Evidence for the effectiveness of botulinum toxin for spasmodic dysphonia from high-quality research designs.

The practice of evidence-based medicine promotes use of the knowledge ascertained from high quality research designs. The objective of this review was to determine what evidence has been provided from high quality research designs (e.g., randomized control trials or high quality prospective, matched group cohort studies), through December of 2006, relative to the effectiveness of botulinum toxin for treating spasmodic dysphonia. Results of the review indicated that no new high quality (Class I or Class II) studies have been published since 2001. One Class I study has been published since 1973, which found significant treatment effects for acoustic and perceptual variables of vocal function. Four Class II studies have been published during this same time frame, all finding significant treatment effects, though the nature of studied factors was variable between investigations. Based on the quality of evidence scale used, botulinum toxin can be considered an effective treatment for adductor spasmodic dysphonia.

Significance of aromatic-backbone amide interactions in protein structure.

Weakly polar interactions between aromatic rings of amino acids and hydrogens of backbone amides (Ar-HN) have been shown to support local structures in proteins. Their role in secondary structures, however, has not been elucidated. To investigate the relationship between Ar-HN interaction and the stability of local and secondary structures of polypeptides and to improve the prediction of this interaction based on amino acid sequence, the structures of 560 nonhomologous proteins, from the Protein Data Bank, were searched for Ar-HN interactions between the aromatic ring of each Phe, Tyr, and Trp residue at position i and the backbone amide group of any residue, except Pro, at the positions i, i - 1, i - 2, i - 3, i + 1, i + 2, and i + 3. Ar-HN interactions were identified by calculating the chemical shift of the amide hydrogen caused by the proximal aromatic ring. Ar(i)-HN(i + 1, i + 2 and i + 3) interactions were more common (7.10%, 2.08%, and 0.54%, respectively) than were Ar(i)-HN(i - 1, i - 2, and i - 3) interactions (0.66%, <0.1%, and 0.18%, respectively). The value of the chi(1) torsion angle of the aromatic residue in position i depended on the direction of the Ar-HN interaction. The position of the aromatic ring in Ar(i)-HN(i + 1, i + 2, and i + 3) interactions was mostly trans, in Ar(i)-HN(i - 1, i - 2, and i - 3) interactions mainly gauche(-), and in Ar(i)-HN(i) interactions mostly gauche(+). The analyses of the secondary structures of the protein fragments containing Ar-HN interactions showed that Ar-HN interactions were in all types of secondary structures. Search results suggest that Ar-HN interactions have a stabilizing effect on all types of secondary structures.

Conformational space comparison of GnRH and lGnRH-III using molecular dynamics, cluster analysis and Monte Carlo thermodynamic integration.

The conformational space available to GnRH and lGnRH-III was compared using 5.2 ns constant temperature and pressure molecular dynamics simulations with explicit TIP3P solvation and the AMBER v. 5.0 force field. Cluster analysis of both trajectories resulted in two groups of conformations. Results of free energy calculations, in agreement with previous experimental data, indicate that a conformation with a turn from residues 5 through 8 is preferred for GnRH in an aqueous environment. By contrast, a conformation with a helix from residues 2 through 7 with a bend from residues 6 through 10 is preferred for lGnRH-III in an aqueous environment. The side chains of His2 and Trp3 in lGnRH-III occupy different regions of phase space and participate in weakly polar interactions different from those in GnRH. The unique conformational properties of lGnRH-III may account for its specific anti cancer activity.

Acoustic measures of phonatory improvement secondary to treatment by oral corticosteroids in a professional singer: a case report.

Short-term administration of corticosteriods is sometimes indicated for professional voice users experiencing laryngeal edema and/or inflammation. Unfortunately, no data are available to document the effectiveness of these medications to improve phonatory parameters. We present a case report of a 32-year-old male professional singer with vocal fold edema experiencing imminent vocal demands who was prescribed a 6-day course (dose-pack) of oral methyl prednisolone. Endoscopic and stroboscopic evaluations were completed premedication and postmedication, and acoustic measures of phonatory function were obtained premedication, 3 days during the dose cycle, 5 days during the dose cycle, and 1 day postmedication. Postmedication results revealed an increase in fundamental frequency (F0) and large decreases in jitter, shimmer, long-term frequency, and amplitude variability. These corresponded with patient and evaluator perceptual measures of improved voice, and with endoscopic observations of reduced edema. The benefits and risks of corticosteroid therapy are discussed, specific to their use in the professional voice population.

