What Do We Know About Fish Allergy at the End of the Decade?

Fish allergy is one of the most common food allergies. It is usually considered to be IgE-mediated and correlates well with diagnostic tests such as prick tests and/or determination of specific IgE. Avoidance is the recommended treatment and is generally extended to all fish species. However, new clinical presentations have been described. These include non-IgE-mediated disease, monosensitization, and new syndromes that are sometimes associated, surprisingly, with cross-reactivity. Advances in molecular allergy have provided insights into new allergens and have increased our understanding of cross-reactivity. This paper focuses on recent publications providing information for clinicians involved in the management of fish allergy.

Limited cross reactivity among arginine kinase allergens from mealworm and cricket edible insects.

Insects are seen as a solution to the increasing demand for protein sources for food. However, entomophagy has unfortunately been linked to allergic reactions in Europe with people with professional contacts. As mealworms (Tenebrio molitor) and crickets (Acheta domesticus) have recently become commercially available (both whole or in food formulation) in several European countries, this research assessed the cross allergenicity of arginine kinase (AK). Based on the collection of sera from a entomology laboratory staff, oven cooked insects but also purified AK fractions were tested. Immunoblotting against the protein extracts revealed different Immunoglobulin E reactivity of sera according to the insect target species: two bands (40 and 14 kDa) for crickets and a pattern including light responses at 17, 25 and 37 kDa for mealworms. Focusing on AK, low specific allergenicity was here illustrated and discussed in relation to the development of a safe edible insect consumption by humans.

What do we know about fish allergy at the End of the Decade?

Fish allergy is one of the most common food allergies. It is usually considered to be IgE-mediated and correlates well with diagnostic tests such as prick tests and/or determination of specific IgE. Avoidance is the recommended treatment and is generally extended to all fish species. However, new clinical presentations have been described. These include non-IgE-mediated disease, monosensitization, and new syndromes that are sometimes associated, surprisingly, with cross-reactivity. Advances in molecular allergy have provided insights into new allergens and have increased our understanding of cross-reactivity. This paper focuses on recent publications providing information for clinicians involved in the management of fish allergy

La alergia al pescado es una de las alergias alimentarias más frecuentes. Constituye habitualmente una alergia IgE mediada que se identifica correctamente mediante las pruebas cutáneas y/o la IgE específica in vitro. El tratamiento recomendado es la evitación de la ingesta habitualmente de todo tipo de pescados. Sin embargo, hay otras formas de presentación como la alergia no-IgE mediada, monosensibilizaciones y nuevos síndromes asociados a otros tipos de reactividad cruzada. Los avances en el diagnóstico molecular han descrito nuevos alérgenos y aumentado nuestro conocimiento sobre la reactividad cruzada. Este artículo analiza las publicaciones recientes que proporcionan nueva información para el tratamiento de la alergia a pescados

Lolium perenne peptide immunotherapy is well tolerated and elicits a protective B-cell response in seasonal allergic rhinitis patients.

BACKGROUND: Systemic allergic reactions are a risk for allergen immunotherapy that utilizes intact allergen preparations. We evaluated the safety, efficacy and immune mechanisms of short-course treatment with adjuvant-free Lolium perenne peptides (LPP) following a 6-week dose-escalation protocol. METHODS: In a prospective, dose-escalation study, 61 grass pollen-allergic patients received 2 subcutaneous injections of LPP once weekly for 6 weeks. Safety was assessed evaluating local reactions, systemic reactions and adverse events. The clinical effect of LPP was determined by reactivity to the conjunctival provocation test (CPT). Specific IgE, IgG4 and blocking antibodies were measured at baseline (V1), during (V6) and after treatment (V8). RESULTS: No fatality, serious adverse event or epinephrine use was reported. Mean wheal diameters after injections were <0.6 cm and mean redness diameters <2.5 cm, independent of dose. Transient and mostly mild adverse events were reported in 33 patients. Two patients experienced a grade I and 4 patients a grade II reaction (AWMF classification). At V8, 69.8% of patients became nonreactive to CPT. sIgG4 levels were higher at V6 (8.1-fold, P < .001) and V8 (12.2-fold, P < .001) than at V1. The sIgE:sIgG4 ratio decreased at V6 (-54.6%, P < .001) and V8 (-71.6%, P < .001) compared to V1. The absolute decrease in IgE-facilitated allergen binding was 18% (P < .001) at V6 and 25% (P < .001) at V8. CONCLUSION: Increasing doses of subcutaneous LPP appeared safe, substantially diminished reactivity to CPT and induced blocking antibodies as early as 4 weeks after treatment initiation. The benefit/risk balance of LPP immunotherapy remains to be further evaluated in large studies.

