Short wheat challenge is a reproducible in-vivo assay to detect immune response to gluten.

It has been reported that interferon (IFN)-γ-secreting T cells reactive to gluten can be detected in the peripheral blood of individuals with treated coeliac disease (CD) after a short consumption of wheat-containing food. By contrast, very little is known about the reproducibility of this in-vivo procedure in the same patient cohort which underwent two, or more, gluten consumptions. Fourteen coeliac patients in remission consumed wheat bread for 3 days; 13 underwent a second gluten challenge after a wash-out of 3-10 months on a strict gluten-free diet. Immune reactivity to gluten was analysed in peripheral blood by detecting IFN-γ before and 6 days after commencing a gluten diet. Gliadin-specific IFN-γ-secreting CD4(+) T cells increased significantly on day 6 of the first challenge. These cells resulted as prevalently human leucocyte antigen (HLA)-DQ restricted and with a phenotype of gut homing, as suggested by the expression of ß7-integrin. Similarly, reactiveness to gliadin was observed after the second wheat consumption, although with an individual variability of responses at each challenge. Our findings confirmed that the short wheat challenge is a non-invasive approach to investigate the gluten-related immune response in peripheral blood of subjects intolerant to gluten. Furthermore, we demonstrated that the in-vivo procedure can be reproduced in the same subject cohort after a gluten wash-out of at least 3 months. Our study has important implications for the application of this procedure to clinical practice.

Update on early cardiovascular and metabolic risk factors in children and adolescents affected with growth hormone deficiency.

Growth hormone (GH), in addition to promote linear growth during childhood, exerts a key role in several processes of substrate metabolism. Adults with untreated GH deficiency and adolescents who discontinued GH therapy at completion of growth, exhibit a cluster of cardiovascular risk factors such as impaired cardiac performance, alteration in body proportion with increased visceral fat, dyslipidemia and hypertension, that could place them at higher risk of cardiovascular morbidity. Although studies on adolescents and children are still scarce, there is evidence that early markers of cardiovascular disease can be already detected in untreated children with GH deficiency and that, as in adults, GH replacement therapy exerts a beneficial role on metabolic alterations. Untreated GH deficiency in childhood and adolescence seems to be associated with reduced cardiac size and impaired cardiac function, dyslipidemia, abnormalities in body composition and in peripheral inflammatory markers. GH replacement therapy exerts a beneficial effects on most of these alterations. Aim of this review is to summarize the current findings on the effects of GH deficiency and GH treatment on early cardiovascular risk factors in children and adolescents.

Deconvolution of 40 Hz steady-state fields reveals two overlapping source activities of the human auditory cortex.

Steady-state auditory evoked fields were recorded from 15 subjects using a whole head MEG system. Stimuli were 800 ms trains of binaural clicks with constant stimulus onset asynchrony (SOA). Seven different SOA settings (19, 21, 23, 25, 27, 29 and 31 ms) were used to give click rates near 40 Hz. Transient responses to each click were reconstructed using a new algorithm that deconvoluted the averaged responses to the different trains. Spatio-temporal multiple dipole modelling in relation to 3D MRI scans revealed two overlapping source components in both the left and right auditory cortex. The primary sources in the medial part of Heschl's gyrus exhibited a N19-P30-N40 m pattern. The secondary, weaker sources at more lateral sites on Heschl's gyrus showed a N24-P36-N46 m pattern. When applied to transient middle latency auditory evoked fields (MAEFs) recorded at SOAs of 95-135 ms, the primary sources imaged activities similar to the deconvoluted steady-state responses, but the secondary source activities were inconsistent. Linear summation of the deconvoluted source waveforms accounted for more than 96% of the steady-state variance. This indicates that the primary activity of the auditory cortex remains constant up to high stimulation rates and is not specifically enhanced around 40 Hz.

Thyroid medullary carcinoma with thyroglobulin immunoreactivity in sporadic multiple endocrine neoplasia type 2-B.

BACKGROUND: Thyroid carcinomas historically have been divided into two groups according to their presumedly separate embryonic origins: those of neuroectodermal derivation (parafollicular or medullary carcinoma [MCT]) and those of foregut endodermal origin (follicular and papillary carcinomas). The validity of this concept has been questioned by the recognition that some MCT may show immunocytochemical and ultrastructural evidence of follicular components, and display features of follicular function (e.g., organification of iodine, immunoreactivity for thyroglobulin). METHODS: A 14-year-old boy presented with the physical features of multiple endocrine neoplasia type 2-B (MEN 2B) and a thyroid mass. His thyroid lesion was studied by light microscopy; electron microscopy; immunohistochemistry using antisera to calcitonin, thyroglobulin, and other peptides; and in situ hybridization. RESULTS: The tumor was identified as an MCT by light microscopy. It stained positively with calcitonin, thyroglobulin, chromogranin, neuron-specific enolase, and serotonin. At the ultrastructural level, the tumor cells contained numerous neurosecretory granules and showed evidence of follicular differentiation (luminal microvilli, follicle formation, and tight junctions), suggesting a dual neuroendocrine and follicular differentiation. CONCLUSIONS: The morphologic findings suggest that a small number of MCTs arise from a common stem cell (possibly the ultimobranchial body) that may give rise to both MCT and follicular carcinoma. This patient and patients in similar cases documented in the literature challenge the classic concept of separate pathways of embryogenesis for these two cell types.