Paediatric dacryocystorhinostomy

Of 258 cases of dacryocystorhinostomy performed on children in the period September 1981 to September 1991, 130 were for simple, unresolved congenital nasolacrimal duct obstruction. Other indications for surgery included punctal agenesis, lacrimal fistula, post-traumatic and post-inflammatory canalicular obstruction. Of 177 children without canalicular pathology, 171 (96%) were relieved of symptoms with one operation, without canalicular intubation. Of 81 cases with canalicular disease, 55 of 70 (79%) who underwent DCR plus canalicular intubation, and 10 of 11 who underwent DCR plus Lester-Jones tube, were substantially improved with one operation. No child required peroperative or postoperative blood transfusion. Dacryocystorhinostomy in childhood, in experienced surgical hands, is a safe procedure, achieving relief of symptoms in most cases, particularly in the absence of canalicular disease.     

Instrumentation and patient characteristics that influence postoperative haemorrhage rates following tonsil and adenoid surgery

Objectives: To investigate the effect of the type instrumentation used and the age and gender characteristics of patients on postoperative haemorrhage rates following tonsil and adenoid surgery. Design: A retrospective analysis of 13 593 procedures was performed from The Patient Episode Database for Wales between 1 January 1999 and 31 March 2004. Setting: National health policy changes created four periods of different instrument usage (reusable, single‐use with diathermy, single‐use alone, specified single‐use with diathermy). These and the age and gender distribution of the patients were examined against four categories of postoperative haemorrhage. Main outcome measures: Postoperative haemorrhage rates were expressed as the number of complications per operations performed. Primary postoperative haemorrhage that occurred during the initial admission either required a return to theatre [R1] or was managed conservatively [N1]; secondary postoperative haemorrhage that required a return to hospital either returned to theatre [R2] or was managed conservatively [N2], were compared. Results: Primary haemorrhage with return to theatre doubled, from the baseline rate with reusable instruments, from 0.6% (CI 0.5–0.8) to 1.2% (CI 0.7–1.9) when single‐use instruments were introduced and remained high at 1.4% (CI 0.9–2.1) after the withdrawal of single‐use diathermy. This haemorrhage rate returned to the baseline rate (0.6% CI 0.3–1.0) when specified single‐use instruments were introduced. None of the other haemorrhage rates changed significantly throughout the four observation periods. Adenotonsillectomy and tonsillectomy patients have different age and gender patterns. In a univariate analysis, males over the age of 12 years were twice as likely to have haemorrhage with return to theatre than girls of the same age, 3.8% (CI 3.0–4.7) versus 1.7% (CI 1.4–2.1). Conclusions: A significant rise in serious postoperative primary haemorrhage but not secondary haemorrhage was seen following the initial introduction of single‐use instruments that reverted to baseline with the introduction of specified single‐use instruments. Diathermy does not appear to have affected the haemorrhage rates. There is a distinct age and gender pattern for tonsil and adenoid surgery and risk of postoperative haemorrhage. The use of arbitrary divisions of age may be misleading in studies that examine post‐tonsillectomy haemorrhage.     

GDF-8 propeptide binds to GDF-8 and antagonizes biological activity by inhibiting GDF-8 receptor binding

GDF-8 is a new member of the TGF-beta superfamily which appears to be a negative regulator of skeletal muscle mass. Factors which regulate the biological activity of GDF-8 have not yet been identified. However, the biological activities of TGF-beta superfamily members, TGF-beta1, -beta2 and -beta3, can be inhibited by noncovalent association with TGF-beta1, -beta2 and beta3 propeptides cleaved from the amino-termini of the TGF-beta precursor proteins. In contrast, the propeptides of other TGF-beta superfamily members do not appear to be inhibitory. In this investigation, we demonstrate that purified recombinant GDF-8 propeptide associates with purified recombinant GDF-8 to form a noncovalent complex, as evidenced by size exclusion chromatography and chemical crosslinking analysis. Furthermore, we show that GDF-8 propeptide inhibits the biological activity of GDF-8 assayed on A204 rhabdomyosarcoma cells transfected with a (CAGA)12 reporter construct. Finally, we demonstrate that GDF-8 propeptide inhibits specific GDF-8 binding to L6 myoblast cells. Collectively, these data identify the GDF-8 propeptide as an inhibitor of GDF-8 biological activity.     

