Wojciech Gawęcki

Screening of the General Polish Population for Deafness-Associated Mutations in Mitochondrial 12S rRNA and tRNASer(UCN) Genes

Mutations in mitochondrial DNA are associated potentially with nonsyndromic and aminoglycoside-induced hearing loss. Several nucleotide changes associated with hearing impairment were described; however, a variable frequency of deafness-associated mutations in different populations has been observed. The aim of the present study was to determine the frequency of pathological mutations in mitochondrial 12S rRNA and tRNA(Ser(UCN)) genes in a group of 500 individuals representative of the general population of Poland. Mutational screening of 12S rRNA revealed the presence of three deafness-associated mutations, A827G, T961C, and A1555G, and one potentially pathogenic substitution, T669C. The carrier frequency of pathological mutations was estimated to be 1.2% (6/500) in the general Polish population. A deafness-associated G7444A mutation in the precursor of tRNA(Ser(UCN)) gene was identified in 8/500 (1.6%) unrelated blood donors. Seven nucleotide changes identified in 12S rRNA (G709A, G750A, G930A, T1243C, T1420C, and G1438A) and tRNA(Ser(UCN)) (C7476T), based on a frequency exceeding 1.0%, were considered as polymorphisms of 12S rRNA and tRNA(Ser(UCN)) in the studied population. Mitochondrial 12S rRNA gene seems to be the hot spot for deafness-associated mutations in the Polish population. The relatively high carrier frequency of tRNA(Ser(UCN)) G7444A (1/62) suggests that this substitution might be a nonpathogenic polymorphism in the Polish population.

New insight into Baha® implant stability measurements: observations on resonance frequency analysis results.

Objective To analyze the results of multiple measurements of resonance frequency analysis (RFA) repeated in patients implanted with Cochlear Baha® BI300 implants to look for trends, which potentially might serve as indicators of successful osseointegration. Patients Forty-five patients implanted with the BI300 implants at the Department of Otolaryngology, Poznan University of Medical Sciences; consecutive values were available for 14 of these 45 patients. Intervention(s) Evaluation of the implant stability through resonance frequency analysis; 4 to 10 measurements in each patient were performed during the surgery and after 1 week and 1 month. Main Outcome Measure(s) Attention was focused on the results of RFA, defined as the differences between recorded marginal values of the implant stability quotient (ISQ): the average-ISQ value [(maximal ISQ value + minimal ISQ value)/2] and delta-ISQ (maximal ISQ value - minimal ISQ value). Results The average-ISQ value increased from 58.43 at the time of implant placement to 61.89 at the end of the observation period, with a minimum recorded value of 56 and a maximum of 64.5. Delta-ISQ showed a maximal drop from 3.86 at the time of surgery to 1.93 after 1 month. Significant differences were observed between surgery and a month later but also between 1 week and 1 month after surgery. Conclusion Our data demonstrate that differences between recorded stabilities of the implant in different planes based on ISQ values tend to decrease over time, indicating that the implant acquires symmetrical stability, which may reflect the good quality of the bone-implant interface.

Essential metals profile of the hair and nails of patients with laryngeal cancer

Trace elements have an impact on numerous physiological processes. The monitoring of their levels in the organism allows you to detect not only their deficiencies, but also several illnesses. The aim of this study was to compare the levels of essential elements (calcium, magnesium, zinc, copper, iron, manganese) in hair, nails and serum of both patients with laryngeal cancer and healthy people. The determination of six metals was performed by an inductively coupled plasma mass spectrometry (ICP-MS) and an inductively coupled plasma optical emission spectrometry (ICP-OES). The concentration of essential elements in hair and nails of the control group was statistically significantly higher than in the group of patients with laryngeal cancer. In the case of serum, differences were found between the patients and controls in respect of the level of three metals. The results of principal component analysis (PCA) revealed the strong and similar clustering behavior of essential elements in hair and nails. The metals did not correlate between two alternative materials. The present study indicated that, using the level of essential elements in hair and nails as a basis, it is possible to distinguish cancer patients from healthy people. The alternative materials are independent of homeostasis and therefore seem to be more useful in the detection of diseases and mineral deficiencies in human than the classical biological materials, such as blood.

