A conserved linkage group on chromosome 6, the 8.1 ancestral haplotype, is a predisposing factor of chronic rhinosinusitis associated with nasal polyposis in aspirin-sensitive Hungarians.

Inflammation plays a central role in the pathogenesis of chronic rhinosinusitis (CRS), and TNFα is a key pro-inflammatory cytokine in the pathogenesis of this disease. In our previous studies, we showed that the TNFA -308A allele is a genetic predisposition factor in a subgroup of aspirin-sensitive (ASA+) CRS patients suffering from nasal polyps (NP) in the Hungarian population. To determine whether the TNF -308A allele or the presence of a complex, extended ancestral haplotype (8.1AH) located on chromosome 6 is responsible for the previously observed genetic effect, we performed a case-control study for examining the frequency of 8.1AH carriers in controls and in subgroups of CRS patients. Our novel observations demonstrate that the presence of the 8.1AH may be responsible for the development of severe forms of CRS (CRSwNP, ASA+) and strengthen the clinical observation that CRS patients can be classified into clinically and genetically different subgroups.

The -308 G>A SNP of TNFA is a factor predisposing to chronic rhinosinusitis associated with nasal polyposis in aspirin-sensitive Hungarian individuals: conclusions of a genetic study with multiple stratifications.

Single nucleotide polymorphisms (SNPs) of the tumour necrosis factor alpha (TNFα) gene (TNFA) have been extensively studied and shown to be associated with an increased risk of the development of various chronic inflammatory diseases. Inflammation has been demonstrated to play a central role in the pathogenesis of chronic rhinosinusitis (CRS), and TNFα is a key pro-inflammatory cytokine with important functions in these processes. In order to determine whether the well-known TNFA -308 G>A SNP has a role in a genetic predisposition to CRS in the Hungarian population, we analyzed our genomic collection containing control and CRS patient samples in a case-control study, and compared the genotype and allele frequencies. There was no significant difference in the observed genotype or allele frequencies between the controls and the total CRS group. However, after careful stratification of the patient group on the basis of the observed clinical symptoms, we found a significantly higher carriage rate of the rare A allele-containing genotypes among the CRS patients with nasal polyposis (NP) who also exhibited sensitivity to aspirin (acetylsalicylic acid, ASA(+)). It is concluded that genetic variants of the TNFA gene may affect the risk of CRS in a clinically well-defined group of CRSNP(+)ASA(+) patients in the Hungarian population. Our results also emphasize that the group of CRS patients is not homogenous in that patients exhibiting different clinical symptoms exist. Their carried genetic predisposing factors, and as a result, the exact molecular events leading to the development of various forms of CRS, may also differ.

Long-term results of the use of autogenous cortical bone columellas to replace the stapes at stapedectomy.

The first author has been using an autogenous cortical bone columella to replace the stapes removed during stapedectomy since 1965. The audiograms of 21 of the 271 patients operated on with this method between 1965 and 1989 (i.e. 7.7% of the possible candidates) were available 20-35 (average 26.8) years postoperatively. The operation could be regarded as successful in 20 and unsuccessful in 1 patient in the long run. The audiological data are presented individually as averages of the values obtained at 0.5, 1, 2 and 3 kHz. The averaged data (n = 21): preoperative air conduction, 58.27; bone conduction, 24.46; and air-bone gap, 33.81 dB. Postoperative best air conduction, 19.07; bone conduction, 14.10; and air-bone gap, 4.97 dB. Postoperative recent air conduction, 45.77; bone conduction, 38.45; and air-bone gap, 7.32 dB. The best values were measured 1-8 (average 1.57) years postoperatively. In relation to the postoperative best value, the recent value of the air-bone gap had deteriorated by 2.35 dB, and that of the bone conduction by 24.35 dB. The small air-bone gap indicates that the deterioration of the hearing is mainly caused by the deterioration of the function of the inner ear and not by that of the conductive apparatus. The progression of the deterioration differs individually (0.3-1.6, average 0.93 dB/year) and accelerates with age. This finding seems to be a problem that does not depend on the operative technique. The data show that the autogenous bone columella ensures the same good and lasting results as the alloplastic solutions; moreover, there is no problem with the incus-prosthesis connection.

Combination of ionomer cement and bone graft for ossicular reconstruction.

The aim of this study was to investigate the efficacy of the reconstruction of large ossicular chain defects with a combination of ionomer cement and an autogenous cortical bone graft. Different individual solutions are described if at least the handle of the malleus is present: restoration of a large defect of the long process of the incus, formation of the incus body and the long process, and replacement of the missing superstructure of the stapes with a short bone graft standing on the footplate. In a unique case, total reconstruction of the malleus handle was carried out. In further cases where the malleus and the incus were absent, the missing superstucture of the stapes was replaced by a bone graft fixed to the remnant of the anterior crus, supplemented with a cortical bone PORP. Between 1993 and 2005, 84 patients underwent middle ear operations with the use of ionomer cement. In 16 ears (9 males, 7 females), a combination of ionomer cement and autogenous cortical bone graft was used for ossicular reconstruction, with a documented follow-up of at least 6 months to 7 years. All operations were performed under general anesthesia. The components of the cement were mixed by hand and transferred to the bare bone surface with a curved needle. Complex structures were built up step by step. In seven cases, the tympanic membrane was simultaneously reconstructed. The postoperative air-bone gap was < 20 dB in 11/16, 68% of the cases. No columella rejection occurred. The reconstructed malleus handle is still intact, though the hearing has deteriorated. The audiological results are encouraging and a further prospective study is under design in order to analyze the efficacy of the combination of ionomer cement and an autogenous cortical bone graft for ossicular reconstruction. The simultaneous reconstruction of the superstructure of the stapes and the long process of the incus or the whole incus makes PORPs or TORPs superfluous, if at least the handle of the malleus is present.

A randomized comparison of the effects of budesonide and mometasone furoate aqueous nasal sprays on nasal peak flow rate and symptoms in perennial allergic rhinitis.

BACKGROUND: Using conventional methods, it has been difficult to show differences in efficacy between intranasal corticosteroids in perennial rhinitis. OBJECTIVE: To compare the effects of budesonide and mometasone on nasal symptoms and nasal airflow in perennial allergic rhinitis. METHODS: Four hundred thirty-eight patients (age > 18 years old) were randomized to budesonide, 256 microg or 128 microg, mometasone furoate 200 microg, or placebo, once daily for 4 weeks. Efficacy was evaluated by nasal index score (NIS; the sum of scores for blocked nose, runny nose, and itchy nose/sneezing) and peak nasal inspiratory flow (PNIF). RESULTS: All three active treatments significantly reduced the NIS compared with placebo. There was no significant difference between the treatments, although the effect of budesonide, 256 microg, tended to be greater than that of the other regimens. PNIF was significantly improved with all three active treatments: the effect of budesonide 256 microg on morning and evening PNIF was significantly greater than that of mometasone furoate and 128 microg budesonide. Budesonide had a rapid onset of action, showing a significantly greater effect on evening PNIF than mometasone furoate during the first 10 days. For all active treatments, significant improvements in NIS were seen within 4 hours of the first dose. All three treatments were well tolerated. CONCLUSION: The objective parameter PNIF was capable of demonstrating greater efficacy of budesonide 256 microg compared with budesonide 128 microg and mometasone furoate 200 microg, whereas the combined nasal symptom score could only distinguish active treatment from placebo.