Topical application of epidermal growth factor with no scaffold material on the healing of human traumatic tympanic membrane perforations.

OBJECTIVE: We evaluated the effects of conservative treatment and topical application of epidermal growth factor (EGF) with no scaffold material on the healing of human traumatic tympanic membrane perforations (TMPs). STUDY DESIGN: Prospective, randomised clinical trial. METHODS: A prospective analysis was performed between January 2015 and March 2015 for the treatment of human traumatic TMPs. The closure rate, closure time, hearing gain and rate of purulent otorrhoea were compared between the topical application of EGF and conservative treatment. RESULT: In total, 97 patients were analysed. The total closure rates did not significantly differ between the observation and EGF groups (83.0% versus 92.0%, P = 0.182). The total average closure time in the observation group was significantly longer than in the EGF group (25.1 ± 10.5 versus 11.7 ± 5.2 days, P = 0.001). When the closure rate was evaluated according to perforation size, no significant difference was seen for medium or large perforations (P = 0.18 and 0.21, respectively). When closure time was evaluated according to perforation size, a significant difference was seen for medium and large perforations (P = 0.001). CONCLUSIONS: This study suggests that topical application of EGF with no scaffold material may significantly shorten the closure time of human traumatic TMPs. Such a shorter recovery time may lead to reduced healthcare costs. This alternative technique to a classic myringoplasty is particularly beneficial and suitable for the closure of large human traumatic TMPs.

Healing outcomes of large (>50%) traumatic membrane perforations with inverted edges following no intervention, edge approximation and fibroblast growth factor application; a sequential allocation, three-armed trial.

OBJECTIVE: The goal of this study was to evaluate the effects of perforation edge approximation and direct application of basic fibroblast growth factor (bFGF) each alone on the healing of large traumatic tympanic membrane perforations with inverted edges in humans. STUDY DESIGN: Prospective, sequential allocation, three-armed, controlled clinical study. SETTING: University-affiliated teaching hospital. PARTICIPANTS: Fifty-eight patients with large traumatic tympanic membrane perforations (i.e. affecting >50% of the surface area) with inverted edges were recruited. They were sequentially allocated to three groups: no intervention (n = 18), edge approximation alone (n = 20) and direct application of bFGF (n = 20). Otoscopy were performed before the treatment and at follow-up visits. MAIN OUTCOME MEASURES: The closure rate, closure time and rate of otorrhoea. RESULTS: Application of bFGF yielded a significantly higher average rate of perforation closure (100%) than edge approximation (60%) and no intervention (56%) (P < 0.05). It also significantly shortened the average closure time (12.4 ± 3.6 days) as compared to edge approximation (46.3 ± 8.7 days) and no intervention control (48.2 ± 5.3 days) (P < 0.05). Purulent otorrhoea was observed in none of the three groups. CONCLUSION: Edge approximation of inverted edges has little benefit in improving the healing outcome of large traumatic tympanic membrane perforations and thus is not an ideal treatment option for large traumatic tympanic membrane perforations. Application of bFGF materially improves the closure rate of large traumatic tympanic membrane perforations and significantly shortens the closure time.

A randomised controlled trial comparing spontaneous healing, gelfoam patching and edge-approximation plus gelfoam patching in traumatic tympanic membrane perforation with inverted or everted edges.

