Botulinum toxin injection into the intrinsic laryngeal muscles to treat spasmodic dysphonia: A multicenter, placebo-controlled, randomized, double-blinded, parallel-group comparison/open-label clinical trial.

BACKGROUND AND PURPOSE: Botulinum toxin (BT) injection into the laryngeal muscles has been a standard treatment for spasmodic dysphonia (SD). However, few high-quality clinical studies have appeared, and BT is used off-label in most countries. METHODS: We performed a multicenter, placebo-controlled, randomized, double-blinded, parallel-group comparison/open-label clinical trial to obtain approval for BT (Botox) therapy in Japan. Twenty-four patients (22 with adductor SD and two with abductor SD) were enrolled. The primary end point was the change in the number of aberrant morae (phonemes) at 4 weeks after drug injection. The secondary end points included the change in the number of aberrant morae, GRBAS scale, Voice Handicap Index (VHI), and visual analog scale (VAS) over the entire study period. RESULTS: In the adductor SD group, the number of aberrant morae at 4 weeks after injection was reduced by 7.0 ± 2.30 (mean ± SE) in the BT group and 0.2 ± 0.46 in the placebo group (p = 0.0148). The improvement persisted for 12 weeks following BT injections. The strain element in GRBAS scale significantly reduced at 2 weeks after BT treatment. The VHI and VAS scores as subjective parameters also improved. In the abductor SD group, one patient responded to treatment. Adverse events included breathy hoarseness (77.3%) and aspiration when drinking (40.9%) but were mild and resolved in 4 weeks. CONCLUSIONS: Botulinum toxin injection was safe and efficacious for the treatment of SD. Based on these results, BT injection therapy was approved as an SD treatment in Japan.

Perioperative complications and safety of type II thyroplasty (TPII) for adductor spasmodic dysphonia.

Type II thyroplasty (TPII) is one of the surgical options offered in the management of adductor spasmodic dysphonia (AdSD); however, there have been no detailed reports of its safety and associated complications during the perioperative period. Our aim was to assess the complications and safety of TPII. TPII was performed for consecutive 15 patients with AdSD from April 2012 through May 2014. We examined retrospectively the perioperative complications, the degree of surgical invasion, and recovery process from surgery. All patients underwent successful surgery under only local anesthesia. Vocal fold erythema was observed in 14 patients and vocal fold edema in 10 patients; however, all of them showed complete resolution within 1 month. No patient experienced severe complications such as acute airway distress or hemorrhage. Fourteen patients were able to have oral from the 1st postoperative morning, with the remaining patient able to have oral intake from the 2nd postoperative day. In addition, no patient experienced aspiration postoperatively. In conclusion, only minor complications were observed in association with TPII in this study. No dysphagia was observed postoperatively, which is an advantage over other treatments. The results of our study suggest that TPII is a safe surgical treatment for AdSD.

Validity of intraoperative voice monitoring undergoing type 2 thyroplasty with titanium bridges for adductor spasmodic dysphonia.

Objectives: The success of type 2 thyroplasty (TP2) for adductor spasmodic dysphonia (AdSD) depends on the selection of optimally sized titanium bridges, which requires accurate assessment of intraoperative vocal changes. While this procedure has traditionally been performed according to the laryngologist's experience, the most appropriate method for voice monitoring and selection of titanium bridge size remains to be determined. This study aimed to investigate evaluation parameters useful for voice monitoring, as these may allow less experienced surgeons to perform TP2 properly. Methods: In this prospective study, voice monitoring was performed in 18 patients with AdSD patients undergoing TP2. Evaluations were performed preoperatively, intraoperatively, 13 weeks postoperatively, and 52 weeks postoperatively using GRBAS (grade, roughness, breathiness, asthenia, and strain), as well as perceptual judgment and acoustic analyses. Results: Preoperative and intraoperative assessments of the G, R, B, and S parameters, perceptual judgment, and harmonic-to-noise ratio (HNR) were in moderate or better agreement. Intraoperative and 13- or 52-week postoperative measurements of the R, B, and G parameters and strangulation, tremor, and HNR were also in high agreement. When two different sizes of titanium bridges were compared (unselected vs. selected), ratings for G, R, S, strangulation, tremor, jitter, shimmer, HNR, standard deviation of F0, and degree of voice breaks were better for the selected width than the unselected width. Conclusion: The candidate items for intraoperative voice monitoring during TP2 for AdSD are G, R, strangulation, tremor, and HNR. The use of these items may help to ensure successful TP2 and contribute to the advancement of laryngeal framework surgery. Level of evidence: Level 4.

