Association of CYP1B1 codon 432 mutant allele in head and neck squamous cell cancer is reflected by somatic mutations of p53 in tumor tissue.

Tobacco use is causally associated with head and neck squamous cell cancer (HNSCC). Here, we present the results of a case-control study that investigated the effects that the genetic variants of the cytochrome (CYP)1A1, CYP1B1, glutathione-S-transferase (GST)M1, GSTT1, and GSTP1 genes have on modifying the risk of smoking-related HNSCC. Allelisms of the CYP1A1, GSTT1, GSTM1, and GSTT1 genes alone were not associated with an increased risk. CYP1B1 codon 432 polymorphism was found to be a putative susceptibility factor in smoking-related HNSCC. The frequency of CYP1B1 polymorphism was significantly higher (P < 0.001) in the group of smoking cases when compared with smoking controls. Additionally, an odds ratio (OR) of 4.53 (2.62-7.98) was discovered when investigating smoking and nonsmoking cases for the susceptible genotype CYP1B1*2/*2, when compared with the presence of the genotype wild type. In combination with polymorphic variants of the GST genes, a synergistic-effect OR was observed. The calculated OR for the combined genotype CYP1B1*2/*2 and GSTM1*2/*2 was 12.8 (4.09-49.7). The calculated OR for the combined genotype was 13.4 (2.92-97.7) for CYP1B1*2/*2 and GSTT1*2/*2, and 24.1 (9.36-70.5) for the combination of CYP1B1*2/*2 and GSTT1-expressors. The impact of the polymorphic variants of the CYP1B1 gene on HNSCC risk is reflected by the strong association with the frequency of somatic mutations of the p53 gene. Smokers with susceptible genotype CYP1B1*2/*2 were 20 times more likely to show evidence of p53 mutations than were those with CYP1B1 wild type. Combined genotype analysis of CYP1B1 and GSTM1 or GSTT1 revealed interactive effects on the occurrence of p53 gene mutations. The results of the present study indicate that polymorphic variants of CYP1B1 relate significantly to the individual susceptibility of smokers to HNSCC.

Sensorineural hearing loss in patients with chronic progressive external ophthalmoplegia or Kearns-Sayre syndrome.

In the present study we assessed the prevalence and nature of hearing loss in patients with chronic progressive external ophthalmoplegia (CPEO) or Kearns-Sayre syndrome (KSS) due to single large-scale mitochondrial DNA (mtDNA) deletion or mtDNA tRNA (Leu (UUR)) A3243G point mutation (A3243G PM). 14 patients with mtDNA deletion and three patients with A3243G PM underwent audiological evaluation comprising pure-tone and speech audiometry as well as transient evoked otoacoustic emissions (OAE). Audiological evaluation revealed hearing impairment in 10/17 patients. Hearing loss was mild to moderate predominantly affecting high frequencies in five patients with subjective hearing problems (three patients with mtDNA deletions, two patients with A3243G PM). Subclinical hearing deficits restricted to high frequencies were seen in further five asymptomatic patients (four patients with mtDNA deletions, one patients with A3243G PM). Audiological findings suggested a cochlear origin of hearing loss in all subjects. Our results demonstrate that CPEO or KSS patients due to mtDNA deletion or A3243G PM are at high risk of developing sensorineural hearing deficits.

Cricopharyngeal achalasia is a common cause of dysphagia in patients with mtDNA deletions.

To assess dysphagia, the authors examined 12 patients with Kearns-Sayre syndrome (KSS) or chronic progressive external ophthalmoplegia (CPEO) due to mitochondrial DNA (mtDNA) deletion by videofluoroscopy and manometry. Cricopharyngeal achalasia was documented in nine of 12 patients (75%), whereas deglutitive coordination problems were found in one patient. Cricopharyngeal myotomy may be an effective treatment in selected cases with severe cricopharyngeal obstruction.

Pediatric tracheal homograft reconstruction: a novel approach to complex tracheal stenoses in children.

