A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family.

A candidate gene for Branchio-Oto-Renal (BOR) syndrome was identified at chromosome 8q13.3 by positional cloning and shown to underlie the disease. This gene is a human homologue of the Drosophila eyes absent gene (eya), and was therefore called EYA1. A highly conserved 271-amino acid C-terminal region was also found in the products of two other human genes (EYA2 and EYA3), demonstrating the existence of a novel gene family. The expression pattern of the murine EYA1 orthologue, Eya1, suggests a role in the development of all components of the inner ear, from the emergence of the otic placode. In the developing kidney, the expression pattern is indicative of a role for Eya1 in the metanephric cells surrounding the 'just-divided' ureteric branches.

[Long term results of congenital middle ear cholesteatoma in children]. / Résultats à long-terme des cholestéatomes congénitaux de l'oreille moyenne de l'enfant.

OBJECTIVES: To report the long term results of congenital cholesteatoma of the middle ear in children. PATIENTS AND METHODS: Retrospective study of thirty two children with 33 congenital cholesteatoma (1 bilateral cholesteatoma) operated on by the same surgeon. The mean age was 6 years. The most common clinical presentation was unilateral hearing loss. A trans-canal approach was performed in 4 cases and an intact canal wall technique in 29 cases. A two staged surgery was necessary in 28 patients, whom a residual cholesteatoma was observed in 7 patients. A third stage was performed in 11 patients because of a residual cholesteatoma in 2 two cases and a functional failure in 9 cases. RESULTS: At five years postoperative audiometry (air bone gap inferior or equal to 20 dB HL), a functional success was obtained in 50% of cases. CONCLUSION: The diagnosis of congenital cholesteatoma must be evoked in every atypical otitis media with effusion or unilateral transmission hypoacusis. The intact canal wall technique in two stages is the most appropriate treatment, since congenital cholesteatoma in children appears aggressive in a well pneumatized mastoid. The choice for an intact canal wall technique is also justified by the ambition of a conservative surgery in the young child. The functional results are generally satisfactory in early diagnosed cases. Thus, ENT and pediatric physicians have a unique role in detecting congenital cholesteatoma in the early period of life, and in ensuring a long term follow-up.

Coexistence of plasma cell granulomas of lung and central nervous system.

A rare case of concurrent plasma cell granulomas (PCG) of the lung and the central nervous system (CNS) is reported. A 30-year-old man was presented with recurrent left headaches lasting for two years. Computerized tomographic (CT) scan and magnetic resonance imaging (MRI) of the head disclosed a process extending from the lateral aspect of the left cavernous sinus to the tentorium cerebelli and the infratemporal fossa through the foramen ovale. At the same time, chest-X ray and CT scan showed three symptomless masses of the pulmonary right lower lobe. Histological examination of cerebral samples and of one of the pulmonary nodules revealed the presence of a fibrous tissue containing numerous lymphocytes and plasma cells as well as remnants of vascular and respiratory structures. Immunohistochemical study proved these cells to be polyclonal. Ultrastructural analysis confirmed the presence of lymphoid cells and failed to disclose any argument for meningioma or histiocytosis X. The differential diagnostic problems of PCG are discussed as well as considerations about clinicopathological features, histogenesis and pathogenesis of inflammatory pseudotumours (IPT).

Clinical experience with the Vibrant Soundbridge implant device.

OBJECTIVE: To evaluate the full degree and range of benefits provided by the Vibrant Soundbridge (VSB; Symphonix Devices, Inc., San Jose, CA, U.S.A.) and analyze pre-and postoperative results of audiologic tests. STUDY DESIGN: Single-subject study with each subject serving as his or her own control. SETTING: Multicenter clinical study conducted at 10 centers in Europe. PATIENTS: 47 patients who met the selection criteria for participation in the study. INTERVENTIONS: Implantation of the VSB direct-drive middle ear hearing device. MAIN OUTCOME MEASURES: Average change in unaided thresholds with the patient wearing headphones at each frequency pre-and postsurgery was measured. A mean threshold change less than 5 dB across all frequencies was considered clinically nonsignificant. RESULTS: 47 patients had successful surgery for implantation and fitting with the VSB device. CONCLUSION: The VSB is a new middle ear implant device that can be used safely in the treatment of patients with moderate to severe sensorineural hearing loss.

