Direct application of basic fibroblast growth factor improves tympanic membrane perforation healing

Topical application of basic fibroblast growth factor (b-FGF) on tympanic membrane (TM) perforations was studied in guinea pigs. One-millimeter simple round TM perforations or 2-mm TM perforations with medially flapped borders were performed. Either b-FGF or placebo was instilled in each ear on the day of surgery and daily thereafter. Treatment was applied either directly to the perforation or to a Gelfoam pledget over the defect. When no scaffolding material was interposed, b-FGF induced a faster healing response characterized by a hyperplastic but linear subepidermal connective tissue reaction compared to the control. When Gelfoam was interposed as a scaffold, a voluminous scar protruding into the middle ear cavity and involving the ossicles was observed in both b-FGF and control animals. Gelfoam-induced scars did not decrease after long-term observation, therefore discouraging its use.     

Autologous tissue in initial type I and type III tympanoplasty operations in chronic suppurative otitis media

We reviewed 192 patients who had been treated for chronic otitis media. All operations were carried out at the Department of Otolaryngology, University of Tübingen. No patient had a previous ear operation and revision operations were excluded. The observation period varied from a minimum of 1 year to a maximum of 4 1/2 years. The ossicular chain was partially destroyed in 43 ears (22.4%). Ossiculoplasty was performed using autologous ossicles. An inens was used in 31 ears and a malleus in 12 cases. The overall failure rate was 20.8%. Most recurrent perforations were found in middle-aged patients. Children had only a 14% incidence of recurrent perforations. Fascia was the material associated with the highest failure rate (28.6%). After using perichondrium 6.8% of the cases had recurrent perforations, whereas the perichondrium-cartilage transplant was not successful in 4.8%. Overall, 62.7% of the patients were found to have an air-bone gap of 10 dB or less at 1.5 kHz 3-6 months after surgery. An air-bone gap of 20 dB or less was found in 91.2% of the patients. The main problem seen in the patients with chronic otitis media was not reconstruction of the ossicular chain but a lasting closure of the tympanic membrane. The perichondrium-cartilage transplant permitted the best results and is now recommended especially for patients with unfavorable middle ear conditions. A long-lasting closure of the tympanic membrane was also found in children (< or = 15 years of age). For this reason we also recommend an early operation in order to allow children to lead a normal life.     

Immunotherapy with Alpare in patients with respiratory allergy to Parietaria pollen: a two year double-blind placebo-controlled study

The recent literature on the healing of tympanic membrane perforations is reviewed. Research on the migratory phenomena, epithelial migration and keratin dispersion on top of the tympanic membrane, is discussed. The etiology and pathogenesis of tympanic membrane perforations is then briefly described. The literature on the healing process of tympanic membrane on animal experiments as well as observations in humans is amply discussed. Finally different non invasive and or office procedures for tympanic membrane repair are reported.     