The accuracy of (18)[F]-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography, ultrasonography, and enhanced computed tomography alone in the preoperative diagnosis of cervical lymph node metastasis in patients with papillary thyroid carcinoma.

BACKGROUND: The aim of this study was to evaluate the accuracy of [(18)F]-fluoro-2-deoxy-D: -glucose-positron emission tomography/computed tomography, ultrasonography, and enhanced computed tomography alone in the preoperative diagnosis of lymph node metastasis in patients with papillary thyroid carcinoma. METHODS: In a prospective study performed between January 2007 and December 2009, 74 patients with a diagnosis of papillary thyroid carcinoma confirmed by fine-needle aspiration biopsy were referred to our institution for surgery. Preoperative assessment of metastasis in the central and lateral cervical lymph nodes was done using [(18)F]-fluoro-2-deoxy-D: -glucose-positron emission tomography/computed tomography, ultrasonography, and enhanced computed tomography. The results for each level of cervical node assessed using these methods were correlated with the pathology reports after surgery. We determined the sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of the three methods for all levels of cervical lymph node. RESULTS: There were no significant differences in the diagnostic results obtained by [(18)F]-fluoro-2-deoxy-D: -glucose-positron emission tomography/computed tomography and enhanced computed tomography. However, ultrasonography images gave significantly better results than either [(18)F]-fluoro-2-deoxy-D: -glucose-positron emission tomography/computed tomography or enhanced computed tomography alone in identifying metastases on the basis of the level of cervical lymph node. In addition, the overall diagnostic accuracy tended to be higher for the lateral compartment than for the central compartment. CONCLUSIONS: Preoperative assessment by ultrasonography of metastases in the central and lateral cervical lymph nodes might be the best methodology for determining the extent of surgical resection required to remove metastatic lymph nodes adequately in patients with papillary thyroid carcinoma.

Reliability and Validity of Speech Evaluation in Adductor Spasmodic Dysphonia.

OBJECTIVES: The aim of this study was to evaluate speech in patients with adductor spasmodic dysphonia (ADSD) by perceptual evaluations and acoustic measures, and to examine the reliability and validity of these measures. METHODS: Twenty-four patients with ADSD and 24 healthy volunteers were included in the study. Speech materials consisted of three sentences constructed from serial voiced syllables to elicit abductor voice breaks. Three otolaryngologists rated the degree of voice symptoms using a visual analog scale (VAS). VAS sheets with five 100-mm horizontal lines were given to each rater. The ends of the lines were labeled normal vs severe, and the five lines were labeled as overall severity of each of the four speech symptoms (strangulation, interruption, tremor and strained speech). Nine words were selected for acoustic analysis, and abnormal acoustic events were classified into one of the three categories. To evaluate the intra- and inter-rater and intermeasurer reliabilities of the VAS scores or acoustic measures, Pearson r correlations were calculated. To examine the validity of perceptual evaluations and acoustic measures, the sensitivity and the specificity were calculated. RESULTS: Pearson r correlation coefficients for overall severity showed the highest intra- and inter-rater reliabilities. For acoustic events, the intrameasurer reliabilities were r = .645 (frequency shifts), r = .969 (aperiodic segments), and r = 1.0 (phonation breaks), and the intermeasurer reliability ranged from r = .102 to r = 1.0. Perceptual evaluation showed high sensitivity (91.7%) and specificity (100%), whereas acoustic analysis showed low sensitivity (70.8%) and high specificity (100%). CONCLUSION: Both perceptual evaluation and acoustic measures alone were found likely to overlook patients with true ADSD.

