Generation of effective zinc-deficient agar-solidified media allows identification of root morphology changes in response to zinc limitation.

Earlier, we demonstrated that transcript levels of METAL TOLERANCE PROTEIN2 (MTP2) and of HEAVY METAL ATPase2 (HMA2) increase strongly in roots of Arabidopsis upon prolonged zinc (Zn) deficiency and respond to shoot physiological Zn status, and not to the local Zn status in roots. This provided evidence for shoot-to-root communication in the acclimation of plants to Zn deficiency. Zn-deficient soils limit both the yield and quality of agricultural crops and can result in clinically relevant nutritional Zn deficiency in human populations. Implementing Zn deficiency during cultivation of the model plant Arabidopsis thaliana on agar-solidified media is difficult because trace element contaminations are present in almost all commercially available agars. Here, we demonstrate root morphological acclimations to Zn deficiency on agar-solidified medium following the effective removal of contaminants. These advancements allow reproducible phenotyping toward understanding fundamental plant responses to deficiencies of Zn and other essential trace elements.

Regulation of acetylation of plant cell wall components is complex and responds to external stimuli.

Previously, we reported that the allelic de-etiolated by zinc (dez) and trichome birefringence (tbr) mutants exhibit photomorphogenic development in the dark, which is enhanced by high Zn. TRICHOME BIREFRINGENCE-LIKE proteins had been implicated in transferring acetyl groups to various hemicelluloses. Pectin O-acetylation levels were lower in dark-grown dez seedlings than in the wild type. We observed Zn-enhanced photomorphogenesis in the dark also in the reduced wall acetylation 2 (rwa2-3) mutant, which exhibits lowered O-acetylation levels of cell wall macromolecules including pectins and xyloglucans, supporting a role for cell wall macromolecule O-acetylation in the photomorphogenic phenotypes of rwa2-3 and dez. Application of very short oligogalacturonides (vsOGs) restored skotomorphogenesis in dark-grown dez and rwa2-3. Here we demonstrate that in dez, O-acetylation of non-pectin cell wall components, notably of xyloglucan, is enhanced. Our results highlight the complexity of cell wall homeostasis and indicate against an influence of xyloglucan O-acetylation on light-dependent seedling development.

Stressful life events in childhood and allergic sensitization.

Stressful life events evidently have an impact on development of allergic diseases, but the mechanism linking stress to pathological changes of immune system function is still not fully understood. The aim of our study was to investigate the relationship between stressful life events, neuropeptide and cytokine concentrations in children as well as the association between early stressful life events and atopic eczema (AE). Within the LISA plus (Life style - Immune system - Allergy) study, blood samples from children of 6 years of age were analyzed for concentration of the neuropeptides vasoactive intestinal peptide (VIP), somatostatin (SOM), substance P (SP) and the Th1/Th2 cytokines IFN-γ and IL-4. Life events such as severe disease or death of a family member, unemployment or divorce of the parents were assessed with a questionnaire filled in by the parents. Furthermore, lifetime prevalence of AE and incidence after the assessment period of life events were compared. Our data suggest that separation/ divorce of parents increase childrens risk of developing AE later in life. Children with separated/divorced parents showed high VIP levels and high concentrations of the Th2 cytokine IL-4 in their blood. Severe diseases and death of a family member were neither associated with neuropeptide levels nor with cytokine concentrations. Unemployment of the parents was associated with decreased IFN-γ concentrations in childrens blood but not with neuropeptide levels. Thus, the neuropeptide VIP might be a mediator between stressful life events and immune regulation contributing to the Th2-shifted immune response in children with separated/divorced parents.

First report of robot-assisted transperineal fusion versus off-target biopsy in patients undergoing repeat prostate biopsy.