Analiza kliniczna i histopatologiczna raków płaskonabłonkowych głowy i szyi u młodych dorosłych

Summary Squamous cell carcinoma of the head and neck (HNSCC) is the malignant tumor arising most frequently in non-keratinized epithelial tissue of the upper part of the respiratory or gastrointestinal tracts. These tumors develop most commonly in the sixth or seventh decade of life and significantly less frequently in patients younger than 45 years defined as young adults. In literature, there are still many controversies concerning the clinical course of these tumors in this group of patients. Aim Clinical and histopathological analysis of HNSCC in young adults. Material and methods The study group consisted of 95 young adults (≤45 years) with HNSCC and the control group of 95 older patients (>45 years) with HNSCC, who were treated in the Department of Otolaryngology and Laryngological Oncology of Karol Marcinkowski University of Medical Sciences in Poznan during the period 2000–2004. The analysis was based on medical records of patients. Results and conclusions 1. In the young adults group and particularly in patients younger than 40 years there is a higher percentage of patients with oral cancer and lower percentage of patients with larynx cancer in comparison to older patients group, but in all analysed groups larynx cancer is the most frequent localization. 2. The tumors in young adults are clinically more advanced than in older patients, because young adults tend to delay the visit to physician, in spite of evident clinical symptoms. 3. HNSCC in young adults are histological more mature and less malignant.

Węzły chłonne przytchawicze u chorych na raka krtani i gardła dolnego w ocenie radiologicznej i klinicznej

INTRODUCTION Paratracheal lymph nodes receive the lymph from the larynx, hypopharynx, esophagus, thyroid gland and trachea. It is evaluated, that metastases to these nodes occur in about 10-30% of patients with cancer of the larynx, hypopharynx or cervical esophagus. These metastases can lead to the most tragic complication after total laryngectomy, which is the stomal recurrence, Paratracheal lymph nodes are not accessible to examine by palpation or ultrasonography. AIM The aim of this study was to estimate the usefulness of CT, MRI and clinical intraoperative investigation in the search for enlarged paratracheal lymph nodes. MATERIAL AND METHODS The investigation was performed in 15 patients with advanced larynx and/or hypopharynx cancer. In all the patients we carried out palpation and ultrasonography of the neck, in 7 cases CT and in another 8 cases MRI of the neck. In all the patients who were operated (14 cases) the exact search for enlarged paratracheal lymph nodes during operation was performed. RESULTS Palpation and ultrasonography of the neck did not found any enlarged paratracheal lymph nodes in anybody of the patients. CT showed one enlarged prelaryngeal lymph node in one patient. MRI showed one enlarged pretracheal lymph node in another one patient. During operation we found one enlarged paratracheal lymph node, which was not seen in MRI. All these nodes were pathologically not metastatic. CONCLUSIONS The analysis of the state of paratracheal lymph nodes is very important in prophylaxis of stomal recurrence after total laryngectomy. However preoperative estimation of these nodes is very difficult and limited. It seems to us, that the best way of estimation of the state of paratracheal lymph nodes is intraoperative exploration of the area between trachea and esophagus and excision even loose tissue to pathological examination.Summary Introduction Paratracheal lymph nodes receive the lymph from the larynx, hypopharynx, esophagus, thyroid gland and trachea. It is evaluated, that metastases to these nodes occur in about 10–30% of patients with cancer of the larynx, hypopharynx or cervical esophagus. These metastases can lead to the most tragic complication after total laryngectomy, which is the stomal recurrence. Paratracheal lymph nodes are not accessible to examine by palpation or ultrasonography. Aim The aim of this study was to estimate the usefulness of CT, MRI and clinical intraoperative investigation in the search for enlarged paratracheal lymph nodes. Material and methods The investigation was performed in 15 patients with advanced larynx and/or hypopharynx cancer. In all the patients we carried out palpation and ultrasonography of the neck, in 7 cases CT and in another 8 cases MRI of the neck. In all the patients who were operated (14 cases) the exact search for enlarged paratracheal lymph nodes during operation was performed. Results Palpation and ultrasonography of the neck did not find any enlarged paratracheal lymph nodes in anybody of the patients. CT showed one enlarged prelaryngeal lymph node in one patient. MRI showed one enlarged pretracheal lymph node in another one patient. During operation we found one enlarged paratracheal lymph node, which was not seen in MRI. All these nodes were pathologically not metastatic. Conclusions The analysis of the state of paratracheal lymph nodes is very important in prophylaxis of stomal recurrence after total laryngectomy. However preoperative estimation of these nodes is very difficult and limited. It seems to us, that the best way of estimation of the state of paratracheal lymph nodes is intraoperative exploration of the area between trachea and esophagus and excision even loose tissue to pathological examination.

