Peanut components measured by ISAC: comparison with ImmunoCap and clinical relevance in peanut allergic children.

BACKGROUND: Specific IgE (sIgE) against the peanut component Arachis hypogaea (Ara h) 2 has been shown to be the most important allergen to discriminate between peanut allergy and peanut tolerance. Several studies determined sIgE cut off values for Ara h 2, determined by singleplex measurements. However, cut off values for Ara h 2 from multiplex arrays are less well defined. The aim of this study was to evaluate the correlation between Ara h 2 sIgE determined by singleplex versus multiplex measurements and to assess the diagnostic value of the different peanut components included in Immuno Solid-phase Allergen Chip (ISAC) multiplex analysis in children with a suspected peanut allergy. METHODS: In this retrospective study we analyzed Ara h 2 sIgE values with singleplex Fluorescence Enzyme Immunoassay (FEIA, ImmunoCap) and multiplex microarray (ISAC) measurements in 117 children with a suspected peanut allergy. Also, other peanut components measured by ISAC were analyzed. Double blinded placebo controlled oral food challenges were used as golden standard. RESULTS: Among all studied peanut components FEIA Ara h 2 sIgE showed the highest area under the curve (AUC, 0.922), followed by ISAC Ara h 6 and Ara h 2 sIgE with AUCs of respectively 0.906 and 0.902. Best cut off values to diagnose peanut allergy were 4.40 kU/l for FEIA Ara h 2 sIgE and, 7.43 ISU and 8.13 ISU for respectively Ara h 2 and Ara h 6 sIgE in ISAC microarray. Ara h 2 sIgE determined in FEIA and ISAC showed a good correlation (r = 0.88; p < 0.01). CONCLUSION: Ara h 6 and Ara h 2 sIgE in multiplex ISAC are both good predictors of clinical peanut allergy in Dutch children, and their performance is comparable to the use of Ara h 2 in singleplex FEIA. The simultaneous measurement of different peanut components using ISAC is an advantage and clinically useful to detect peanut allergic children that are Ara h 2 negative but sensitized to other peanut proteins such as Ara h 6.

Effect of conservative treatment in aortoiliac occlusive disease.

Objective: To determine the effect of primary conservative treatment without revascularization in patients with proven aortoiliac occlusive disease (AIOD) presenting with intermittent claudication (IC).Background: The initial treatment of IC should focus on supervised exercise therapy (SET) and pharmacotherapy. Nowadays, primary endovascular revascularization (EVR) has become increasingly popular in patients with all types of AIOD. But in daily practice, EVR is often performed without initially extensive exercise.Method: This is a single centre retrospective study from December 2012 to September 2017. Primary outcomes were maximum walking distance (MWD) and patient satisfaction. Secondary outcomes were revascularization rate and mortality.Results: Twenty-four patients were included. Mean age was 64 years (SD: 9). Mean follow-up was 28 months (SD: 17). Nineteen patients (80%) had SET. In 18 (75%) patients, the MWD was improved compared to the initial situation. In five (21%) patients, the MWD stayed the same. The MWD of one (4%) patient decreased. Overall satisfaction rate was 87%. Three patients (13%) were not satisfied with the conservative treatment and eventually got an EVR. There was no disease related death.Conclusions: Conservative treatment, especially with SET, has acceptable subjective symptom outcomes in selected patients with AIOD. It could be a good alternative treatment for certain patients with AIOD and IC.

The Role of Delirium and Other Risk Factors on Mortality in Elderly Patients with Critical Limb Ischemia Undergoing Major Lower Limb Amputation.

BACKGROUND: Delirium in patients with critical limb ischemia (CLI) is associated with increased mortality. The main goal of this study was to investigate the association between delirium and mortality in patients undergoing major lower limb amputation for CLI. In addition, other risk factors associated with mortality were analyzed. METHODS: An observational cohort study was conducted including all patients aged ≥70 years with CLI undergoing a major lower limb amputation between January 2014 and July 2017. Delirium was scored using the Delirium Observation Screening Score in combination with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Risk factors for mortality were analyzed by calculating hazard ratios using a Cox proportional hazards model. RESULTS: In total, 95 patients were included; of which, 29 (31%) patients developed a delirium during admission. Delirium was not associated with an increased risk of mortality (hazard ratio [HR] = 0.84; 95 % confidence interval [CI]: 0.51-1.73; P = 0.84). Variables independently associated with an increased risk of mortality were age (HR 1.1; 95% CI 1.0-1.1), cardiac history (HR 3.3; 95% CI 1.8-6.1), current smoking (HR 2.9; 95% CI 1.6-5.5), preoperative anemia (HR 2.8; 95% CI 1.1-7.2), and living in a nursing home (HR 2.2; 95% CI 1.1-4.4). CONCLUSION: Delirium was not associated with an increased mortality risk in elderly patients with CLI undergoing a major lower limb amputation. Factors related to an increased mortality risk were age, cardiac history, current smoking, preoperative anemia, and living in a nursing home.