PURPOSE: To clarify the value of targeted versus off-target biopsies in men with a suspicion of prostate cancer (PC) and a visible lesion in multi-parametric magnetic resonance imaging (mpMRI) using transperineal robot-assisted biopsy. METHODS: Fifty-five consecutive men with one non-palpable suspicious lesion in mpMRI after negative 12-core transrectal ultrasound-guided biopsy were enrolled in 2014-2015. Lesions were scored using the Prostate Imaging Reporting and Data System. A robot-assisted system was utilized to collect four robot-assisted targeted transperineal biopsy cores (RA-TB) within the lesion using mpMRI-TRUS elastic fusion. Untargeted transperineal 14-core biopsy was performed only outside the lesion (RA-UB). Histological grade was compared in biopsies and available prostatectomy specimens. RESULTS: Overall, 34 of 55 patients (62%) were diagnosed with PC based on biopsy. 85% of cancers were clinically significant PC (csPC) defined as GS ≥ 7. 85% of biopsy-proven cancers were detected with RA-TB alone. RA-UB identified only one additional patient with csPC and lead to upgrading in five biopsy cases (14.7%). Pathological evaluation of 14 prostatectomy specimens showed upgrading in 2 patients (14.3%), while all other patients were correctly classified by RA-TB without need of additional RA-UB. Mean procedure duration was 43 (±6) min, and only minor complications according to Clavien-Dindo were recorded during 30-day follow-up. CONCLUSIONS: This is the first report of transperineal robot-assisted elastic mpMRI-TRUS fusion biopsy. RA-TB of positive MR lesions enabled reliable detection of csPC, while RA-UB in MRI-negative regions is of minor importance.

The German Infant Nutritional Intervention Study (GINI) for the preventive effect of hydrolyzed infant formulas in infants at high risk for allergic diseases. Design and selected results.

In the complex interaction between certain environmental factors and genetic disposition, the early allergen exposure plays a major role in the development of allergic diseases. In aiming to reduce the allergen burden for the infant at risk during early infancy, cow's milk protein hydrolysate infant formulas (hypoallergenic infant formulas) are appropriate alternatives to breastfeeding for primary allergy prevention. The German Infant Nutritional Intervention-Program (GINI) was supported for the first 3 years by the German Ministry for Education and Research (BMBF) (FKZ 01 EE 9401-4). It is a birth cohort which was primarily scheduled until the children were 3 years old. The aim of the prospective, randomized, double-blind intervention study was to investigate the impact of different cow's milk protein hydrolysate infant formulas in the first 4 - 6 months on the development of allergic diseases in children at risk due to at least one parent or biological sibling with a history of allergic disease. The allocation to one of the 4 intervention formulas (partial whey hydrolysate, extensive whey hydrolysate, extensive casein hydrolysate or standard cow's milk formula) was randomised and stratified by family history (single/biparental) and the respective obstetric clinic. Recruitment was carried out by the three clinical centers (Research Institute Marien-Hospital Wesel, Children's Department, Ludwigs-Maximilians-University Munich and Children's Department Technical University Munich) in 18 obstetric clinics between 01.09.1995 and 30.06.1998. Along with the intervention study a non-interventional, complementary observational cohort of children with or without allergy risk was recruited and followed by annual self-reporting parental questionnaires. The GINI intervention study (GINI-I, N = 2.252) and the non-interventional observation study (GINI-NI, N = 3.739) are combined in the population-based GINIplus study (see article J. Heinrich et al. in this journal). The results of the GINI intervention study confirm that, cow's milk protein hydrolysate infant formulas have a preventive effect on allergic manifestation compared with a standard cow's milk formula, until school age. However, the dimension of the effect is different between the formulas. This effect, which is mainly driven by the effect on atopic eczema, develops in the first months of life and persists without rebound. In the formula groups the cumulative incidence of atopic eczema until school age is reduced between 26% and 45% compared with standard cow's milk formula. A beneficial effect of the hydrolysate formulas on the respiratory manifestations asthma and rhinoconjunctivitis, however, could not be shown. By comparing the GINI intervention and non-intervention arm of the GINIplus study it was demonstrated, that a family history for allergy doubles the risk for eczema in the offspring. Early intervention with cow's milk protein hydrolysate infant formulas is able to substantially compensate this risk for eczema until the age of 6 years. In contrast, by randomization to standard cow's milk formula this risk showed a trend towards a higher incidence compared with children at risk from the non-intervention group. Thus, the results of the GINIplus study have contributed to answer some of the controversially discussed questions.

