Demonstration of in vivo stability and lack of immunogenicity of a polyethyleneglycol-conjugated recombinant CHO-derived butyrylcholinesterase bioscavenger using a homologous macaque model.

Human serum and recombinant butyrylcholinesterase (rHuBChE) are the most advanced prophylactics against organophosphate (OP) toxicity due to nerve agent or insecticide exposure. For ethical reasons, such potential multi-use treatments cannot be tested in humans and will require extensive testing in animal models and the "Animal Rule" 21 (21 CFR 601.90) for regulatory approval. This will involve multiple injections of rHuBChE into heterologous animals, e.g. macaques, rodents with inevitable immunogenicity and subsequent elimination of the enzyme on repeat injections. In order to accurately assess pharmacokinetics, efficacy and safety of a candidate rBChE in an "antibody free" system, a homologous macaque (Ma) model has been developed. In these studies, macaques received single or multiple intravenous injections of native MaBChE as well as unmodified or PEG-conjugated forms of rMaBChE produced in CHO cells. Compared to the poor plasma retention of unmodified rBChE (MRT: <10h), three injections of 1.5-2.3mg/kg of PEG-conjugated tetrameric rBChE resulted in high circulatory stability (MRT: >134h) and lack of immunogenicity similar to native MaBChE. PEG-conjugation of the monomeric rMaBChE form also exhibited pharmacokinetic profiles comparable to the tetrameric form (MRT: >113h). However, despite the increased bioavailability of PEG-rBChE, antigenicity studies using sandwich ELISA showed that while macaque BChE was not immunogenic in macaques, PEGylation of rMaBChE did not prevent binding to anti-BChE antibodies, suggesting PEGylation may not be sufficient to mask non-human epitopes on rBChE. This homologous model can provide necessary preclinical protection data for the use of PEG-rHuBChE in humans and bodes well for a safe and efficacious CHO-derived rHuBChE therapeutic.

[Effects of two surgical techniques for vocal cord cyst].

OBJECTIVE: To compare the effectiveness of vocal cord cyst excision with electronic laryngoscope (EL) and self-retaining laryngoscope (SRM). METHOD: Nightly-two patients, diagnosed as vocal cord cyst with strobolaryngoscope or electronic laryngoscope, were randomly divided into two groups. One group was 48 cases treated with electronic laryngoscope and another group was 44 cases treated with self-retaining laryngoscope. Electronic laryngoscopy examination and voice function assessments were performed to all patients, preoperatively and postoperatively at one week, three months and six months. RESULT: One failed cases under SRM, difficult exposure of glottic portion, were treated under EL. The recurrence rate of the two groups was of no statistical significance in three months after operation. Voice function assessment of the two groups was of no statistical significance at one week, three months and six months after operation. CONCLUSION: The operation under electronic laryngoscope is a minimal invasive procedure to the laryngeal mucosa. Electronic laryngoscope had advantages such as clear view, accurate operation. Furthermore, it can be used for those that could not be treated under self-retaining laryngoscope.

[Glottic measurement and vocal evaluation after three surgical techniques in the treatment of bilateral vocal cord paralysis].

OBJECTIVE: To evaluate postoperative glottic area and vocal quality of three various surgical techniques for treating bilateral vocal cord paralysis, including laser arytenoidectomy (Group A, 24 cases), reinnervation of the posterior cricoarytenoid muscle by phrenic nerve (Group B, 9 cases) and arytenoidectomy accompanying lateral cordopexy by extralaryngeal approach (Woodman's procedure, Group C, 13 cases). METHODS: 46 cases suffered from bilateral recurrent laryngeal nerve injury were included in our study. The pre-postoperative glottic measurement and vocal acoustic parameters were analyzed. RESULTS: The decannulated cases in group A and group B and group C were 22, 8, 13 respectively. The post-operative mean maximal glottic area was (47.2 +/- 7.4) mm2, (78.3 +/- 16.0) mm2, (48.1 +/- 6.5) mm2 respectively. Group B cases glottic area was larger than that of group A and group C (t value were 4.46 and 3.85, P value were 0.000 and 0.001). No significant difference was found between group A and group C (t = 1.68, P = 0.101). After surgery, in group A, 17 cases voice quality was the same compared with that of before surgery, and 7 cases voice quality had become worse; In group B, the voice quality had become better in 5 cases, completely recovered in 1 case, and had not change in 3 cases; In group C, the voice quality had become deteriorated in 10 cases and no change in 3 cases. And in group B, ipsilateral diaphragm paralysis in 9 cases after surgery, whose vital capacity and forced vital capacity had decreased to 72%-84%, 76%-84% of that before the surgery respectively; and the diaphragm mobility had recovered by 35%-76% respectively, while vital capacity and forced vital capacity had become 93%-97%, 91%-98% of that before the surgery. In Group B, all cases' pulmonary function was normal half a year postoperatively. CONCLUSIONS: Reinnervation of the posterior cricoarytenoid muscle by phrenic nerve seems to be best procedure with better post-operative voice and larger glottic area. Although the sufficient airway for decannulation can be acquired in Group A and Group C, but most of patients in Group A had pre-operative vocal level and badly abnormal in Group C.

[Intratumor bleomycin-A5 injection under electrolaryngoscope for treatment of large laryngopharyngeal and laryngeal hemangioma].

OBJECTIVE: To study the therapeutic effect of bleomycin-A5 injection under eletrolaryngoscope for treatment of large laryngopharyngeal and laryngeal hemangioma. METHODS: Intratumor bleomycin-A5 injection under eletrolaryngoscope was performed in 18 cases of large laryngopharyngeal and laryngeal hemangioma with surface anaesthesia, for totally 7 to 14 (mean 10.2) injections in each case. RESULTS: Twelve patients were cured and 6 showed obvious improvement. Follow-up of the patients for over one year found no recurrence of the hemangioma. CONCLUSION: Bleomycin-A5 injection is a minimal invasive procedure for treatment of large laryngopharyngeal and laryngeal hemangioma, causing less pain and better preserving the laryngeal function without the necessity of tracheotomy.