Multicenter audiometric results with the Vibrant Soundbridge, a semi-implantable hearing device for sensorineural hearing impairment.

The Vibrant Soundbridge, a semi-implantable hearing device for subjects with moderate to severe sensorineural hearing impairment was introduced commercially. First audiologic results are presented on 63 patients from 10 European implant centers. Hearing loss was at 0.5, 1, 2, and 4 kHz varying between 43 and 81 dB HL. The patients used the analogue audio processor, type 302. Measured sound-field gain was compared with NAL-R target values. For most patients an acceptable agreement was found. There was a subgroup of patients, however, with relatively low gain. The results suggest that this was related to the suboptimal positioning and fixation of the transducer to the incus.

Ototoxicity of kanamycin in developing guinea pigs. An electrophysiological study.

Pregnant guinea pigs were treated with Kanamycin at three different stages of gestation (dating by method of post-partum ovulation). Twenty-nine newborn guinea pigs were tested electrophysiologically by recording the cochlear microphonic potential and the compound action potential from the round window in response to clicks and filtered clicks at 8,000 Hz. Six of the test animals showed the same electrophysiological changes as those found in adult mammals after Kanamycin intoxication. The results suggest a relationship between the ototoxicity of Kanamycin and the onset of auditory function. Cochlear potential and compound action potential were mostly affected when intoxication was performed during the last 15 days of gestation. This study confirms the results previously published by Uziel 1979.

New immunobiological tests in the investigation of Menière's disease and sensorineural hearing loss.

The aim of the study was to determine the usefulness of new immunobiological tests using fractioned human inner ear antigen in the investigation of 4 Menière's disease and 12 rapidly progressive sensorineural hearing loss (RPSNHL). Each patient underwent a full ENT examination and a full range of immunobiological tests comprising ESR, electrophoresis, IgG, A, M, circulating immune complexes, cryoglobulins, complement, organ and non-organ auto-antibodies. The two new tests were the lymphocyte transformation test (LTT) and the immunoperoxidase test against total or fractioned human inner ear antigens. Four main bands were found in electrophoresis with the following molecular weights: 130,000, 45,000, 22,000, and 14,000. The heaviest band corresponded to IgG contained in the inner ear extract. Three cases of bilateral RPSNHL had positive LTT against inner ear antigens. No serum of patients showed a characteristics band with the immunoperoxidase test with regard to the serum of healthy subjects. At least four abnormal inflammatory non-specific tests were shown in the cases of positive LTT. Out of 3, 2 patients received steroids and improved their hearing.

Results of an ultrastructural study comparing stria vascularis with organ of Corti in guinea pigs treated with kanamycin.

Ultrastructural study of ototoxicity is well documented with two points of interest: organ of Corti for aminoglycosides and stria vascularis for loop diuretics. As a previous study suggested initial lesions of stria vascularis, an attempt of comparison and of chronological study was made between the organ of Corti and stria vascularis lesions by kanamycin intoxication. The method was devised by J. M. ARAN, with electrophysiological control. We failed to find in the stria vascularis a radial or longitudinal pattern of lesions. We could not discern a chronological injury between the organ of Corti and stria vascularis because both were damaged even in the less deafened animals. Nevertheless, two facts were clarified: hair cell lesions are lysosomial as for the kidney lesions, while stria vascularis lesions are mitochondrial, melanine granulations play a part in drug metabolism (increased number, secretory aspect) and deserve further study.

Indirect immunofluorescence in the investigation of rapidly progressive sensorineural hearing loss and Menière's disease.