Therapeutic approach in blast injuries of the ear

Otic blast injury is caused by arrhythmic air blast wave. The perforation of the tympanic membrane is the commonet finding associated with lacerations of mucosa in the middle ear. Makki [6] published 34 cases of myringoplasty after war blast injuries. However, healing of such perforations is common; Kerr [7] noted a healing rate of 83% after the blast injury. The aim of the study was to evaluate different therapic procedures of otic blast injuries. There were 74 patients with bilateral otic blast injuries, who underwent otomycroscopic examination. The following parameters were noted: Integrity of tympanic membrane and size of perforation, presence of haemorrhagic exudate in the middle ear and median value of conductive deafness (Table 2). Main symptoms, presented in Table 1 were: pain, deafness and otohaematorrhoea. The first group of 19 patients received antibiotics by parenteral way during 7 days according to the bacterial finding in ear exudate. Healing rate was dependent on the size of tympanic membrane perforation, and rated from 71% in perforation of one third of tympanic membrane to 25% in total perforation of tympanic membrane. Data are presented in Table 3. The second group of 24 patients received the same therapy as the first treatment, plus otomycroscopic removal of haemorrhagic exudate, lacerated middle ear mucosa, and repair of tympanic membrane lacerations. Healing rate was significantly better than the one obtained in the first group (Table 4). Persistent tympanic perforation, as indicator of failed therapy, was present in 5 (35%) of all examined ears with two thirds of tympanic membrane perforation in the first group, while in the second group the rate was 3 (12%). The third group received the same therapy as the second treatment, including administration of amicacyn into the external auditory canal. The results were statistically compared by chi 2 test, and we found that the second therapy protocol was significantly better. There was no significant difference between the second and the third therapy protocols. We found blast ruptures of tympanic membrane and auditory ossicles chain discontinuity in 88% of examined ears. In our material the high incidence of total tympanic membrane ruptures and subtotal ruptures (48%) is quite different in comparison to other authors [5-7]. We consider it as the effect of high power blast wave. Loss of conductive hearing was present in 91% of blast injured patients, while 7.4% of patients had mixed, predominantly senzoneural deafness. Consequently, in addition to mechanic blast injuries acoustic trauma could profoundly damage the inner ear. Spontaneous healing of tympanic membrane occurred in 71% of injured persons and this was a better result than the results obtained by other authors [3, 4, 6]. The spontaneous healing of tympanic membrane failed if infection of the middle ear occurred or blast caused the total tympanic membrane perforation. In the second and third therapy protocols significantly higher healing of tympanic membrane ruptures was evident; it rated from 88% to 91%. Better results could be explained by the effect of optimal healing conditions, based on removal of exudate from the middle ear and necrotic parts of tympanic membrane, completed by fitting of lacerated parts of tympanic membrane and antibiotic prophylaxis. Healing of tympanic membrane without scars and adhesions was more frequent than in patients treated only with antibiotics. Incidence of undesired outcome of persistent perforation of tympanic membrane was reduced. To prevent posttraumatic complications in the middle ear, we recommend early cleaning of margins, reposition of lacerated fragments of tympanic membrane, and removal of haemorrhagic exudate. Myringoplasty should be performed if spontaneous healing of tympanic membrane did not occur after 6 months. CONCLUSION: Otic blast injury was frequently found in war induced trauma. (ABSTRACT TRUNCATED)     

Methodical aspects of pneumatic segment plethysmography. III. Measuring tourniquet problems

A retrospective study was made of 200 chronic otitis media patients. Simple chronic otitis media was observed in 76 per cent of cases; the rest were associated with cholesteatoma. In about one third of the patients, the contralateral ear showed some inflammatory middle ear disease as well. The average time lapse between initial symptoms and hospitalization was about 10 years. The events leading to the tympanic perforation were difficult to ascertain, but included probably acute otitis media, possibly external otitis, trauma, and a rather large group (35-40 per cent) of insidious 'essential perforations'. The aetiology of the 'essential perforations' is so far not known, but might be non-inflammatory in nature but related to insufficient middle ear aeration and hypo-pneumatization as well as to what is termed atelectatic ears. The bacteria isolated from chronic otitis media ears (usually gram negative bacteria and staphylococcus aureus) are usually not the types of micro-organisms found in association with any primary or acute otitis media. It is proposed that the bacterial infection encountered in what is termed 'chronic otitis media' is often a secondary infection of a primary perforated tympanic membrane, the perforation originating or persisting in underventilated ears, and having arisen from various causes--some of them as yet unknown.     

Staying in or leaving rural practice: 1996 outcomes of rural doctors'' 1986 intentions

OBJECTIVE: The purpose of this study is to investigate the recovery rate in paper-patch and fat-plug myringoplasty in rats. METHOD: Small and large perforations were inflicted on the tympanic membranes of 60 rats. Fat-plug and paper-patch myringoplasties were performed to different groups and another group was left for spontaneous healing. RESULTS: We found that for small perforations, the recovery rate was 94.7% in fat-plug myringoplasty, 94.4% in paper-patch myringoplasty, and 66.6% in control group. The recovery rates in large perforations were 52.9%, 56.2%, and 26.6%, respectively. On the other hand, in larger perforations, paper-patch or fat-plug myringoplasty have not been found effective. CONCLUSION: We believe that due to significant operational advantages, fat-plug or paper-patch myringoplasty can be suggested for the reconstruction of small and dry perforations of the tympanic membrane.     

