[Anesthesiologic management in the treatment of patients with cystic fibrosis]. / Anästhesiologisches Management bei der Versorgung von Mukoviszidose-Patienten.

OBJECTIVE: Improvements in the management of patients with cystic fibrosis (CF) result in increased life expectancy. Thus it is likely that anesthetists will see this patients with increasing frequency. This study describes our experiences in the anesthetic management of CF patients. METHODS: We descriptively and retrospectively reviewed the records of all CF patients from 1981 until 1997 who underwent elective surgery in our department of ear, nose and throat and in whom general anesthesia was required. RESULTS: 199 anesthetics in 53 patients were reviewed. Premedication with midazolam (0.4 +/- 0.07 mg/kg) were given orally in 163 of the 199 anesthetics (82%). In 45 anesthetics the induction was performed by Inhalation with halothane (23%). Atropine (0.21 +/- 0.11 mg/kg) was used in 69 cases for induction. 57 pulmonary function tests were performed preoperatively mostly showing no severe abnormalities. We documented 10 perioperative respiratory complications (5%) in 199 procedures. No patient died at hospital. CONCLUSION: In patients with cystic fibrosis undergoing minor ear, nose and throat surgery who do not show significant reduction in pulmonary function anesthesia can be safely carried out.

Minor role of Cl- secretion in non-cystic fibrosis and cystic fibrosis human nasal epithelium.

Na+ and Cl- currents were studied in primary cultures of human nasal epithelium derived from non-cystic fibrosis (non-CF) and cystic fibrosis (CF) patients. We found that Na+ absorption dominates transepithelial transport and the Na+ current contains an amiloride-sensitive and amiloride-insensitive component. In non-CF tissue both components contribute about equally to the entire short-circuit current (ISC), whereas in CF tissues the major part of the current is amiloride-sensitive. Na+ removal reduced ISC to values close to zero. Several Cl- channel blockers were used to identify the remaining tiny Na+-independent current. Under unstimulated, physiological conditions in the presence of Cl- on both sides and amiloride on the apical side of the epithelium diphenylamine-2-carboxic acid (DPC), 4,4'-diisothiocyanatostilbene-2, 2'- disulfonic acid (DIDS) and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) failed to induce clearcut inhibition of ISC. cAMP as well as ATP did not affect ISC either in CF or in non-CF epithelia. Reduction of apical Cl- increased ISC and depolarized transepithelial potential; however, the observed increase was insensitive to DIDS, DPC and NPPB. From these data we conclude that Cl- conductances in primary cultures of human nasal epithelium derived from CF patients as well as from non-CF patients are present only in low numbers or do not contribute significantly to transepithelial ion transport.

[Ion transport in nasal and paranasal sinus mucosa in mucoviscidosis and chronic sinusitis]. / Ionentransporte über die Nasen- und Nasennebenhöhlenschleimhaut bei Mukoviszidose und chronischer Sinusitis.

Cystic fibrosis (CF) is the most commonly inherited disease in Caucasians and is caused by a mutation in the gene encoding a membrane transport protein. This cystic fibrosis transmembrane conductance regulator (CFTR) is thought to be an apical Cl- channel activated by intracellular cAMP. Most recent findings suggest that CFTR is more than a pure Cl- channel and might be involved in the regulation of other transport systems. In the present study we show that CFTR as a Cl- channel plays only a minor role in primary cultured human nasal epithelium derived from non-CF and CF patients. These findings are especially of interest for non-CF human nasal epithelia in which CFTR is correctly inserted. In both tissues Cl- secretion is negligible as compared with Na+ absorption. We confirm and expand our previous observations that Na+ absorption in human nasal epithelium is the dominant ion transport process and that Cl- secretion is detectable in both CF and non-CF tissue. Moreover, we show that cAMP and ATP were not able to stimulate any silent Cl- channels in CF or non-CF human nasal epithelial cells. We further give evidence that in human nasal CF and non-CF epithelium Na+ absorption is mediated by epithelial Na+ channels (ENaC) that are either different from those of other epithelia or which exhibit altered regulation. These differences between Na+ channels of human nasal epithelium and "classical" epithelial Na+ channels include lack of activation by the intracellular second messenger cAMP and the steroid hormone aldosterone. We show further that human nasal Na+ channels are inhibited by Cl- channel blockers and exhibit a different pharmacology towards common Na+ channel blockers.

