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.

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.

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).

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.

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.

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.

[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.

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.

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.

Mechanics of the anterior drawer test at the ankle: the effects of ligament viscoelasticity.

The anterior drawer test at the human ankle joint is a routine clinical examination. The relationship between the mechanical response of this joint and the flexion angle was elucidated by a recent mathematical model, using purely elastic mechanical characteristics for the ligament fibres. The objective of the present work was to assess the effect of ligament viscoelasticity on the force response of the ankle joint for anterior displacements of the foot relative to the tibia, at different ankle flexion positions. A viscoelastic model of the ligaments from the literature was included in the recently proposed mathematical model. Drawer tests were simulated at several flexion angles and for increasing velocities of the imposed anterior displacement. The stiffness of the model ankle joint increased only modestly with velocity. The response force found for a 6mm displacement at 20 degrees plantarflexion increased by only 13% for a one hundred-fold increase in velocity from 0.1 to 10 mm/s. The flexion angle was confirmed as the most influential parameter in the mechanical response of the ankle to anterior drawer test.

Natural killer (NK) cells inhibit human umbilical cord blood erythropoiesis.

To examine the role of NK cells on in vitro human umbilical cord (HUC) blood erythropoietic progenitor growth, 25 normal HUC blood samples were depleted of CD56+ cells by using immunomagnetic beads coated with CD56 monoclonal antibodies (mAb). When stimulated by erythropoietin (Epo) to form colonies in plasma clot medium, the CD(56+)-depleted preparations demonstrated a two-fold increase in the number of early erythropoietic progenitors (BFU-E) over nondepleted preparations. This stimulatory effect of CD56+ depletion on BFU-E growth was not due to artifactual stimulations of other accessory cells by the mAb or the dynabeads used in the depletion procedure, since separate addition of these materials to culture did not exert any stimulatory effect on BFU-E growth. Direct co-culture of purified NK and autologous cord blood mononuclear cells (MNC) in plasma clot medium resulted in a dose-dependent decrease in BFU-E population. In addition, when NK and MNC were cocultured separately in double-layer cultures, the expansion of BFU-E was significantly decreased. Because direct cell-to-cell contact is prohibited in double-layer cultures, the observed inhibition of BFU-E proliferation could be mediated at least in part through soluble factors. To test this hypothesis, NK cell supernatant fluid obtained 24 hours after NK cell incubation was added to plasma clot culture medium. A significant decrease in BFU-E number was again observed. In conclusion, our results indicate that HUC blood BFU-E proliferation is inhibited by NK cells, and that the mechanism of this inhibition is mediated, at least in part, by one or more humoral factors.

Lithium inhibits calcitriol-stimulated formation of multinucleated cells in human long-term marrow cultures.

We observed that lithium (3 mM) blocked the 1,25-dihydroxyvitamin D [1,25-(OH)2D3]-stimulated bone resorption in fetal rat long bones in culture. Because this inhibitory effect was not seen when bone resorption was stimulated by parathyroid hormone or interleukin-1, we reasoned that Li specifically inhibited events involved in the 1,25-(OH)D3-stimulated bone resorption. The increased bone resorption induced by vitamin D in culture is associated with differentiation and/or fusion of osteoclast progenitors. In the present work, we studied the effect of Li on the basal and 1,25-(OH)2D3-stimulated generation of multinucleated osteoclast-like cells (MNC) and MNC containing tartrate-resistant acid phosphatase (TRAP+) in long-term human bone marrow cultures. Total MNC and TRAP+ cells were counted after 3 weeks of culture. In the absence of both lithium and 1,25-(OH)2D3, total MNC and TRAP+ cell numbers were 146 +/- 22 and 110 +/- 18 per well, respectively (mean +/- SEM); in the presence of Li, corresponding figures were 79 +/- 17 and 59 +/- 14. When the generation of MNC and TRAP+ cells was stimulated with 1,25-(OH)2D3, (10(-8) M), total MNC and TRAP+ cells were 521 +/- 66 and 473 +/- 63, respectively, in the absence of Li and 251 +/- 44 and 155 +/- 27 in the presence of Li (p < 0.05). The inhibitory effect of Li was dose dependent and was not observed when the cultures were exposed to parathyroid hormone instead of 1,25-(OH)2D3.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis of subtype 2B von Willebrand disease in a patient with 2A phenotype of plasma von Willebrand factor.