Transient leukaemia cutis in chronic lymphocytic leukaemia

The sequelae of secretory otitis media (SOM) were monitored in 72 adult patients with SOM who were followed up for an average of 33 months. It was found that SOM became chronic and retraction of the tympanic membrane appeared as a function of the pneumatization of the mastoid. Ears with poor pneumatization (less than 6 cm2) developed chronic SOM in 52.2% of cases, as compared with 20% in cases with well-pneumatized ears (6 cm2 and above). Atelectasis developed in 37.3% of poorly pneumatized ears, and in only 5.7% of well-pneumatized ears. These sequelae may therefore be linked pathogenetically to the extent of pneumatization, as both the SOM and the sequelae appeared many years after formation and maturation of the pneumatic system. This study supports other studies that view the mastoid pneumatic system as an organ, as a middle ear pressure buffer. Well-pneumatized ears rarely develop a negative pressure and are seldom associated with chronic sequelae. Ears with poorly pneumatized mastoids lack the physiological function of such a pressure buffer. Ears with a tendency to develop a negative gas balance, whether as a result of deficient ventilation or excessive diffusion, will therefore develop a negative pressure more readily when their pneumatic system is underdeveloped, and consequently will be more prone to develop chronic sequelae.     

Day-stay myringoplasty

Grafting of the tympanic membrane (myringoplasty) has traditionally been performed as an in-patient procedure in the UK. We have performed day-stay myringoplasty on 21 consecutive patients (15 adults and six children) under general anaesthesia using an underlay temporalis fascia graft. In 18 cases there was complete healing of the tympanic membrane and in three cases the patients developed perforations at four weeks. This success rate is consistent with previously reported studies. All patients were discharged on the day of admission with no major complications. We have compared the results with a group of patients having the same operation as an in-patient and have concluded that day-stay myringoplasty under general anaesthesia is as safe and effective as in-patient surgery for the majority of patients.     

Effect of chronic alcohol ingestion on buccal mucosal expression of bFGF and Cdk2 during ulcer healing

In this study, we investigated the effect of chronic alcohol ingestion on the interplay between the receptor-bound basic fibroblast growth factor (bFGF-R) and the expression of cyclin-dependent kinase (Cdk2) in buccal mucosa during ulcer healing. Chronic ulceration was induced by a topical application of acetic acid to the buccal mucosa of rats maintained for 5 weeks on alcohol-containing or control liquid diet. In both groups, the ulcer healing was accompanied by an increase in buccal mucosal expression of bFGF and Cdk2. In the control group, the ulcer healed within 10 days and maximum induction in bFGF (2.6-fold) and Cdk2 (2.4-fold) occurred by the 2nd day of healing. In contrast, the alcohol diet group showed a marked delay in ulcer healing (14 days), associated with the shift in maximum of bFGF and Cdk2 expression to the 4-6th day, and the values were reduced by 35 to 38%. The findings show that chronic alcohol ingestion exerts detrimental effect on the signaling events initiated by bFGF-receptor activation and propagated by Cdk2 that propels the cell cycle progression essential for rapid mucosal repair.     

Comparison of earlobe and promontorium recording sites in electrocochleography

A compound cochlear action potential can be recorded in man from the promontorium, after perforation of the tympanic membrane. This same cochlear action potential (along with the responses of the brain stem auditory nuclei) can also be recorded by means of earlobe-vertex electrodes. Recordings were made in patients with chronic perforations of the tympanic membrane from the promontorium and simultaneously from the earlobe (-vertex) in order to see if there is a difference in response threshold. As click intensity was decreased, the responses disappeared in both recordings at about the same stimulus intensity (threshold). At near-threshold click intensities, the response seen in the promontorium recording was the compound cochlear action potential while in the earlobe vertex recording, the response often seen was seen was that from the inferior colliculus. Thus, in most cases, there is no real advantage to be gained by perforating the tympanic membrane in order to record from the promontorium since an identical response threshold can be obtained using surface electrodes.     

In vitro wound repair by human gastric fibroblasts: implications for ulcer healing

Fibroblasts modulate epithelial biological activities and play a key role in the ulcer healing process. There is no information regarding the biological response of human gastric fibroblasts to regulatory compounds. The aim of this study was to assess the effects of growth factors and prostaglandins on an in vitro model of human gastric fibroblast wound repair. Subconfluent fibroblast cultures were used to study proliferative responses, determined by [3H]thymidine incorporation into DNA. In vitro wound repair was determined in confluent fibroblast monolayers after mechanical denudation. The presence of putative growth factors secreted by fibroblasts was studied in conditioned medium by heparin-affinity chromatography and immunodetection with specific antibodies. Serum and platelet-derived growth factor (PDGF) -BB induced a dramatic increase in both gastric fibroblast proliferation and closure of wounded cell monolayers, whereas these activities were inhibited by both transforming growth factor (TGF) -beta1 and prostaglandin E1. Basal activities in unstimulated gastric fibroblasts were lower than those obtained in skin fibroblasts. Conditioned medium stimulated fibroblast proliferation and wound repair activity, which was inhibited by the addition of suramin, and was partially dependent on the presence of PDGF-like factor. PDGF is a major, autocrine promotor of human gastric fibroblast-dependent wound repair activities, which are inhibited by prostaglandins and TGF-beta. These findings might be important for future therapeutic ulcer healing approaches.     