OBJECTIVE: To compare the outcome of patients with dry traumatic tympanic membrane perforation after spontaneous healing and gelfoam patching with or without perforation edge approximation. DESIGN: Prospective clinical study. SETTING: University-affiliated teaching hospital. PARTICIPANTS: Ninety-one patients with acute dry traumatic tympanic membrane perforation inverted or everted edges were recruited. They were randomly allocated to three groups: spontaneous healing (n=31), gelfoam patching (n=30) and edge-approximation plus gelfoam patching (n=30). Otoscopy and tympanometry were performed before the treatment and at follow-up visits. MAIN OUTCOME MEASURES: Healing rate, healing time, ear infection rate and morphological changes during healing process. RESULTS: The overall healing rate was 85% in the spontaneous healing group, lower than that in the two gelfoam patching groups (97%), but the difference failed to reach a statistical significance (P>0.05). The average healing time was 30 ± 10.1 days in the spontaneous healing group, significantly longer (P<0.01) than that in the other two groups (16 ± 5.6 and 18 ± 4.7 days, respectively). Middle ear infection rate did not differ significantly (7%, 3% and 3%, respectively). Spontaneous healing resulted in formation of scabs at the perforation edges, which was effectively prevented by gelfoam patching. CONCLUSIONS: Gelfoam patching may facilitate healing of traumatically perforated tympanic membrane. Approximation of folded perforation edges is not necessary in gelfoam patching.

A prospective study evaluating spontaneous healing of aetiology, size and type-different groups of traumatic tympanic membrane perforation.

OBJECTIVES: To evaluate the outcome of spontaneous healing of aetiology-, size- and type-different groups of acute traumatic eardrum perforation and to characterise changes in the morphology of the healing eardrum in various conditions. STUDY DESIGN: Prospective clinical study. SETTING: University-affiliated teaching hospital. PARTICIPANTS: A total of 126 patients who visited the Outpatient Department of the Otolaryngology Clinic of Yiwu Central Hospital, Yiwu, China between January 2008 and June 2009 with acute traumatic tympanic membrane perforations. MAIN OUTCOME MEASURES: All participants were allowed to heal spontaneously for 12 months. The clinical outcome including healing rate, healing time, hearing function and air-bone gap recovery as well as morphological changes of the healing tympanic membrane was evaluated on the bases of perforation aetiology, size and type, etc. RESULTS: By perforation size, the overall healing rate at the end of the 12-month follow-up was comparable to each other in the three (small, medium and large) size groups (P > 0.05); however, there were significant perforation size-dependent differences in the average closure time (P < 0.05). For serosanguinous discharge and dry perforations, the healing rate at the end of 12-month follow-up was similar (95%versus 85%, P > 0.05), but the average healing time was different (16 versus 28 days, P < 0.01) and so was the sequence of granulation tissue formation and epithelial migration in the course of perforation healing. The inverted or everted edges as compared with no curled edges did not significantly affect the healing rate (95%versus 82%, P > 0.05) or closure time (24 versus 27 days). Hearing loss differed significantly between perforations of different causes (P < 0.01), but the perforation cause did not affect recovery of the air-bone defect. Pre-existing tympanosclerosis was the most prominent cause of healing failure. CONCLUSION: The clinical outcome of spontaneous healing of acute tympanic membrane perforations is generally associated with perforation size, aetiology and whether dry or with a serosanguenous discharge. The sequence of granulation tissue formation and epithelial migration differs during the healing of traumatic tympanic membrane formation in serosanguinous discharge conditions and dry perforation.

Analysis of nasal foreign bodies in 341 children.

OBJECTIVE: This study aimed to analyse the common presentations and treatment outcomes in cases involving nasal foreign bodies. METHODS: A retrospective study was carried out over three years, from January 2014 to December 2017. Patient biodata, clinical presentation, nasal foreign body type and management outcome data were obtained from the medical records and analysed. RESULTS: A total of 341 cases were analysed. The average patient age was 3.7 ± 1.2 years (range, 1-19 years).Of the nine cases involving button batteries, septal perforation was initially seen in four cases and three cases had subsequent septal perforation. CONCLUSION: Only button battery nasal foreign bodies were associated with increased septal perforation. Use of physiological seawater nasal spray was found to reduce the likelihood of septal perforation. Most nasal foreign bodies could be removed under local anaesthesia.

Does epistaxis with an unknown bleeding site originate from the posterior part of the nasal cavity?