Automated point-of-care testing for ABO agglutination test: proof of concept and validation.

BACKGROUND AND OBJECTIVES: ABO-incompatible red blood cell transfusions still represent an important hazard in transfusion medicine. Therefore, some countries have introduced a systematic bedside ABO agglutination test checking that the right blood is given to the right patient. However, this strategy requires an extremely time-consuming learning programme and relies on a subjective interpretation of ABO test cards agglutination. We developed a prototype of a fully automated device performing the bedside agglutination test that could be completed by reading of a barcoded wristband. This POCT checks the ABO compatibility between the patient and the blood bag. MATERIALS AND METHODS: Proof of concept and analytical validation of the prototype has been completed on 451 blood samples: 238 donor packed red blood cells, 137 consecutive unselected patients for whom a blood group determination had been ordered and on 76 patient samples selected with pathology that could possibly interfere with or impair performances of the assay. RESULTS: We observed 100% concordance for ABO blood groups between the POCT and the laboratory instrument. CONCLUSION: These preliminary results demonstrate the feasibility of ABO determination with a simple POCT device eliminating manipulation and subjective interpretation responsible for transfusion errors. This device should be linked to the blood bank system allowing all cross-check of the results.

The "normobaric oxygen paradox": a new tool for the anesthetist?

Hypoxia is the natural trigger for endogenous EPO production but recently the use of intermittent hyperoxia to stimulate EPO has been postulated and this phenomenon has been called the "normobaric oxygen paradox" (NOP). The "NOP" is a mechanism by which oxygen regulates the expression of the Hypoxia Inducible Factor 1 alpha (HIF-1α). The HIF-1α-depending gene regulation is responsible for many different genetic expressions including EPO and VEGF. It has been proposed that relative changes of oxygen availability rather than steady state hypoxic or hyperoxic conditions, play an important role in HIF transcriptional effects. According to this hypothesis, the cell interprets the return to normoxia after a hyperoxic event as an oxygen shortage, and induces HIF-1-regulated gene synthesis, including EPO. Being both a hormone and a cytokine, the actual actions of EPO are complex; its clinical utility has been postulated for neuroprotection and cardioprotection. The precise level of inspired oxygen and the exact timeframe for its iterative administration are not totally known. N-Acetyl-L-Cysteine (NAC) supplementation has been shown to help. All the reported data demonstrate how hyperoxic and hypoxic states can potentially be manipulated if oxygen is been considered as a multifaceted molecule more than just a gas.

Potassium content of irradiated packed red blood cells in different storage media: is there a need for additive solution-dependent recommendations for infant transfusion?

Prevention of transfusion-associated graft versus host disease (TA-GVHD) by gamma irradiation is known to induce increased K+ in supernatant of packed red blood cells (PRBCs) stored in CPDA-1 and SAGM conservative solutions. However, no data exist for PRBCs in AS-3 medium which is considered safe for neonatal transfusion. We evaluated haemolysis and K+ release from irradiated AS-3 PRBCs and compared our results with reported data for SAGM and CPDA-1 PRBCs. Our results indicate that irradiated PRBCs stored in AS-3 after more than 7 days post-irradiation should not be used in massive and/or rapidly infused transfusions in neonates and infants.

Anti-cyclic citrullinated peptide antibodies: a comparison of different assays for the diagnosis of rheumatoid arthritis.

OBJECTIVES: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are highly specific markers of rheumatoid arthritis (RA). Considering the heterogeneity of the target antigens involved, and the test platforms and conjugates proposed in commercial anti-CCP assays, we assessed the diagnostic performances of four fully automated anti-CCP assays in a cohort of patients with RA compared to patients with other autoimmune and inflammatory disorders. We also evaluated the agreement between the qualitative results of these immunoassays. METHOD: We evaluated three anti-CCP2 assays [Eurodiagnostica enzyme-linked immunosorbent assay (ELISA), Elecsys electrochemiluminescence immunoassay (ECLIA) on the Modular E170 Analyzer, and Zenit chemiluminescence immunoassay (CLIA) on the Zenit RA Analyzer] and one anti-CCP3 assay (Inova ELISA). ELISAs were performed on an automated workstation. Samples from 112 patients with RA and a disease control group of 136 patients (53 with autoimmune diseases, 65 non-autoimmune disorders, and 18 infectious diseases) were studied (included 161 samples submitted consecutively to the laboratory). RESULTS: At a fixed specificity of 92%, the anti-CCP3 assay presented the highest sensitivity (75%) compared to the anti-CCP2 assays evaluated (63-72%). The Zenit anti-CCP2 assay gave the most false-positive results (especially in patients with viral infections and connective tissue diseases). The agreement between assays ranged from 86.3% to 95.2% and Kappa coefficients ranged from 0.724 to 0.899. CONCLUSIONS: Recently released automated workstations provide a valuable alternative to ELISA to diagnose RA. However, differences in diagnostic performances are highlighted in our experience, especially for the Zenit assay. In our cohort, the anti-CCP3 assay gave slightly better performances than the anti-CCP2 assays (with the exception of the Zenit assay).