Being aware of the conservation of antigenicity, we performed indirect immunofluorescence on non fixed non decalcified frozen hamster's cochlea. Once killed, the heads of the hamsters were immediately dipped into liquid nitrogen and then stored at -20 degrees C until cutting. The sections were done at the same temperature, with Tissue-Tek embedding the heads to avoid breaking, using a sharp tungsten knife. The immunofluorescence itself was performed with the sera of the patients which were revealed through donkey fluorescein-conjugated antiserum to human immunoglobulins. For counterstaining, we used Evans blue. Twenty patients with rapidly progressive sensorineural hearing loss (according to the clinical criteria of MacCabe) and 6 with Menière's disease were tested. Five had a specific fluorescence on the stria vascularis. A correlation with the lymphocyte transformation test on human inner ear antigen has been found (p = 0.055).

Melanine value in the stria vascularis of pigmented guinea-pigs treated by kanamycin.

In a previous report, kanamycin (400 mg/kg/d) seemed to increase the number of melanine granulations in intermediate cells of the stria vascularis, especially in the second and third turns. To precise these data, melanine was studied in those turns by ultrastructural morphometry in a control group with 12 animals. We observed a large intra-individual and inter-individual variation before intoxication. Thus, the meaning of melanine modifications by kanamycin must be carefully evaluated.

Immunohistochemical detection of p53 protein in preneoplastic lesions and squamous cell carcinoma of the head and neck.

Alterations in the p53 tumor suppressor gene are the most frequent genetic abnormalities in human cancers. The p53 protein is present in normal cells, and is assumed to induce G1 arrest or apoptosis in the presence of DNA lesion. The mutant protein lacks this property. Squamous cell carcinomas of the head and neck (SCCHN) are related to carcinogens in tobacco and alcohol, and provide a good model of multiple-step carcinogenesis in association with DNA damage and p53-related tumorigenesis. Stabilization of the mutant p53 protein allows immunohistochemical analyses (IHC) to be routinely used to demonstrate the mutant p53 protein in tissue samples, whereas normal p53 protein is undetectable. Ninety-nine squamous cell carcinomas, 8 in situ carcinomas, 31 preneoplastic lesions and 79 normal carcinogen-exposed mucosas of the head and neck from a total of 107 patients were examined for the expression of p53 tumor suppressor gene protein. Samples were collected before treatment, and stained with p53 specific mono- and polyclonal antibodies (DO-7, Pab 1801 and 240, CM1) using an indirect immunoperoxidase technique. Proliferating cell nuclear antigen (PCNA) provided semiquantitative estimates of proliferation. The main localizations were the pharynx (64/107) and the larynx (21/107). Positive IHC detection of p53 was observed in 9% of normal-appearing carcinogen-exposed mucosas, 37% of hyperplasias, 68% of dysplasias, 75% of in situ carcinomas, and 56/99 (56.5%) of primary tumor samples. Mucosas from 15 control patients under 10 years of age were negative. There was no correlation between p53 IHC and localization, differentiation or TNM staging.(ABSTRACT TRUNCATED AT 250 WORDS)

Nucleus 20-channel and 21-channel auditory brain stem implants: first European experiences.

Central electrical stimulation of the auditory pathway can allow hearing in patients suffering from deafness localized in the auditory nerve. Developments in a multichannel auditory brain stem implant based on the Nucleus Mini 22 cochlear implant with transcutaneous signal transmission is discussed. The device has been implanted in seven European patients who suffered from neurofibromatosis type 2. Preliminary speech perception results and patient satisfaction are encouraging, and the data presented include some limited open-set speech recognition.

Surgery of cholesteatoma in children.

Cholesteatoma is usually very extensive in children. There are two possible explanations: the speed of tissue growth and the degree of infection and inflammation brought by the Eustachian tube. The cholesteatoma develops rapidly in a pneumatized mastoid which it takes by surprise. All these factors explain the extensive, finger-like shape taken by cholesteatoma in children.

[Primary sclerosing cholangitis and autoimmune cochlear deafness: a new syndrome?]. / Cholangite sclérosante primitive et surdité endocochléaire auto-immune: nouveau syndrome?