GINIplus and LISAplus - Design and selected results of two German birth cohorts about natural course of atopic diseases and their determinants.

The increasing prevalence of asthma, hay fever, and allergic sensitization in Western Germany after east-west division in 1949 and their rapid increase in East German children after re-unification in 1990 are strong indications for the role of life-style and/or environmental factors in the development of atopic diseases. Obviously, the perinatal period is crucial for priming the immune system. Therefore, explorations of determinants of atopic diseases need pregnancy or birth cohorts as the most appropriate epidemiological study designs. This review presents the design and selected results of the two German birth cohorts GINIplus and LISAplus. GINIplus and LISAplus recruited 5.991 and 3.097 healthy, term newborns, respectively, from Munich, Wesel, Leipzig, and Bad Honnef. Approximately 55% could be followed for the first 10 years. We analyzed the natural course of atopic diseases and the role of life-style, environmental, and genetic factors for disease onset, intermediate phenotypes, and genes involved in detoxification and oxidative stress. The results of these two large birth cohorts contributed substantially to the understanding of atopic diseases and their determinants.

The yield of video-EEG telemetry evaluation for non-surgical candidate children.

BACKGROUND: Video EEG (VEEG) is performed for most pediatric patients in order to evaluate unclear paroxysmal events and improve our understanding of difficult to control epileptic patients. PURPOSE: To characterize the video EEG studies on children who are not candidates for surgery in order to identify the parameters that affect results in level of improving the rate of acquisition, as well as improving the ability to expect the likelihood of epilepsy and of gathering new information as a result of the VEEG. METHODS: Retrospective chart analysis of all consecutive patients who underwent VEEG in two VEEG monitoring units. RESULTS: 323 children of a mean age of 7 years (STD 4.73, range 0-17 years) were monitored for a mean duration of 2 days (STD 1.65, range 1-10 days). The main reasons for monitoring were: evaluation of unclear events (n = 234), evaluation of previously diagnosed epilepsy (n = 36) and confirmation of Electrical Status Epilepticus in Sleep (ESES) (n = 34). The main event types for evaluation were: staring episodes (n = 67), myoclonic jerks (n = 35) and abnormal eye movement (n = 22). Suspected events were captured in 70% of the patients. There was a positive correlation between acquisition of suspected events and each of the following: duration of the monitoring, the frequency of investigated events per history, the type of investigated events. A prior interictal epileptic activity on routine EEG was a positive predictor of an event to be epileptic (p = 0.003). Amongst the group of known epileptic patients, VEEG had role in changing diagnosis in 53% of patients. Many of them had focal interictal epileptiform activity in their routine EEG. CONCLUSIONS: Selecting patients with frequent events and longer monitoring periods increase the yield of VEEG. Looking carefully into clinical characteristics of the patient prior to VEEG can clarify diagnosis therefore render the VEEG test superfluous to subgroups of patients. Prior routine epileptic EEG, coexistence of other seizure types, behaviors accompanying the investigated habitual behavior and abnormalities in other investigations (MRI, cognitive function and EEG) are the parameters that can predict diagnosis of epilepsy. Precise diagnosis in known epileptic patients as a result of VEEG is more likely for those with focal interictal epileptiform discharges in routine EEG.

Allergic manifestation 15 years after early intervention with hydrolyzed formulas--the GINI Study.