OBJECTIVE: To review the origins of epistaxis in patients with unknown bleeding sites. METHODS: This consecutive case series included 26 patients with unknown bleeding sites previously considered to have posterior epistaxis. All patients had previously been examined endoscopically at least once, and were again examined with 30°, 45° and 70° endoscopes. RESULTS: The bleeding site was at the: anterior end of the lateral wall of the inferior meatus in one patient (3.8 per cent); anterosuperior lateral wall of the nasal cavity in five patients (19.2 per cent); anterior nasal cavity roof in seven patients (26.9 per cent); anterosuperior part of the cartilaginous septum in nine patients (34.6 per cent); ostium pharyngeum tubae in two patients (7.7 per cent); and anterior nasal base in two patients (7.7 per cent). The morphology of the bleeding point showed: nasal mucosa ulceration in 1 patient, isolated primary telangiectasia in 3 patients, prominent vessels in 5 patients and capillary angioma in 17 patients. CONCLUSION: Epistaxis originating from the anterosuperior nasal cavity and nasopharynx can be easily misdiagnosed as posterior epistaxis or unknown bleeding sites. Areas that should be considered as possible origins of epistaxis in cases with unknown bleeding sites were identified.

The effects of everted or inverted edges on healing of traumatic-induced tympanic membrane perforations.

OBJECTIVES: To evaluate the healing and hearing outcomes related to the everted or inverted edge area on slap- and fist-induced large tympanic membrane perforations. METHODS: A total of 120 patients with slap- or fist-induced tympanic membrane perforations, with inverted or everted edges, affecting 50-75 per cent of the entire tympanic membrane, were randomly divided into 2 groups: an edge approximation group and a spontaneous healing group. The edge approximation group was divided into subgroups A and B based on the reversed edge area (reversed edge was more or less than 50 per cent of the total perforation, respectively). Healing outcomes and hearing improvements at six months were compared. RESULTS: The data of 118 patients were analysed. The closure rate of perforations in subgroup A, subgroup B, and the spontaneous healing group was 90.9 per cent, 92.1 per cent and 84.5 per cent, respectively; the difference between the three groups was not significant (p = 0.393). CONCLUSION: The area of reversed edges for slap- or fist-induced tympanic membrane perforations did not seem to affect healing and hearing outcomes, regardless of edge approximation and everted or inverted edges.

The distribution of bleeding sites in idiopathic hidden arterial epistaxis.

OBJECTIVE: To determine the frequency distribution of bleeding sites in idiopathic hidden arterial epistaxis. METHODS: In this retrospective cohort study, 107 patients with hidden arterial epistaxis were endoscopically examined for sites of bleeding. RESULTS: All sites of hidden arterial epistaxis were identified by endoscopic examination. Bleeding sites were identified at initial surgery in 103 patients and during the second surgery in 4. The bleeding sites included: the olfactory cleft region in 47 patients, the inferior meatus region in 29, the middle meatus region in 11, multiple bleeding sites (olfactory cleft and anterior septum) in 3, the anterior roof of the nasal cavity in 4, the nasal floor in 11 and the nasopharynx in 2. The bleeding points showed a white or red volcano-like bump in 75 patients, isolated prominent telangiectasia in 21 and mucosal ulceration in 11. CONCLUSION: Common sites of hidden arterial epistaxis include the olfactory cleft, inferior meatus and middle meatus. However, there should be awareness of some uncommon bleeding sites (including the anterior roof of the nasal cavity, the nasal floor and the nasopharynx) and of multiple bleeding sites.

The diagnosis and management of supernumerary nasal teeth.

OBJECTIVE: To discuss the reasons for misdiagnosis of supernumerary nasal teeth. METHODS: Clinical data of four supernumerary nasal tooth patients were analysed retrospectively at visits to our otolaryngology department between 2005 and 2018. RESULTS: All four patients were male and had a supernumerary nasal tooth in the right nasal cavity. Three of the four patients had previously been misdiagnosed. All the supernumerary nasal teeth were surrounded by granulation tissue or hypertrophic nasal mucosa, and were subsequently confirmed by computed tomography and endoscopy. The granulation tissue or hypertrophic nasal mucosa was removed using microwave ablation, and the supernumerary nasal teeth successfully removed by endoscopy. CONCLUSION: Supernumerary nasal teeth are rare, and are usually misdiagnosed because such teeth are surrounded by hypertrophic nasal mucosa or granulation tissue. They can be confirmed by computed tomography and endoscopy.

