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Biomedical subjects

W Szyfter

Publications and source records attributed to W Szyfter.

At least 37 records · Page 2Linked to original sources

Analysis of aromatic DNA adducts in laryngeal biopsies.

Epidemiological studies have confirmed the correlation between tobacco smoking, environmental pollution and the incidence of cancers of the respiratory tract. The occurrence of laryngeal cancer in Poland is relatively high compared to other European countries. Since 1969 the mortality related to larynx cancer appears to be increasing. Tobacco smoke contains an abundance of such carcinogenic compounds as polycyclic aromatic hydrocarbons (PAH), aromatic amines and N-nitrosoamines, which can react with DNA and form adducts. We analyzed aromatic DNA adducts in laryngeal tissues from patients with primary laryngeal, which was confirmed histopathologically to be squamous cell carcinoma. The group consisted of 33 patients (5 women and 28 men). Total laryngectomy was performed in patients. A detergentphenol method was used for DNA isolation. Aromatic DNA adducts were analyzed by a 32P-postlabelling technique with butanol extraction and high performance liquid chromatography. The presence of aromatic DNA adducts was demonstrated in all tissues. Large interindividual differences of DNA adduct levels were seen in each tissue studied. There was a higher mean level of DNA adducts in interarytenoid area non-tumors (51.96/10(8) +/- 91.71 NN) than in non-tumor tissue elsewhere (46.91/10(8) +/- 46.36 NN) and tumor tissue (43.52/10(8) +/- 45.88 NN). Adduct levels were correlated with age, sex, cigarette smoking and TNM stage.

Adult↗

[Diagnostic difficulties in nasopharyngeal tumors].

Diagnostic possibilities in lethal midline granuloma (Wegener's granulomatosis, angiocentric lymphoma) based on the literature were presented. Results of diagnostic examinations in a case of 34 years old man admitted to the Dept. of Otolaryngology in Poznań were described.

Adult↗

[Reconstructive surgery in larynx cancer].

Subtotal laryngectomies with larynx reconstruction are an acceptable alternative to the total laryngectomy in T2, T3 larynx cancer treatment. One procedure resection and reconstruction allow for radical oncological treatment with simultaneous preservation of air passage continuity and the function of the neolarynx. In the years 1988-1997 in ENT Dept. of Karol Marcinkowski University of Medical Sciences 38 subtotal laryngectomies with larynx reconstruction were performed. They were: 34 supracricoid laryngectomies with cricohyoidopexy, 2 with epiglotohyoidopexy and 3 supraglotic laryngectomies with reconstruction. The basic criterion of the evaluation of such procedures effectiveness was their oncological radicality. The follow-up period ranged from 2 to 9 years. Local relapse was observed in none of the cases, nodal relapse was started in 2 patients. Another aspect taken into consideration was the function of the neolarynx. In 3 cases two or three laser procedures were performed because of neolarynx lumen structure which were followed by T-dren plasty. In 10 patients temporary swallowing difficulties, especially liquids, were observed in the first three month. Gastrostomy was performed in one case. The authors discuss indications to this type of surgery, operation technique, oncological and functional results. Spirometry results and voice analyses after larynx resection and reconstruction in these patients are presented.

Follow-Up Studies↗

[First experiences in Neural Response Telemetry in patients with Nucleus 24 cochlear implant system].

Nucleus 24 Cochlear Implant System enables bidirectional communication with the implant-telemetry. Information about implant function can be obtained using telemetry. Neural Response Telemetry is a measurement of neural activity in the cochlea as a response to electrical stimulation. Principle of NRT recording, classification of responses and examples of responses obtained in patients implanted in Poznań are presented.

Adult↗

[Analysis of aromatic DNA adducts in oral cavity and pharyngeal cancer].

An exposure to tobacco smoke carcinogens is followed by an interaction of chemical carcinogens with DNA molecule resulted by the formation of carcinogen: DNA adducts. The study subjects were 40 oral and pharyngeal cancer patients with primary tumours diagnosed as squamous cell carcinoma. The biological samples purchased for analysis included tumour biopsy, the surrounding tissue (histopathologically recognised as non-malignant) and peripheral blood leucocytes. For DNA adducts analysis first DNA was isolated using phenol detergent extraction followed by 32P-postlabelling assay including P1 nuclease enhancement. Aromatic DNA adducts were found in all studied tissues. The average levels of DNA adducts in tumour and non-tumour tissues were found higher than in leucocytes. Biopsies from pharynx contained higher levels of DNA adducts than from oral cavities. Confounding effect of tobacco smoking and alcohol consumption on DNA adducts level was observed but it has not reached statistical significance. Formation of DNA adducts was not depended on such factors as patients age, sex, pulmonary tuberculosis, cancer progression (TNM), environmental pollution and mechanical irritation.