Loss of protein expression and recurrent DNA hypermethylation of the GNG7 gene in squamous cell carcinoma of the head and neck

Although down-regulation of GNG7 in cancer was reported before, its role in carcinogenesis is poorly understood. It belongs to a family of large G-proteins that may be involved in cell-contact-induced growth arrest and function in tumor suppression. In the present study, we stained immunohistochemically 188 tumors derived from larynx or floor of the mouth for GNG7 protein and confronted it with clinicopathologic data. Moreover, we performed bisulfite pyrosequencing to analyze GNG7 promoter methylation. We identified recurrent loss of GNG7 protein expression in 68/188 (36%) cases and promoter hypermethylation in (42/98; 43%) primary tumors, predominantly in young patients (p < 0.001). Loss of GNG7 expression correlated with hypermethylation of GNG7 promoter region (p < 0.001). Moreover, loss of GNG7 protein expression correlated with tumor size (p = 0.012) and lack of cervical metastasis (p = 0.02) whereas sustained expression correlated with keratinization (p = 0.008). Taken together, loss of GNG7 protein expression is a frequent event in head and neck cancer. Moreover, our data suggest that hypermethylation of the promoter region of GNG7 is probably the mechanism of the observed inactivation.

The contribution of the mitochondrial COI/tRNASer(UCN) gene mutations to non-syndromic and aminoglycoside-induced hearing loss in Polish patients

Mutations in mitochondrial DNA have been implicated in both, non-syndromic and aminoglycoside-induced hearing loss. In the present study, we have performed the systematic mutation screening of the COI/tRNA(Ser(UCN)) genes in 250 unrelated Polish subjects with hearing impairment. Three different homoplasmic sequence variants were identified, including one common polymorphism m.7476 C>T in tRNA(Ser(UCN)) and two mutations, m.7444 G>A and m.7445 A>G localized in the COI/precursor of tRNA(Ser(UCN)). The incidence of m.7444 G>A substitution was estimated at 1.6% (4/250), however variable penetrance of hearing loss, age of onset and hearing thresholds among m.7444 G>A carriers was observed. Two subjects had the positive history of aminoglycoside exposure and one of them harbored both m.7444 G>A and 12S rRNA m.1555 A>G mutations. Those suggest that m.7444 G>A itself is not sufficient to produce a clinical phenotype and additional modifier factors are required for pathogenic manifestation of m.7444 G>A substitution. Moreover, we have described the first Polish family with non-syndromic hearing loss, harboring m.7445 A>G mutation. The penetrance of hearing loss in this pedigree was 58% when aminoglycoside-induced hearing impairment was included, and 8% when ototoxic effect was excluded. This finding strongly suggests the possible role of m.7445 A>G in susceptibility to aminoglycoside induced-hearing loss.