Regeneration of the tympanic membrane using fibroblast growth factor-2.

OBJECTIVE: A systematic review was conducted to investigate the effectiveness of fibroblast growth factor-2 on the regeneration of tympanic membrane perforation. METHODS: The PubMed database was searched for relevant studies. Experimental studies, human randomised controlled trials, prospective single-arm studies and retrospective studies reporting acute and chronic tympanic membrane perforations in relation to two healing outcomes (success rate and closure time), were selected. RESULTS: All 11 clinical studies investigating the effect of fibroblast growth factor-2 on traumatic tympanic membrane perforations in humans reported a success rate of 89.3-100 per cent, with a closure time of around 2 weeks. Three studies of fibroblast growth factor-2 combined with Gelfoam showed that the success rate of chronic tympanic membrane perforation was 83-98.1 per cent in the fibroblast growth factor-2 group, but 10 per cent in the gelatine sponge groups. CONCLUSION: Fibroblast growth factor-2 with or without biological material patching promotes regeneration in cases of acute and chronic tympanic membrane perforation, and is safe and efficient. However, the best dosage, application time and administration pathway of fibroblast growth factor-2 are still to be elucidated.

A moist edge environment aids the regeneration of traumatic tympanic membrane perforations.

OBJECTIVE: To review the history of moist therapy used to regenerate traumatic tympanic membrane perforations. STUDY DESIGN: Literature review. METHODS: The literature on topical agents used to treat traumatic tympanic membrane perforations was reviewed, and the advantages and disadvantages of moist therapy were analysed. RESULTS: A total of 76 studies were included in the analysis. Topical applications of certain agents (e.g. growth factors, Ofloxacin Otic Solution, and insulin solutions) to the moist edges of traumatic tympanic membrane perforations shortened closure times and improved closure rates. CONCLUSION: Dry tympanic membrane perforation edges may be associated with crust formation and centrifugal migration, delaying perforation closure. On the contrary, moist edges inhibit necrosis at the perforation margins, stimulate proliferation of granulation tissue and aid eardrum healing. Thus, moist perforation margins upon topical application of solutions of appropriate agents aid the regeneration of traumatic tympanic membrane perforations.

Jennisseensosides C and D, biologically active acylated triterpene saponins from Silene jenisseensis.

We previously reported the isolation and structure elucidation of a new trans-p-methoxycinnamoyl triterpene-saponin along with its cis-p-methoxycinnamoyl isomer as an inseparable mixture from the roots of Silene jenisseensis. In a continuing study on this plant, two additional new acylated triterpene-saponins were obtained as an inseparable mixture. Their structures have been established by chemical means and spectroscopic methods including 1D and 2D homonuclear and heteronuclear correlation NMR spectroscopy as 3-O-[beta-D-galactopyranosyl-(1-->2)-beta-D-glucuronopyranosyl]-28 -O-[{alpha-L-rhamnopyranosyl-(1-->2)}-{4-O-trans-p-methoxycinnamoyl++ +}-beta-D-fucopyranosyl] quillaic acid and its cis-isomer, respectively. They showed a significant enhancement of the granulocyte phagocytosis in vitro.

Acylated triterpene saponins from Silene jenisseensis.

