Sleep characteristics in Goldenhar Syndrome.

OBJECTIVE: To examine the characteristics of sleep in patients with Goldenhar Syndrome. DESIGN: Retrospective review of all polysomnography studies conducted at the University of North Carolina Hospitals between 2003 and 2013 on patients carrying the diagnosis of Goldenhar's Syndrome. RESULTS: A preponderance of patients demonstrated severe obstructive sleep apnea and hypercapnia. CONCLUSIONS: Patients with Goldenhar Syndrome should be screened for sleep apnea and hypercapnia.

Clinical care in craniofacial microsomia: a review of current management recommendations and opportunities to advance research.

Craniofacial microsomia (CFM) is a complex condition associated with microtia, mandibular hypoplasia, and preauricular tags. It is the second most common congenital facial condition treated in many craniofacial centers and requires longitudinal multidisciplinary patient care. The purpose of this article is to summarize current recommendations for clinical management and discuss opportunities to advance clinical research in CFM.

Effect of polymer molecular weight on the production of drug nanoparticles.

Stable, polymer-coated nanoparticles of two hydrophobic drugs, namely nabumetone and halofantrine, have been prepared by a wet-bead milling process performed in the presence of a stabilizing homopolymer, either hydroxypropylmethylcellulose (HPMC) or polyvinylpyrrolidone (PVP), of differing molecular weights and concentrations. Although nabumetone nanoparticles could only be produced when HPMC was used as stabilizing polymer, halofantrine nanoparticles could be prepared using either HPMC or PVP. Stable nanoparticles of nabumetone could be produced using a HPMC solution of viscosity average molecular weight, M(v), of 5 kg/mol over an approximate four fold polymer concentration range (0.63-2.5% w/w) when a drug loading of 20% w/w was used. Increasing the molecular weight of HPMC up to a limiting M(v) of 89 kg/mol did not result in the formation of nanoparticles at any of the polymer concentrations examined. The amount of polymer absorbed onto the nanoparticles was determined by measuring the depletion of polymer from solution based on either an ultra-violet (PVP) or optical rotatory dispersion (ORD) (HPMC) assay. The slightly lower concentration of HMPC found to be present on the surface of the halofantrine nanoparticles compared with the nabumetone nanoparticles suggested a differing affinity of the polymer for the surface of the two drugs.

The effect of otitis media with effusion on complex masking tasks in children.

OBJECTIVE: To determine whether there is a relationship between the presumed complexity of auditory processing and the time course of recovery of auditory function in children with a history of otitis media with effusion (OME). DESIGN: Longitudinal testing over a 1-year period following insertion of tympanostomy tubes in clinical and control groups. SUBJECTS: A total of 34 children with a history of OME were tested. Twenty-five were tested both just before the placement of tympanostomy tubes and on up to 3 separate occasions (1 month, 6 months, and 1 year) after the placement of the tubes. With subject attrition, there were 27, 16, and 10 listeners at the 1-month, 6-month, and 1-year tests, respectively. An age-matched control group of 29 children was tested. METHODS: The comodulation masking release (CMR) paradigm was used to measure the ability of the listener to detect a signal in a noise background composed of a simple (1 amplitude modulation pattern) or more complex (2 amplitude modulation patterns) masking background. RESULTS: Children with a history of OME had reduced masking release before and 1 month after insertion of tympanostomy tubes for both the simple and complex CMR tasks. After surgery, the CMR results for simple task was not significantly different from that in controls by 6 months, but CMR for the complex task remained significantly reduced even 1 year after surgery. CONCLUSION: Our results suggest a slower recovery of auditory function for more complex auditory tasks in children with a history of OME.

Conformational properties of the prion octa-repeat and hydrophobic sequences.

We have used circular dichroism to study synthetic peptides from two important regions of the prion protein: the N-terminal octa-repeat domain and a highly conserved hydrophobic section. Our results show that the octa-repeat sequence in free solution can adopt a non-random, extended conformation with properties similar to the poly-L-proline type II left-handed helix. We also show that the conformation can be changed by temperature, organic solvents (e.g. acetonitrile) and on binding to phospholipid vesicles. We compared CD data from two peptides corresponding to the hydrophobic region between residues 106 and 136 which contained either methionine or valine at position 129. This variation represents a common polymorphism in humans which has been shown to influence predisposition towards iatrogenic and sporadic CJD. There was no detectable difference between the CD spectra of these peptides irrespective of the solvent conditions we used.

Fibromatosis colli: a common cause of neonatal torticollis.

In infants and children, cervical masses originate from a variety of pathologic, congenital and developmental conditions, and it is important to distinguish benign from serious lesions. Fibromatosis colli is a rare cervical lesion that typically presents in the neonatal period. It is the most common cause of neonatal torticollis and should be recognized by physicians caring for neonates and infants.

The interaction between heparin and polylysine: a circular dichroism and molecular modelling study.

The sulfated polysaccharide heparin interacts with both poly-L- and poly-D-lysine, promoting the alpha-helix conformation in the polypeptide. Chemically modified heparins in which one of the three sulfate groups per disaccharide has been removed form the same type of complex with poly-L-lysine; when two of the three sulfate groups are removed this property is lost. Heparin oligosaccharides as small as the octasaccharide can still promote alpha-helix in poly-L-lysine; the hexa- and tetrasaccharides do not, but they do disturb to a lesser extent the dynamic conformation equilibrium associated with poly-L-lysine at pH7 (22 degrees C). A three-dimensional structure for the heparin/polylysine complex is proposed in which the helical heparin molecule and the alpha-helical polypeptide are side-by-side, not intertwining. The regular periodicity of sulfate group clusters along one side of the polysaccharide chain matches the periodicity of the polypeptide alpha-helix, allowing electrostatic interactions every three peptide turns between a heparin sulfate cluster and a zeta-amino group of the polylysine. The heparin octasaccharide is the smallest even-numbered oligosaccharide long enough for two such interactions to take place.

