[Bronchoscopic specimen collection, role of the protected specimen brush in lower respiratory tract infections]. / Bronchoszkópos anyagvételi módszer, a védett hörgókefe szerepe az alsó légúti infekciók kivizsgálásában.

INTRODUCTION: The ineffectiveness of microbiological methods in the lower respiratory tract infections are caused by anachronistic sampling methods. Authors checked the protected specimen brush effectiveness and those of the influencing factors. MATERIALS AND METHODS: 103 patients were involved in the study. The causative agents were identified in 44 cases. These results were compared to last year's classic sampling techniques and they experienced 20.4% improvement of the sensitivity. Further increasing in effectiveness can be reached if we perform bacteriological sampling after the first unsuccessful antibiotic treatment was performed. Out of 103 examined patients only 69 underwent antibiotic treatment. In the case of 13 patients after the course of one type antibiotic treatment 10 positive bacteriological cultures were positive. In the case of 31 patients 2 types of antibiotics were administered sequentially and examined afterwards and the authors found 15 positive bacteriological cultures. In the case of 25 patients the administered sequentially 3 times of antibiotics and examined afterwards, 6 cultures were positive. CONCLUSION: The examinations prove that the protected specimen brush, used in time, raises the sensitivity of microbiological processes.

Squamous-cell carcinoma arising in a non-irradiated child with recurrent respiratory papillomatosis.

We describe a patient with recurrent respiratory papillomatosis (RRP) associated with human papilloma virus (HPV), who developed a fatal squamous cell carcinoma of the lung. At the age of 1 year he presented with hoarseness, dyspnoea and inspiratory stridor but the diagnosis of RRP was made only 1 year later. At the age of 4 years he was tracheostomized because of upper airway obstruction. In spite of multiple surgical excisions and topic treatment with 5-fluorouracil the papillomata extended to the lung parenchyma. At the age of 16 years he developed a squamous-cell carcinoma of the lung and died 4 months later. Transformation to pulmonary carcinoma is a rare complication in non-irradiated patients with lung papillomatosis. We found only 11 similar cases in the literature.

Sites of predilection in recurrent respiratory papillomatosis.

Florid and widespread respiratory papillomatosis is a devastating disorder in a subset of patients with recurrent respiratory papillomatosis, and it poses a major dilemma for the patient and the surgeon. Contrary to common belief, the distribution of papilloma lesions is not random, but follows a predictable pattern, with lesions occurring at anatomic sites in which ciliated and squamous epithelia are juxtaposed. The predominant sites of disease in recurrent respiratory papillomatosis are the limen vestibuli, the nasopharyngeal surface of the soft palate, the midzone of the laryngeal surface of the epiglottis, the upper and lower margins of the ventricle, the undersurface of the vocal folds, the carina, and bronchial spurs. These sites have the common histologic feature of a squamociliary junction. Papillomata also occur at the tracheostomy tract and at the midthoracic trachea in patients with tracheostomies. At the latter sites, abrasion injury to ciliated epithelium heals with metaplastic squamous epithelium and creates an iatrogenic squamociliary junction. The apparent preferential localization of papilloma at squamociliary junctions has at least 2 implications: first, that detection of occult asymptomatic papillomata is enhanced by careful examination of squamociliary junctions, and, second, that iatrogenic papilloma "implantation" is preventable by avoiding injury to nondiseased squamous and ciliated epithelia.

Human papillomavirus infection in papillomas and nondiseased respiratory sites of patients with recurrent respiratory papillomatosis using the polymerase chain reaction.

We examined human papillomavirus (HPV) infection in biopsy specimens and cellular scrapes that were taken from respiratory papillomas and six nondiseased sites from the respiratory tract of seven patients. Human papillomavirus was detected by polymerase chain reaction amplification, followed by DNA hybridization with probes for specific HPV types. All papillomas (100.0%, n = 5) were positive only for HPV type 6 or 11. In the nondiseased site specimens, 61.3% (19/31) of the specimens were positive, again only for HPV type 6 or 11. Among the nondiseased site specimens from the cervical trachea, intrathoracic trachea, and bronchus, 80% to 100% were HPV positive compared with only 25% to 50% of HPV infection detected in the nasopharynx, posterior tonsillar pillar, and aryepiglottic fold. These results support the tenet that HPV infection is present in clinically normal respiratory tract tissue and that the reservoir site of reinfection is more commonly in the lower airway. However, patients with upper-airway involvement were more likely to be diagnosed as having severe disease.

