In vitro tolerability of human nasal mucosa: histopathological and scanning electron-microscopic evaluation of nasal forms containing Sandostatin.

An in vitro human nasal model was developed as a tool to study the local tolerability of nasal powder forms using excised nasal mucosa in a diffusion chamber. The suitability of this model was tested using Sandostatin (SMS) an octapeptide analog of somatostatin, as a reference drug enhanced by Avicel (microcrystalline cellulose) or lactose (100 mesh). The standard nasal spray vehicle was taken as a harmless control and 1% chenodeoxycholate (CDC) as a harmful control in terms of local tolerability. The extent of peptide permeation was determined by measuring SMS concentration in the receiving chamber. The labeling of SMS was detected by immunoperoxidase staining on cross sections. The local tolerability for all tested forms was assessed by histopathological examination and scanning electron microscopy. The apparent permeation coefficient allowed us to rank the absorption of the tested drug forms as Avicel > spray = lactose > 1%CDC. For all formulations, SMS was detected in the epithelium. No changes of the nasal mucosa could be observed with Avicel, lactose or nasal spray vehicle in the presence or absence of SMS. 1%CDC with or without drug showed an immediate destruction of the nasal epithelium. The validation of this in vitro model using human nasal mucosa will be further discussed as a tool for assessing the local tolerability of intranasally applied test substances.

[Role of ENT surgery in the assessment and treatment of snoring and of obstructive sleep apnea syndrome in adults and children]. / Beitrag der HNO-Heilkunde zur Abklärung und Behandlung der Rhonchopathie und des obstruktiven Schlafapnoesyndroms bei Erwachsenen und Kindern.

The otolaryngologist is increasingly involved in the evaluation and management of sleep-related respiratory disorders. Main symptoms of intermittent obstruction in adults and children are snoring and stridulous breathing. Important factors causing pharyngeal obstruction are functional and structural narrowings in the upper airways leading to increased upstream resistance. The ENT's examination has two principal aims: 1. habitual snoring must be separated from an obstructive sleep-apnea syndrome (OSAS), as the later is associated with cardiovascular diseases and an increased mortality; 2. a functional or structural cause of the obstruction must be sought. Flexible nasopharyngoscopy is a valuable diagnostic tool to determine the nature of obstruction. OSAS patients need a differentiated evaluation in a sleep laboratory, and an attempt of therapy with continuous positive airway pressure (CPAP) should be undertaken in most of these cases. Today the otolaryngologist is equipped with a whole range of conservative and surgical therapeutic possibilities. The introduction of compact lasers as well as the endoscopic/microscopic endonasal surgery have revolutionized surgical treatment in patients with habitual snoring and OSAS. In contrast to adults, OSAS in children has still received poor attention and leads often to impaired thriving. Most frequently, hypertrophied tonsils are present, and tonsillectomy eliminates obstruction in nearly all of these cases.

Rhinoorbital mucormycosis: surgical aspects.

The authors present a case of a young woman with a diabetic ketoacidosis and rhinoorbital mucormycosis, successfully treated by resection of necrotic areas without orbital exenteration. The favorable outcome was attributed to early diagnosis and immediate commencement of the adequate therapy, which included correction of diabetic ketoacidosis, debridement of devitalized tissue, daily irrigation of the involved areas with amphotericin B solution and application of intravenous amphotericin B.

Rhinosurgical experience with the transseptal-transsphenoidal hypophysectomy: technique and long-term results.

Many modifications of extracranial transsphenoidal hypophysectomy exist, but knowledge of the rhinological implications of these procedures is rare. At our institution the transseptal approach is performed as a joint rhinosurgical and neurosurgical procedure. Three hundred nineteen patients were operated on from 1979 to 1984, 113 of whom had a rhinological follow-up for 5 years. Most of the complications were asymptomatic. Thirteen percent of the patients had septal perforations, 3.5% epistaxis, and 36% complained of mild dryness of the nose. An improvement in breathing was noted in 24% of the patients. There was no difference in rhinological complaints between patients who underwent the sublabial approach and those operated via a transnasal approach. Twenty percent of the patients operated on with the sublabial approach had additional temporary complaints in the upper lip; therefore, the transnasal-transseptal approach is currently our procedure of choice.