Type 2A of von Willebrand disease refers to qualitative variants with decreased platelet dependent function that is associated with the absence of high molecular weight forms of von Willebrand factor (vWF) multimers. Type 2B refers to qualitative variants with increased affinity for platelet glycoprotein Ib. In this report we describe the study of a patient who has been previously diagnosed as having subtype 2A von Willebrand disease (vWD), because she had no heightened ristocetin-induced platelet aggregation, no large and intermediate molecular weight von Willebrand factor (vWF) multimers in plasma, and no increase in plasma vWF capacity to bind to normal platelets in the presence of low ristocetin concentrations. The DNA sequencing of the 3' part of the exon 28 of the vWF gene where most of the subtype 2A mutations have already been identified, did not detect any nucleotide change. At variance, a G to A transition changing the encoded amino acid residue from Val 553 to Met in mature vWF, was found in the 5' part of this exon. This mutation which has already been found in several unrelated families with 2B vWD and the increased binding of the patient platelet vWF on normal platelets in the presence of low ristocetin concentrations provide evidence for subtype 2B vWD. This study thus illustrates the importance of the molecular characterization of patients in the correct diagnosis and classification of type 2 vWD.

Effects of CGRP on human osteoclast-like cell formation: a possible connection with the bone loss in neurological disorders?

Osteoclast-like cell (OCL-like) differentiation is increased in long term cultures of bone marrow taken from paralyzed areas of paraplegic patients. Among the neuropeptides recently described in bone, calcitonin gene-related peptide (CGRP) has been shown in animal studies to inhibit bone resorption in vivo and OCL-like differentiation in vitro: its deficiency could thus be a link between the neural lesion and increased OCL-like production in paraplegia and some other neurologic disorders. We therefore investigated in this study the effects of CGRP on human OCL-like formation and found that it indeed has an inhibitory effect mediated at least in part via cAMP.

Growth hormone (GH)-releasing hormone-induced GH response in hypothalamic amenorrhea: evidence of altered central neuromodulation.

OBJECTIVE: To evaluate the GH-releasing hormone (GH-RH)-induced response of GH in patients affected by hypothalamic amenorrhea. DESIGN: Patients affected by weight-loss-related hypothalamic amenorrhea (n = 28) were studied and compared with 20 healthy controls. Among patients with weight-loss amenorrhea, both hypogonadotropic and normogonadotropic conditions were present. All subjects underwent a GH-RH test (GEREF, Sereno, Rome, Italy) (1 microgram/kg body weight IV). Plasma GH concentrations were determined using commercially available RIAs. Also, in selected samples insulin-like growth factor-I (IGF-I) levels were measured. RESULTS: Basal plasma IGF-I levels as well as body mass index (BMI) were lower in amenorrheic patients than in healthy controls. No significant correlation was found between BMI and IGF-I or E2 plasma levels or between LH and IGF-I plasma levels. The basal GH plasma levels were comparable in all groups of subjects. The GH-RH--induced GH response evaluated as maximal release and as area under the curve (AUC) was higher in amenorrheic patients than in control subjects. CONCLUSIONS: The amenorrheic condition associated with reduced BMI changes the GH-RH--induced GH response in hypothalamic amenorrhea, supporting a GH and a IGF-I disregulation in weight-loss--related amenorrhea.

Ligament fibre recruitment and forces for the anterior drawer test at the human ankle joint.