sIgE Ana o 1, 2 and 3 accurately distinguish tolerant from allergic children sensitized to cashew nuts.

BACKGROUND: The double-blind, placebo-controlled food challenge test (DBPCFC) is the gold standard in cashew nut allergy. This test is costly, time consuming and not without side effects. Analysis of IgE reactivity to cashew nut components may reduce the need for food challenge tests. METHODS: In a prospective and multicentre study, children with suspected cashew nut allergy underwent a DBPCFC with cashew nut. Specific IgE to cashew nut and to the components Ana o 1, 2 and 3 were determined. A skin prick test (SPT) with cashew nut extract was performed. The association between the outcome of the food challenge test and specific IgE to Ana o 1, 2 and 3 was assessed with logistic regression analyses, unadjusted and adjusted for other diagnostic variables. Discriminative ability was quantified with a concordance index (c). RESULTS: A total of 173 children (103 boys, 60%) with a median age of 9 years were included. About 79% had a positive challenge test outcome. A steep rise in the risk of a positive challenge was observed for specific IgE to each individual component Ana o 1, 2 and 3 with estimated risks up to approximately 100%. Median values of Ana o 1, 2, 3 were 1.29 kU/l (range 0-100 kU/l), 4.77 kU/l (range 0-100 kU/l) and 8.33 kU/l (range 0-100 kU/l) respectively and varied significantly (p < 0.001). Specific IgE to Ana o 1, 2 and 3 was better distinguished between cashew-allergic and tolerant children (c = 0.87, 0.85 and 0.89, respectively) than specific IgE to cashew nut or SPT (c = 0.76 and 0.83, respectively). CONCLUSION: The major cashew nut allergens Ana o 1, 2 and 3 are each individually predictive for the outcome of food challenge tests in cashew-allergic children.

A nurse-led sexual rehabilitation intervention after radiotherapy for gynecological cancer.

PURPOSE: Although vaginal dilator use after combined pelvic radiation therapy and brachytherapy (RT/BT) is recommended to prevent vaginal shortening and stenosis, women fail to use them and experience sexual problems. A nurse-led sexual rehabilitation intervention targeting sexual recovery and vaginal dilatation was developed. Its feasibility was investigated during a prospective, longitudinal, observational pilot study. METHODS: Four oncology nurses were specifically trained to conduct the intervention. Gynecologic cancer patients treated with RT/BT were assessed using (i) questionnaires on frequency of dilator use (monthly), sexual functioning, and sexual distress (at baseline and 1, 6, and 12 months) and psychological and relational distress (at 1, 6, and 12 months); (ii) semi-structured interviews (between 6 and 12 months); and (iii) consultation recordings (a random selection of 21 % of all consults). RESULTS: Twenty participants were 26-71 years old (mean = 40). Eight participants discontinued participation after 3 to 9 months. At 6 months after RT, 14 out of 16 (88 %), and at 12 months 9 out of 12 (75 %), participants dilated regularly, either by having sexual intercourse or by using dilators. Sexual functioning improved between 1 and 6 months after RT, with further improvement at 12 months. Most participants reported that the intervention was helpful and the nurses reported having sufficient expertise and counseling skills. CONCLUSIONS: According to the pilot results, the intervention was feasible and promising for sexual rehabilitation and regular dilator use after RT. Its (cost-)effectiveness will be investigated in a randomized controlled trial.

No difference in health-related quality of life, after a food challenge with cashew nut in children participating in a clinical trial.