BACKGROUND: Data on the long-term impact of hydrolyzed formulas on allergies are scarce. OBJECTIVE: To assess the association between early intervention with hydrolyzed formulas in high-risk children and allergic outcomes in adolescence. METHODS: GINI trial participants (n = 2252) received one of four formulas in the first four months of life as breastmilk substitute if necessary: partial or extensive whey hydrolyzate (pHF-W, eHF-W), extensive casein hydrolyzate (eHF-C) or standard cow's milk formula (CMF) as reference. Associations between these formulas and the cumulative incidence and prevalence of parent-reported physician-diagnosed asthma, allergic rhinitis (AR) and eczema, as well as spirometric indices and sensitization, were examined using generalized linear models. RESULTS: Between 11 and 15 years, the prevalence of asthma was reduced in the eHF-C group compared to CMF (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.26-0.89), which is consistent with the spirometric results. The cumulative incidence of AR was lower in eHF-C (risk ratio (RR) 0.77, 95% CI 0.59-0.99]) and the AR prevalence in pHF-W (OR 0.67, 95% CI 0.47-0.95) and eHF-C (OR 0.59, 95% CI 0.41-0.84). The cumulative incidence of eczema was reduced in pHF-W (RR 0.75, 95% CI 0.59-0.96) and eHF-C (RR 0.60, 95% CI 0.46-0.77), as was the eczema prevalence between 11 and 15 years in eHF-C (OR 0.42, 95% CI 0.23-0.79). No significant effects were found in the eHF-W group on any manifestation,nor was there an effect on sensitization with any formula. CONCLUSION: In high-risk children, early intervention using different hydrolyzed formulas has variable preventative effects on asthma, allergic rhinitis and eczema up to adolescence.

Prostate cancer gene 3 (PCA3) is of additional predictive value in patients with PI-RADS grade III (intermediate) lesions in the MR-guided re-biopsy setting for prostate cancer.

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI) improves diagnostic accuracy in re-biopsies of men with prostate cancer (PC) suspicion, but predictive value is limited despite the use of the new Prostate Imaging Reporting and Data System (PI-RADS). Prognostic value of the PC-specific biomarker prostate cancer gene 3 (PCA3) added to the PI-RADS score was evaluated. METHODS: The study was a retrospective analysis of the institutional database for men with MR-guided biopsy (MR-GB) for suspicious lesion in mpMRI and who had an additional pre-MR-GB PCA3 testing for ongoing PC suspicion. All men had ≥ 1 negative ultrasound GB. Lesions were retrospectively scored by PI-RADS in three MRI sequences (T2w, DCE, and DWI). PCA3 was analyzed with cutoffs of 25 and 35. The prognostic value of mpMRI and PCA3 and the additional value of both were explored. RESULTS: Tumor detection rate (49 men, mean PSA 10 ng/ml, lesion size 40 mm(2)) was 45 % (22/49 patients). In the subgroup of PI-RADS IV°, 17/17 patients had PC; in PI-RADS III° (intermediate) 5/15 had PC, and all 5 had a PCA3 > 35. PCA3 > 35 had no additional prognostic value in the whole cohort. Out of the 10/15 PC negative patients (PI-RADS III°), PCA3 was < 35 in 6. The inclusion of PCA3 value in PI-RADS III° patients improved predictive accuracy to 91.8 %. CONCLUSION: MpMRI and subsequent grading to PI-RADS significantly improves PC detection in the re-biopsy setting. The diagnostic uncertainty in the PI-RADS intermediate group can be ameliorated by the addition of PCA3 cutoff of 35 to avoid potential unnecessary biopsies.

Dissociable cerebellar activity during spatial navigation and visual memory in bilateral vestibular failure.

OBJECTIVE: Spatial orientation and navigation depends on information from the vestibular system. Previous work suggested impaired spatial navigation in patients with bilateral vestibular failure (BVF). The aim of this study was to investigate event-related brain activity by functional magnetic resonance imaging (fMRI) during spatial navigation and visual memory tasks in BVF patients. METHODS: Twenty-three BVF patients and healthy age- and gender matched control subjects performed learning sessions of spatial navigation by watching short films taking them through various streets from a driver's perspective along a route to the Cathedral of Cologne using virtual reality videos (adopted and modified from Google Earth). In the scanner, participants were asked to respond to questions testing for visual memory or spatial navigation while they viewed short video clips. From a similar but not identical perspective depicted video frames of routes were displayed which they had previously seen or which were completely novel to them. RESULTS: Compared with controls, posterior cerebellar activity in BVF patients was higher during spatial navigation than during visual memory tasks, in the absence of performance differences. This cerebellar activity correlated with disease duration. CONCLUSIONS: Cerebellar activity during spatial navigation in BVF patients may reflect increased non-vestibular efforts to counteract the development of spatial navigation deficits in BVF. Conceivably, cerebellar activity indicates a change in navigational strategy of BVF patients, i.e. from a more allocentric, landmark or place-based strategy (hippocampus) to a more sequence-based strategy. This interpretation would be in accord with recent evidence for a cerebellar role in sequence-based navigation.