Timing and intensity variability in the metronomic speech of stuttering and nonstuttering speakers.

The timing and intensity variability of 8 adults who stutter and 8 age-matched fluent speakers was investigated under metronomic conditions. Participants were required to produce double or triple-stress patterns at a slow speech rate (1 syllable/870 ms) when repeating the syllable /staet/or/straet/nine times. Measures that are sensitive to cyclic rather than overall variation in syllable timing and intensity were employed. Specifically, durational variation between successive syllable onsets as well as intensity variation of the beginning consonant and vowel in successive syllables were computed. Results revealed that, although intensity variation was similar, the timing of successive syllables of persons who stutter was significantly more variable than that of persons who do not stutter. These outcomes are discussed in relation to previous experiments of timing control of persons who stutter and normally fluent persons during metronomic stimulation.

Molecular dynamics simulations of epidermal growth factor and transforming growth factor-alpha structures in water.

AMBER v. 4.1 force field in 1.5 ns NPT molecular dynamics simulations of murine epidermal growth factor (mEGF), human epidermal growth factor (hEGF), and human transforming growth factor-alpha (hTGF-alpha) structures with explicit TIP3P solvation were used to investigate differences in backbone stability, changes in secondary structure, interdomain flexibility, and weakly polar interactions. Backbone root mean square deviations of sections of each peptide show that the most stable regions in mEGF and hEGF are the A-, B-, and C-loops, whereas the most stable regions in hTGF-alpha are the A- and B-loops. The secondary structure in the B-loops of mEGF and hEGF differ significantly from the nuclear magnetic resonance (NMR) structures of mEGF and hEGF. The position and type of turns in the B-loop of mEGF and hEGF increase the interstrand distance of the antiparallel beta-sheets thereby disrupting their structure. The interdomain flexibility of simulated hTGF-alpha structure is greater than in either mEGF or hEGF. The phi, psi dihedrals of hTGF-alpha occupy two distinct populations of phase space corresponding to either a Ceq7 or an alpha-helical conformation. This change in dihedral angle is stabilized by Phe15 with Arg42 and Phe17 with Arg42 N-pi weakly polar interactions that are present only in hTGF-alpha but not in mEGF or hEGF.

The use of dodecylphosphocholine micelles in solution NMR.

Dodecylphosphocholine (DPC) micelles are useful as a model membrane system for solution NMR. Several new observations on dodecylphosphocholine micelles and their interactions with opioid peptides are described. The optimal lipid concentration has been investigated for small peptide NMR studies in DPC micelles for two opioid peptides, a 5-mer and a 17-mer. In contrast to reports in the literature, identical 2D spectra have been observed at low and high lipid concentrations. The chemical shift of resolved peptide proton resonances has been followed as a function of added lipid and indicates that there are changes in the chemical shifts above the critical micelle concentration and up to a ratio of 7:1 (lipid:peptide) for the 17-mer, and 9.6:1 for the 5-mer. These results suggest that conformational changes occur in the peptide significantly above the critical micelle concentration, up to a lipid:peptide ratio which is dependent upon the peptide, here ranging from 7:1 to 9.6:1. To address the stoichiometry more directly, the diffusion coefficients of the lipid alone and the lipid with peptide have been measured using pulsed-field gradient spin-echo NMR experiments. These data have been used to calculate the hydrodynamic radius and the aggregation number of the micelle with and without peptide and show that the aggregation number of the peptide-lipid complex increases at high lipid concentrations without a concomitant change in the peptide conformation. Last, several protonated impurities have been observed in the commercial preparation of DPC which resonate in the amide proton region of the NMR spectrum.(ABSTRACT TRUNCATED AT 250 WORDS)