An automated chemiluminescence immunoassay may detect mostly relevant IgG anticardiolipin antibodies according to revised Sydney criteria.

BACKGROUND: Detection of anticardiolipin antibodies (ACA) is an independent laboratory criterion for diagnosis of antiphospholipid syndrome (APS). Alternative methods to ELISA were recently developed such as automated chemiluminescence immunoassay (CLIA). PATIENTS AND METHODS: We compared a CLIA to an ELISA kit for the detection of IgG isotype of ACA. 87 routine samples from 75 patients suspected of having APS were tested using each method. Cut-off values were calculated in our laboratory for each test using 99th percentile of 50 normal controls. RESULTS: Cut-off values were >20 GPL for ELISA and > 2 GPL for CLIA. Overall agreement (OA), agreement for positive (AP) and agreement for negative (AN) cases were 56.3%, 49.2% and 77.2% respectively. Most discrepant results were positive with ELISA and negative with CLIA. However, OA, AP and AN increased to 82.1%, 84.6% and 80% respectively when CLIA was compared to the repeated ELISA performed at least 12 weeks later. When correlated with APS-related clinical background, CLIA showed lower sensitivity, higher specificity and higher likelihood ratio (LR) as compared to first ELISA whereas these parameters were similar to those of the repeated ELISA. No association was found between any test results and APS-related clinical background of the patients. Using our own cut-off value (> 2GPL), sensitivity, specificity and LR of CLIA to identify patients with APS were respectively 100%, 72.3% and 3.6. A ROC curve showed that at 7.5 GPL cut-off value, specificity and LR improved to 91.1% and 11.25 respectively, without affecting sensitivity. A strong correlation was observed between CLIA results and APS (Chi2 = 12.25; p < 0.001). CONCLUSION: The performance of CLIA is as good as a repeated ELISA test to detect IgG ACA in suspected APS patients. It is fully automated, which represents several advantages over semi-manual ELISA techniques for its implementation in a routine laboratory.

Unusual cause of right iliac fossa pain: sigmoid perforation due to ingested rabbit bone. Case report.

Disorders of an organ not usually found in the right iliac fossa, such as the sigmoid colon, are an uncommon cause of right iliac fossa pain. We present a case of right iliac fossa pain caused by a sigmoid perforation due to involuntary ingestion of a rabbit bone, and describe the main features of this condition.

Renal biopsy findings in Belgium: a retrospective single center analysis.

Renal biopsy is the definitive diagnostic test in patients with renal parenchymal disease. Renal biopsy registry is an important tool which can provide valuable data concerning early and correct epidemiological description and clinical correlations of renal diseases. Records of 326 adult renal biopsies performed at our hospital from January 1991 till the end of December 2006 were retrospectively examined. Overall, secondary glomerular diseases (SGD) were predominant (39.9%), followed by primary glomerular diseases (PGD) (30.4%), vascular diseases (13.2%) and TIN (6.7%). Total sclerosis of the kidney did not allow histopathological diagnosis in 5.8% of all biopsied kidneys. Focal and Segmental Glomerular Sclerosis (FSGS), IgA Nephropathy (IgAGN) and Minimal Change Disease (MCD) and Membranous Glomerulopathy (MGN) were the most common PGD, altogether representing 75.7% of all PGD. FSGS was the most frequent (30.3%), followed by IgAGN (21.2%), MCD (19.1%) and MGN in 15.1%. Vasculitis, HIVAN, diabetic nephropathy and amyloidosis were the most common SGD, altogether representing 90% of all SGD. Immune Mediated Glomerulonephritis (IMGN) were the most frequent (32.3%), followed by HIVAN (16.9%), diabetic nephropathy (14.6%) and amyloidosis (10%). Nephroangiosclerosis (benign and malignant nephroangiosclerosis) was the most frequent vascular nephropathy responsible for 79% of all vascular diseases. Thrombotic microangiopathy was seen in 9.3% and atherothrombotic disease in 7% of all vascular diseases. Concerning tubular diseases, chronic TIN accounted for 63.6% of all tubular diseases, followed by light chain-cast nephropathy (22.7%) and acute TIN (13.6%). Because of lack of material, 3.4% of all biopsies could not be analyzed. These data demonstrate that the distribution of biopsy-proved renal diseases in a Belgian population of the Brussels area is strongly influenced by the indications of renal biopsy. Harmonization of these indications might reflect with more accuracy the actual incidence of different nephropathies in a given population. Nation and worldwide renal biopsy registers are important to follow patterns of renal diseases in different populations. This information is important not only for health organizations in order to plan health budget but also for helping clinicians to provide a better care to patients.