Aged↗

[Usefulness of chromosome alteration analysis in cell lines derived from laryngeal tumors for evaluation of laryngeal neoplasms].

A classical cytogenetic analysis was applied to analyse karyotypes of 9 cell lines derived from laryngeal cancer. The most frequent aberration was a deletion of the whole sex chromosome Y. An abundance of somatic chromosome alterations was further analysed to find correlation with tumour staging and grading. A conventional cytogenetic analysis seems to be not sufficient to recognize chromosome alterations specific for a given tumor stage. On the other hand, an analysis in respect to histologic grading has indicated for an association between rearrangement of 9 chromosome and a high tumor aggressiveness. It seems that a combination of conventional cytogenetics with molecular methods (FISH, CGH) would be helpful in diagnosing of laryngeal cancer.

Cell Line↗

DNA copy number losses are more frequent in primary larynx tumors with lymph node metastases than in tumors without metastases.

Comparative genomic hybridization was performed on 38 primary laryngeal carcinomas divided into two groups according to the metastatic phenotype. DNA copy number changes were detected in 22 of the 38 cases (57.9%). Gains were most frequently observed at 3q, 8q, and 9q, and losses were found in decreasing order at 18q, 3p, and 4. The mean value of losses was 2.5 times as high in metastasizing primary tumors (23/38) as in nonmetastasizing tumors. The most frequent losses in metastasizing tumors were at 18q, 3p, and 5q.

Adult↗

Molecular and cellular alterations in tobacco smoke-associated larynx cancer.

Tumours of head and neck belong to the most frequent types of cancer world-wide. In Poland, mortality from larynx cancer among males has been continuously increasing during the last decades up to 8.4 deaths per 100,000 men in 1993, which exceeds epidemiological records from other countries. The aetiology of laryngeal cancer is strongly associated with exposure to carcinogens present in tobacco smoke. The review describes a sequence of molecular and cellular events from carcinogenic exposure, DNA adduct formation, detection of mutations in the p53 gene, loss of heterozygosity (LOH) in chromosomal loci encoding the p53 and p16 genes, and loss of control of the cell cycle. The section concerning DNA adducts includes a discussion of the role of such confounders as exogenous exposure, the age and sex of the subject, and disease progression. The significance of genetic factors as individual risk determinants is discussed in relation to bleomycin-induced chromosome instability and in connection with the occurrence of defects in genes encoding detoxifying enzymes. The question concerning the substantial difference between men and women in larynx cancer morbidity and mortality remains open, even when the significantly higher adduct formation in male DNA compared with female material was taken into account. Preliminary experiments suggest a role of the frequently observed loss of the Y-chromosome.

Carcinoma, Squamous Cell↗

Extended fronto-lateral laryngectomy with simultaneous reconstruction by means of a mucochondral nasal septum flap.

As treatment for laryngeal cancers the extended fronto-lateral laryngectomy allows tumor to be removed that involves the glottis with the vestibule of the larynx. Since 1979 we have performed 417 extended fronto-lateral laryngectomies with simultaneous reconstruction of the anterior part of the larynx using a mucoperichondral flap from the anterior septum. This operation was indicated for stage T1b cancer (175 cases), stage T2 tumor (231 tumors) and T3 extended operations with epiglottectomy (11 cases). For the total number of 417 patients operated on, 19 cases during the 5-year period of following had local recurrences that required total laryngectomy. In 11 cases, metastases to the cervical lymph nodes required surgical neck dissection. In the remaining 387 cases, a normal air passage and a large laryngeal lumen were found. In 15 cases graft rotation into the larynx made respiration and phonation difficult but without dyspnea occurring. Follow-up to a maximum of 18 years showed that the oncological and functional results after this surgical procedures are encouraging.

Aged↗

[Otitis media in patients with Down's syndrome].

61 patients with Down's syndrome were examined. Otitis media was diagnosed in 19 patients. Conductive hearing impairment after otitis media was observed in pure tone audiometry and speech audiometry. It was emphasized that conductive hearing loss in children with Down's syndrome is a very important factor in retarded speech development. Children with recurrent otitis media were treated by surgery (9 adenotomies) and conservative treatment such as insufflation and catheterisation of Eustachian tubes, pharmacotherapy. Treatment of otitis media was difficult because of anatomical anomalies of facialocranium, atrophic mucous membrane of upper respiratory tract, reduced immunity.

Adolescent↗

[Hidden chromosome instability and risk of laryngeal cancer incidence].

