The safety of spinal pedicle screws in children ages 1 to 12

Background contextPedicle screws have shown to be a safe and effective method of spinal fixation, offering superior multiplanar correction compared with hooks or sublaminar wires in selected situations. Though only food and drug administration (FDA) approved in the adolescent population, they are commonly used in an off-label manner in the preadolescent population.PurposeTo determine if the complication rate of the off-label use of pedicle screws for spinal fixation in the preadolescent 0- to 12-year-old population is comparable with the complication rate in the FDA-approved 13- to 18-year-old population.Study design/settingRetrospective medical record and radiograph review.Patient sampleA total of 726 pediatric patients who underwent a spinal fusion procedure at a single tertiary institution between January 2003 and December 2008 were reviewed.Outcome measuresIncidence of instrumentation failure, infection, neurological complication, and total complications.MethodsThe study population was divided into two groups based on age: the younger group included 0- to 12-year olds and the older group included 13- to 18-year olds at the time of surgery. Groups were further subdivided based on diagnosis: “A,” neuromuscular scoliosis; “B,” idiopathic scoliosis, and “C,” other spinal deformities. Rates of neurovascular complications, infections, and instrumentation complications were compared statistically between the younger and the older groups. Only patients with greater than or equal to 1-year follow-up and greater than or equal to 2-year follow-up were included in the calculations for infection and instrumentation complication rates, respectively.ResultsThere were 206 patients (33% males, 67% females) in the younger group (0 to 12 years) and 520 (41% males, 59% females) in the older group (13 to 18 years). Overall, younger group had a 13.6% complication rate compared with 16.9% in the older group. Younger subjects showed a 13.4% complication rate because of instrumentation-related complications, 0.5% for neurovascular complications, and an infection rate of 9.2%. The older group showed a 15.4% complication rate because of instrumentation-related complications, 1.92% for neurovascular complications, and an infection rate of 11.0%. Complication rates were statistically insignificant between the two groups. Other complications in the younger group included one patient with aspiration pneumonia, two with ileus, and one with pulmonary and other complications in the older group included one patient with aspiration pneumonia, two with ileus, three with superior mesenteric artery syndrome, and three with wound dehiscence.ConclusionsThe complication rates in the young pediatric population associated with the off-label use of pedicle screws for spinal fusions are not statistically different from the complication rates associated with the FDA-approved adolescent population.     

Analysis of core circadian feedback loop in suprachiasmatic nucleus of mCry1-luc transgenic reporter mouse

The suprachiasmatic nucleus (SCN) coordinates circadian rhythms that adapt the individual to solar time. SCN pacemaking revolves around feedback loops in which expression of Period (Per) and Cryptochrome (Cry) genes is periodically suppressed by their protein products. Specifically, PER/CRY complexes act at E-box sequences in Per and Cry to inhibit their transactivation by CLOCK/BMAL1 heterodimers. To function effectively, these closed intracellular loops need to be synchronized between SCN cells and to the light/dark cycle. For Per expression, this is mediated by neuropeptidergic and glutamatergic extracellular cues acting via cAMP/calcium-responsive elements (CREs) in Per genes. Cry genes, however, carry no CREs, and how CRY-dependent SCN pacemaking is synchronized remains unclear. Furthermore, whereas reporter lines are available to explore Per circadian expression in real time, no Cry equivalent exists. We therefore created a mouse, B6.Cg-Tg(Cry1-luc)01Ld, carrying a transgene (mCry1-luc) consisting of mCry1 elements containing an E-box and E′-box driving firefly luciferase. mCry1-luc organotypic SCN slices exhibited stable circadian bioluminescence rhythms with appropriate phase, period, profile, and spatial organization. In SCN lacking vasoactive intestinal peptide or its receptor, mCry1 expression was damped and desynchronized between cells. Despite the absence of CREs, mCry1-luc expression was nevertheless (indirectly) sensitive to manipulation of cAMP-dependent signaling. In mPer1/2-null SCN, mCry1-luc bioluminescence was arrhythmic and no longer suppressed by elevation of cAMP. Finally, an SCN graft procedure showed that PER-independent as well as PER-dependent mechanisms could sustain circadian expression of mCry1. The mCry1-luc mouse therefore reports circadian mCry1 expression and its interactions with vasoactive intestinal peptide, cAMP, and PER at the heart of the SCN pacemaker.     

