotherapy (AIT) is a promising approach, since it aims building immunotolerance against allergens, therewith establishing long-term efficacy. The evaluation of AIT has been investigated in many randomised controlled trials, whereas few real-world evidence studies are available. METHODS: We used data from the longitudinal prescription data base IQVIA™ LRx. Data on initial AIT prescriptions against HDM from January 2009 to December 2013 was analysed regarding treatment (subcutaneous AIT with either depigmented polymerised allergen extract [dSCIT] or other allergens [oSCIT], or sublingual immunotherapy [SLIT]) and treatment duration. Treatment groups were compared with a control group of AR patients not receiving AIT. Data on symptomatic medication was collected until February 2017 and progression of AR and AA was compared. RESULTS: Data of 7260 patients with AIT prescriptions and of 21,780 control patients was analysed. AIT was associated with a significant decrease of AR medication intake compared with control (dSCIT: -34.0%, p < 0.0001; oSCIT: -25.7%, p < 0.0001; SLIT: -37.7%, p = 0.0026). In asthmatics, SCIT was associated with a significant decrease of asthma medication compared with control (dSCIT: -45.2%, p < 0.0001; oSCIT: -32.9%, p < 0.0001). Further, a significantly reduced likelihood for onset of asthma medication was demonstrated in patients treated with SCIT compared with controls (dSCIT OR: 0.759, p = 0.0476; oSCIT OR: 0.815, p = 0.0339). CONCLUSION: Real-world data analyses indicate that AIT, particularly given via a subcutaneous route, reduces the need of medication against AR and AA and might delay the onset of asthma medication in patients with AR.

Frequency modulation spectroscopy with a THz quantum-cascade laser.

We report on a terahertz spectrometer for high-resolution molecular spectroscopy based on a quantum-cascade laser. High-frequency modulation (up to 50 MHz) of the laser driving current produces a simultaneous modulation of the frequency and amplitude of the laser output. The modulation generates sidebands, which are symmetrically positioned with respect to the laser carrier frequency. The molecular transition is probed by scanning the sidebands across it. In this way, the absorption and the dispersion caused by the molecular transition are measured. The signals are modeled by taking into account the simultaneous modulation of the frequency and amplitude of the laser emission. This allows for the determination of the strength of the frequency as well as amplitude modulation of the laser and of molecular parameters such as pressure broadening.

Drug delivery with topically applied nanoparticles: science fiction or reality.

The efficacy of topically applied drugs is determined by their action mechanism and their potential capacity of passing the skin barrier. Nanoparticles are assumed to be efficient carrier systems for drug delivery through the skin barrier. For flexible nanoparticles like liposomes, this effect has been well demonstrated. The penetration properties of solid nanoparticles are currently under intensive investigation. The crucial advantage of nanoparticles over non-particulate substances is their capability to penetrate deeply into the hair follicles where they can be stored for several days. There is no evidence, yet, that solid particles ≥40 nm are capable of passing through the healthy skin barrier. Therefore and in spite of the long-standing research efforts in this field, commercially available solid nanoparticle-based products for drug delivery through the healthy skin are still missing. Nevertheless, the prospects for the clinical use of nanoparticles in drug delivery are tremendous. They can be designed as transport systems delivering drugs efficiently into the hair follicles in the vicinity of specific target structures. Once deposited at these structures, specific signals might trigger the release of the drugs and exert their effects on the target cells. In this article, examples of such triggered drug release are presented.

[Development of epidural spinal cord stimulation. Fortieth anniversary of the first implantation in Germany]. / Entwicklung der epiduralen Rückenmarkstimulation. 40 Jahre seit der Erstimplantation in Deutschland.

Spinal cord stimulation is nowadays an established therapy for various neuropathic and vasculopathic pain syndromes after more conservative measures have failed. However, 40 years ago, only 5 years after the first worldwide implantation in the US, this therapy was promoted in Germany. In 1972, the first devices were implanted in the Departments of Neurosurgery at the Universities Hannover and Freiburg. These pioneering efforts and the establishment of the therapy are intimately associated with three names: Jörg-Ulrich Krainick, Uwe Thoden, and Wolfhard Winkelmüller. Nowadays about 1700 spinal cord stimulation systems are implanted annually in Germany. The development of spinal cord stimulation from the beginnings up to now taking into special consideration the early years in Germany are presented.

Ascorbate prevents placental oxidative stress and enhances birth weight in hypoxic pregnancy in rats.