BACKGROUND: Previous studies showed that health-related quality of life (HRQL) significantly improved after the food challenge, with greater improvements in HRQL after a negative outcome than after a positive outcome. It is currently unknown whether this also occurs in patients undergoing DBPCFCs with cashew nut in the context of a clinical trial. METHODS: Quality of life was studied in children enrolled in a cashew nut study using Food Allergy Quality of Life Questionnaires (FAQLQs). Children, teenagers and parents of the children completed the questionnaires before the challenge test and 6 months after the DBPCFC with cashew nut. The difference in the change in HRQL between the children with a positive and negative DBPCFC outcome was studied by Mann-Whitney U-test. RESULTS: In total, 112 children (67 boys, median age of 9 years) were included. The children, teenagers and parents of the children completed 143 sets of questionnaires in total. There were no significant differences in baseline total and domain scores compared to the follow-up scores in the FAQLQ-CF, FAQLQ-TF and FAQLQ-PF. In children, the delta FAIM score in the negative DBPCFC tested group was significantly better than the delta FAIM score in the positive challenged group (p = 0.026). There were no significant differences in the changes in the scores of the FAQLQ-CF and FAQLQ-PF in the children with a positive challenge outcome, compared to the children with a negative challenge result. However, there was a significant difference in the change in score between the latter groups in the domain 'accidental exposure' of the FAQLQ-TF (p = 0.049). CONCLUSION: This study showed no difference in the change in HRQL scores after a DBPCFC with cashew nut in children participating in a clinical trial. The utility of HRQL as an outcome for clinical trials in food allergy may be limited if participant baseline HRQL is relatively unimpaired.

TNF-alpha and melphalan-based isolated limb perfusion: no evidence supporting the early destruction of tumour vasculature.

BACKGROUND: Isolated limb perfusion with TNF-alpha and melphalan (TM-ILP) is a highly effective treatment for locally advanced tumours of the extremities. Previous research suggests an almost immediate disintegration of the blood supply of the tumour. The aim of the present study was to verify this hypothesis using non-invasive measurements of microvascular perfusion and tissue oxygenation. METHODS: A total of 11 patients were included in the study. TM-ILP was performed under mildly hyperthermic conditions (39 °C) in the extremities via proximal vascular access. Capillary-venous microvascular blood flow, haemoglobin level (Hb) and oxygen saturation (SO2) were determined using laser Doppler and white-light spectroscopy, respectively, before TM-ILP and at 30 min, 4 h, 1 day, 4 days, 1 week, 2 weeks and 6 weeks after TM-ILP from tumour and healthy muscle tissues. RESULTS: Blood flow and Hb were mostly higher, whereas SO2 was lower, in tumour tissue compared with muscle tissue. In both tumour and muscle tissues, blood flow significantly increased immediately after TM-ILP and remained elevated for at least 2 weeks, followed by a return to the initial values 6 weeks after the procedure. CONCLUSION: No signs were found of early destruction of the tumour vasculature. The observations suggest that an inflammatory reaction is one of the key elements of TM-ILP.

Perfluorodecalin-soluble fluorescent dyes for the monitoring of circulating nanocapsules with intravital fluorescence microscopy.

Perfluorodecalin (PFD) is an established artificial oxygen carrier due to its physical capability to solve the respiratory gases oxygen and carbon dioxide. PFD-filled poly(n-butyl-cyanoacrylate) (PACA) nanocapsules are already discussed as effective artificial oxygen carriers, and their principal suitability for intravenous administration had been shown. To further elucidate their action in vivo, it is imperative to characterise their preclinical safety and particularly their biodistribution. For these purposes, intravital fluorescence microscopy would display an attractive technique in order to monitor the PACA nanocapsules in vivo, but unfortunately, it is impossible to stain the PACA nanocapsules with a fluorescent dye fulfilling special criteria required for in vivo microscopy. In order to develop such a dye, a long-chained fluorinated thiol was used to modify a BODIPY derivative that is a highly fluorescent organic compound belonging to the difluoro-boraindacene family, as well as to functionalise mesoscopic systems, such as CdSe/ZnS-quantum dots and gold nanoparticles. Furthermore, a functionalisation of porphyrin derivatives was investigated by placing divalent ions in the centre of these systems. Due to the high solubility of all synthesised dyes in PFD, it should be possible to stain PFD-filled particles in general. However, only the functionalised BODIPY derivative was suitable for in vivo monitoring of the PFD-filled PACA nanocapsules.

