Skin prick test to egg white provides additional diagnostic utility to serum egg white-specific IgE antibody concentration in children

BACKGROUND: Levels of IgE antibody to egg white of greater than 7 kIU/L are highly predictive of clinical reactivity to egg, and lower levels often require evaluation with oral food challenge (OFC) to establish definitive diagnosis. OFCs have inherent risks, and diagnostic criteria indicating high likelihood of passing would be clinically useful. OBJECTIVE: We sought to determine whether the size of the skin prick test (SPT) to egg white adds diagnostic utility for children with low egg white-specific IgE antibody levels. METHODS: A retrospective analysis of clinical history, egg white-specific IgE antibody levels, SPT responses, and egg OFC outcomes was performed. RESULTS: Children who passed (n = 29) egg OFCs and those who failed (n = 45) did not differ significantly in age, clinical characteristics, or egg white-specific IgE levels. There were, however, significant differences between both egg white SPT wheal response size and egg/histamine SPT wheal index. Children who failed egg OFCs had a median wheal of 5.0 mm; those who passed had a median wheal of 3.0 mm (P = .003). Children who failed egg OFCs had a median egg/histamine index of 1.00; those who passed had a median index of 0.71 (P = .001). For egg white-specific IgE levels of less than 2.5 kIU/L, an SPT wheal of 3 mm or an egg/histamine index of 0.65 was associated with a 50% chance of passing. CONCLUSION: In children with low egg white-specific IgE levels, those with smaller SPT wheal responses to egg were more likely to pass an egg OFC than those with larger wheal responses. The size of the egg white SPT response might provide additional information to determine the timing of egg OFC. CLINICAL IMPLICATIONS: The size of the egg white SPT wheal response might provide the clinician with additional information to determine the timing of egg OFC in children with low egg white-specific IgE antibody levels.     

Biopsy proven morphea treated with tacalcitol ointment: case report

A 43-year-old woman presented with a widespread morphea, which had its onset three months before. The patient had several plaques of active, pigmented, lilac halo disease on the trunk, arms and thighs. A biopsy confirmed that the patient was suffering from morphea. Therapy with clobetasol propionate ointment 0.05% was introduced, applied twice a day, 5 days a week. After a month, the ointment failed to significantly improve the lesions. Then the patient was treated with clobetasol ointment in the morning and tacalcitol ointment 4 mcg/g in the evening. This combination resulted in marked improvement of the disease after 20 days of therapy, and we decided to stop topical steroid. After three months of treatment with topical tacalcitol once a day, the plaques regressed considerably and only a very slight pigmentation remained. Therapy was further reduced to one evening, every other day for six months more, and then was suspended completely. No side effects were observed and there was no recurrence at 24-month follow up.     

Curcumin-conjugated nanoliposomes with high affinity for Aβ deposits: Possible applications to Alzheimer disease

Accumulation of amyloid peptide (Aβ) in senile plaques is a hallmark lesion of Alzheimer disease (AD). The design of molecules able to target the amyloid pathology in tissue is receiving increasing attention, both for diagnostic and for therapeutic purposes. Curcumin is a fluorescent molecule with high affinity for the Aβ peptide but its low solubility limits its clinical use. Curcumin-conjugated nanoliposomes, with curcumin exposed at the surface, were designed. They appeared to be monodisperse and stable. They were non-toxic in vitro, down-regulated the secretion of amyloid peptide and partially prevented Aβ-induced toxicity. They strongly labeled Aβ deposits in post-mortem brain tissue of AD patients and APPxPS1 mice. Injection in the hippocampus and in the neocortex of these mice showed that curcumin-conjugated nanoliposomes were able to specifically stain the Aβ deposits in vivo. Curcumin-conjugated nanoliposomes could find application in the diagnosis and targeted drug delivery in AD.From the Clinical EditorIn this preclinical study, curcumin-conjugated nanoliposomes were investigated as possible diagnostics and targeted drug delivery system in Alzheimer’s disease, demonstrating strong labeling of Aβ deposits both in human tissue and in mice, and in vitro downregulation of amyloid peptide secretion and prevention of Aβ-induced toxicity.     

Imaging of neoplasms of the paranasal sinuses

The assessment of sinonasal malignancies requires a multidisciplinary team approach. Advances in pretherapeutic imaging have significantly contributed to the management of sinonasal tumors. CT and MR imaging play complementary roles in the assessment and staging of these malignancies by determining the presence or absence of extension of disease into the skull base and its foramina, the orbit, and the intracranial compartment.     

Familial primary mediastinal nonseminomatous germ-cell tumors

In this article, we describe the case of 4 brothers, 2 of which had primary mediastinal nonseminomatous germ cell tumors (PMNSGCT), while the other 2 had benign mediastinal disease. We discuss the relationship between these diseases of the mediastinum and the thymic microenvironment. Additionally, we suggest that a genetic predisposition for germ-cell tumors (GCT) may be involved since the parents were relatives.     

Human-Relevant Sensitivity of iPSC-Derived Human Motor Neurons to BoNT/A1 and B1

The application of botulinum neurotoxins (BoNTs) for medical treatments necessitates a potency quantification of these lethal bacterial toxins, resulting in the use of a large number of test animals. Available alternative methods are limited in their relevance, as they are based on rodent cells or neuroblastoma cell lines or applicable for single toxin serotypes only. Here, human motor neurons (MNs), which are the physiological target of BoNTs, were generated from induced pluripotent stem cells (iPSCs) and compared to the neuroblastoma cell line SiMa, which is often used in cell-based assays for BoNT potency determination. In comparison with the mouse bioassay, human MNs exhibit a superior sensitivity to the BoNT serotypes A1 and B1 at levels that are reflective of human sensitivity. SiMa cells were able to detect BoNT/A1, but with much lower sensitivity than human MNs and appear unsuitable to detect any BoNT/B1 activity. The MNs used for these experiments were generated according to three differentiation protocols, which resulted in distinct sensitivity levels. Molecular parameters such as receptor protein concentration and electrical activity of the MNs were analyzed, but are not predictive for BoNT sensitivity. These results show that human MNs from several sources should be considered in BoNT testing and that human MNs are a physiologically relevant model, which could be used to optimize current BoNT potency testing.     

Serial re-challenge with influenza vaccine as a tool to study individual immune responses

With new treatments of inflammatory diseases targeting key inflammatory pathways follows an increased risk for infections. The aim of the present study was to identify an immunological readout where consecutive immunizations induce reproducible immune responses. Such a method could be used as a tool to assess drug-induced immunomodulation in individual patients by comparing responses to the immunizations before and after introduction of a specific treatment. Importantly, the vaccine is merely used as a model antigen and protective immunity is not the primary aim of the method. Eleven volunteers were immunized with influenza vaccine three times, four weeks apart. In order to find the optimal readout for the method, immune responses to the immunizations were measured as circulating antigen-specific B-cells, serum antibody titers and avidity, T-cell proliferation and cytokine secretion. The first exposure to the influenza vaccine induced a stronger B- and T-cell responses than the consecutive immunizations. The second and third immunizations induced comparable but lower B-cell responses as measured by ELISPOT. In summary, we have measured immune responsiveness by using repeated immunizations with influenza virus vaccine as the model antigen. The induction of comparable B-cell responses after the second and third serial immunizations provides a possibility to investigate effects on immune responsiveness by immunomodulatory drugs. The method also allows humoral memory and immune competence per se to be studied on a cellular level in different patient groups.