EBV DNA in nodal and extranodal non-Hodgkin's lymphomas: impact of cell lineage, morphology, and site of origin.

The Epstein-Barr virus (EBV) is a transforming herpes virus which is found in high frequencies in lymphoproliferative disorders arising in immunocompromised patients. To address the question of viral involvement in lymphomas of immunocompetent patients, we investigated 299 nodal and extranodal non-Hodgkin's, non-Burkitt's lymphomas of B- and T-cell lineage for the presence of EBV DNA. Epstein-Barr nucleic acid sequences were detected in 23 of 226 (10%) cases of B-cell lymphomas, in 24/72 (33%) T-cell lymphomas and one non-B, non-T lymphoma. Our data imply a possible role for the EBV in lymphoma development or propagation, an influence of viral factors on morphology and an impact of the anatomic site in which lymphoma development occurs.

Detection of human papillomavirus infection in diseased and nondiseased sites of the respiratory tract in recurrent respiratory papillomatosis patients by DNA hybridization.

We examined 12 recurrent respiratory papillomatosis patients, who were undergoing treatment for recurrence of their disease, for the presence of human papillomavirus (HPV). Biopsies were obtained from their respiratory papillomas and nondiseased sites (NDS) of the respiratory tract: the nasopharynx, posterior tonsillar pillar, aryepiglottic fold, cervical trachea, intrathoracic trachea, and bronchi. The presence of HPV DNA was determined by using the ViraPap/ViraType DNA hybridization procedure. Two thirds of the patients were infected with HPV 6/11 in either the diseased papilloma or NDS: 50% of patients with papilloma specimens typed positive (6 of 12), and 40% of the patients typed HPV-positive in one or more biopsies from the NDS (4 of 10). No single NDS was more likely to be infected with HPV than any other. No oncogenic HPV types 16/18 or 31/33/35 were detected in the papillomas or NDS of these patients. Only patients with multiple, and not isolated, papilloma involvement were found to harbor HPV DNA in NDS; and 80% of those with infected NDS, compared to 20% of those without infected NDS, required a shorter (no more than 3 months) surgical treatment interval. Our results show that HPV infection frequently persists in adjacent, clinically normal sites, and suggest that the extent of NDS involvement may predict both the extent of disease and the likelihood of recurrence.

Human papillomaviruses and upper airway oncogenesis.

This review summarizes the relationship between human papillomaviruses (HPVs) and upper airway tumors. The epidemiology of HPV in benign and malignant tumors, the life cycle of the virus, the effects of the virus on laryngeal papillomas, possible mechanisms of malignant conversion, and the molecular biology of the virus are described.

[Demonstration of DNA tumor viruses in carcinomas of the upper respiratory tract]. / Nachweis von DNS Tumorviren in Karzinomen des oberen Respirationstraktes.

In situ hybridization (ISH) using 35S-labeled probes was applied to the detection of viral DNAs in 115 epithelial tumours from various sites. Epstein-Barr virus (EBV) DNA was detected in 83% of undifferentiated nasopharyngeal carcinomas (NPC) while none of seven squamous cell NPC displayed an EBV-specific autoradiographic signal. Also, all other tumours investigated, including thymomas, thymic carcinomas, tonsillar carcinomas and medullary breast carcinomas were negative upon ISH to EBV-specific probes. These results suggest a unique association of undifferentiated NPC with EBV. 28 tonsillar carcinomas were further analyzed for the presence of human papillomavirus (HPV) DNA. Six carcinomas showed an HPV16-specific signal while hybridization to HPV6- and HPV11-specific probes yielded negative results. No HPV-DNA was detected in any of 30 tonsils with chronic inflammation, thus excluding that the finding of HPV16 in a proportion of tonsillar carcinomas is merely circumstantial. These results point to a possible etiologic role of HPV16 in the pathogenesis of some tonsillar carcinomas.