Two new otolaryngologic findings in child abuse.

We reviewed cases of early childhood hoarseness caused by vocal nodules and functional hearing loss as being possible manifestations of child abuse. This is a retrospective review set in two urban referral centers. The patients consisted of four children with vocal nodules and known histories of abuse, and four children with functional hearing loss and histories suggestive of abuse. Vocal nodules or functional hearing loss may be indicators of an abusive situation. Child abuse should be considered in the differential diagnosis of these problems.

The importance of extended conformations and, in particular, the PII conformation for the molecular recognition of peptides.

Crystallographic, isotopic labeling nmr and transferred nuclear Overhauser effect studies have highlighted the extended conformation as a very important element of secondary structure at the binding site of many peptide/protein complexes including peptide inhibitors-enzymes, B-cell epitopes-antibodies, and T-cell epitopes-major histocompatibility complex (MHC) of class I and II complexes. This paper discusses the peptide ligand conformation consequences of these findings particularly in view of the identification of the PII conformation (left-handed extended polyproline II) in free solution.

Control of the mucosal microcirculation in the upper respiratory tract.

This study was designed to investigate the regulatory mechanisms of the mucosal microvascular network in the upper respiratory tract. Tracheal mucosal circulation was observed using a specially constructed chamber that allowed direct microscopic visualization of mucosal arterioles. Solutions of increasing hypertonicity (500 and 900 mOsm) applied to the tracheal epithelium resulted in increasing dilation of the underlying mucosal arterioles (p < 0.001). N(omega)-nitro-L-arginine methyl ester (L-NAME, 1 mmol/L), a specific inhibitor of nitric oxide synthesis, added to a hypertonic solution inhibited dilation of mucosal arterioles (p < 0.001). Addition of the substrate for nitric oxide synthesis, L-arginine (0.6 mmol/L) to the hypertonic solution containing L-NAME resulted in dilation of mucosal arterioles once again. These data demonstrate that nitric oxide is a crucial mediator in the response of mucosal arterioles to the hypertonic stimulus presented to the epithelial surface of the trachea. Further elucidation of the control of the mucosal microcirculation in the upper respiratory tract could be implemented in new treatment for pathologic processes of the upper respiratory tract such as mucosal congestion and edema.

Cleft nose. Form and function.

Clefts of the lip and palate frequently produce nasal deformities that tend to reduce the size of the nasal airway. Surgical correction of nasal, palatal, and pharyngeal structures may compromise breathing further. A significant number of individuals with cleft noses mouthbreathe to some extent because of the high prevalence of airway compromise.

A CD strategy for the study of polypeptide folding/unfolding. A synthetic foot-and-mouth disease virus immunogenic peptide.

The circular dichroism spectrum of the 20-residue immunogenic peptide from the foot-and-mouth disease virus (VP1; 141-160 of serotype A, subtype 12) was solvent- and temperature-dependent. Careful solvent titration revealed two isodichroic points and plateaux consistent with stepwise unfolding of specific stable conformations. Variable temperature studies in cryogenic solvents and urea perturbation were consistent with the existence of three conformational moieties, the left-handed extended helix, the alpha-helix, and the 3(10) helix. The number of residues in each helix was confirmed by CD spectral simulations. The strategy described here can be used to determine the components of a conformational equilibrium and their statistical weights, to study peptide folding and unfolding and to determine the bioactive conformation(s) of linear peptides. The conclusions were supported by 2D-NMR studies. A new mechanism for the stabilization of left-handed extended helices and destabilization of alpha-helices by urea is proposed. The structure of the peptide as resolved by CD spectroscopy is of particular significance since the conformation of this antigenic sequence in situ has so far not been solved by X-ray crystallography.

The prevention of postoperative stridor and laryngospasm with topical lidocaine.

Tonsillectomy and adenoidectomy can predispose to stridor and laryngospasm in the immediate postextubation period. A prospectively randomized study of 133 patients undergoing tonsillectomy and adenoidectomy was undertaken to determine if the topical application of 4 mg/kg of 4% lidocaine at the time of intubation would decrease the incidence of postoperative stridor and laryngospasm. Taken together, eight (12%) of 67 control patients suffered stridor or laryngospasm vs two (3%) of 66 patients receiving lidocaine. It is concluded that lidocaine administered topically at the time of intubation for adenotonsillectomy helps prevent postoperative stridor and laryngospasm. Surgery of the upper aerodigestive tract often involves not only the technical aspects of the surgical procedure but also concomitant management of the airway. This can present a challenge to even the most adept otolaryngologist and anesthesiologist. Accidental extubation is always possible, and reintubation can be difficult in the presence of blood and saliva. The difficulty is often compounded with a patient who is not completely paralyzed.

Isolation and characterization of the diastereoisomers of a series of phosphate-ethylated dinucleoside monophosphates.

Internucleotide phosphate esterification is a common reaction of many potent carcinogenic alkylating agents. It can give rise to two stereochemically distinct molecules about a triesterified phosphorus atom. The eight individual diastereoisomers derived from phosphate ethylation of d-ApT, d-CpT, d-GpT, and d-TpT were prepared from o-chlorophenyl phosphotriester intermediates and isolated by reverse-phase HPLC. Each pair of isomers, together with its parent analog, was examined by variable temperature circular dichroism. The results are interpreted in terms of secondary structure changes from which the absolute configurations of the ethylated phosphate groups can be inferred. These configurational assignments were confirmed by 31P NMR.