Osteoradionecrosis of the hyoid bone after intra-arterial chemoradiotherapy for oropharyngeal cancer: MR imaging findings.

BACKGROUND: Osteoradionecrosis (ORN) of the hyoid bone sometimes induces severe front neck infection and can cause laryngeal stenosis and carotid rupture. Although ORN of the hyoid bone is known to be a complication of chemoradiotherapy for head and neck cancer, there has been no basis for its evaluation. Our purpose is to present the clinical and MR imaging features of ORN of the hyoid bone. METHODS: The study group comprised patients with advanced oropharyngeal cancer treated with targeted intra-arterial cisplatin infusion with concomitant radiotherapy. ORN of the hyoid bone was identified on the basis of decreased signal intensity of the bone marrow on T1WI images. Signal intensity on T2WI images was used to distinguish between inflammation and fibrosis. RESULTS: A total of 39 pre-treatment MR images and follow-up MR images were reviewed. ORN of the hyoid bone were detected in 30% of patients after treatment, with 23% of them showing inflammation and 7.7% fibrosis. Two patients developed severe neck infection and received antibiotics and underwent surgical intervention by tracheostomy and resection of the hyoid bone. CONCLUSION: Our MR imaging study showed that ORN of the hyoid bone is not particularly rare in patients with oropharyngeal cancer treated with chemoradiotherapy. Clinicians should evaluate images carefully to prevent the development of severe complication due to infection associated with ORN of the hyoid bone.

Atypical adenoma of the thyroid diagnosed as anaplastic cancer by cytopathology.

Atypical adenoma of the thyroid is a rare form of tumor, and its accurate diagnosis prior to surgical resection is difficult as the histological and pathological morphologies are very similar to those of anaplastic thyroid carcinoma (ATC), and its anaplastic transformation remains to be elucidated. We reported a case of a 75-year-old female with a thyroid isthmus nodule diagnosed repeatedly by FNAC as anaplastic carcinoma. Both the first and second FNAC specimen slides showed a large number of scattered or aggregated atypical cells consisting of large, pleomorphic nuclei with irregular membranes, chromatin clumps and prominent nucleoli. The morphology of the surgical specimen was similar to that of an anaplastic carcinoma and although it showed signs of transition from a normal follicular epithelium, there was no invasive growth or mitosis. This lesion was diagnosed as an atypical adenoma, and a papillary carcinoma was also present in the right lobe of the thyroid. Here we evaluate the molecular features of atypical adenomas in comparison with 9 ATC samples, and discuss whether or not atypical adenomas represent a form of premalignant lesion. Ki-67 expression was found to be very low in atypical adenomas whereas all ATC samples showed high levels of Ki-67 expression. Epithelial-mesenchymal transition (EMT) marker expression suggested that atypical adenomas maintain their epithelial phenotype to a higher degree than do ATCs. Differential diagnosis between ATC and atypical adenoma is difficult by cytological and histological methods alone, and Ki-67 and EMT marker expression may support the diagnosis.

Voice Onset Time for the Word-Initial Voiceless Consonant /t/ in Japanese Spasmodic Dysphonia-A Comparison With Normal Controls.

OBJECTIVES: Voice onset time (VOT) for word-initial voiceless consonants in adductor spasmodic dysphonia (ADSD) and abductor spasmodic dysphonia (ABSD) patients were measured to determine (1) which acoustic measures differed from the controls and (2) whether acoustic measures were related to the pause or silence between the test word and the preceding word. METHODS: Forty-eight patients with ADSD and nine patients with ABSD, as well as 20 matched normal controls read a story in which the word "taiyo" (the sun) was repeated three times, each differentiated by the position of the word in the sentence. The target of measurement was the VOT for the word-initial voiceless consonant /t/. RESULTS: When the target syllable appeared in a sentence following a comma, or at the beginning of a sentence following a period, the ABSD patients' VOTs were significantly longer than those of the ADSD patients and controls. Abnormal prolongation of the VOTs was related to the pause or silence between the test word and the preceding word. CONCLUSIONS: VOTs in spasmodic dysphonia (SD) may vary according to the SD subtype or speaking conditions. VOT measurement was suggested to be a useful method for quantifying voice symptoms in SD.