Heterogeneity in mRNA of human papillomavirus type-6 subtypes in respiratory tract lesions.

We have analyzed the structure of viral transcripts in six HPV-6c-induced respiratory tract lesions, which included four benign laryngeal papilloma, one benign nasopapilloma, and one malignant tumor, in four benign laryngeal papilloma induced by HPV-6e, and in one benign laryngeal papilloma induced by HPV-6f. Northern analysis and S1 nuclease digestion with subgenomic RNA probes demonstrated that the major exon of 1050 bases had a 5' end in the E4 open reading frame and a 3' end in E5B. Primer extension from a synthetic oligonucleotide in E4 was used to examine sequences 5' to the major exon. Differences were found in length, start sites, and relative abundance of the first exon in transcripts produced in HPV-6c-induced infections as compared to HPV-6e- and HPV-6f-induced infections. Primer extension in the presence of dideoxynucleotides facilitated sequence analyses of the first exon. HPV-6c transcripts contained common sequences from E1 that in different transcripts extended farther upstream in the 5' direction into E7 resulting in different lengths. All of the mRNAs had the same splice junction at nucleotide 847 in E1 and 3325 in E4. Similarly, the HPV-6e transcripts shared common sequences in the first exon that differed in length as a result of different starting points and had the same splice junction as the HPV-6c transcripts. No differences were found in the structure of viral transcripts in a malignant vs benign lesions, nor in those of nasopapilloma vs laryngeal papilloma when induced by the same HPV-6 subtype.

Papilloma viruses in cancers and papillomas of the aerodigestive tract.

Reports demonstrating the presence of human papillomaviruses in benign and malignant tumours of the head and neck, lung tumours and tumours of the aerodigestive tract are increasing. Because of different methods used, all varying in sensitivity and specificity, a critical evaluation of results is required. Although the majority of papillomatous lesions of the oral cavity and the larynx contain papillomavirus DNA sequences, other benign and malignant lesions still remain negative. The identification of a new papillomavirus from an agressively growing inverted papilloma of the paranasal sinuses could lead to the isolation of as yet unidentified papillomaviruses which could play a role in the etiology of these benign and malignant lesions.

Papillomavirus. Effects upon mother and child.

Papillomaviruses are widespread, sexually transmitted agents with an increasing prevalence. They are associated with a significant risk of genital carcinoma in infected women. Because they can be transmitted to the fetus before or during birth, they are also a risk to the infant born to an infected woman. Laryngeal HPV infections, while presumably much less prevalent than genital tract infections, are associated with a high degree of morbidity and a significant degree of mortality when they cause laryngeal papillomas. Therefore, transmission of these viruses to the fetus is a major problem. Much more information regarding mode of transmission and possible cure for this infection is needed in order to reduce the risk of laryngeal papillomatosis in infants in the future.

Papillomaviruses in human cancer.

Twelve types of human papillomaviruses (HPV) have been isolated thus far from papillomatous and Bowenoid lesions of the human genital tract. Four type, HPV 6, 11, 16 and 18 are most frequently found. HPV 6 and 11 cause the typical genital warts (condylomata acuminata) and mild dysplastic lesions of the cervix characterized by a high degree of koilocytotic atypia. HPV 16 and 18 are preferentially found in Bowenoid papulosis and Bowen's disease at external genital sites. Moderate and severe cervical dysplasias with little or no koilocytosis appear to be common manifestations of these infections at cervical sites. HPV 16 is found in approximately 50% of all cervical, penile and vulvar cancers, HPV 18 in close to 20%. The majority of the remaining tumors reveals evidence for infections with additional types of HPV. Several cell lines have been identified containing either HPV 18 or HPV 16 genomes. The state of viral DNA in Bowenoid precursor lesions differs from that of cervical carcinomas. The former contain episomal DNA whereas integration seems to be a regular event in carcinomas. Integration regularly affects the E1-E2 open reading frames of HPV 16 or HPV 18 DNA. Fusion transcripts from the integrated HPV DNA (E6-E7 region) and adjacent host cell DNA have been documented. The available data support a causative role of specific HPV infections in the etiology of human genital cancer.