A confocal microscope position sensor for micron-scale target alignment in ultra-intense laser-matter experiments.

A diagnostic tool for precise alignment of targets in laser-matter interactions based on confocal microscopy is presented. This device permits precision alignment of targets within the Rayleigh range of tight focusing geometries for a wide variety of target surface morphologies. This confocal high-intensity positioner achieves micron-scale target alignment by selectively accepting light reflected from a narrow range of target focal planes. Additionally, the design of the device is such that its footprint and sensitivity can be tuned for the desired chamber and experiment. The device has been demonstrated to position targets repeatably within the Rayleigh range of the Scarlet laser system at The Ohio State University, where use of the device has provided a marked increase in ion yield and maximum energy.

Is the diagnostic yield of myocardial stress perfusion MRI impaired by three-vessel coronary artery disease?

BACKGROUND: Three-vessel coronary artery disease (CAD) comes along with globally reduced myocardial perfusion potentially restricting the demarcation of regional hypoperfusion in stress perfusion cardiac magnetic resonance imaging (MRI). PURPOSE: To evaluate whether stress perfusion cardiac MRI is capable of detecting myocardial hypoperfusion in patients with 3-vessel CAD reliably. MATERIAL AND METHODS: Two hundred and five patients with symptoms of CAD were included. The examination protocol comprised imaging of myocardial perfusion at stress (0.14 mg/kg/min adenosine for 4 min) using a 2D saturation recovery gradient echo sequence after administration of gadobutrol (0.1 mmol/kg body weight). Perfusion sequences were assessed qualitatively by two experienced observers. Coronary angiography served as standard of reference. RESULTS: Sensitivity and specificity for hemodynamically relevant stenoses in patients with 0-, 1-, 2-, 3-vessel coronary artery disease were 100%/91%, 91%/73%, 90%/71%, 92%/64%; positive/negative predictive value, 67%/100%, 91%/73%, 83%/81%, 93%/58%; diagnostic accuracy, 93%/87%/83%/87%, respectively. The negative predictive value in patients with 3-vessel CAD was lower than in patients with 0- and 2-vessel CAD and the specificity lower than in patients with no CAD whereas the positive predictive value was higher than in patients with no CAD. The other proportions did not differ significantly between the groups. CONCLUSION: The diagnostic value of stress perfusion cardiac MRI in patients with 3-vessel CAD is comparable to results in patients with 1- or 2-vessel CAD. In the rare event that stress perfusion images do not depict regional hypoperfusion in patients with severe 3-vessel CAD, myocardial ischemia could be identified by reduced semi-quantitative perfusion parameters.

Feasibility of Noninvasive Diagnosis and Treatment Planning in a Case Series with Carotid-Cavernous Fistula using High-Resolution Time-Resolved MR-Angiography with Stochastic Trajectories (TWIST) and Extended Parallel Acquisition Technique (ePAT 6) at 3 T.

PURPOSE: The evaluation of carotid-cavernous fistulas (CCFs) and the intracranial vasculature has been predominantly carried out using conventional digital subtraction angiography (DSA). Recent developments in time-resolved magnetic resonance angiography (MRA) provide the opportunity to assess both multiple arterial and venous phases with high temporal and spatial resolution. Here, we investigated the feasibility of this technique to functionally assess CCF prior to intervention. METHODS: Six consecutive patients with clinical symptoms of a CCF were scheduled for clinically indicated MRA and underwent a protocol that comprised conventional imaging sequences and high resolution time-resolved MRA with interleaved stochastic trajectories (TWIST). The location of the fistulous communication, the flow pattern, and venous drainage were determined by time-resolved MRA and compared with DSA which was available in five out of six patients. RESULTS: Typical morphological findings (including enlargement of the superior ophthalmic vein, exophthalmos) were found in all cases in both conventional MRI and time-resolved MRA source data. The temporal resolution of time-resolved MRA enabled a good separation of the early filling of the cavernous sinus during the arterial phase. Direct fistulous communication was assessed in three patients with good correlation to DSA, whereas indirect CCF could not definitely be visualized. The time-resolved MRA provided information about the flow pattern and the venous drainage of the fistula in all patients, which is essential for therapy planning. CONCLUSION: Time-resolved MRA provides important morphological and functional information in patients with CCF. Although DSA remains the gold standard for diagnosis and exact classification of fistulas, time-resolved MRA can provide the relevant hemodynamic information to plan interventional treatment as a one-step procedure with a focused diagnostic workup.