Structural rearrangements and reaction intermediates in a di-Mn water oxidation catalyst.

By using first-principles molecular dynamics simulations combined with metadynamics to simulate rare events we analyse competing reaction coordinates for a di-Mn water oxidation catalyst ([(bis(imino)pyridine)(H(2)O)Mn(IV)(µ-O)(2)Mn(V)(O)(bis(imino)pyridine)](3+)). The catalytic water oxidation cycle of the complex is examined by addressing the thermodynamic accessibility of the hydroperoxo species that is considered a critical and rate-limiting intermediate. To achieve this, hybrid quantum-mechanics/molecular-mechanics (QM/MM) and full QM simulations have been performed for an explicit treatment of the water environment that plays an active role in the reaction processes. Starting from a likely active species for the O-O bond formation, we observe that during the water approach to the oxo ligand a facile structural rearrangement of the complex takes place, leading to the opening of one µ-O bridge and the release of a water ligand, and resulting in two pentacoordinated Mn centers. This complex appears weakly active in the water oxidation process, since a concerted reaction is required to establish a Mn-OOH hydroperoxo intermediate. The slow kinetics of a concerted reaction can allow other processes, including linear degradation of the catalyst, to take precedence over catalytic water oxidation.

The necessity for the coating of perfluorodecalin-filled poly(lactide-co-glycolide) microcapsules in the presence of physiological cholate concentrations: Tetronic-908 as an exemplary polymeric surfactant.

Recently, we demonstrated that biodegradable poly(lactide-co-glycolide) (PLGA) micro- and nanocapsules with a liquid content of perfluorodecalin are principally useful for the development of artificial oxygen carriers. In order to solve a decisive and well-known problem with PLGA microcapsules, i.e. the spontaneous agglomeration of the capsules after depletion of the emulsifying agent (i.e. cholate), coating with the ABA block copolymer, Tetronic-908 was studied. After Tetronic-908 treatment at concentrations that were harmless to cultured cells, the clustering of the microcapsules was prevented, the adsorption of opsonins was decreased and the attachment to cells was inhibited, but the oxygen transport capacity of PLGA microcapsules was even increased. The present data clearly show that perfluorodecalin-filled PLGA microcapsules must be coated before decreasing the emulsifying agent cholate to physiological concentrations, in order to develop a solution that has the capabilities to function as a potential artificial oxygen carrier suspension.

[Cereal related complaints in children]. / Granengerelateerde klachten bij kinderen.

There's a lot of attention for gluten-free diets on social media. Doctors get many questions about gluten sensitivity or possible wheat allergy. With some basic knowledge, it's easier to give answers to these questions and to prevent unnecessary and sometimes harmful diets. This article gives basic information about cereals, gluten, grasses and their crossreactivity. We give an overview about the differences between celiac disease, gluten sensitivity and IgE-mediated wheat allergy. We also describe diagnostics, treatment and natural history of coeliakie, gluten sensitivity and wheat or cereal allergy.

Occupational rhinitis in bell pepper greenhouse workers: determinants of leaving work and the effects of subsequent allergen avoidance on health-related quality of life.

BACKGROUND: Avoidance of occupational allergens or reduction in exposure has been advocated as the mainstay of the management of occupational rhinitis. Sparse data to the effect of allergen avoidance are available. OBJECTIVE: To identify factors that may lead to leaving work and to address the effect of subsequent allergen avoidance on quality of life. METHODS: A survey to the prevalence of occupational allergy to bell pepper performed in 1999 comprised 472 employees, of which 254 had work-related rhinitis and 228 completed the Rhinitis-related Quality of Life Questionnaire. After 8-year follow-up in 2007, 91 workers with rhinitis in 1999 were available to fill out the questionnaire again and were used to evaluate the course of nasal disease in terms of perceived severity and impact on daily life. RESULTS: Workers with rhinitis at baseline were more likely to leave their job in bell pepper cultivation for another job (OR = 1.62, 95% CI 0.95-2.75). Among the 91 workers, 58 subjects were still at work, whereas 33 subjects had left work. The subjects who left jobs reported substantial improvement in quality of life. The magnitude of the changes ranged from -0.31 to -1. The effect of quitting work on the mean quality of life score amounted -0.76 ± 0.15. CONCLUSIONS: The current study is the first large longitudinal studies showing that leaving work and subsequent occupational allergen avoidance have a beneficial effect on rhinitis-related quality of life. The study suggests that occupational rhinitis can be a reason to leave work.