Increased levels of soluble tumor necrosis factor-alpha receptors in serum from pregnant women and in serum and urine samples from newborns

Results of surgery in a series of 175 ears with attic cholesteatoma were studied in relation to the experience of the surgeons. Residents receive an annual course in temporal bone dissection and are given daily surgical instruction in the operating theater. Their performance as to hearing results, healed tympanic membrane, postoperative discharge, and number of recurrences were statistically not different from those of the faculty. The method of intact canal skin surgery is described in detail because training in this type of surgery develops skill in soft tissue conservation. Continuous clinical instruction and frequent evaluation of progress are necessary to guarantee specialist-level results.     

Effect of chronic duodenal ulceration and its treatment with lanzoprazole or sucralfate on gastroduodenal mucosal protein turnover and TGF-alpha, bFGF, and EGF receptor expression in humans

In order to investigate whether chronic duodenal ulcer disease is a consequence of disturbed mucosal turnover and growth factor expression, we studied 16 patients with duodenal ulcers before, during, and after endoscopic healing with lansoprazole or sucralfate. Before treatment, gastric fundal and antral mucosal protein turnover rates were higher in patients than controls, without parallel increases in growth factors. Both forms of therapy produced similar changes, with overall increases in duodenal mucosal turnover and transforming growth factor-alpha (TGF-alpha) and epidermal growth factor receptor (EGF-r) levels. Measurements after healing showed persistent elevations of mucosal turnover in the antrum and duodenum and depressions of basic fibroblast growth factor (bFGF) in gastric fundal and duodenal mucosa. We conclude that mucosal turnover is abnormally high in patients with chronic duodenal ulcer disease and is not easily explained by growth factor changes. The failure of lansoprazole and sucralfate to normalize rates, despite endoscopic healing, may explain the high ulcer relapse rates in non-HP-eradicated patients.     

A simple method for extracting crude sesquiterpene lactones from Compositae plants for skin tests, chemical investigations and sensitizing experiments in guinea pigs

The increased populatiry of surfing has produced a marked augmentation in the incidence of ear canal exostosis. However, when it becomes moderately severe, I prefer to call it "hyperostosis." Exposure to cold ocean water for many years can be an important etiologic factor in hyperostosis. There is a serious risk, and a high incidence of tympanic membrane perforations during the removal of large external canal hyperostosis. This injury can be prevented by placing a sheet of Silastic against the tympanic membrane beforehand. I describe the method. Serious degrees of hyperostosis, causing transient hearing loss and otitis externa, are increasingly common in coastal towns, where cold-water surfing is a popular year-around sport.     

Adhesive otitis: 30 surgical cases (author's transl)

Adhesive otitis accounts for 3% of all cases of chronic otitis. It is characterized by the attachment of the entire epidermal layer of the drum to the inner wall of the cavity. Three causative factors are identified: abnormal permeability of the auditory tube; absence of the fibrous layer of the tympanic membrane; a predisposing milieu. This is a very different condition from tympanosclerosis and its scleroadhesive sequelae. It can, however, be associated with cholesteatoma. An analysis of 30 cases in which surgery was performed points to the real progress brought about by the use of tympanic homografts. One problem remains: permanent aeration of the new tympanic cavity.     

Lightning injury of the tympanic membrane

Lightning injury to the ear is known, but specific reports are lacking. Four patients with tympanic membrane perforations who were managed surgically are reported. Their presentations, evaluations, intraoperative findings, and outcomes are discussed as they relate to the proposed pathogenic mechanisms. The authors' standard wide exposure tympanoplasty approach with two layer tympanic membrane repair is described. The added steps in performing this procedure may be necessary to ensure a good result in this unique group of patients.     