Human nasal septal cartilage: analysis of intracellular enzyme activities, glycogen content, cell density and clonal proliferation of septal chondrocytes of healthy adults and acromegalic patients.

The human septal cartilage is of ectodermal origin and contributes to midfacial growth and development. Acromegaly is an endocrine disease due to growth hormone (Gh) excess originating from a somatotrophic adenoma of the pituitary gland. Excessive Gh levels lead to high insulin-like growth factor I (IGF I) concentrations, which are known to stimulate cartilage growth in vivo and in vitro. One of the salient clinical pictures is coarsening of the midface and enlargement of the septal cartilage. Septal cartilage was obtained from 8 acromegalic patients during transnasal hypophysectomy and from 10 healthy adults during septoplasty to analyse the following aspects of cartilage biochemistry, metabolism and growth. 1. Intracellular glycogen, the major source of energy of chondrocytes, was determined enzymatically and found to be drastically reduced in acromegaly. 2. Several intracellular enzymes, related to biomatrix degradation, showed a strict local pattern of distribution. Cathepsin B activity, a neutral proteinase degrading both the helical and nonhelical region of the collagen molecule was significantly increased in acromegaly, whereas alkaline phosphatase activity, an enzyme related to mineralization of the cartilage at the chondroosseous junction was depressed in acromegaly. 3. The cell density in some areas of the septal cartilage was increased in acromegaly, whereas the clonal proliferation rate of its chondrocytes in response to serum and growth factors was decreased. Chondrocytes both of healthy adults and acromegalic patients could be effectively stimulated by insulin-like growth factor I and II and to a lesser extent by epidermal growth factor.

[Normal values in rhinomanometry]. / Beitrag zu den Normwerten in der Rhinomanometrie.

Despite various methods of investigation, there are few reports as to the normal values of nasal airway resistance. A total of 56 adult subjects free of any nasal disease underwent nasal airway resistance measurement using active anterior rhinomanometry according to the guidelines of the international committee on standardization of rhinomanometry. Inspiratory and expiratory resistance was measured before and after application of a topical decongestant spray. This test was reproducible in that 46 of the subjects underwent a second study with resistance values quite close to that of the initial measurement. The upper range of the total inspiratory nasal airway resistance was 0.45 Pa s/cm3 before and 0.3 Pa s/cm3 after decongestant administration. There was no statistically significant difference between the inspiratory and expiratory resistance measurements. No correlation could be made between nasal airway resistance, age, sex, height or weight.

[Clinical comparison of 2 modern rhinomanometers]. / Klinischer Vergleich zweier moderner Rhinomanometer.

Two rhinomanometers (the NR 6 manufactured by Mercury, Scotland and the Rhino-Comp manufactured by Cintec, Sweden) were tested and compared in five subjects. Both instruments are suitable for clinical use and produced equal measurements of nasal airway resistance. The Rhino-Comp device is easier to handle. Technical improvements would be desirable in both machines.

The influence of climatic factors on the nasal mucosa of rats.

The influence of indoor climate on goblet cells and intraepithelial glands of nasal mucosa was analysed. A cold and heat adapted group of twenty rats were compared with a neutral adapted group after eight weeks of climatic exposure. There was a decrease of density of the goblet cells and the intrapeithelial glands in cold adapted rats. It is suggested that the adaptive changes of the mucous membranes of the rats may be correlated with the increased ventilation rate in the cold.

Human nasal septal cartilage: local distribution of different enzyme activities in healthy adults and acromegalic patients.

Septal cartilage was obtained during septoplasty from healthy adults or during transnasal hypophysectomy from acromegalic patients. Small strips of cartilage were excised from five different areas of the septum: the anterior free end, the suprapremaxillary area, the central area, the posterior area, and the caudal prolongation of the septum. Five different enzymatic pathways were analyzed in these areas. Cathepsin D, an acid proteinase, did not show a specific local activity pattern and was not influenced by the augmented growth hormone level in acromegaly, whereas cathepsin B, a neutral proteinase, showed its highest activity in the caudal prolongation and the posterior area and was significantly increased in all areas in acromegaly. Beta-hexosaminidase activity was highest in the central and posterior area and caudal prolongation of the septum. In acromegaly, a significant increase of its activity was found in the suprapremaxillary and posterior area. Acid phosphatase activity was highest in the caudal prolongation of the septum, but its activity was significantly increased in all tested areas in acromegaly. Alkaline phosphatase activity could only be found in the posterior area and the caudal prolongation in healthy adults. However, in acromegaly this enzyme could be detected in the central area and the posterior end of the suprapremaxillary area suggesting an altered process of mineralization. A distinct local pattern of enzymes related to intercellular substance metabolism and mineralization can be demonstrated in the septal cartilage of healthy adults and acromegalic patients.