The bleomycin test is a recognised method of evaluation of hidden genetical instability. The concept of the test consists in inducing chromosome aberrations in lymphocytes exposed in vitro to bleomycin and subsequent quantitative analysis of chromosome breaks. The study material was whole venous blood from 61 laryngeal cancer patients and from 30 healthy persons taken as a control. For each patient two parallel cultures where carried out in the standard procedure. Bleomycin was added to one of the cultures to induce chromosome breaks. Then, in microscopic metaphasal plates stained by Giemsa dye, the chromosome instability index estimated as a number of chromosome breaks per cell (b/c) and the percentage of cells with chromosome breaks were calculated. Higher indices of chromosome instability were demonstrated in laryngeal cancer patients in comparison to the controls. The persons with chromosome instability (b/c > 0.8) or with chromosome oversensitivity to mutagens (b/c > 1) were identified only among larynx cancer subjects. Furthermore, it was established that an increased chromosome instability is associated with high aggressiveness recognised by histological grading. The latter finding requires confirmation on an enlarged group of subjects.

Adult↗

[Estimation of bleomycin-induced chromosome aberrations in lymphocytes of laryngeal cancer subjects. Preliminary report].

Chromosome instability is associated with an increased risk of malignancy. However, the quantitative analysis of chromosome breaks provided by the bleomycin test requires additional analysis aimed for the localisation of chromosome aberrations. For this reason, the metaphasis slides prepared for bleomycin test were stained with fluorochrome DAPI to estimate chromosome breaks in particular chromosomes. The additional staining of chromosomes can be recognised as an extension of the classical bleomycin test addressed for identification of structural aberrations. Preliminary results indicate that the most frequent chromosome breaks were found in chromosomes 1, 2, 3, 7 and 13.

Aged↗

Carcinogen: DNA adducts in tobacco smoke-associated cancer of the upper respiratory tract.

Mortality connected with tobacco smoke-associated laryngeal cancer in Poland markedly exceeds the relevant epidemiological data from other European countries. The main groups of genotoxic agents considered as potential carcinogens present in tobacco smoke are polycyclic aromatic hydrocarbons, aromatic amines, N-nitrosoamines and reactive oxygen species. Aromatic DNA adducts, N7-alkylated guanosines and oxidative DNA damage derived from tobacco smoke exposure were detected in laryngeal and oral (tumour and non-tumour) biopsies, and white blood cells of cancer subjects. Further, DNA lesions were analysed to estimate the significance of such confounders as intensity of smoking, subject's sex, age, topography of larynx, cancer staging and genetic factor. The number of cigarettes smoked per day was found to be the main determinant of an individual's DNA adduct level. The occurrence of DNA lesions was established as a reliable marker of former exposure to tobacco smoke genotoxicants. On the other hand, a comparison of DNA lesion levels in various regions of larynx indicates limited usefulness of DNA adduct analysis as an estimate of cancer risk. For a better risk estimation one has to take into account DNA lesions in proto-oncogenes and tumour suppressor genes and the efficacy of DNA repair. Altogether, DNA adducts formation and removal has to be considered as a single stage in the multistep carcinogenesis.

Carcinogens↗

[20-year-long experience in the large-scale fronto-lateral laryngectomy with a simultaneous reconstruction by muco-cartilagenous nasal septum flap: results of 460 cases].

The late results of the larynx reconstruction by means of the mucoseptal nasal graft after an enlarged fronto-lateral laryngectomy were described. The analysis of 460 patients showed a satisfying larynx lumen in almost all cases. In 21 cases due to the neoplasm recurrence a total laryngectomy were performed. The voice after surgery was socially good, and the wide larynx lumen was obtained.

Cartilage↗

[Chromosome damage in the course of laryngeal squamous cell carcinoma].

The aim of the article is a review of own cytogenic studies on laryngeal cancer confronted with the literature data. Spontaneous and bleomycin-induced chromosome instability was analysed in peripheral blood lymphocytes in relation to genetic risk of cancer incidence and progression. Comparative genome hybridization (CGH) was applied to demonstrate gains and losses of DNA copy number in tumour and non-tumour laryngeal mucosa. The profiles of imbalances of DNA copy number were shown to differ between metastazing and non-metastazing tumours. Preliminary data indicate a frequent loss of Y chromosome in tumour cells. The loss of heterozygosity at chromosome p53 locus (17p) has been shown to be more frequent than at chromosome locus coding 16 gene (9p). Altogether, the experiments have proven that a dynamics of chromosome aberrations is highest at the stage of metastasis.

Antibiotics, Antineoplastic↗

[Otitis media with effusion].

The authors present monographic data as regards causes, epidemiology, patomechanism and treatment of otitis media with effusion. The attention is paid to connections between this pathology and acute, recurrent otitis media and chronic eustachian tube insufficiency. The authors underline occult onset, asymptomatic and chronic character of this disease, irreversible consequences and hearing impairment. Among treatment methods the most effective seemed to be the surgery one: adenotomy with simultaneous tympanostomy. The authors give the schedule of management of otitis media with effusion and indications to ventilation tube insertion.

Acute Disease↗