What can reunification of East and West Germany tell us about the cause of the allergy epidemic?

The increase of allergies in East Germany--reaching West German prevalence shortly after the reunification--is considered a model for the allergy epidemic in the western world. Whether such a pattern was observed in all comparison studies and for all allergic manifestations is not known because a complete overview is missing. Hints about possible causal factors for the allergy epidemic could be gained by identifying known risk factors, which explain the observed pattern of allergy development in Germany. Again, an overview about these efforts is missing. We identified 14 cross-sectional studies conducted after 1989 and calculated prevalence ratios (West/East) for asthma, hayfever, eczema and allergic sensitization. Additionally, a tabular overview about the explanatory power of risk factors hypothesized in the nineties and covering outdoor exposure, indoor factors, early childhood influences, nutrition as well as awareness is given. At the time of the German reunification, the prevalence ratio West/East was largest for hayfever and sensitization to birch pollen, less pronounced for the other phenotypes and even less than one for atopic eczema. Hayfever and sensitization to birch pollen also showed the steepest increase in East Germany afterwards. Single-room heating with fossil fuels and living as only child in a family were identified as explaining up to 23.5% of the excess trend in East compared to the trend in West. Hayfever as most typical atopic disease showed the difference in allergy pattern between East and West Germany clearest. Risk factors identified for these phenotypes are completely different (single child) or even act in the opposite direction (single-room heating) from classical risk factors for airway diseases. This might be the most important lesson from the West/East German experience. It already stimulated many other studies focussing on protective factors such as microbial stimulation.

Measurement procedure for glucose in serum using liquid chromatography isotope dilution--tandem mass spectrometry (LC-ID-MS/MS).

BACKGROUND: We developed and validated a measurement procedure for glucose using liquid chromatography-isotope dilution tandem mass spectrometry. The proposed method is intended to be used for setting target values in EQAS samples and for certification of glucose reference materials, including those in biological matrices. METHODS: Serum samples were spiked with internal standard 13C6 D-glucose. Protein precipitation was performed with ethanol. The samples were vortexed and centrifuged. An aliquot of the supernatant was evaporated to dryness, the residue dissolved in elution buffer and injected into the LC-MS/MS system. Measurements were performed in the positive ion mode monitoring the Cs+ adducts for glucose at m/z 313 --> 132.9 and m/z 319 --> 132.9 for the internal standard. RESULTS: The coefficient of variation (CV) of the measurement procedure for lyophilized, liquid, and fresh serum samples was between 0.27 and 1.77%. The bias from certified target values for NIST reference materials was < or = 0.62%. A Deming regression comparison demonstrated a good correlation of results obtained with the proposed LC-ID-MS/MS method and target values obtained in the internationally accepted IFCC-RELA ring trial using JCTLM-recognized reference measurement procedures. CONCLUSIONS: The proposed LC-ID-MS/MS measurement procedure with traceability to SI units shows excellent accuracy and precision and is suitable for use as reference measurement procedure for certification of target values in lyophilized and fresh serum samples.

Very early indicators of response to systemic therapy in lymphoma patients based on alterations in water diffusivity--a preliminary experience in 20 patients undergoing whole-body diffusion-weighted imaging.