PURPOSE: Tracheal stenosis can be a life-threatening problem in children. Long-segment tracheal stenosis and recurrent tracheal stenosis are especially problematic. Tracheal homograft reconstruction represents a novel therapeutic modality for these patients. METHODS: Cadaveric trachea is harvested, fixed in formalin, washed in thimerosal (Methiolate), and stored in acetone. The stenosed tracheal segment is opened to widely patent segments proximally and distally. The anterior cartilage is excised and the posterior trachealis muscle or tracheal wall remains. A temporary silicone rubber intraluminal stent is placed and absorbable sutures secure the homograft. Regular postoperative bronchoscopic treatment clears granulation tissue. The stent is removed endoscopically after epithelialization over the homograft. Twenty-four children with severe tracheal stenosis (age 5 months to 18 years, mean +/- standard error of the mean = 8.18 +/- 1.21 years) underwent tracheal homograft reconstruction. All but one had had previous unsuccessful reconstructive attempts. Ten lesions were congenital, nine were posttraumatic, and five were due to prolonged intubation. RESULTS: Follow-up ranged from 5 months to 10 years (3.79 +/- 0.70 years). Twenty patients survive (20/24 = 83%), 16 without any airway problems. Four patients are still undergoing treatment. One patient requiring emergency extracorporeal membrane oxygenator support before the operation died 10 days after tracheal homograft reconstruction. Another patient with severe preoperative mediastinal sepsis died 3.5 months after tracheal homograft reconstruction. Two patients with functional airways died late of unrelated problems. CONCLUSIONS: Tracheal homograft reconstruction demonstrates encouraging short-term to medium-term results for children with severe recurrent tracheal stenosis. Postoperative bronchoscopic and histologic studies provide evidence of epithelialization and support the expectation of good long-term results.

Successful complete tracheal resection in a three-month-old infant.

We report an infant with severe long-segment tracheal stenosis in whom the posterior trachea was formed by complete cartilage rings and the anterior trachea was almost totally formed by a solid cartilage plate. The child was successfully treated initially by complete resection of the trachea and primary end-to-end repair and subsequently with tracheal homograft transplantation for secondary stenosis.

Tracheal allograft reconstruction: the total North American and worldwide pediatric experiences.

BACKGROUND: We reviewed both the North American and the total worldwide pediatric experience with tracheal allograft reconstruction as treatment for patients with long segment and recurrent tracheal stenosis. METHODS: The stenosed tracheal segment is opened to widely patent segments. The anterior cartilage is resected and the posterior trachealis muscle or tracheal wall remains. A temporary silastic intraluminal stent is placed and absorbable sutures secure the chemically preserved cadaveric trachea. After initial success with this technique in Europe, several North American centers have now performed the procedure. The cumulative North American experience includes 6 patients (3 adults and 3 children). Worldwide, more than 100 adults and 31 children, aged 5 months to 18 years, with severe long segment tracheal stenosis have undergone tracheal allograft reconstruction. RESULTS: In North America, 5 of 6 patients have survived, with one early death due to bleeding from a tracheal-innominate artery fistula in a previously irradiated neck. Worldwide, 26 children survived (26 of 31 = 84%) with follow-up from 5 months to 14 years. Only 1 of 26 pediatric survivors (1 of 26 = 3.8%) had a tracheostomy. CONCLUSIONS: Tracheal allograft reconstruction demonstrates encouraging short- to medium-term results for patients with complex tracheal stenosis. Allograft luminal epithelialization supports the expectation of good long-term results.

In situ measurement of articular cartilage deformation in intact femoropatellar joints under static loading.

The deformational behavior of articular cartilage has been investigated in confined and unconfined compression experiments and indentation tests, but to date there exist no reliable data on the in situ deformation of the cartilage during static loading. The objective of the current study was to perform a systematic study into cartilage compression of intact human femoro-patellar joints under short- and long-term static loading with MR imaging. A non-metallic pneumatic pressure device was used to apply loads of 150% body weight to six joints within the extremity coil of an MRI scanner. The cartilage was delineated during the compression experiment with previously validated 2D and 3D fat-suppressed gradient echo sequences. We observed a mean (maximal) in situ deformation of 44% (57%) in patellar cartilage after 32 h of loading (mean contact pressure 3.6 MPa), the femoral cartilage showing a smaller amount of deformation than the patella. However, only around 7% of the final deformation (3% absolute deformation) occurred during the first minute of loading. A 43% fluid loss from the interstitial patellar matrix was recorded, the initial fluid flux being 0.217 +/- 0.083 microm/s, and a high inter-individual variability of the deformational behavior (coefficients of variation 11-38%). In conjunction with finite-element analyses, these data may be used to compute the load partitioning between the solid matrix and fluid phase, and to elucidate the etiologic factors relevant in mechanically induced osteoarthritis. They can also provide direct estimates of the mechanical strain to be encountered by cartilage transplants.

Tracheal reconstruction in children using cadaveric homograft trachea.