Although the anterior drawer test at the ankle joint is commonly used in routine clinical practice, very little is known about the sharing of load between the individual passive structures and the joint response at different flexion angles.A mathematical model of the ankle joint was devised to calculate ligament fibre recruitment and load/displacement curves at different flexion angles. Ligaments were modelled as three-dimensional arrays of fibres, and their orientations at different flexion angles were taken from a previously validated four-bar-linkage model in the sagittal plane. A non-linear stress/strain relationship was assumed for ligament fibres and relevant mechanical parameters were taken from two reports in the literature. Talus and calcaneus were assumed to move as a single rigid body. Antero/distal motion of the talus relative to the tibia was analysed. The ankle joint was found to be stiffer at the two extremes of the flexion range, and the highest laxity was found around the neutral position, confirming previous experimental works. With a first dataset, a 20N anterior force produced 4.3, 5.5, and 4.4mm displacement respectively at 20 degrees plantarflexion, at neutral, and at 20 degrees dorsiflexion. At 10 degrees plantarflexion, for a 6mm displacement, 65% of the external force was supported by the anterior talofibular, 11% by the deep anterior tibiotalar and 5.5% by the tibionavicular ligament. Corresponding results from a second dataset were 1.4, 2.4 and 1.8mm at 40N force, and 80%, 0% and 2% for a 3mm displacement. A component of the contact force supported the remainder.

Acute inflammation effects on in vivo granulopoiesis: comparative studies in healthy and leukaemic mice.

Mice undergoing an inflammatory reaction, induced by subcutaneous implantation of copper rods, elaborate two kinds of humoral stimulatory factors: the diffusible granulopoietic stimulator (DGS) that enhances diffusion chamber (DC) granulopoiesis, and the serum colony stimulating factor (CSF) that stimulates in vitro granulocyte-monocyte colony growth. We demonstrate here that mice suffering from acute myeloid leukaemia (AML) are unable to augment the production of these humoral stimulatory factors when acute inflammation is induced. Moreover, our results show that increased levels of normal humoral stimulatory factors (DGS and CSF) do not influence the proliferation and/or the differentiation of leukaemic cells implanted in DC.

[Discrepancy between histopathological diagnosis based on guided biopsy and cone biopsy of the cervix uteri: analysis of 346 cases of laser conization]. / Discrepanza tra diagnosi istopatologica su biopsia mirata e su biopsia conica della cervice uterina: analisi di 346 casi di laser-conizzazione.

The conservative management of cervical intraepithelial neoplasia (CIN) essentially depended on the introduction and improvement of colposcopy. This technique, allowing to locate the lesion, to estimate its extension and to perform multiple punch biopsies, becomes discriminant in therapeutic choice. Whether colposcopy reveals endocervical involvement or abnormal transformation zone (ANTZ) may be only partially explored, excisional conization should be preferred to ablative therapy since the former advantageously can verify histopathologic diagnosis, confirm completely excision of lesion and rule out invasive carcinoma. The literature shows that cases of invasive lesions can be underestimated and therefore inadequately treated by ablative therapy, emphasizing colposcopy and punch biopsy limitations about suspect and diagnosis of microinvasion. We analyzed data concerning preliminary diagnostic investigations and results of 346 CO2 laser excisional conizations performed between 1984 and 1993. Histopathologic diagnosis on punch biopsy, performed in 111 cases of ANTZ1 and in 235 cases of ANTZ2, shows an agreement with cone biopsy in 30.8% of the cases of CIN1, of 40.9% in cases of CIN2 and of 66.3% in cases of CIN3. Whereas the lesion is overestimated in 30.6% of cases, in which it is likely that punch biopsy has removed the epicenter of the lesion or the lesion in toto, we had an underestimation in 15% of cases, particularly in 4 cases of CIN2, in 38 cases of CIN3 and in all microinvasive processes. The rate of invasive lesions previously ignored and detected only by histopathologic diagnosis on cone biopsy is 2.9%. In only one of these cases colposcopy, even if attributing to each of these the higher grading, shows the suspicion of invasion, whereas the detection of invasive processes is missed in every case by punch biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

[Regulation of erythropoiesis: recent progress and current uncertainties]. / La régulation de l'érythropoïèse: acquisitions récentes et incertitudes actuelles.

Rapid progress has occurred recently in characterizing the molecular structure of the glycoproteins controlling the growth, maturation and functional activities of hematopoietic cells. Several of these factors have been purified and cDNAs have been cloned, providing them in sufficient quantities for study and eventual clinical use. Both availability of these molecules and in vitro colony assays have revealed a large number of effects on erythroid differentiation. But, except erythropoietin (EPO), the physiological role of these hormones and their relative contributions to normal erythropoiesis remain to be specified. This paper attempts to review the most important data on this topic in 1990.