Acetyl group orientation modulates the electronic ground-state asymmetry of the special pair in purple bacterial reaction centers.

Recent experimental data point to an asymmetric ground-state electronic distribution in the special pair (P) of purple bacterial reaction centers, which acts as the primary electron donor in photosynthesis. We have performed a density functional theory investigation on an extended model including the bacteriochlorophyll dimer and a few relevant surrounding residues to explore the origin of this asymmetry. We find strong evidence that the ground-state electron density in P is intrinsically asymmetric due to protein-induced distortions of the porphyrin rings, with excess electron charge on the P(M) bacteriochlorophyll cofactor. Moreover, the electron charge asymmetry is strongly modulated by the specific orientation of the C3(1) acetyl group, which is hydrogen bonded to His168. The electronic excitation has a significant charge transfer character inducing a displacement of electron charge from P(L) to P(M), in agreement with experimental data in the excited state. These results are relevant for the understanding of the unidirectional electron transfer path in photosynthesis.

Protection from glycine at low doses in ischemia-reperfusion injury of the rat small intestine.

BACKGROUND: Glycine at high doses is known to protect the small intestine against ischemia-reperfusion (I/R) injury. Here, we studied whether glycine at low clinically applicable doses has a protective effect. METHODS: In series 1, intestinal I/R was induced in male Wistar rats by occlusion (90 min)/reopening (120 min) of the superior mesenteric artery. Glycine was intravenously infused for 30 min before ischemia (pre-ischemic infusion), and once again from 30 min before until 60 min after reperfusion. Total glycine doses applied over the 120-min infusion were 5, 10, 20, and 75 mg glycine/kg. In series 2, pre-ischemic blood plasma glycine concentrations were determined under the conditions of series 1. RESULTS: In series 1, attenuation of I/R injury was comparable at 10, 20, and 75 mg glycine/kg, but less at 5 mg/kg (as indicated by less intestinal hemorrhages and better preserved mean arterial blood pressure, among other signs). In series 2, pre-ischemic blood plasma glycine concentrations increased with increasing glycine doses from 280 to 330, 340, 380, and 680 µM, respectively. CONCLUSION: These results demonstrate that even at a dose 50 times lower than previously applied - and at only slightly elevated plasma concentrations - glycine provides full protection against I/R injury of the small intestine.

Ruptured abdominal aortic aneurysm: endovascular or open approach in a Dutch general hospital.

AIM: We compared the outcomes of 56 patients with a ruptured abdominal aortic aneurysm (RAAA) who underwent either open repair or emergency endovascular aneurysm repair (eEVAR) in a general hospital. It seems feasible that the availability of eEVAR for treatment of RAAA could lead to a decrease in hospital mortality. METHODS: We analyzed all admitted patients with a RAAA, between January 2006 and April 2008, eEVAR is compared to open repair. We studied 30 days mortality, intensive care unit stay, hospital stay, total blood loss and complications. RESULTS: Fifteen eEVAR procedures (26.8%) were performed. Mortality in the eEVAR-group was 26%, in the open repair-group 46%. Mean intensive care unit stay was 3.9 days and 4.8 days in the eEVAR-group and open repair-group, respectively. Mean hospital stay was 13 days and 10.5 days. The average blood loss was 210cc and 2760cc. The amount of blood products for transfusion was significantly higher in the open repair. Overall complication rate was not significantly different in both treatment groups. CONCLUSION: Treatment in a Dutch general hospital of a RAAA with an eEVAR procedure has a lower mortality in comparison to the open repair. Therefore, whenever possible the eEVAR is the preferred treatment method.

Sensitization to lupine flour: is it clinically relevant?