OBJECTIVE: To assess feasibility of whole-body diffusion-weighted MRI (wbDWI) for very early evaluation of response to therapy in different lymphoma subtypes. MATERIALS AND METHODS: 20 patients (10 male, 10 female; mean age 50.7±16.1±17.2 years) underwent wbDWI (calculation of apparent diffusion coefficient [ADC] with b=0, 800s/mm(2)) at baseline and within a median of 7 days after therapy onset. Lymphoma manifestations were evaluated with respect to changes in ADC and size at follow-up with up to six of the largest lesions per patient undergoing quantification. An increase in ADC as well as a decrease in size at follow-up was classified as responder, whereas neither change in ADC nor in size (or progression) was considered non-responder. Results were confirmed at interim measurements (after 3-4 chemotherapy cycles) and 6 months after treatment. RESULTS: 90 lymphoma lesions were analyzed. 18 patients were classified as responders and 2 as non-responder at FU (mean, 1 week). DWI results accurately (100%) correlated with the subsequent interim course of all lesions. mean baseline ADC was 0.79±0.28×10(-3)s/mm(2). For responders mean follow-upADC increased by 64.6±56.5% (p<0.001) whereas lesions size decreased by mean 14.4±13.3% (p<0.001). In the non-responder, both values did not significantly change. In patients classified as responders six months after treatment, meanADC increase at FU was 70.3±57.8% (p<0.001) whereas mean size decrease vs. baseline was 15.8±13.6% as compared to non-responders (22.4±39.9%) and 5.4±0.9%, respectively. CONCLUSION: wbDWI with ADC analysis represents a feasible diagnostic tool for very early response assessment in lymphoma patients enabling also prediction of long-term response.

The relation of airway obstruction to asthma, chronic rhinosinusitis and age: results from a population survey of adults.

RATIONALE: There is conflicting evidence on whether patients with asthma experience an accelerated decline in lung function with age. We examined the association between postbronchodilator lung function, asthma, chronic rhinosinusitis (CRS), and atopy with age using a large European sample. METHODS: In 17 centers in 11 European countries, case-control studies were nested within representative cross-sectional surveys of adults aged less than 75 years. Representative samples of participants with asthma, CRS or both and controls were assessed for postbronchodilator ventilatory function, smoking history, atopy, and treatment. Multiple regression was used to assess the interactive effects of age and diagnostic group on decline in postbronchodilator ventilatory function. RESULTS: A total of 3337 participants provided adequate data (778 with asthma, 399 with CRS, 244 with both asthma and CRS and 1916 controls who had neither asthma nor CRS). Participants with asthma had lower FEV1 /FVC (-4.09% (95% CI: -5.02, -3.15, P < 0.001) and a steeper slope of FEV1 /FVC against age (-0.14%/annum [95%CI: -0.19, -0.08]) equivalent to smoking 1-2 packs of cigarettes per day. Those with atopy had a slope equivalent to controls. CONCLUSIONS: People with asthma have a steeper decline in postbronchodilator lung function with age, but neither CRS nor atopy alone were associated with such decline.

Geographical variation in the prevalence of sensitization to common aeroallergens in adults: the GA(2) LEN survey.

BACKGROUND: Geographical variation in the prevalence of sensitization to aeroallergens may reflect differences in exposure to risk factors such as having older siblings, being raised on a farm or other unidentified exposures. OBJECTIVE: We wanted to measure geographical variation in skin prick test positivity and assess whether it was explained by differences in family size and/or farm exposure. We also compared prevalence in younger and older subjects. METHODS: Within the Global Allergy and Asthma European Network (GA(2) LEN) survey, we measured the prevalence of skin prick positivity to a panel of allergens, and geometric mean serum total immunoglobulin E (IgE), in 3451 participants aged 18-75 years in 13 areas of Europe. Estimated prevalence was standardized to account for study design. We compared prevalence estimates in younger and older subjects and further adjusted for age, gender, smoking history, farm exposure, number of older siblings and body mass index (BMI). RESULTS: Skin prick test positivity to any one of the measured allergens varied within Europe from 31.4% to 52.9%. Prevalence of sensitization to single allergens also varied. Variation in serum total IgE was less marked. Younger participants had higher skin prick sensitivity prevalence, but not total IgE, than older participants. Geographical variation remained even after adjustment for confounders. CONCLUSION: Geographical variation in the prevalence of skin prick test positivity in Europe is unlikely to be explained by geographical variation in gender, age, smoking history, farm exposure, family size and BMI. Higher prevalence in younger, compared to older, adults may reflect cohort-associated increases in sensitization or the influence of ageing on immune or tissue responses.