Localization of Staphylococcus aureus in infected airways of patients with cystic fibrosis and in a cell culture model of S. aureus adherence.

Staphylococcus aureus causes chronic respiratory tract infections in patients with cystic fibrosis (CF). Using immunofluorescence and scanning and transmission electron microscopy we located S. aureus in lung specimens of three infected CF patients, in a nasal polyp of one CF patient, and in a suspension cell culture system of primary nasal epithelial cells in vitro. Very little of S. aureus was attached to the lung epithelium, whereas abundant S. aureus was detectable in the mucus of obstructed airways. Similarly, S. aureus adhered to components of secreted mucus on primary nasal epithelial cells of CF patients and healthy control subjects, grown as cell balls in vitro (bacteria/cell +/- SD: CF: 21.9 +/- 1.5; controls: 22. 0 +/- 5.8). Mucus depletion of cell balls prior to incubation with S. aureus resulted in a significantly reduced binding (bacteria/cell +/- SD: CF: 4.2 +/- 0.3; P < 0.001; controls: 5.0 +/- 1.3; P < 0. 007). Binding of S. aureus to cell balls from CF patients or control subjects did not differ significantly. When cell balls were treated with human neutrophil elastase, hypersecretion caused removal of S. aureus from cell-associated mucus. The results suggest that S. aureus adheres primarily to mucus components of the respiratory epithelium and that significant differences do not exist in binding of S. aureus to CF or non-CF cells.

Amiloride-sensitive Na+ channels in human nasal epithelium are different from classical epithelial Na+ channels.

We characterized Na+ absorption in confluent monolayers of primary cultured epithelia derived from human nasal cystic fibrosis (CF) and non-CF epithelium in modified Ussing chambers. Amiloride-sensitive Na+ channels in cells obtained from CF as well as from non-CF patients showed properties different from all previously described epithelial Na+ channels (ENaC). DPC, a potent Cl- channel blocker, which has never been described to block ENaC, inhibited a considerable portion of the amiloride-sensitive Na+ absorption. In contrast to classical ENaC, cAMP induced no activation of amiloride-sensitive short-circuit current. Aldosterone failed to induce any functional stimulation of Na+ absorption in vitro when applied to the cell culture medium prior to measurements. Together with the reportedly reversible inhibition by phenamil we propose that Na+ absorption in human nasal epithelia is either regulated differently or is mediated by a yet still unknown member of the ENaC superfamily.

Cystic fibrosis and non-cystic-fibrosis human nasal epithelium show analogous Na+ absorption and reversible block by phenamil.

Transepithelial short-circuit current (ISC), potential (VT) and resistance (RT) of confluent monolayers of human nasal epithelium cultured from patients with and without cystic fibrosis (CF) were measured. In our Ussing chamber experiments with monolayers derived from non-CF and CF patients neither ISC (non-CF: 14.1 +/- 1.0 microA/cm2, n = 77; CF: 16.7 +/- 1.5 microA/cm2, n = 42), nor RT (non-CF: 288 +/- 15 Omega . cm2; CF: 325 +/- 20 Omega . cm2) showed any significant differences, only VT showed moderate but significant different values (non-CF: -3.6 +/- 0.4 mV; CF: -5.6 +/- 0.7 mV, respectively). Total ISC in CF cells was nearly completely inhibited by amiloride (92 +/- 9.6%), while in non-CF tissue amiloride-insensitive conductances mediated a considerable amount of the ISC (36.3 +/- 6.1%), indicating a lower activity of amiloride-sensitive Na+ conductances in non-CF cells. In both tissues the amiloride-sensitive ISC could also be blocked by the amiloride analogues benzamil, phenamil and 5-(N-ethyl-N-isopropyl)2', 4'-amiloride (EIPA) with different affinities. However, amiloride had a significant lower affinity in CF tissue (half-maximal blocker concentration, K1/2 = 586 +/- 59 nM) compared with non-CF tissue (K1/2 = 294 +/- 22 nM). Astonishingly, phenamil, a blocker which irreversibly blocks all epithelial Na+ channels hitherto described, inhibited the Na+ conductances of human nasal epithelium in a completely reversible way, but nevertheless with high affinity (non-CF: K1/2 = 12.5 +/- 1.2 nM; CF: K1/2 = 17.1 +/- 1.1 nM). Even in high doses none of these blockers had any effect on intracellular Ca2+ concentration as measured with Fura-2. From these findings, we conclude that the epithelial Na+ conductances of human CF nasal epithelium show modified regulation or are functionally different from those of other tissues.