Electronic states of DNA and M-DNA studied by optical absorption.

To unveil the electronic states of divalent metal ion incorporated M-DNAs, where M is Mg, Mn, Ni, Co, or Fe, optical absorption spectra have been studied in aqueous solutions of single-stranded (SS) 30 mer DNA of poly(dA) (adenine), poly(dG) (guanine), poly(dT) (thymine), poly(dC) (cytosine), salmon-sperm DNA (B-DNA), and M-DNA. The absorption spectrum of the double-stranded (DS) B-DNA can be reproduced with the sum of the four absorption spectra of the SS oligo-DNAs in the ratio corresponding to the composition of B-DNA. This observation suggests that the interactions between complementary strands of DS DNA are negligibly weaker than the bandwidths of the optical spectra. In the metal-incorporated M-DNAs, except for Fe-DNA, the absorption spectra show no significant qualitative change from that of B-DNA. Quantitatively, however, the absorption intensity decreases by ≈ 15% uniquely in a DS poly(dA)-poly(dT) solution with adding MCl(2), while nothing happens quantitatively and qualitatively in any SS oligo-DNA and DS poly(dG)-poly(dC) solutions, suggesting some suppression of the electronic excitation only in the Adenine-M-Thymine complex. In contrast, remarkable differences have been observed in Fe-DNA, prepared with FeCl(2) and B-DNA. New absorption bands appear in the intragap energy of Fe-DNA, in addition to the suppression of the interband absorption peak of DNA at 4.8 eV. The intragap absorption is attributed to the appearance of Fe(3+) species with the same spectral feature as that of FeCl(3), that is, purely ionic Fe(3+) species. This observation suggests that FeCl(2) + B-DNA forms Fe-DNA with hydrated Fe(3+) ions with ionic bonds. Thus, it is concluded that the charge transfer from Fe(2+) to DNA has occurred in Fe-DNA and that the transferred charges are expected to be located in the nearby bases.

Paranasal sinus mucoceles with visual disturbance.

OBJECTIVE: Paranasal sinus mucoceles may cause visual disturbance in patients because of their close proximity to the orbit. We aimed to investigate visual prognosis to determine whether it is influenced by the interval before surgery and the severity of visual disturbance, and to heighten the physician's awareness of the occurrence of this disease. METHODS: We retrospectively reviewed eight surgically treated patients with paranasal sinus mucoceles accompanied by visual disturbances between March 2005 and January 2009, and examined the visual acuity outcome of the patients. RESULTS: Four patients with a mild visual acuity loss showed improvement after surgical drainage within 1 month after onset. Two patients with visual disturbances persisting for more than 1 year did not show postoperative improvements. Although two patient's preoperative visual acuity loss was worse than the ability to count fingers, they showed a remarkable improvement after surgery. CONCLUSIONS: These results show the importance of diagnosing and treating paranasal sinus mucoceles with visual disturbance as soon as possible. In addition, the improvement of visual acuity can be expected if surgery is performed within 1 month after onset, and the patient's preoperative visual acuity loss is mild. However, if patients with severe visual acuity loss consult otolaryngologists at a later date, surgery may still be considered worthwhile.

Synthesis and properties of DNA complexes containing 2,2,6,6-tetramethyl-1-piperidinoxy (TEMPO) moieties as organic radical battery materials.

