Abstract-Genes contributing to common forms of hypertension are largely unknown. A number of studies in humans and in animal models have revealed associations between insulin resistance, dyslipidemia, and elevated hypertension. To identify genes contributing to blood pressure (BP) variation associated with insulin-resistant dyslipidemia, we conducted a genome-wide scan for BP in a set of 18 Dutch families exhibiting the common lipid disorder familial combined hyperlipidemia. Our results reveal a locus on chromosome 4 that exhibits a significant lod score of 3.9 with systolic BP. In addition, this locus also appears to influence plasma free fatty acid levels (lodϭ2.4). After adjustment for age and gender, the lod score for systolic BP increased to 4.6, whereas the lod score for free fatty acid levels did not change. The chromosome 4 locus contains an attractive candidate gene, ␣-adducin, which has been associated with altered BP in animal studies and in some human populations. However, we found no evidence for an association between 2 intragenic ␣-adducin polymorphisms and systolic BP in this sample. We also observed suggestive evidence for linkage (lodϭ1.8) of diastolic BP to the lipoprotein lipase gene locus on chromosome 8p, supporting a finding previously observed in a separate insulin-resistant population. In addition, we also obtained suggestive evidence for linkage of systolic BP (lodϭ2.4) and plasma apolipoprotein B levels (lodϭ2.0) to a locus on proximal chromosome 19p. In conclusion, our genome scan results support the existence of multiple genetic factors that can influence both BP and plasma lipid parameters. Key Words: genetics Ⅲ hypertension, essential Ⅲ dyslipidemia Ⅲ genome scan Ⅲ linkage analysis S ignificant progress has been made in elucidating the genetic basis for certain mendelian forms of hypertension, but the genetic factors contributing to essential hypertension are largely unknown. 1,2 A number of candidate gene studies and genome scans have been conducted but with varying results. [3][4][5][6] The variation in these latter linkage results could be due the different racial make-up of the study populations and/or the underlying genetic heterogeneity of essential hypertension, which can clearly confound genefinding efforts.One strategy to reduce genetic heterogeneity is to stratify the study population by hypertension that is associated with other pathophysiologic processes, such as insulin-resistant dyslipidemia. A number of studies, those of Williams and colleagues 7 in particular, have revealed associations between hyperlipidemia, insulin resistance, and elevated blood pressure (BP). These studies led to the definition of a condition similar to the metabolic syndrome termed familial dyslipidemic hypertension (FDH), involving a clustering of traits, including central obesity, lipid abnormalities, hypertension, and elevated fasting insulin levels. Several studies have demonstrated a high degree of heritability of this trait, which occurs in Ϸ1% of the general population but in Ϸ12% of pat...

Pathophysiological responses to peripheral nerve injury include alterations in the activity, intrinsic membrane properties and excitability of spinal neurons. The intrinsic excitability of α-motoneurons is controlled in part by the expression, regulation, and distribution of membrane-bound ion channels. Ion channels, such as Kv2.1 and SK, which underlie delayed rectifier potassium currents and afterhyperpolarization respectively, are localized in high-density clusters at specific postsynaptic sites (Deardorff et al., 2013; Muennich and Fyffe, 2004). Previous work has indicated that Kv2.1 channel clustering and kinetics are regulated by a variety of stimuli including ischemia, hypoxia, neuromodulator action and increased activity. Regulation occurs via channel dephosphorylation leading to both declustering and alterations in channel kinetics, thus normalizing activity (Misonou et al., 2004; Misonou et al., 2005; Misonou et al., 2008; Mohapatra et al., 2009; Park et al., 2006). Here we demonstrate using immunohistochemistry that peripheral nerve injury is also sufficient to alter the surface distribution of Kv2.1 channels on motoneurons. The dynamic changes in channel localization include a rapid progressive decline in cluster size, beginning immediately after axotomy, reaching maximum within one week. With reinnervation, the organization and size of Kv2.1 clusters do not fully recover. However, in the absence of reinnervation Kv2.1 cluster sizes fully recover. Moreover, unilateral peripheral nerve injury evokes parallel, but smaller, effects bilaterally. These results suggest that homeostatic regulation of motoneuron Kv2.1 membrane distribution after axon injury is largely independent of axon reinnervation.

Necrotizing enterocolitis (NEC) is the most common acquired gastrointestinal disease of premature neonates and is a serious cause of morbidity and mortality. NEC is one of the leading causes of death in neonatal intensive care units. Surgical treatment is necessary in patients whose disease progresses despite medical therapy. Surgical options include peritoneal drainage and laparotomy, with studies showing no difference in outcome related to approach. Survivors, particularly those requiring surgery, face serious sequelae.

DVT occurs in one third of moderately to severely brain injured patients. Isolated head injuries have a lower incidence. Older age, male gender, higher ISS, and the presence of a lower extremity injury are strong predictors for developing DVT. Regular screening and the use of prophylactic inferior vena cava filters in patients with risk factors should be strongly considered.