Zwężenie podgłośniowe w ziarniniakowatości Wegenera – problem diagnostyczny i terapeutyczny

Summary Wegeners granulomatosis (WG) is a disease caused by necrotising vasculitis of small and middle blood vessels of upper and lower respiratory tract and kidneys of unknown etiology. ENT symptoms develop in more than 90% of patients and tracheobronchial involvement occurs in about 20% of patients, most often as a subglottic stenosis. Subglottic stenosis occurs usually as a late complication of disease, but sometimes it may be an early isolated symptom. It is usually irregular, no longer than 2–4 cm and affects mucosa and submucosa but sometimes also cartilage. The diagnosis is based on clinical symptoms, X-ray of the chest, urine analysis, c-ANCA detection and histological examination of the granulation from the stenosis. The main treatment of subglottic stenosis in WG is a causal immunosuppressive treatment, however an equally important is a preservation of respiratory tract passage, because a dominant symptom in this form of WG is problem with breathing or even dyspnoea. In this publication basing on literature review different methods of treatment of laryngotracheal stenosis and its importance in WG are described and discussed. In literature presently less invasive operations are recommended. The treatment of choice is endoscopic treatment with repeated dilatations and injections of steroid into the stenosis. In big stenosis in immunologically active disease patient sometimes requires tracheotomy and after remission of disease and maturation of the subglottic scar laryngotracheal resection can be considered.

Odległe wyniki leczenia choroby Ménière’a za pomocą dobębenkowych wstrzyknięć gentamycyny

Summary Objective To estimate the results of treatment of Menieres disease with intratympanic injections of gentamicin. Material 37 patients with defined, pharmacological treatment resistant Menieres disease treated in Department of Otolaryngology and Laryngological Oncology of University of Medical Sciences in Poznan with intratympanic injections of gentamicin from 2001 to 2010 year. Methods Patients were injected intratympanic with 0.3 ml (12 mg) of gentamicin once or few times with 7 days or longer breaks and a number of injections depended on the reaction of the inner ear. We estimated the patients’ subjective feelings and results of equilibrium and hearing organ examination in early (3 months) and late (2 years) period after treatment. Results Complete control of vertigo (class A) was achieved in 84.6%, and complete and essential control (class A and B) in 96.1%. Hearing deterioration usually mild or moderate was observed directly after treatment in 16.2% and after 2 years in 23% patients. The results of pure tone audiometry showed deterioration of hearing in 16.2% (early) and 26.9% (late). In 1 patient hearing deterioration was essential. Conclusions Intratympanic injections of gentamicin are effective and not troublesome method of treatment of pharmacological treatment resistant Menieres disease. In most of patients hearing can be preserved, but they should be always informed about possible risk of hearing deterioration. The number of injections and breaks between them depends on the effect of therapy and of expectations of patients.

Przyczyny zwężeń krtaniowo-tchawiczych na podstawie przeglądu literatury i doświadczeń własnych

Summary Laryngo-tracheal stenosis (LTS) is a relatively rare disease, caused usually by iatrogenic reasons (intubation, tracheotomy, radiotherapy and surgery of the larynx and trachea) or by trauma. However they may be caused by another rare diseases effecting the wall of the larynx and trachea (primary stenosis) or by compression of pathological process near by (secondary stenosis). Among the primary stenosis except iatrogenic and posttraumatic there are also: congenital, postinfective (tuberculosis, syphilis, scleroma, diphtheria, histoplasmosis and the other), in connective tissue diseases (Wegeners granulomatosis, relapsing polychondritis), in blister diseases (pemphigoid cicarticans, epidermolysis bullosa hereditaria), in amyloidosis, in sarcoidosis and tracheobronchopathia osteochondroplastica. Secondary stenosis may be effected by thyroid diseases, diseases of the big blood vessels of the thorax, hypertrophic thymus, enlargement of the lymph nodes near by the trachea, tumors and cysts of the neck and mediastinium, retrotracheal abscess and cold abscess in vertebral column tuberculosis. If the reason of stenosis is unknown, the stenosis is called idiopathic. In this publication basing on the literature review the reasons of LTS were described in details. We also present our clinical experience concerning 124 patients. The authors underline, that in most of patients the reason of LTS can be find after taking the history of a patient. However, in the cases, when the reason is not clear, a lot of specific examination should be done to find another rare reason, and only after exclusion it the diagnosis of idiopathic LTS can be established.