Pseudoaneurysm: a complication of faulty technique in femoral arterial puncture

Pseudoaneurysm is a well-documented but rare complication of retrograde femoral arterial puncture. We present six patients in whom pseudoaneurysm complicated this procedure. The pseudoaneurysm arose from the superficial femoral artery in five patients and from the profunda femoris artery in one. An arteriovenous fistula also arose from the superficial femoral artery in one patient. In no patient did the pseudoaneurysm arise from the common femoral artery. Two mechanisms are postulated as to why pseudoaneurysms rarely complicate puncture of the common femoral artery.     

Ring substituents on substituted benzamide ligands indirectly mediate interactions with position 7.39 of transmembrane helix 7 of the D4 dopamine receptor

In an effort to delineate how specific molecular interactions of dopamine receptor ligand classes vary between D2-like dopamine receptor subtypes, a conserved threonine in transmembrane (TM) helix 7 (Thr7.39), implicated as a key ligand interaction site with biogenic amine G protein-coupled receptors, was substituted with alanine in D2 and D4 receptors. Interrogation of different ligand chemotypes for sensitivity to this substitution revealed enhanced affinity in the D4, but not the D2 receptor, specifically for substituted benzamides (SBAs) having polar 4- (para) and/or 5- (meta) benzamide ring substituents. D4-T7.39A was fully functional, and the mutation did not alter the sodium-mediated positive and negative allostery observed with SBAs and agonists, respectively. With the exception of the non-SBA ligand (+)-butaclamol, which, in contrast to certain SBAs, had decreased affinity for the D4-T7.39A mutant, the interactions of numerous other ligands were unaffected by this mutation. SBAs were docked into D4 models in the same mode as observed for eticlopride in the D3 crystal structure. In this mode, interactions with TM5 and TM6 residues constrain the SBA ring position that produces distal steric crowding between pyrrolidinyl/diethylamine moieties and D4-Thr7.39. Ligand-residue interaction energy profiles suggest this crowding is mitigated by substitution with a smaller alanine. The profiles indicate sites that contribute to the SBA binding interaction and site-specific energy changes imparted by the D4-T7.39A mutation. Substantial interaction energy changes are observed at only a few positions, some of which are not conserved among the dopamine receptor subtypes and thus seem to account for this D4 subtype-specific structure-activity relationship.     

Hepatic manifestations of tuberous sclerosis complex: a genotypic and phenotypic analysis

Black ME, Hedgire SS, Camposano S, Paul E, Harisinghani M, Thiele EA. Hepatic manifestations of tuberous sclerosis complex: a genotypic and phenotypic analysis. A retrospective review of the clinical records and radiological images of 205 patients with tuberous sclerosis complex (TSC) was performed to evaluate the prevalence and progression of hepatic lesions; examine the association of hepatic phenotype with genotype, age, and gender; and investigate the relationships between hepatic, renal, and pulmonary involvement. Hepatic angiomyolipomas (AML), cysts, and other benign lesions were identified in 30% of the cohort, and some lesions grew significantly over time. However, no patient had clinical symptoms or complications from hepatic lesions. TSC2 patients exhibited a higher frequency of AML compared to TSC1 patients (p = 0.037), and patients with no mutation identified exhibited a higher frequency of cysts compared to TSC2 patients (p = 0.023). Age was positively correlated with frequency of hepatic involvement (p < 0.001), whereas hepatic phenotype was independent of gender. Presence of hepatic AML was associated with presence of renal AML (p = 0.001). These findings confirm a high rate of asymptomatic hepatic lesions in TSC and further characterize the TSC phenotype.     

Malaria in pregnancy

This review summarizes the epidemiology, clinical course, and diagnosis of malaria. The influence of infection during pregnancy upon maternal and neonatal anemia, stillbirth, preterm labor, low birth weight, and congenital malaria is discussed. Options for treatment and prophylaxis during pregnancy are presented.     

Functional effect of the R110Q IL13 genetic variant alone and in combination with IL4RA genetic variants

BACKGROUND: IL-13 is a key mediator of allergic asthma. IL-13 mediates its effects via its receptor, a heterodimer composed of IL-4R alpha and IL-13R alpha1. Polymorphic variants of both IL-13 and IL-4R alpha have been shown to be associated with atopy. OBJECTIVE: We examined the functional consequences of the Q110 IL-13 variant in vitro and in vivo to determine whether it displays enhanced functional activity compared with R110 IL-13, both in the context of I50Q551 IL-4R alpha and of the atopy-associated variant V50R551 IL-4R alpha. METHODS: We used a mouse cell line stably expressing human IL-4R alpha and IL-13R alpha1 that readily responds to human IL-4 and IL-13. For in vivo analyses, we used BALB/c mice. RESULTS: The Q110 IL-13 variant displayed significantly increased activity compared with R110 IL-13. Furthermore, mice treated with Q110 IL-13 variant displayed increased airways hyperresponsiveness relative to R110 IL-13. We then examined the functional consequences of Q110 IL-13 variant in combination with an atopy-associated variant of its receptor, IL-4R alpha (V50R551). Q110 IL-13 variant had increased activity on these cells as well, and, strikingly, the effect was greater than that observed in cells expressing I50Q551 IL-4R alpha. CONCLUSION: Either Q110 IL-13 variant or V50R551 IL-4R alpha variant has enhanced function alone, but the 2 together have a synergistic effect on IL-13-dependent gene induction. Our data demonstrate the importance of relatively small individual differences in gene products from common single nucleotide polymorphisms that may result in larger combined differences. Furthermore, a relatively modest change in function from a single nucleotide polymorphism can result in an important biological difference in vivo.