Bacterial cholangitis causing secondary sclerosing cholangitis: A case report

Background  

Although bacterial cholangitis is frequently mentioned as a cause of secondary sclerosing cholangitis, it appears to be extremely rare, with only one documented case ever reported.     

Human interleukin-5 (IL-5) regulates the production of eosinophils in human bone marrow cultures: comparison and interaction with IL-1, IL-3, IL-6, and GMCSF

Recombinant human interleukin-5 (rhIL-5), in either liquid or semi- solid cultures, selectively induced eosinophil production from normal human bone marrow, with no activity on other cell lineages. The time course of eosinophil production induced by murine IL-5, rhIL-3, and rh granulocyte-macrophage colony stimulating factor (GMCSF) was similar to rhIL-5. The rate of eosinophil maturation in vitro was independent of the stimulating cytokine, mature eosinophils being produced after 4 to 5 weeks in liquid culture with each of these cytokines. The eosinophils produced in response to each cytokine were morphologically indistinguishable, and had the ultrastructural features of maturity except that the electron-dense material in the granules had not formed into crystalline cores. Neither rhIL-1 nor rhIL-6 alone, or in combination with rhIL-5 or rhIL-3, induced eosinophil differentiation or proliferation under the conditions used. rhIL-3 and rhGMCSF induced more eosinophil colonies than rhIL-5, rhIL-5 had an additive, not synergistic, effect on eosinophil colony production when combined with either rhIL-3 or rhGMCSF, suggesting that rhIL-5 stimulates a smaller and possibly different population of eosinophil progenitors. However, rhIL-5 induced the greatest eosinophil production in liquid cultures, suggesting that although it may act on a smaller population of precursors, it is able to stimulate more proliferative steps than either rhIL-3 or rhGMCSF.     

The diagnostic value of the fibrinogen/fibrin fragment E antigen assay in clinically suspected deep vein thrombosis

We have evaluated the fibrinogen/fibrin fragment E antigen assay as a diagnostic test in patients with clinically suspected venous thrombosis by comparing the results of this assay with venography in 272 patients. The result of the fragment E antigen assay was elevated in 79 of 80 patients with positive venograms for recent venous thrombosis (sensitivity 99%) and within the normal range in 161 of 192 patients with normal venograms (specificity 84%). The fragment E assay was also evaluated in 130 medical and surgical controls without evidence of venous thrombosis by leg scanning and the test was found to be relatively nonspecific. However, in the patient group under study, a correct clinical diagnosis of no thrombosis, based on a normal fragment E result, was made in 161 of 162 cases (negative predictive value of 99%). Therefore, a normal test result effectively excludes a diagnosis of venous thrombosis in clinically symptomatic patients. The assay, as currently performed, is technically demanding and takes 24 hr to complete. Therefore, it will have to be simplified before it can be applied to clinical practice.     

Synthesis and Biological Evaluations of Electrophilic Steroids Inspired by the Taccalonolides

Natural products have served as inspirational scaffolds for the design and synthesis of novel antineoplastic agents. Here we present our preliminary efforts on the synthesis and biological evaluation of a new class of electrophilic steroids inspired by the naturally occurring taccalonolides. We demonstrate that these simplified analogs exhibit highly persistent antiproliferative properties similar to the taccalonolides and retain activity against resistant cancer cell lines that warrants further preclinical development.     

Children's dynamic RSA change during anger and its relations with parenting,temperament, and control of aggression

This study examined the moderating effects of child temperament on the association between maternal socialization and 4–6-year-old children's dynamic respiratory sinus arrhythmia (RSA) change in response to anger-themed emotional materials (N = 180). We used latent growth curve modeling to explore adaptive patterns of dynamic RSA change in response to anger. Greater change in RSA during anger-induction, characterized by more initial RSA suppression and a subsequent return to baseline, was related to children's better regulation of aggression. For anger-themed materials, low levels of authoritarian parenting predicted more RSA suppression and recovery for more anger-prone children, whereas more authoritative parenting predicted more RSA suppression and recovery for less anger-prone children. These findings suggest that children's adaptive patterns of dynamic RSA change can be characterized by latent growth curve modeling, and that these patterns may be differentially shaped by parent socialization experiences as a function of child temperament.