[Topical anesthesia of the tympanic membrane and tubal function--is there a correlation?]. / Topische Trommelfellanästhesie und Tubenfunktion--gibt es Zusammenhänge?

The influence of topical anaesthesia of the tympanic membrane on Eustachian tube function was investigated using the pressure chamber impedance method, thus obtaining quantitative data. Anaesthesia was performed by application to the tympanic membrane of small cotton balls containing lidocaine and dimethylsulfoxide. We did not observe significant alterations of tubal parameters after unilateral or bilateral anaesthesia. Our observations are in contrast to investigations published by Nagai. We suppose that differences in methods of topical anaesthesia are responsible for this discrepancy. Our technique of topical anaesthesia of the tympanic membrane excludes any effect on the Eustachian tube, thereby avoiding negative consequences of middle ear pressure on wound healing.

Eustachian tube function in sudden hearing loss and in healthy subjects.

The relationship between sudden hearing loss and an ipsilateral patulous tube was tested in our Eustachian tube laboratory. Fifty patients suffering from sudden hearing loss were examined by the pressure chamber impedance method, giving objective data on Eustachian tube function. Results were compared to those obtained from 56 healthy volunteers in a preceding investigation. Our investigation did not show any associations between patulous tube syndrome and sudden hearing loss, as had been claimed by several authors previously. There was even indication of a decreased patency of Eustachian tube in our patients in active and passive tubal tests. We could demonstrate a high reproducibility of values obtained by our method, indicating that results are representative in healthy persons as well as in patients. In a case report the importance of objective diagnostic methods in differential diagnostics of Eustachian tube pathology is emphasized.

[Is there a drug therapy for sero-mucotympanum?]. / Gibt es eine medikamentöse Therapie beim Sero-Mucotympanon?

A critical review of the literature (including the authors' own randomized double-blinded studies) does not support the widespread use of drugs for treatment of otitis media with effusion (secretory otitis media).--Neither mucolytic agents, nor decongestants, nor antihistamines have any favourable effect on the course of the disease. Success with steroids or antibiotic agents in selected cases is very limited.

[Sniff-induced negative pressure--a cause for the development of middle ear diseases?]. / Sniff-induzierter Unterdruck--eine Ursache für die Entstehung von Mittelohrerkrankungen?

The significance of "sniffing" causing tubal dysfunction and thus leading to the development of cholesteatoma is discussed. We examined 244 healthy ears (18% sniff-positive), 21 ears with a traumatic perforation of the tympanic membrane (10% sniff-positive), 46 ears with chronic mesotympanic otitis (17% sniff-positive) and 40 ears with cholesteatoma (60% sniff-positive). Two different methods were used: on intact tympanic membranes the pressure chamber impedance method described by Munker-Pedersen (1972), and for perforated tympanic membranes a pressure transducer. Our results show that: (1) "sniffing" can cause negative pressure in the middle ear space; (2) the traditional concept of opening failure is no longer sufficient to explain tubal dysfunction; (3) sniff-induced negative pressure is a further possible cause of tubal dysfunction; (4) sniff-induced negative pressure seems to be an important factor in the development of cholesteatoma.

The motor innervation of the tympanic muscles in the guinea pig.

The number and the location of the motor neurons innervating the stapedius or tensor tympani muscles in the guinea pig were identified by retrograde axonal transport of the tracer horseradish peroxidase. Tracer injections were made either into the stapedius or tensor tympani muscle and effected the retrograde labeling of neurons in the ipsilateral brain stem. These findings showed that the stapedius motor neurons lie outside the traditionally recognized facial nucleus and are present in two cell columns: ventromedial and dorsomedial to the facial nucleus. These labeled neurons are dissimilar to cells within the facial nucleus, i.e. they are smaller and more fusiform in shape. The tensor tympani motor neurons were found outside the trigeminal motor nucleus. At a rostral level they were located in a region ventral and ventrolateral to the latter nucleus. These labeled neurons were smaller than the trigeminal motor neurons and polygonal in shape. In the animals studied there were about six times more tensor tympani motor neurons than stapedius motor neurons.

[Giant cell tumour of bone in the cavum tympani and petrous bone]. / Ossärer Riesenzelltumor im Bereich von Pauke und Felsenbein.