The normobaric oxygen paradox: a novel way to administer oxygen as an adjuvant treatment for cancer?

The "normobaric oxygen paradox" is a dual mechanism by which oxygen regulates the expression of the Hypoxia Inducible Factor 1 alpha (HIF-1α). The HIF-1α-depending gene regulation is responsible for many different genetic expressions including EPO and VEGF that are usually expressed in parallel. First, VEGF under-expression could decrease tumor angiogenesis leading to a decrease in tumor growth or even apoptosis of cancer cells. Second, induction of EPO-expression can provide cytoprotection. Altogether, this could be deleterious for cancer cells while helping non-malignant cells (at least neural and cardiac) cells to be protected from the side effects of chemotherapy. Eventually, HIF induction could boost immune response by inflammatory cells, increasing their antitumor activity.

Recurrent haemophagocytic syndrome in an HIV-infected patient.

We describe a case of recurrent haemophagocytic syndrome (HS) in an HIV-infected patient.The first episode was associated with active human herpesvirus 8 infection and progressive Kaposi's sarcoma which was successfully treated with splenectomy, foscarnet and chemotherapy. The second episode was triggered by a Clostridium difficile colitis and resolved completely after treatment with metronidazole only. Recurrent HS has rarely been described in adult patients out of the setting of relapsing malignancy or autoimmune disease.The chronic immune dysregulation and suppression due to HIV-infection may predispose our patient to development of associated HS. Prognosis of HS remains poor, especially in HIV-infected patients. Rapidly unmasking the causative factor and timely instauration of adequate treatment are critical and may improve outcome.

Evaluation of the procoagulant activity in the plasma of cancer patients using a thrombin generation assay.

INTRODUCTION: Circulating microparticles are reported to play a role in cancer hypercoagulability. The procoagulant properties of microparticles derive from the amount of tissue factor and/or phosphatidylserine that they can expose. The aim of our study is to assess the procoagulant activity, including microparticles' activity, in the plasma of newly diagnosed cancer patients with a simple assay, easy to implement in the laboratory. MATERIAL AND METHODS: Newly diagnosed cancer patients (n=31) before the start of anticoagulant or chemotherapy were compared to matched controls. We used a thrombin generation assay in four conditions: 1: addition of 1 pM tissue factor and 4 µM procoagulant phospholipids, 2: without any trigger, 3 and 4: addition of tissue factor or procoagulant phospholipids alone respectively. RESULTS: When we added only phospholipids, so that thrombin generation is dependent upon endogenous tissue factor, the lag time was significantly shorter in cancer patients. When we added only tissue factor, i.e. made the results dependent upon phospholipids, the endogenous thrombin potential, the peak, and the velocity index were significantly higher and the time-to-peak was significantly shorter. This suggests that the plasma of cancer patients contained a higher activity of endogenous phospholipids and/or tissue factor which may be borne by microparticles. CONCLUSION: This new simple methodology can demonstrate a procoagulant activity in the plasma of newly diagnosed cancer patients which can be explained by higher procoagulant phospholipids and tissue factor activity and thus, brings potentially useful information that current coagulation tests cannot provide.

Helical axis calculation based on Burmester theory: experimental comparison with traditional techniques for human tibiotalar joint motion.

In prosthetics and orthotics design, it is sometimes necessary to approximate the multiaxial motion of several human joints to a simple rotation about a single fixed axis. A new technique for the calculation of this axis is proposed, originally based on Burmester's theory. This was compared with traditional approaches based on the mean and finite helical axes. The three techniques were assessed by relevant optimal axis estimation in in vitro measurements of tibiotalar joint motion. A standard jig and radiostereometry were used in two anatomical specimens to obtain accurate measurements of joint flexion. The performance of each technique was determined by comparing the motion based on the resulting axis with the experimental data. Random noise with magnitude typically similar to that of the skin motion was also added to the measured motion. All three techniques performed well in identifying a single rotation axis for tibiotalar joint motion. Burmester's theory provides an additional method for human joint motion analysis, which is particularly robust when experimental data are considerably error affected.