From the roots of Silene jenisseensis a new trans-p-methoxycinnamoyl triterpene saponin has been isolated along with its cis-p-methoxycinnamoyl isomer as an inseparable mixture. Their structures were established by chemical means and spectroscopic methods including 1D- and 2D-homonuclear and heteronuclear correlation NMR spectroscopy as 3-O-[beta-D-galactopyranosyl-(1 --> 2)-beta-D-glucuronopyranosyl]-28-O-[beta-D-glucopyranosyl-(1 --> 2)-alpha-L-rhamnopyranosyl- (1 --> 2)-beta-D-4-O-trans-p-methoxycinnamoyl-fucopyranosyl] quillaic acid and its cis-isomer, respectively. They did not show any activity in the in vitro chemoluminescence granulocytes assay, but exhibited only a weak inhibitory effect in the cyclooxygenase inhibition assay.

[Quality evaluation of twelve species of Chinese Ephedra (ma huang)].

The contents of six Ephedra alkaloids, namely ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, methylephedrine and methyl-pseudoephedrine, in 12 species of Chinese Ephedra collected in 24 districts were determined by high performance liquid chromatography (HPLC). Zorbax CN column (25 cm x 4.6 mm I.D.) was used and the temperature of column oven was 23-25 degrees C. Dibutylamine phosphate solution 0.0009 mol/L (pH 2.2) was used as the mobile phase at flow rates: 0.8 ml/min for the first 7 minutes, raised to 1.5 ml/min in 30 sec and maintained for 16 minutes. The alkaloids eluted were detected at wave-length 210 nm. The results showed that ephedrine and pseudoephedrine are the main components in these Ephedra herbs, but the contents of the six Ephedra alkaloids vary greatly with the plant species. The contents of total alkaloids are higher and ephedrine is the main component in samples derived from Ephedra sinica, E. equisetina, E. monosperma and E. intermedia var. tibetica; but in E. intermedia and E. lomatolepis, the content of pseudoephedrine is higher than that of ephedrine. Methylephedrine content is higher in E. intermedia var. tibetica produced in Xizang (Tibet) and in E. sinica produced in north-eastern China than that in other species. The results also showed that the samples derived from E. przewalskii and E. lepidosperma contain so little alkaloids (less than 0.1%) that they are considered not suitable to be used as the drug Ma Huang. It is of interest that the cultivated Ephedra sinica showed lower alkaloids content compared with that growing wild.

[Quality evaluation of Chinese licorice].

The contents of 12 compounds, viz. glycyrrhizinic acid, uralsaponin A, uralsaponin B, liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, glycycoumarin, isoglycycoumarin, licochalcone A, glycyrol and isoglycyrol, present in Chinese licorice, the roots and rhizomes of 8 Glycyrrhiza species collected from 15 districts in China, were determined by high performance liquid chromatographic method. The quality evaluation of Chinese licorice was discussed according to the results of the determinations.

[Separation and quantitative determination of three saponins in licorice root by high performance liquid chromatography].

A new analytical method for the separation and simultaneous determination of three saponins in Licorice root by high performance liquid chromatography has been developed. The saponins, glycyrrhizic acid (S-I), uralsaponin B (S-II) and uralsaponin A (S-III) were separated and determined by use of the solvent system CH3CN-3% HOAc (H2O) (47:53) at 248 nm, and with gradient increasing flow rate, the operation can be completed in 20 min. This method is sensitive and acuate with good reproducibility. The contents of three saponins in Chinese Licorice roots derived from four Glycyrrhiza species were determined.

[Morphological and histological studies of Chinese Ephedra mahuang. I. Seven species produced in north China].