Keratinocyte growth factor-2 accelerates wound healing in incisional wounds

BACKGROUND: Keratinocyte growth factor-2 (KGF-2) also described as fibroblast growth factor-10 (FGF-10) is a newly identified member of the fibroblast growth factor family. KGF-2 is 96% identical to the recently identified rat FGF-10 and specifically stimulates growth of normal human epidermal keratinocytes. The present study was undertaken to examine the effects of topically applied KGF-2 in an incisional wound healing model. KGF-2 treatment resulted in an improvement in incisional wound healing as characterized by an increase in breaking strength, collagen content, and epidermal thickness. METHODS: KGF-2 was topically applied to linear incisions made in the dorsal skin of Sprague-Dawley rats. Biomechanical testing was done using an Instron tensiometer for breaking and tensile strength determinations. Wound collagen content was determined using the Sircol collagen assay. Epidermal thickness measurements were conducted using Masson's trichrome-stained sections of the wound. RESULTS: A single topical application of KGF-2 at the time of wounding resulted in an increase in wound breaking and tensile strength at Day 5 after wounding. Breaking strength of KGF-2-treated wounds was significantly higher compared with the buffer control (1 microgram, 222.1 +/- 13.5 g, P = 0.0007; 4 microgram, 248.7 +/- 15.4 g, P = 0.0001; 10 microgram, 247.2 +/- 21.9 g, P = 0.001; buffer, 141.0 +/- 9.7 g). Epidermal thickness and wound collagen content were significantly increased following treatment with KGF-2. CONCLUSIONS: Based on our findings, KGF-2 is a potent stimulator of wound healing as demonstrated by increased mechanical strength accompanied by an increase in wound collagen content. KGF-2 could be an important cellular mediator responsible for the initiation and acceleration of wound healing and may enhance the healing of surgical wounds.     

Long-term outcome of tympanoplasty in chronic suppurative middle ear infection in childhood

Controversy continues regarding tympanoplasty for central perforations due to chronic otitis media in children. Between 1972 and 1988, 144 children (160 cases) were operated on for central perforations after chronic otitis media and were managed at the ENT Hospital of the University of the Saarland, Homburg/Saar. Eighty-seven of these children were evaluable for this study. Post-operative follow-up was more than 5 years in 94% of the cases. The tympanic membrane was closed in 90% of the cases at follow-up examination. The age of the patient did not influence the success rate. Social hearing was improved from 49% before operation to 86% after operation and at follow-up. At follow-up, air-bone gaps were closed to within 10 dB in 67% of the cases, within 20 dB for 88% and within 30 dB for 96%. These very good and stable results show that an early operation can be recommended for children with chronic otitis media to prevent further damage to the middle ear.     

Nerve growth factor in normal and psoriatic skin equivalent models

Our objective was to determine the pattern and time course of nerve growth factor expression in an established skin equivalent model that we have used in the past to study wound healing and psoriasis phenotypes. Skin equivalents were constructed in triplicate using normal neonatal foreskin keratinocytes plated on collagen gels containing fibroblast lines. These lines were derived from five specimens of psoriatic lesions, three specimens of normal skin from patients with psoriasis, and three specimens of eyelid skin from normal donors. Immunohistochemistry and a monoclonal nerve growth factor-b antibody were used to determine the pattern of protein staining over 2 weeks. We looked at the wound healing phenotype using the skin equivalent model for 7-14 days. When keratinocytes invaginate into the dermis of skin equivalents (beginning at around 7 days of growth), dark staining of nerve growth factor was seen under the basal membrane zone, suggesting that nerve growth factor serves in the development of the basal membrane zone and the epidermis, and may influence the migration of nerves through the basal membrane zone into the regenerated skin.     

Randomised placebo-controlled trial of use of topical recombinant bovine basic fibroblast growth factor for second-degree burns

BACKGROUND: Wound healing is a dynamic process that could be accelerated by growth factors. We investigated the effect of recombinant bovine basic fibroblast growth factor (rbFGF) on burn healing in a randomised placebo-controlled trial. METHODS: We recruited 600 patients with superficial or deep second-degree burns. Patients received 150 AU/cm2 daily topical rbFGF (n=300) or placebo (n=300) plus vehicle. We assessed healing by photography, punch-biopsy, and clinical examination. FINDINGS: All patients treated with rbFGF had faster granulation tissue formation and epidermal regeneration than those in the placebo group. Superficial and deep second-degree burns treated with rbFGF healed in a mean of 9.9 (SD 2.5) days and 17.0 (4.6) days, respectively, compared with 12.4 (2.7) and 21.2 (4.9) days (p=0.0008 and p=0.0003, respectively). No adverse effects were seen locally or systemically with rbFGF. INTERPRETATION: rbFGF effectively decreased healing time and improved healing quality. Clinical benefits would be shorter hospital stays and the patient's skin quickly becoming available for harvesting and grafting.