Citations

Objective. Surgery for craniosynostosis has evolved rapidly over the past two decades, with increased emphasis on early, extensive operations. Older published series may not accurately reflect more recent experience. Our study was designed to analyze outcome in a large series of consecutive patients treated recently at a single center.Methods. We reviewed 250 consecutive patients who underwent surgical treatment of craniosynostosis between January 1, 1987 and December 31, 1992. They were divided into nine groups by suture involvement: sagittal, unilateral coronal, bilateral coronal, unilateral lambdoid, bilateral lambdoid, metopic, multiple suture, the Klee-blattschädel deformity (cloverleaf skull), and acquired craniosynostosis. Outcome was analyzed in terms of residual deformities and irregularities, complications, mortality, as well as the need for additional surgery.Results. There were 157 males (62.8%) and 93 females (37.2%), with most of the male preponderance accounted for by the large sagittal synostosis group, which consisted of 82 males and 25 females. Median age at first operation was 147 days. A named syndrome was present in 23 patients (9.2%) and was more common than expected with bilateral and unilateral coronal synostosis, the Kleeblattschädel deformity, and multiple suture synostosis. There were two deaths (0.8%), both with Klee-blattschädel patients, and 17 other complications (6.8%). Morbidity and mortality were significantly associated with secondary vs primary operations and syndromic vs nonsyndromic patients. Outcome analysis revealed the best surgical results with metopic synostosis and significantly less good results with the Kleeblattschädel deformity, multiple suture synostosis, and bilateral coronal synostosis.Conclusions. Using modern surgical techniques, craniosynostosis can be corrected with good outcomes and relatively low morbidity and mortality, particularly for otherwise healthy, nonsyndromic infants.

Objective. To determine the usefulness of measurements of the vaginal opening and amount of hymenal tissue present inferiorly and laterally in the diagnosis of vaginal penetration. Methods. The transhymenal diameters and the amount of tissue present between the hymenal edge and vestibule inferiorly at 6 o’clock and laterally at 3 o’clock and 9 o’clock were measured from photographs of 189 prepubertal children with a validated history of digital or penile penetration and 197 children who denied previous sexual abuse. Statistical analyses were conducted to compare the mean values and hymenal symmetry between groups as well as to determine the sensitivity and specificity of various cutoff points. Results. Comparison of the mean diameters demonstrated that children with a penetration history had a significantly larger transverse opening than nonabused children when examined in the knee-chest position (5.6 vs 4.6 mm). However, there was extensive overlap in measurements between the 2 groups. No significant differences were noted between groups in the size of the vertical diameter, the amount of tissue present inferiorly or laterally, or the symmetry of the hymen in either position. Children with previous penetration were more likely than nonabused children to have a horizontal opening measuring >6.5 mm in the knee-chest position, but the sensitivity and specificity of this test were low (29% and 86%, respectively). Higher values had better specificity but very low sensitivity. Less than 1.0 mm of hymenal tissue was detected at 6 o’clock only in those with a history of penetration (100% specificity), but the sensitivity was low (1%–2%). Conclusion. Most hymenal measurements lack adequate sensitivity or specificity to be used to confirm previous penetration. Less than 1.0 mm of hymenal tissue at 6 o’clock was detected only in victims of abuse, but the usefulness of this test is limited by the rarity of this finding.

The isolation and identification of a novel, slow-growing, scotochromogenic, mycobacterial species is reported. A strain, designated MUP 1182T, was isolated from a cervical lymph node of a 3-year-old child. MUP 1182T is alcohol- and acid-fast, with a lipid pattern that is consistent with those of species that belong to the genus Mycobacterium. It grows slowly at 25–37 °C, but does not grow at 42 °C. The isolate was revealed to be biochemically distinct from previously described mycobacterial species: it has urease and Tween hydrolysis activities and lacks nitrate reductase, 3-day arylsulfatase and β-glucosidase activities. Comparative 16S rDNA sequencing showed that isolate MUP 1182T represents a novel, slow-growing species that is related closely to Mycobacterium lentiflavum and Mycobacterium simiae. On the basis of these findings, the name Mycobacterium parmense sp. nov. is proposed, with MUP 1182T (=CIP 107385T=DSM 44553T) as the type strain.

ABSTRACT Human immunodeficiency virus type 1 (HIV-1), feline immunodeficiency virus (FIV), and Moloney murine leukemia virus (MoMLV) integrases were stably expressed to determine their intracellular trafficking. Each lentiviral integrase localized to cell nuclei in close association with chromatin while the murine oncoretroviral integrase was cytoplasmic. Fusions of pyruvate kinase to the lentiviral integrases did not reveal transferable nuclear localization signals. The intracellular trafficking of each was determined instead by the transcriptional coactivator LEDGF/p75, which was required for nuclear localization. Stable small interfering RNA expression eliminated detectable LEDGF/p75 expression and caused dramatic, stable redistribution of each lentiviral integrase from nucleus to cytoplasm while the distribution of MoMLV integrase was unaffected. In addition, endogenous LEDGF/p75 coimmunoprecipitated specifically with each lentiviral integrase. In vitro integration assays with preintegration complexes (PICs) showed that endogenous LEDGF/p75 is a component of functional HIV-1 and FIV PICs. However, HIV-1 and FIV infection and replication in LEDGF/p75-deficient cells was equivalent to that in control cells, whether cells were dividing or growth arrested. Two-long terminal repeat circle accumulation in nondividing cell nuclei was also equivalent to that of LEDGF/p75 wild-type cells. Virions produced in LEDGF/p75-deficient cells had normal infectivity. We conclude that LEDGF/p75 fully accounts for cellular trafficking of diverse lentiviral, but not oncoretroviral, integrases and is the main lentiviral integrase-to-chromatin tethering factor. While lentiviral PIC nuclear import is unaffected by LEDGF/p75 knockdown, this protein is a component of functional lentiviral PICs. A role in HIV-1 integration site distribution merits investigation.

Objective— Mechanisms of renal injury distal to renal artery stenosis (RAS) remain unclear. We tested the hypothesis that it involves microvascular remodeling consequent to increased oxidative stress. Methods and Results— Three groups of pigs (n=6 each) were studied after 12 weeks of RAS, RAS+antioxidant supplementation (100 IU/kg vitamin E and 1 g vitamin C daily), or controls. The spatial density and tortuousity of renal microvessels (<500 μm) were tomographically determined by 3D microcomputed tomography. The in situ production of superoxide anion and the expression of vascular endothelial growth factor (VEGF), its receptor VEGFR-2, hypoxia-inducible-factor (HIF)-1α, von Hippel-Lindau (VHL) protein, and NAD(P)H oxidase (p47phox and p67phox subunits) were determined in cortical tissue. RAS and RAS+antioxidant groups had similar degrees of stenosis and hypertension. The RAS group showed a decrease in spatial density of cortical microvessels, which was normalized in the RAS+antioxidant group, as was arteriolar tortuousity. RAS kidneys also showed tissue fibrosis (by trichrome and Sirius red staining), increased superoxide anion abundance, NAD(P)H oxidase, VHL protein, and HIF-1α mRNA expression. In contrast, expression of HIF-1α, VEGF, and VEGFR-2 protein was downregulated. These were all significantly improved by antioxidant intervention. Conclusions— Increased oxidative stress in the stenotic kidney alters growth factor activity and plays an important role in renal microvascular remodeling, which can be prevented by chronic antioxidant intervention.