Iodine-induced hypothyroidism in full-term infants with congenital heart disease: more common than currently appreciated?

CONTEXT: Iodine is a micronutrient essential for thyroid hormone synthesis. Thyroid hormone is critical for normal neurocognitive development in young infants, and even transient hypothyroidism can cause adverse neurodevelopmental outcomes. Both iodine deficiency and excess can cause hypothyroidism. Although iodine-induced hypothyroidism is well recognized in premature infants, full-term neonates have received less attention. Infants with congenital heart disease (CHD) are commonly exposed to excess iodine from administration of iodinated contrast agents during cardiac catheterization as well as topical application of iodine-containing antiseptics and dressings; hence, this is a vulnerable population. OBJECTIVE: We report three cases of iodine-induced hypothyroidism in full-term neonates with CHD after cardiac angiography and topical application of iodine-containing antiseptics and dressings in the operative setting. RESULTS: Three neonates with CHD and normal thyroid function at birth developed hypothyroidism after exposure to excess iodine. Two of these infants had transient hypothyroidism, and one had severe hypothyroidism requiring ongoing thyroid replacement therapy. All infants were asymptomatic, with hypothyroidism detected incidentally in the inpatient setting due to repeat newborn screening mandated by the long duration of hospitalization in these infants. CONCLUSIONS: Iodine-induced hypothyroidism may be under-recognized in infants with CHD exposed to excess iodine. Systematic monitoring of thyroid function should be considered to avoid potential long-term adverse neurodevelopmental effects of even transient thyroid dysfunction in this susceptible population.

Association of CD247 with systemic lupus erythematosus in Asian populations.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. CD247 (CD3Z, TCRZ) plays a vital role in antigen recognition and signal transduction in antigen-specific immune responses, and is known to be involved in SLE pathogenesis. Weak disease association was reported for genetic variants in this gene in Caucasian studies for SLE, Crohn's disease and systemic sclerosis, but its role as a genetic risk factor was never firmly established. METHODS: In this study, using a collection of 612 SLE patients and 2193 controls of Chinese ethnicity living in Hong Kong in a genome-wide study, single nucleotide polymorphisms (SNPs) in and around CD247 were identified as being associated with SLE. The two most significant SNPs in this locus were selected for further replication using TaqMan genotyping assay in 3339 Asian patients from Hong Kong, Mainland China, and Thailand, as well as 4737 ethnically and geographically matched controls. RESULTS: The association of CD247 with SLE in Asian populations was confirmed (rs704853: odds ratio [OR] = 0. 81, p = 2.47 × 10(-7); rs858543: OR = 1.10, p = 0.0048). Patient-only analysis suggested that rs704853 is also linked to oral ulcers, hematologic disorders and anti-double-stranded DNA (dsDNA) antibody production. CONCLUSION: A significant association between variants in CD247 and SLE was demonstrated in Asian populations. Understanding the involvement of CD247 in SLE may shed new light on disease mechanisms and development of new treatment paradigms.

Two missense variants in UHRF1BP1 are independently associated with systemic lupus erythematosus in Hong Kong Chinese.

UHRF1BP1 encodes a highly conserved protein with unknown function. Previously, a coding variant in this gene was found to be associated with systemic lupus erythematosus (SLE) in populations of European ancestry (rs11755393, R454Q, P=2.22 x 10⁻8, odds ratio=1.17). In this study, by a combination of genome-wide study and replication involving a total of 1230 patients and 3144 controls, we confirmed the association of this coding variant to SLE in Hong Kong Chinese. We also identified another coding variant in this gene that independently contributes to SLE susceptibility (rs13205210, M1098T, P=4.44 x 10⁻9, odds ratio=1.49). Cross-population confirmation establishes the involvement of this locus in SLE and indicates that distinct alleles are contributing to disease susceptibility.

Antibiotic distribution in a bone cement spacer model.

PURPOSE: To mix high dose antibiotic powder to the bone cement more easily, Hanssen et al reported mixing the antibiotics with the cement during its liquid phase but made no comments about the relevance of cement viscosity and antibiotic distribution. The purpose of this study was to investigate the effect of the cement mixing technique and cement viscosity on the antibiotics distribution in a cement spacer model. METHODS: Thirty cylindrical models from three groups were examined. Group A was made by mixing the antibiotics with medium viscosity cement prior to adding the liquid monomer (traditional technique). Group B was made by mixing the antibiotics with medium viscosity cement during its liquid phase (Hanssen's technique). Group C was made by traditional technique with low viscosity cement. In all groups 2 g of tetracycline was used. Three 0.1 mm thick cross sections from each spacer model were examined under the fluorescent microscope. The fluorescent spots of tetracycline were calculated automatically in pixels. To evaluate the distribution of the antibiotics in the spacer model, we selected the cross section with the highest number of pixels and the one with the lowest number of pixels from each of the three cross sections and calculated the difference between them. The distribution disequilibrium was compared between group A and B, A and C. RESULTS: No significant difference was observed in either comparison. CONCLUSION: The Hanssen's mixing technique can be used when using high dose antibiotics, and either medium or low viscosity cement could be used in terms of antibiotic distribution.

Activation of low density lipoprotein receptor synthesis by treatment with partially delipidated low density lipoprotein.

The role of apo-low density lipoprotein in the regulation of low density lipoprotein receptor synthesis was studied. Fibroblasts preincubated in the presence of a cholesterol-free low density lipoprotein preparation showed an increase of 50% in receptor activity. In contrast, when cells were preincubated with a similar amount of normal low density lipoproteins a 2- to 3-fold decrease of receptor activity was observed. The increase of receptor activity induced by delipidated LDL was probably due to an increase of synthesis rather than an unmasking effect since treatment with puromycin essentially abrogated the activation. The ability of the partially delipidated low density lipoproteins to elicit receptor synthesis could not be accounted for by a depletion of cellular cholesterol because a similar preparation of delipidated high density lipoproteins was unable to induce receptor synthesis but was able to reduce cellular cholesterol to the same extent. Treatment with chloroquine, a lyzosome inhibitor, blocked the ability of the delipidated low density lipoprotein to activate receptor synthesis. This suggests that degraded fragments rather than the intact delipidated lipoprotein are necessary to trigger the cell to synthesize more receptors.

Binding of homologous versus heterologous low density lipoproteins by different tissues of the rat.

1. The ability of five different tissues of the rat to bind homologous and heterologous (human) low density lipoprotein (LDL) was compared. 2. Human LDL was as effective as rat LDL in displacing rat [125I]LDL from the plasma membrane fraction of rat skeletal muscle. 3. Membranes from rat liver appeared to have no affinity for homologous LDL, while human LDL was slightly more effective in displacing labeled rat LDL from this tissue. 4. A similar pattern of displacement was observed in membranes derived from rat heart. 5. In contrast, membranes from both the aorta and adrenal glands of the rat displayed a significantly greater affinity for binding LDL of homologous origin. 6. These results suggest that lipoprotein receptors analogous to those described for cultured human cells may exist in the rat and that individual tissues exhibit distinctly different affinities for binding LDL of both homologous and human origin.