Growth activities of the nasal septal cartilage in acromegaly.

Growth activity in different areas of human septal cartilage was measured by in vitro incorporation of 35 S-labelled sulfate and 3 H-labelled thymidine in 6 acromegalic patients. Septal cartilage was obtained during transnasal hypophysectomy. The growth activities in the posterior area, which is situated anterior to the septo-ethmoidal junction were significantly enhanced compared to a control group of hormonally normal adults. Growth activities of the septal cartilage in the anterior free end and the suprapremaxillary area were not different in both groups. This indicates that growth hormone excess in acromegaly enhances human septal growth by stimulation of growth activities in the posterior area and not at the anterior free end and suprapremaxillary area.

[Our concept concerning treatment of septal perforations (author's transl)]. / Unser Konzept zur operativen Behandlung von Septumperforationen.

There are still some problems of the surgical treatment of septal perforations (s.p.). Only patients with s.p. having complaints i.e. bleeding, crusting, whistling and headache should be treated. More than 60% of 61 operated patients had an iatrogenic perforation. The complete closure of the s.p. is not abosulutely necessary. More important seems to be the protection of the posterior circumference of the s.p. In small perforations (up to 5 mm) an interposition of fascia combined with a rotating mucosa flap is a safe technique. In middle size s. p. (up to 15 mm) a two stage technique is recommended by using a vestibular-conchal flap which gives satisfactory results in 80% of the operated patients. In great s. p. (more than 15 mm) a septal button is preferred.

[Histomorphology and resorption of longtime-implanted cartilage chips conserved in merthiolat in rhinoplasty (author's transl)]. / Zur Histomorphologie und Resorption langzeitimplantierter Merthiolat-konservierter Knorpelspäne in der Rhinoplastik.

A histological study is presented on 18 cartilage grafts, conserved in Merthiolat TM, which had been implanted for reconstruction of the caudal border of the nose for time periods of 1 month up to 11 years. These cartilage graft preparations were compared to non graft cartilage from patients died in an age of 37, 51 and 53 years respectively. Our findings show that cartilage grafts are eroded from the edge by resorption granulations of the host. Besides resorption one case showed purulent chondritis and another one osteoneogenesis. The extent of the erosion and the resorption rate seem to depend strongly on the original quality of the cartilage graft. This is possibly due to degenerative focuses which could be found in all of the natural cartilage preparations. After our opinion these focuses regarded like "loci minoris resistentiae". Therefore cartilage material to be used for rhinoplasty ought to be checked for such degenerative focuses.

[Artificial mesh in the reconstruction of the posterior auditory canal wall (author's transl)]. / Erfahrungen mit einem Kunststoffnetz bei der Rekonstruktion der Gehörgangshinterwand.

Mersilene mesh was used in the reconstruction of the posterior wall of the auditory canal in 12 radical mastoidectomy and attico-antrotomy cavities. Reestablishment of a stable metal wall occurred in 7 patients. In 2 the mesh had to be covered with soft tissue in a second procedure. 3 implants required removal. This technique because of the 25% failure rate can only be recommended reservedly.

[Tympanoplasty with human dura mater preserved in cialit (author's transl)]. / Tympanoplastik mit in Cialit konservierter humaner Dura mater (Klinische und tierexperimentelle Untersuchungen).