We report here the first example of organic radical battery with DNA. Though there is a growing interest in DNA/cationic-lipid complexes as promising gene delivery vehicles, few efforts have been focused on the use of such complexes as advanced materials for organic optoelectronic applications. The present article describes how substitution of the sodium counter cation of DNA with cationic amphiphilic lipid(1-4) provided novel DNA-lipid complexes that contain TEMPO radicals, in which the actual mole ratio of phosphate to lipid was 1:0.84 to 1:0.16. All the TEMPO-containing DNA-lipid complexes displayed reversible two-stage charge/discharge processes, the discharge capacities of which were 40.5-60.0 A h kg(-1). In particular, the capacity of a DNA-lipid(3)-based cell reached 60.0 A h kg(-1), which corresponds to 192 % relative to its theoretical value for the single-electron one-stage process, indicating a two-electron process.

Synthesis and charge/discharge properties of polyacetylenes carrying 2,2,6,6-tetramethyl-1-piperidinoxy radicals.

The 2,2,6,6-tetramethyl-1-piperidinoxy (TEMPO)-containing acetylenic monomers HC[triple bond]CC(6)H(3)-p,m-(CONH-4-TEMPO)(2) (1), HC[triple bond]CC(6)H(3)-p,m-(COO-4-TEMPO)(2) (2), (S,S,S,S)-HC[triple bond]CC(6)H(3)-p,m-[CO-NHCH{COO-(4-TEMPO)}CH(2)COO-(4-TEMPO)](2) (3), (S,S)-HC[triple bond]CC(6)H(4)CO-NHCH{COO-(4-TEMPO)}CH(2)COO-(4-TEMPO) (4), HC[triple bond]CC(6)H(4)-p-OCO-4-TEMPO (5), HC[triple bond]CCH(2)C(CH(3))(CH(2)OCO-4-TEMPO)(2) (6), HC[triple bond]CCH(2)NHCO-4-TEMPO (7), and HC[triple bond]CCH(2)OCO-4-TEMPO (8) were polymerized to afford novel polymers containing the TEMPO radical at high densities. Monomers 1, 3-6, and 8 provided polymers with average molecular weights of 10 000-136 500 in 62-99 % yield in the presence of a rhodium catalyst, whereas monomers 2 and 7 gave insoluble polymers in 100 % yield. The formed polymers were thermally stable up to approximately 274 degrees C according to thermogravimetric analysis (TGA). All the TEMPO-containing polymers demonstrated reversible charge/discharge processes, whose discharge capacities were 21.3-108 A h kg(-1). In particular, the capacity of poly(1)-, poly(4)-, and poly(5)-based cells reached 108, 96.3, and 89.3 A h kg(-1), respectively, which practically coincided with their theoretical values.

Magnetic properties of (BEDT-TTF)(ClMeTCNQ) studied by ESR under pressure: a neutral-ionic crossover and thermoinduced mesophase.

The neutral-ionic (NI) phase transition in (BEDT-TTF)(ClMeTCNQ) is studied with ESR under pressure to tune the transition temperature. Broad peak structures observed in the spin susceptibility around T(NI) are analyzed with the assumption of a spin-Peierls gap of 1100 K, which demonstrates the continuous evolution of ionic domain fraction through T(NI) over the extent T(W) proportional, variantT(NI). An unexpected feature is the presence of sizable ionic droplets even at T>>T(NI), which is ascribed to the tiny energy difference between the two phases.

Charge transport in the insulating state of (DMe-DCNQI)2Li above T(SP): a possible fractional charge soliton conduction with +/-1 / 2e.

A spin-Peierls system (DMe-DCNQI)2Li is studied with W-band electron paramagnetic resonance (EPR) ( approximately 94 GHz) to unveil a charge transport mechanism in the insulating 4k(F) charge density wave state above T(SP). The electron hopping between the neighbor DCNQI columns provides an additional broadening of the EPR linewidth, since the neighbor columns are generally nonequivalent to each other with respect to g shift. The obtained intercolumn hopping rates lead us to the conclusion that the electron hopping to a hole soliton carrying a fractional charge of e / 2 in the neighbor column dominates the intercolumn charge transport.