Association of autoimmune cochlear hearing loss with primary sclerosing cholangitis is reported in two patients. Endocochlear sensorineural hearing loss was associated with the presence of anti-cochlear antibodies in the serum directed against the walls of vessels in the stria vascularis. The hearing loss appeared at the same time or shortly after the diagnosis of cholangitis. This association, which has never been described, may reinforce the theory of the role of immunologic factors in the pathogenesis of primary sclerosing cholangitis, possibly linked to or initiated by vasculitis.

Spontaneous retraction pockets in chronic otitis media medical and surgical therapy.

Results of a series of 228 spontaneous retraction pockets in chronic otitis media are reported and a classification is proposed. Under medical therapy, 78 retraction pockets of stage I and II (out of 95) were followed for five years. Sixteen percent deteriorated into stage III and were operated on; the others stabilized or improved towards normal tympanic membrane (23%). Different methods of surgical therapy were used in 150 retraction pockets (all the stages III and many stages II). Even with silastic sheeting and strengthening of the tympanic membrane, a recurrent retraction pocket was observed in 24 cases (16%). Functional results were obviously better when the ossicular chain was rebuilt from an intact malleus to an intact stapes and either from an intact malleus to a mobile footplate or from the tympanic membrane to an intact stapes. Surgery of retraction pockets must be used not only to prevent cholesteatoma formation but also to prevent erosion of the stapes.

Reconstruction of radical mastoidectomy by obliteration technique.

Reconstruction of radical mastoidectomy was performed by obliteration tympanoplasty using Palva flap in 199 ears either in one stage (normal mucosa, normal stapes, no risk of residual cholesteatoma behind the flap) or in two stages. At the 2nd stage, middle ear was reopened and the posterior cavity was checked in 34 cases. Bony pâté or ceramic granules may be added behind the flap, especially at this second stage. The closure of the tympanic membrane was achieved in 97% of cases. Residual cholesteatoma was removed in the middle ear at the 2nd stage in 17% of the ears. Late residual cholesteatoma behind the flap appeared in 5 cases where the posterior cavity had not been checked. Three early retraction pockets were due to technical failures which were more recently corrected by the use of fibromuscular graft placed between the fascia graft an the Palva flap. Three late retraction pockets progressed under the tympanic membrane from above to below. Hearing results were better in the 1st stage procedures, obviously selected: ABG within 20 dB in 83% of the ears with a normal stapes. On the contrary, in 2 stage procedures, ABG within 20 dB was achieved only in 50% of cases with a normal stapes and 29% of the ears where the crura were missing.

[Signal symptoms in tumours of the petrous bone (author's transl)]. / Signes révélateurs des tumeurs du rocher.

Supra-labyrinthic tumours usually produce lesions of the Vth and VIth cranial nerves, whereas infra-labyrinthic tumours affect the sensory-motor nerves. Both types of tumour may reveal themselves by cochleo-vestibular disorders and/or middle ear symptoms. The author has treated a series of patients with such tumours and describes the most frequent types of intrapetrosal growth: cholesteatoma (12 cases), glomic tumours (11 cases), facial nerve tumours (3 cases), metastases (2 cases). Meningiomas can also be encountered, as well as rarer tumours (4 cases), such as embryonic sarcoma, chordoma, chondroma and chondrosarcoma, cavernous angioma, eosinophilic granuloma, solitary plasmocytoma and fibrous dysplasia of the petrous bone. Some signal symptoms (sudden deafness, mucous otitis media, paralysis of vocal cords) can be particularly misleading.

[Electrophysiological study of the ototoxicity of kanamycin via transplacental transmission in the guinea pig (author's transl)]. / Etude électrophysiologique de l'ototoxicité de la kanamycine par voie transplacentaire chez le cobaye.