[Physiopathologic aspects of anemia and thrombocytopenia in children with cancers: the roles of erythropoietin and thrombopoietin]. / Aspects de la physiopathologie de l'anémie et de la thrombocytopénie associées a une affection néoplasique chez l'enfant: rôles de l'erythropoïétine et de la thrombopoïétine.

Physiopathology of anaemia and thrombocytopaenia in children with malignancy: the role of erythropoietin and thrombopoietin. The aim of our work was to determine the role of an impaired erythropoietin (EPO) and thrombopoietin (TPO) production in development of, respectively, the anaemia and thrombocytopaenia in children with malignancy. Simultaneous dosage of EPO and of serum transferrin receptor have shown that anaemia in these patients is of central origin but related to a blunted EPO production. The same observation has been made in children at diagnosis either with acute leukaemia or solid tumour as well as during chemotherapy. In patients under maintenance chemotherapy for acute leukaemia, using long-term bone marrow cultures, we could detect an impaired supportive capacity of bone marrow micro-environment for erythropoiesis. The last part of this work has shown that thrombocytopaenia associated with acute leukaemia in children is accompanied by very high TPO levels as observed in other thrombocytopaenia of central origin, excepted in patients with acute leukaemia of myeloid origin. In these patients, TPO levels are inappropriately low in most cases. The low TPO levels are related to the presence of TPO receptor-expressing myeloid leukaemic cells, suggesting that TPO is "consumed" by blast cells expressing a functional TPO receptor.

Application of Origanum majorana L. essential oil as an antimicrobial agent in sausage.

This work reports on the antimicrobial activity in fresh sausage of marjoram (Origanum majorana L.) essential oil against several species of bacteria. The in vitro minimum inhibitory concentration (MIC) was determined for 10 selected aerobic heterotrophic bacterial species. The antimicrobial activity of distinct concentrations of the essential oil based on the highest MIC value was tested in a food system comprising fresh sausage. Batch food samples were also inoculated with a fixed concentration of Escherichia coli and the time course of the product was evaluated with respect to the action of the different concentrations of essential oil. Results showed that addition of marjoram essential oil to fresh sausage exerted a bacteriostatic effect at oil concentrations lower than the MIC, while a bactericidal effect was observed at higher oil concentrations which also caused alterations in the taste of the product.

Hemophagocytic syndrome associated with extracerebral toxoplasmosis in an HIV-infected patient.

Hemophagocytic syndrome (HPS) is a clinical entity that combines non-specific clinical and biological features. The diagnosis is usually confirmed by a bone marrow examination. HPS may be primary or secondary to a malignancy or to an infectious or autoimmune disease. Since it was first described, various agents have been implicated, including viruses, bacteria, and parasites. In HIV patients, many cases occur with lymphoma or with a variety of opportunistic infections due to CMV, HHV8, Pneumocystis carinii, Mycobacterium tuberculosis, MAC, toxoplasmosis, and even pneumococcus. We report here a case of an AIDS patient presenting a HPS secondary to an extracerebral form of systemic toxoplasmosis that was only revealed by specific PCR in tissue other than the CNS.

Finite element analysis of a total ankle replacement during the stance phase of gait.

Total ankle replacement (TAR) designs have still several important issues to be addressed before the treatment becomes fully acceptable clinically. Very little is known about the performance, in terms of the contact pressures and kinematics of TAR when subjected to daily activities such as level gait. For this purpose, an explicit finite element model of a novel 3-component TAR was developed, which incorporated a previously validated mechanical model of the ankle ligament apparatus. The intermediate mobile polyethylene meniscal bearing was modelled as an elastic-plastic continuum while the articulating surfaces of the tibial and talar metal components as rigid bodies. Overall kinematics, contact pressures and ligament forces were analysed during passive, i.e. virtually unloaded, and active, i.e. stance phase of gait, conditions. Simulation of passive motion predicted similar kinematics as reported previously in an analytical four-bar linkage model. The meniscal bearing was observed to move 5.6 mm posteriorly during the simulated stance and the corresponding antero-posterior displacement of the talar component was 8.3 mm. The predicted pattern and the amount (10.6 degrees ) of internal-external rotation of the ankle complex were found to be in good agreement with corresponding in vivo measurements on normal ankles. A peak contact pressure of 16.8 MPa was observed, with majority of contact pressures below 10 MPa. For most ligaments, reaction forces remain within corresponding physiological ranges. A first realistic representation of the biomechanical behaviour of the human ankle when replaced by prosthetic joints is provided. The applied methodology can potentially be applied to other TAR designs.