This study isolated the effects of maternal hypoxia independent of changes in maternal nutrition on maternal circulatory and placental molecular indices of oxidative stress and determined whether maternal antioxidant treatment conferred protection. Pregnant rats were subjected to normoxic pregnancy or 13% O2 chronic hypoxia for most of gestation with and without maternal treatment with vitamin C in the drinking water. Maternal hypoxia with and without vitamin C did not affect maternal food or water intake and led to a significant increase in maternal and fetal haematocrit. At gestational day 20, maternal plasma urate and L-cysteine concentrations, and placental levels of 4-hydroxynonenal and heat shock protein 70 were increased while placental heat shock protein 90 levels were decreased in hypoxic pregnancy. The induction of maternal circulatory and placental molecular indices of oxidative stress in hypoxic pregnancies was prevented by maternal treatment with vitamin C. Maternal hypoxia during pregnancy with or without vitamin C increased placental weight, but not total or compartmental volumes. Maternal treatment with vitamin C increased birth weight in both hypoxic and normoxic pregnancies. The data show that maternal hypoxia independent of maternal undernutrition promotes maternal and placental indices of oxidative stress, effects that can be prevented by maternal treatment with vitamin C in hypoxic pregnancy. While vitamin C may not be the ideal candidate of choice for therapy in pregnant women, and taking into consideration differences in ascorbic acid metabolism between rats and humans, the data do underlie that antioxidant treatment may provide a useful intervention to improve placental function and protect fetal growth in pregnancy complicated by fetal hypoxia.

5-year continence rates, satisfaction and adverse events of burch urethropexy and fascial sling surgery for urinary incontinence.

PURPOSE: We characterized continence, satisfaction and adverse events in women at least 5 years after Burch urethropexy or fascial sling with longitudinal followup of randomized clinical trial participants. MATERIALS AND METHODS: Of 655 women who participated in a randomized surgical trial comparing the efficacy of the Burch and sling treatments 482 (73.6%) enrolled in this long-term observational study. Urinary continence status was assessed yearly for a minimum of 5 years postoperatively. Continence was defined as no urinary leakage on a 3-day voiding diary, and no self-reported stress incontinence symptoms and no stress incontinence surgical re-treatment. RESULTS: Incontinent participants were more likely to enroll in the followup study than continent patients (85.5% vs 52.2%) regardless of surgical group (p<0.0001). Overall the continence rates were lower in the Burch urethropexy group than in the fascial sling group (p=0.002). The continence rates at 5 years were 24.1% (95% CI 18.5 to 29.7) vs 30.8% (95% CI 24.7 to 36.9), respectively. Satisfaction at 5 years was related to continence status and was higher in women undergoing sling surgery (83% vs 73%, p=0.04). Satisfaction decreased with time (p=0.001) and remained higher in the sling group (p=0.03). The 2 groups had similar adverse event rates (Burch 10% vs sling 9%) and similar numbers of participants with adverse events (Burch 23 vs sling 22). CONCLUSIONS: Continence rates in both groups decreased substantially during 5 years, yet most women reported satisfaction with their continence status. Satisfaction was higher in continent women and in those who underwent fascial sling surgery, despite the voiding dysfunction associated with this procedure.

Mistletoes and mutant albino shoots on woody plants as mineral nutrient traps.

BACKGROUND AND AIMS: Potassium, sulphur and zinc contents of mistletoe leaves are generally higher than in their hosts. This is attributed to the fact that chemical elements which are cycled between xylem and phloem in the process of phloem loading of sugars are trapped in the mistletoe, because these parasites do not feed their hosts. Here it is hypothesized that mutant albino shoots on otherwise green plants should behave similarly, because they lack photosynthesis and thus cannot recycle elements involved in sugar loading. METHODS: The mineral nutrition of the mistletoe Scurrula elata was compared with that of albino shoots on Citrus sinensis and Nerium oleander. The potential for selective nutrient uptake by the mistletoe was studied by comparing element contents of host leaves on infected and uninfected branches and by manipulation of the haustorium-shoot ratio in mistletoes. Phloem anatomy of albino leaves was compared with that of green leaves. KEY RESULTS: Both mistletoes and albino leaves had higher contents of potassium, sulphur and zinc than hosts or green leaves, respectively. Hypothetical discrimination of nutrient elements during the uptake by the haustorium is not supported by our data. Anatomical studies of albino leaves showed characteristics of release phloem. CONCLUSIONS: Both albino shoots and mistletoes are traps for elements normally recycled between xylem and phloem, because retranslocation of phloem mobile elements into the mother plant or the host is low or absent. It can be assumed that the lack of photosynthetic activity in albino shoots and thus of sugars needed in phloem loading is responsible for the accumulation of elements. The absence of phloem loading is reflected in phloem anatomy of these abnormal shoots. In mistletoes the evolution of a parasitic lifestyle has obviously eliminated substantial feeding of the host with photosynthates produced by the mistletoe.