Pregnant guinea pigs were treated with Kanamycin at three different times during gestation (dating by the post-partum ovulation method) : 11th-20th day, 31st-40th day, 53rd-62nd day of gestation. 29 newborn guinea pigs were studied electrophysiologically by the recording of cochlear microphonics and the action potential obtained at the fenestra cochlear in response to clicks and filtered clicks 8000. Certain animals were tested with filtered clicks 2000 and 4000. 6 tested animals showed electrophysiological results identical to those usually seen in adult guinea pigs intoxicated with Kanamycin. The results obtained suggest the existence of a relationship between the ototoxicity of Kanamycin and the time of installation of auditory function. Microphonic potentials and auditory nerve action potentials were found to be more affected when intoxication took place during the last 15 days of gestation.

[Fibro-adhesive otitis: nosology and treatment]. / L'otite fibro-adhésive: nosologie et traitement.

The term fibro-adhesive otitis is considered to correspond to filling of the middle ear with fibro-inflammatory tissue with an intact drum. When the fibrous tissue is very thin, that is to say when the mucosa is replaced by malpighian epithelium, the term epidermization or retraction pocket is preferred, this corresponding to different surgical problems, even though the roles of tubal insufficiency and seromucous otitis are probably the same in the etiology of fibro-adhesive otitis and epidermizations of the middle ear. Fibro-adhesive otitis presents as two different stages: a fibro-inflammatory phase in which the middle ear is filled with fibrous tissue and contains cystic spaces full of mucus; a fibro-adhesive phase when the whole middle ear is full of fibrous tissue and contains cholesterol granulomata but no cystic spaces. A study was conducted on 37 ears (8 at the fibro-inflammatory and 29 at the confirmed fibro-adhesive stage). Small cholesteatomas were associated in 15 ears and a posterior retraction pocket in 4. Results were frankly very poor for one-stage operations (exploration of the tympanic cavity with silastic and mastoidectomy (3 cases), tympanoplasty using a closed technique (1 case), and tympanoplasty using an open technique with obliteration (4 cases). Best results were obtained by a two-stage operation with prolonged inclusion of silastic between the two stages.(ABSTRACT TRUNCATED AT 250 WORDS)

[Cholesteatoma of the middle ear. Choice of technique and results in the adult and child]. / Le cholestéatome de l'oreille moyenne. Choix des techniques et résultats chez l'adulte et chez l'enfant.

On the basis of a series of 577 tympanoplasties performed between January 1968 and December 1978 for 424 cholsteatomas and 153 epidermisations involving 464 adults and 113 children aged less than 15 years, the authors describe techniques, results and indications. An open technique was used in only 28 cases. Since 1973, the authors have preferred the closed technique in two stages (227 cases) to a, closed technique in 1 stage (113 cases). The open technique with obliteration was used in 68 cases in one stage and in 141 cases in 2 stages. This latter group included 17% of patients referred from elsewhere and already operated upon. Rates of tympanic closure varied between 93% for open techniques and 97% for closed techniques and open techniques with obliteration. The presence of silastic caused a fall in this closure rate of a little more than 2% both in the closed technique (94,8%) as well as in the open technique with obliteration (94,4%). An appreciably difference between the adult and child was seen only with the open technique with obliteration in two stages: 96% in the adult, 83% in the child. Residual cholesteatoma pearls extirpated during the 2nd stage were found in 28% of cases in the adult and in 36% of cases in the child in closed techniques and in 21% of cases in the adult and 33% of cases in the child in open techniques with obliteration. Retraction pockets were fairly common after the closed technique in one stage (6 out of 35 at 5 years). They were nevertheless also seen after closed techniques in two stages (5 out of 81 at one year and 3 out of 29 at 3 years). The best functional results were obtained with closed techniques in 2 stages. The air-bone gap was 10 dB or less in 44% of cases and 20 dB or less in 63% of cases when the stapes was intact. It was 10 dB or less in 31% of cases and 20 dB or less in 45% of cases when the stapes was destroyed. There was no appreciable difference between adults and children for a given technique. The closed technique in two stages is preferable, in particular when the mastoid is pneumatised and/or if the cholesteatoma is large or papillary, which is customary in the child. The open technique with obliteration is preferable if the wall of the mastoid antrum is destroyed if the mastoid is severely retracted and if the eustachian tube functions poorly. It is also the method indicated in the presence of a large retraction pocket.