In 26 cases allogenetic human dura mater, conserved in CialitTM 1:5000, was used to close perforations of the eardrum instead of commonly used autogenetic fascia of the temporal muscle. In preceding animal studies, it had been found that "Cialit dura" acts as guideline and stimulates the development of new host connective tissue. In 25 human ear drums the perforations healed up without any problems. The healing process took times of up to 8 weeks. Only in one case a new perforation was found. The moderate flexibility of "Cialit dura" proved as a special advantage during the surgery procedure. Human dura is easily to acquire and its conservation is simple and cheep. Therefore it can serve as a grafting material for tympanoplasty available at any time and in any size. For very large transplants and a lack of postoperative treatment the prolonged healing period could be of some disadvantage. For normal sized transplants, however, there seems not to be a difference in healing time between the commonly used fascia and the "Cialit dura".

[Is the prophylactic hemithyreoidectomy indicated in radical neck dissection? (author's transl)]. / Ist die prophylaktische Hemithyreoidektomie bei der radikalen Halslymphknotenausäumung notwendig?

To find an explanation for tumor-recurrences around the tracheostoma, in 59 cases of squamous cell cancer of larynx, hypopharynx, oropharynx and tongue the ipsilateral hemithyreoidectomy was included into the tumorexstirpation and radical neck dissection. This histological work up of the thyroid showed no evidence of metastases within the gland. However in cases of extended metastasis or difficult surgical approach to the prae- and paratracheal areas the hemithyreoidectomy is advised.

[The histological changes in cartilage (incus) in the middle ear after conservation--an animal study (author's transl)]. / Uber das histologische Verhalten von Knorpel (Ambossgelenkpfanne) im Mittelohrraum nach unterschiedlicher Konservierung. Eine tierexperimentelle Studie.

This study demonstrates the histological changes of incus cartilage after transplantation into the middle ear space of rabbits. Conservation was performed by deep-freezing, lyophilisation in connection with gamma-irradiation, or with Cialit in differing dilutions. Controlled deep-freezing at about -196 degrees C and uncontrolled deep-freezing at about -20 degrees C guarantee after transplantion the survival of some vital chondrocytes. The other methods of conservation cause death of all chondroxytes. Cartilage prepared by these methods demonstrates potential for new bone formation. Only the xenogenetic cartilage loses its osteogenic potential after treatment by lyophilisation in connection with gamma-irradiation. The histological value of the transplant differs according to the method of conservation. No special tendency for resorption or inflamatory reactions could be seen.

[A simplified method of the endolaryngeal laterofixation of the vocal cord (author's transl)]. / Eine vereinfachte Methode der endolaryngealen Glottiserweiterung.

In a modification of Thornell's procedure of surgical treatment of bilateral abductor paralysis of the vocal cords, the arytenoid cartilage is preserved, but only its vocal process is removed. After preparing of a pedicled subglottic mucosaflap a partial resection of the vocal cord and of the vocal muscle is followed. An endolaryngeal packing with a soft foam-rubber stent allows an optimal adaptation of the mucosaflap. Two years follow-up studies have shown that all 14 patients had a satisfying respiration, their voice was either partially hoarse or almost as good as before the operation. All 14 cases could be decannulated, 12 of them within 12 days.

[Long term experience of using preserved cartilage in reconstructive surgery of the nose (author's transl)]. / Langzeiterfahrungen mit konserviertem Knorpel in der Wiederherstellungschirurgie der Nase.

Long term experience of nasal surgery using cartilage homografts preserved in merthiolate shows the implants to have the following properties: 1. They heal without complications and are well tolerated. 2. Rate of resorption varies according to the quality of the recipient site and the stresses on it from outside. 3. Very suitable for support to replace resected or destroyed cartilage. 4. Limited use in reconstructing weight bearing areas because of unduly high resorption rate in 50% of implanted struts. 5. No clinical evidence of resorption in areas not subject to stress. 6. Resorption in areas of stress varies from a virtual absence to a rapid process.

[Incus, controlled deepfrozen or in cialit conserved, after allogenetic implantation. An animal-experimental study with comparing histology (author's transl)]. / Der kontrolliert tiefgefrorene und der in Cialit konservierte Amboss nach allogenetischer Implantation. Eine tierexperimentelle Studie mit vergleichender Histologie.

The histological reactions to the implantation of allogenetic incus after conservation in Cialit or after controlled deepfreezing are described. After 5 months the incusses of both conservation technics show the same good tendency of revitalisation. Therefore the controlled deep-freezing technic does not offer an advantage compared to the Cialit conservation method at least for the present state of knowledge.