BACKGROUND: Lupinus angustifolius (blue lupine) is used for human and animal consumption. Currently, the lupine content in bread varies from 0% to 10% and from 0.5% to 3% in pastry. Although lupine flour is present in many products, anaphylaxis on lupine flour is rarely seen. OBJECTIVE: The aim of our study was to determine the clinical relevance of sensitization to lupine flour. METHODS: From October 2004 until October 2005, we performed skin prick tests (SPT) with lupine flour, peanut and soy extracts in consecutive patients attending our allergy clinic with a suspected food allergy. In patients sensitized to lupine flour, double-blind placebo-controlled food challenges (DBPCFC) were performed and specific IgE was measured. RESULTS: We tested 372 patients. SPTs with peanut, soy and lupine flour were positive in 135, 58 and 22 patients, respectively. Nine patients with sensitization to lupine flour underwent DBPCFC, which was negative in eight cases. In contrast, one patient experienced significant symptoms. Four of these nine patients suspected lupine by history. Two other patients with a positive history to lupine declined from challenges. In these patients, a 3-day dietary record showed that they could consume lupine without symptoms. Specific IgE in the serum was positive for L. angustifolius, peanut and soy in all nine patients. CONCLUSION: These results demonstrate that clinical lupine allergy is very uncommon, even in the presence of sensitization to lupine flour. The estimated prevalence of lupine allergy, among patients with a suspected food allergy, referred to a tertiary allergy centre in the Netherlands is 0.27-0.81%. In most, although not all cases, sensitization is not clinically relevant and is most likely caused by cross-sensitization to peanut. In selected cases, eliciting doses are low, making significant reactions possible.

Occupational allergy in strawberry greenhouse workers.

BACKGROUND: Employees in strawberry greenhouses are highly exposed to several (potential) allergenic agents. However, no occupational allergy in this branch has been described before. First, the presence of work-related allergic symptoms in strawberry workers was explored. Second, we aimed to prove the concept that an IgE-mediated allergy could be responsible for work-related symptoms. To test the possibility of an IgE response secondary to cross-reactivity to birch or grass pollen, inhibition experiments were performed. METHODS: First, a questionnaire survey concerning work-related allergic symptoms among strawberry workers in the Netherlands was carried out. Second, 3 workers with work-related symptoms were investigated in detail. Skin tests, serum-specific IgE tests with home-made extracts of strawberry pollen and other possible allergenic agents of the strawberry greenhouse environment were executed. Furthermore, immunoblots and nasal provocations with strawberry pollen extract were performed. In addition, inhibition experiments were performed. RESULTS: 29 of 75 questionnaire respondents (38.7%) reported work-related symptoms. Sensitization to strawberry pollen was found in skin tests in all 3 employees with work-related symptoms. ELISA and immunoblotting with strawberry pollen showed positive results in 2 employees. Birch and grass pollen failed to inhibit IgE binding to strawberry pollen in 1 of 2 employees. Partial inhibition was seen in the second employee. Nasal provocation validated clinically relevant allergy to these pollens in 2 of 3 subjects. CONCLUSIONS: Allergic symptoms attributable to the workplace are present among a proportion of strawberry greenhouse employees. An IgE-mediated occupational allergy to strawberry pollen may contribute to these symptoms.

Evaluation of A-V impulse technology as a treatment for oedema following polytetrafluoroethylene femoropopliteal surgery in a randomised controlled trial.

OBJECTIVE: To investigate the efficacy of A-V impulse technology (A-V) for oedema prevention and treatment following PTFE femoropopliteal surgery. DESIGN: Prospective randomized clinical trial. MATERIALS: 36 patients undergoing PTFE femoropopliteal bypass reconstructions, either being treated postoperatively with a compression stocking (CS) (Group-1, n = 19) or with A-V (Group-2, n = 17). METHODS: Patients in treatment group-1 used a CS postoperatively during 1 week day and night, patients in group-2 were treated with A-V postoperatively at night during one week. The lower leg circumference was measured preoperatively and at five postoperative time points. RESULTS: Limb circumference has increased postoperatively on day 1 (CS 1.5%/A-V 1.4%), on day 4 (5.7%/6.3%), on day 7 (6.6%/6.1%), on day 14 (7.9%/7.7%) and on day 90 (5.8%/5.2%). Differences between treatment groups were not significant. A re-operation gives a significant 3.9% increase in circumference as compared to a first operation (95% CI: 1.5-6.4%; p = 0.002). CONCLUSION: No significant differences were found in the extent of developed edema between the groups following PTFE femoropopliteal bypass surgery. A redo peripheral bypass operation results in significantly more postoperative oedema than a first-time performed bypass operation.