The Chinese drug Ma Huang, Herba Ephedrae, is well known in the East and West. The botanical origin specified in the Chinese Pharmacopoeia (1985 edition) includes the dried herbaceous stems of Ephedra sinica Stapf, E. equisetina Bunge and E. intermedia Schrenk ex Mey. A survey of the botanical origin of this drug, however, revealed that other Eqhedra spp. are also used in certain districts in China. In order to find means for the identification of drugs derived from different plant origins, it is necessary to make a comparative study of the morphology and histology of all the Eqhedra spp. growing in China. In this paper, the morphological and histological characters of the crude drugs derived from the Eqhedra spp. chiefly growing in north China, viz. E. sinica Stapf, E. equisetina Bunge, E. intermedia Schrenk ex Mey., E. qrzewaskiistaqs E. monosperma Gmel. ex Mey., E. fedtschenkoae Pauls, and E. regeliana Florin are described, compared and illustrated with line drawings. It is discovered that the following characters are useful for their differentiation, viz. (1) the presence, shape and height of cuticular papillae of the stem; (2) the presence, amount and arrangement of sclereids at stem-nodes; (3) vessels and tracheids with bordered pits and spiral thickenings, tracheids with bordered pits and reticulate thickenings, and xylem parenchyma cells with reticulate thickenings, (4) the ratios of longitudinal and transverse diameters of stomata on the epidermis of stem and leaf. Observation with scanning electron microscope (SEM) revealed that the perforations of the end walls of vessel element in Eqherda spp. are bordered. It is also found that the degree of lignification of fibres and medullary cells of the herbaceous stems is related to the positions and diameters of the stems. It is therefore unsuitable as a diagnostic feature for the differentiation of Eqhedrra species.

[Morphological and histological studies of Chinese Ephedra, ma huang. II. Species produced in southwestern China and other species].

In this paper, the morphological and histological characters of crude drugs derived from Ephedra likiangensis Florin, E. likiangensis f. mairei (Florin) C. Y. Cheng, E. saxatilis Royle ex Florin, E. gerardiana Wall, E. gerardiana var. congesta C. Y. Cheng, E. minuta Florin, E. minuta var. dioeca C. Y. Cheng, E. lepidosperma C. Y. Cheng, E. lomatolepis Schrenk and E. intermedia var. tibetica Stapf are described, compared and illustrated with line drawings. It was found that all the Ephedra spp. growing in southwester nChina possess the following features in common, viz. (1) numerous distinct longitudinal ridges are present on the stem; (2) xylem fibres and tracheids possess steep, tertiary spiral thickenings; (3) stone cells (sclereids) are absent from the nodes. According to the above characters, the drugs produced in southwestern China can be differentiated from those produced in northern China. The results also show that the histological characters of E. intermedia var tibetica Stapf produced in southeast ern Xizang (Tibet) are different from those produced in north western Xizang. The former possesses the xylem fibres and tracheids with steep, tertiary spiral thickenings, while the latter possesses sclereids at stem-nodes. It may be related to their habitat factors and interspecies hybridization. A key for identification of all the crude drugs derived from Chinese Ephedra spp. studied in this series of paper, including thirteen species, three varieties and one form is presented.

[Simultaneous determination of five bitter secoiridoid glycosides in nine Chinese Gentiana species used as the Chinese drug "long dan" by high performance liquid chromatography].

A new and rapid analytical method for the simultaneous determination of five bitter secoiridoid glycosides (gentiopicroside, GTP; swertiamarin, SWT; sweroside, SWO; amarogentin, AMG; amaroswerin, AMS) in the Chinese drug "Long Dan", roots of Gentiana manshurica and 8 allied species by high performance liquid chromatography (HPLC) has been developed. The HPLC system consisting of an apparatus from Shimadzu (model LC-4A), with a UV-detector (SPD-2AS), a data processor (Chromatopac C-R2AX), a column oven (CTO-2AS), and a Zorbax ODS column (25 cm x 4.6 mm ID) was used. Using MeOH--H2O as the mobile phase, the linear concentration-program of methanol was [time (min):C (MeOH)]: [0:20]----[6:20]----[6.01:40]----[23:stop]. The temperature of column oven was 40 degrees C. The bitter secoiridoid glycosides eluted were detected at a wavelength of 254 nm and the analysis was successfully carried out within 23 minutes. This method is sensitive, rapid, accurate and has good reproducibility. Recoveries of each secoiridoid glycoside were 100.0-101.5% with coefficients of variation 0-2.5% (n = 3). The contents of five bitter secoiridoid glycosides in the roots of G. manshurica and eight allied species indigenous to China were determined and reported.