OBJECTIVE: We report the use of cadaveric human tracheal homograft in the treatment of severe long segment congenital tracheal stenosis in children. METHODS: Five children (aged 5 months-8 years) with severe life-threatening airway obstruction due to long segment congenital tracheal stenosis had failed conventional management. All were ventilator dependent or rapidly deteriorating at the time of surgery, two were on extracorporeal membrane oxygenation, and no alternative therapy was available. The stenosed trachea was removed and the posterior trachealis muscle left in situ when possible. Surgical technique involved the use of cardiopulmonary bypass in four of five cases. Stored cadaveric tracheal homograft tissue was shaped and inserted over a silastic intra-luminal stent which was kept in place for up to 3 months. Regular bronchoscopy was necessary postoperatively to clear granulation tissue, which resolved on removal of the stent. RESULTS: Four patients are all now without stents, intubation or tracheostomy. Three are without airway problems 16, 14, and 9 months after surgery and one attends for occasional dilatation of a distal tracheal stenosis, but is now at home despite other severe multiple congenital problems. One patient presented with complete disruption of the trachea and mediastinal sepsis and was supported on extracorporeal membrane oxygenation prior to surgery; this patient eventually died of airway failure and sepsis. CONCLUSIONS: The application of cadaveric human tracheal homograft to congenital tracheal stenosis is novel. Its use in five children who would otherwise have died has provided an extra therapy in an extremely difficult group of patients.

The role of airway stents in the management of pediatric tracheal, carinal, and bronchial disease.

OBJECTIVE: A variety of stents are available to aid in the management of complex tracheal, carinal and bronchial stenoses. We reviewed our multi-institutional experience with airway stents in children. METHODS: Thirty-three children (age, 13 days-18 years) from four institutions have had a total of 40 stents placed to aid in the management of complex airway stenoses. Three stent types were utilized: 29 silastic stents, five expandable metal stents and six customized carinal stents (four patients had two stents and one patient had four stents). Thirty children had tracheal stents, six children had bronchial stents, and two infants had carinal stents (three children had stenting of more than one area and two had stenting of all three locations). Twenty-eight patients (age, 5 months-18 years; mean, 8.06 years; SEM, 1.13 years) had stents placed after a variety of airway reconstructive procedures. Four underwent stenting in a non-operative setting and one as preoperative stabilization. RESULTS: Twenty-seven patients survived. One patient died early due to bleeding. Five patients died late: two due to bleeding, one from mediastinitis, and two patients with functional airways died late from unrelated problems. Complications are related to stent type and location. Carinal stents can migrate; several techniques are available to help manage this problem. Wire stents are essentially non-removable requiring periodic dilation. Silastic stents stimulate granulation tissue formation requiring periodic bronchoscopic removal. CONCLUSION: Tracheal stenting can aid in the management of pediatric airway problems. Complications are common, but can be managed with appropriate intervention.

[Computer tomographic volume determinations of the pneumatised portions of the ear (author's transl)]. / Computertomographische Volumenbestimmung des Luftgehaltes des pneumatischen Systems des Ohres.

A method for the volumetric measurement of the pneumatized parts of the ear by computer tomography is described. The boneair boundaries are determined by density measurements. The appropriate slices produce values which are automatically added under optical control. Thirty-four normal and abnormal ears have been examined in this way. The greatest air volume observed was 12.9 ml., the smallest 0.0 ml. The volumes are related to age and provide information concerning various types of disease.

[Computed tomographic volumetry of the pneumatic system of the ear. Comparison of normal subjects and patients with ear diseases]. / Computertomographische Volumetrie des pneumatischen Systems des Ohres. Ein Vergleich zwischen Normalkollektiv und Patienten mit Ohrerkrankungen.

The volume of the pneumatised portion of the ear was determined by computed tomography in 235 patients. Amongst the 470 ears examined, 320 had no disease in the ear, nose or throat. Normal pneumatisation of the ear can be quantified by CT and strict correlation has been demonstrated between the air content and age from ten to 17 years. Chronic inflammatory processes of the middle ear occurring during childhood interfere with pneumatisation on one or both sides. The most severe failure of pneumatisation occurs with congenital abnormalities of the ear, most cases never showing significant pneumatisation. Chronic infection of the tonsils or adenoids causes much less interference with pneumatisation.

A method for quantifying time dependent changes in MR signal intensity of articular cartilage as a function of tissue deformation in intact joints.

A method is proposed to determine accurately the signal intensity changes of the articular cartilage from sectional MR images and its related cartilage deformation under compression in an intact joint. Image processing methods are developed to delineate and register the cartilage boundaries in consecutive MR images in order to track corresponding tissue sectors during the loading experiment. Regions of interest can then be defined and traced during the compression, making a spatial and temporal analysis of signal intensity changes possible. In addition, the cartilage deformation is calculated in the respective tissue sectors and is related to the MR signal changes. Using a fat-suppressed FLASH 3D sequence, the preliminary results showed location-dependent slight changes of the signal intensity varying from individual to individual. The quantitative analysis of the signal intensity changes as a function of cartilage deformation with magnetic resonance imaging (MRI) aims to characterize microstructural properties of the articular cartilage that may lead to a better understanding of degenerative joint disease.