恶性肿瘤患者血清与尿液中一氧化氮含量测定

0 引言一氧化氮（Nitric oxide,NO）是一种具有活跃生物化学性质的无机小分子. NO对许多肿瘤细胞和微生物有细胞毒性［1］,为探讨NO与肿瘤的关系,我们检测了119例恶性肿瘤患者血清及尿液中的NO.     

A novel ENT iBook: what do junior doctors think?

Exposure to the specialty of Otolaryngology is limited. It may be consolidated by the use of an iBook as a self-study tool. The purpose of this study was to ascertain the perceptions of junior doctors on the clinical relevance of this novel educational resource. Three focus groups were formed each consisting of five junior doctors (eight female: seven male, median age 27 years). The iBook was found to be clinically relevant to the work of junior doctors, have a clear layout, with adequate interactivity and a good range of integrated multimedia elements.     

Characterization of an ester-based core-multishell (CMS) nanocarrier for the topical application at the oral mucosa

Objectives

Topical drug administration is commonly applied to control oral inflammation. However, it requires sufficient drug adherence and a high degree of bioavailability. Here, we tested the hypothesis whether an ester-based core-multishell (CMS) nanocarrier is a suitable nontoxic drug-delivery system that penetrates efficiently to oral mucosal tissues, and thereby, increase the bioavailability of topically applied drugs.

Material and methods

To evaluate adhesion and penetration, the fluorescence-labeled CMS 10-E-15-350 nanocarrier was applied to ex vivo porcine masticatory and lining mucosa in a Franz cell diffusion assay and to an in vitro 3D model. In gingival epithelial cells, potential cytotoxicity and proliferative effects of the nanocarrier were determined by MTT and sulphorhodamine B assays, respectively. Transepithelial electrical resistance (TEER) was measured in presence and absence of CMS 10-E-15-350 using an Endohm-12 chamber and a volt-ohm-meter. Cellular nanocarrier uptake was analyzed by laser scanning microscopy. Inflammatory responses were determined by monitoring pro-inflammatory cytokines using real-time PCR and ELISA.

Results

CMS nanocarrier adhered to mucosal tissues within 5 min in an in vitro model and in ex vivo porcine tissues. The CMS nanocarrier exhibited no cytotoxic effects and induced no inflammatory responses. Furthermore, the physical barrier expressed by the TEER remained unaffected by the nanocarrier.

Conclusions

CMS 10-E-15-350 adhered to the oral mucosa and adhesion increased over time which is a prerequisite for an efficient drug release. Since TEER is unaffected, CMS nanocarrier may enter the oral mucosa transcellularly.

Clinical relevance

Nanocarrier technology is a novel and innovative approach for efficient topical drug delivery at the oral mucosa.

     

POLD1 variants leading to reduced polymerase activity can cause hearing loss without syndromic features

DNA polymerase δ, whose catalytic subunit is encoded by POLD1, is responsible for synthesizing the lagging strand of DNA. Single heterozygous POLD1 mutations in domains with polymerase and exonuclease activities have been reported to cause syndromic deafness as a part of multisystem metabolic disorder or predisposition to cancer. However, the phenotypes of diverse combinations of POLD1 genotypes have not been elucidated in humans. We found that five members of a multiplex family segregating autosomal recessive nonsyndromic sensorineural hearing loss (NS‐SNHL) have revealed novel compound heterozygous POLD1 variants (p.Gly1100Arg and a presumptive null function variant, p.Ser197Hisfs*54). The recombinant p.Gly1100Arg polymerase δ showed a reduced polymerase activity by 30–40%, but exhibited normal exonuclease activity. The polymerase activity in cell extracts from the affected subject carrying the two POLD1 mutant alleles was about 33% of normal controls. We suggest that significantly decreased polymerase δ activity, but not a complete absence, with normal exonuclease activity could lead to NS‐SNHL.