In the great majority of cases, the giant-cell tumour of bone (synonymous with osteoclastoma of bone) is localised at the end of a long tubular bone. Most of the patients are between 20 and 40 years of age. A case of a grade II giant-cell tumour in a female patient of 32 years of age is reported, which was localised in the middle ear and petrous bone.

[The "transposition-rotation flap" in the one stage reconstruction of auricle defects (author's transl)]. / Einseitige Rekonstruktion von Ohrmuscheldefekten mit einem "Transpositions-Rotationslappen."

To close full thickness auricle defects (Fig. 1 a) we use a hairbearing rotation flap to transport the non-hairbearing transposition flaps in the right, retroauricular position (Fig. 1 b). The scars are lying in the hair and in the RSTL of the neck. If the helix is not resected (Fig. 6 a), we have to remove epithelium to fix the folded transposition flap in the defect (Fig. 6 c). In the same way we use this flap to close large defects in the retro- and postauricular region and to reconstruct auricle deformities.

[The TTL-computer flash and the operating microscope OPMI I. A new system for microphotography (author's transl)]. / TTL-Computerblitz und Zeiss Operationsmikroskop OPMI I.

The autodynamic controller TTL-computer flash (TTL = through the lens) with combined cold light fountain was adapted to the operating microscope OPMI I. The TTL-computer flash system facilitates the handling of the photomicroscope and provides accurately exposed photos in microphotography.

Inner ear hearing loss in acute and chronic otitis media.

Temporary or permanent threshold shift of bone conduction occurs frequently in acute or chronic otitis media. The sensorineural hearing loss is dependent on the age of the patient and the duration of the illness. Fluid in the middle ear may impede sound transmission and oxygen transport to the inner ear. In middle ear inflammation noxious substances may pass across the round window membrane leading to serous labyrinthitis. In therapy ototoxic drugs and operations (tympanoplasty) can cause sensorineural deafness.

Growth influence on tubal function.

The influence of growth on tubal function was studied in 26 children by means of tubal function tests in a pressure chamber and by geometric analysis of lateral cephalograms. Good tubal function coincided with mesoor brachycephalic skeletons, poor tubal function with dolichocephalic morphologic patterns. According to our results, tubal function seems to be strongly influenced by the growth processes of the skull.

[Simultaneous multiple flaps in head and neck surgery (author's transl)]. / Mehrfachlappen in der Chirurgie des Gesichtes und des Halses.

We have developed several variations of the "bilobed flap" for the reconstruction of large defects of the head and neck. In so doing, we use pedicled bi- and tri-lobed flaps, transposition-rotation skin flaps or double-rotation skin flaps. Some examples are described to illustrate the technique employed.

Relationship between tubal function, craniofacial morphology and disorder of deglutition.

26 children without hearing impairment have been examined by otolaryngologists and orthodontists. According to the tubal function test in a pressure chamber they were classifed into a group with good and poor tubal function. The E.N.T. examination was unconclusive for a possible relationship between rhinological findings, mode of breathing, sinusitis, size of tonsils, nasal airway resistance and tubal function. Adenoids proved to be a mechanical impairment for active tubal function as stated by many authors. The cephalometric analysis of lateral head films combined with a static and dynamic-functional evaluation of tongue posture revealed significant differences between children with good and poor tubal function. Subjects with a vertical craniofacial growth pattern seem to be predisposed for poor tubal function. Analysing static tongue posture in children with poor tubal function the tongue lies more retracted in a backward position. The back of the tongue is flattened in relation to the palatal arch. In children with good tubal function there is a much closer contact between the back of tongue and the hard palate. Subjects with poor tubal function have an increased incidence of abnormal deglutition combined with tongue-thrust, teeth-apart swallowing, lack of sealing off the anterior oral cavity and contraction of the circumoral musculature. In children with good tubal function one can find the somatic type of swallowing that means no contractions of the circumoral muscles, no tongue-thrust during deglutition but contact of the molars and contraction of the masseter muscle.

[Bone conduction changes in secretory otitis media (author's transl)]. / Knochenleitungsveränderungen beim Sero-Mukotympanon.

In serous and secretory otitis media a reduction of bone conduction frequently exists besides the loss of air conduction. In 304 audiograms of ears with serous and viscous fluid in the middle ear there was a depression of the bone conduction between 15 and 40 dB in 40%. This bone conduction loss was reversible after the aeration of the tympanic cavity. That means that we deal with a false nerve deafness in many of these cases.