Nasal ventilation measured in forced respiratory flow.

First results of measurements of a forced respiratory flow for the evaluation of nasal ventilation performance are provided. The obtained data indicate that the chronometric registration of the flow-volume-curve provides a clearer indication as to the dynamism of nasal respiration than the measurement of statistical nasal resistance or, in other words, the respiration flow with a specific resistance.

Typical results of computer-olfactometry.

After pulsed peripheral olfactory impulses it is possible, under suitable testing conditions, for specific sensory potentials to be read from the surface of the skull and, after repetitions, added up (olfactorially evoked cortical potentials). Typically, there developes a so-called twin-potential containing the equivalents of the electrical activites of the nervus trigeminus and the nervus olfactorius in two peaks of the cortex equivalents. In an objective manner, in other words without intentional or vegetative influence by the test person, it is possible by the weakening or lack of one or the other or both part-potentials to obtain information about the functioning of the olfactory sense. Typical examples will be presented.

[Immunopathologic reactions in chronic sialadenitis of the submandibular gland (so-called Küttner tumor)]. / Immunpathologische Reaktionen im Ablauf der chronischen Sialadenitis der Glandula submandibularis (sog. Küttner-Tumor).

The aim of this study was to investigate immunological aspects of the inflammatory reaction in the submandibular gland during chronic sialadenitis. Specimens of 54 patients registered at the Institute of Pathology at the University of Hamburg were stained according to the indirect immunoperoxidase method. The distribution patterns of Ig-secreting plasma cells (IgA, IgG, IgM) and of the enzymes lactoferrin, lysozyme, and secretory component were analysed. The formation of lymph follicles was also examined. The results were as follows: Stage 1 of the chronic sialadenitis starts as a simple inflammation with an increase of IgA-secreting plasma cells around the ducts. During stage 2 the unspecific, humoral part of the immune system is stimulated. The production of lactoferrin and lysozyme is enhanced. The titer of IgA rises due to activation of the local, specific immune system. The simultaneous rise of the IgG titer is probably caused by production at different sites. During the course of stage 3--4, the cells involved in the local, unspecific immune system are destroyed. The number of IgG secreting plasma cells also decreases. The formation of lymph follicles and the infiltration of the gland by lymphocytes is interpreted as a transition to the cellular immune response. Stage 4 of the Küttner tumor shows similarities to the autoimmune disease of Sjögren's syndrome.

[Système International d'Unités = SI-units. Temporary prescriptions are finished now (author's transl)]. / Système International d'Unités = SI-Einheiten Die Ubergangsfristen sind abgelaufen.

After a description of the legal basis for the use of the so-called SI-Units the problems of changing into the new system are discussed. The essential changes, especially in the ENT--field are demonstrated. According to the present international recommendations the new legal units should be used in medicine as soon as possible.

[Evaluating function and disorders of smell]. / Funktionsprüfungen und Störungen des Geruchssinnes.

Firstly the review deals with the olfactometry after discussing the olfactory and trigeminal sensitivity of the sense of smell. The term olfactometry will be newly fixed concerning the present problems of odor analysis. Under clinical aspects the methods of subjective olfactometry are discussed and valued. Olfactory tests basing on registering several psychosomatic reflexes (e.g. cardial and/or respiratory frequencies) cannot be described as "objective". Rather methods are objective which record poststimulatory electrophysiological events at different steps of olfactory pathways. The electric response olfactometry representing a cortical evoked so-called twin-potential containing equivalents for trigeminal and olfactory sense activity starts to demonstrate its efficiency. At least a complete test of olfactory function today includes the rhinomanometry for recording ability in nasal odor transport capacity. In the second part are discussed the olfactory disorders with clinical importance. Air borne disorders are confronted with sensorineural, which again are divided in prebulbar, bulbar, and postbulbar ones so far as possible. Respiratory smell disorders depend on nasal ventilation and occur in nasal deformations, in abnormalities of respiratory pathways, in cases of foreign bodies, mucosal inflammations, tumors, intoxications and allergy. Sensorineural olfactory disorders can be attached to age, to malformations or idiopathic defects, inflammations of the olfactory-neural apparatus, head injuries, brain tumors, metabolic or endocrinological diseases. Furthermore often they are accompanied with neurological and psychiatric diseases or professional and chemical intoxications and/or iatrogenic influences. The poor therapeutical possibilities are demonstrated as far as possible. Finally the experting problems in olfactory disorders are delineated, at which the evidence of objective olfactometry can be distincted.