[Upper airway stimulation in obstructive sleep apnea]. / Stellungnahme der Taskforce "Neurostimulation bei Schlafapnoe" zur Stimulation der oberen Atemwege.

The stimulation of the upper airway represents an effective treatment option in case of CPAP failure in patients with moderate to severe obstructive sleep apnea. The stimulation with respiratory sensing (Inspire Medical Systems) has shown a high level of evidence in larger cohorts and longer follow-up studies. Whether the results of the stimulation without respiratory sensing (ImThera Medical) can be compared with the therapy with sensing, remains open up to now. Additional data are awaited after the planned phase III study THN#2. To optimize both procedure and to provide long term results, more studies are needed. The workgroup "sleep medicine" of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery supports theses activities with the help of the newly founded task force "Neurostimulation in Sleep Apnea".

[Principals of high frequency surgery]. / Hochfrequenzchirurgie -- Prinzipien und Anwendungen.

Electrosurgical instruments are routinely and daily applied at a variety of indications in Otorhinolaryngology. They can be used for cutting, coagulation and devitalisation. All have in common that the high frequency energy is transported into the tissue via an instrument and by this causes a thermal change. Depending on the duration and characteristic of the electricity a vaporisation of the tissue is effected through coagulation, devitalisation and carbonisation. The knowledge of the effects on the tissue by the choice of the different instrument parameters and application systems is essential for an ingenious therapeutically indication. In principal the following application methods for electrosurgery by modulation of the high frequency parameters are distinguished: the monopolar and the bipolar coagulation and devitalisation and the monopolar and the bipolar cutting. This article deals with the physical basis, the effects in the tissue as well as the single application methods of the high frequency surgery.

[Effect of high frequency application on the tongue base. In vitro results of "radiofrequency application" on the porcine tongue base]. / Auswirkung der Hochfrequenzapplikation auf den Zungengrund. In-vitro-Ergebnisse der "radio-frequency application" an Schweinezungen.

BACKGROUND AND OBJECTIVE: A newly developed radio-frequency monopolar needle electrode was evaluated in vitro on porcine tongues. PATIENTS AND METHODS: Porcine tongues with different tissue temperatures (20+/-1) degrees C and (32+/-2) degrees C were coagulated for 90 s. In a second step, 23 coagulations at 7 W were applied (34+/-2) degrees C. RESULTS: The volume of the lesion correlated well with increasing temperature. In step two, the mean energy was 238 J and the mean volume of the lesion was 507 mm(3) (100+/-15)%. Prolonged energy application did not correlate with a larger volume of the lesion. CONCLUSION: The new radio-frequency needle electrode can reduce tongue volume in a precise and controlled manner (SD+/-15%).

[Argon plasma coagulation and topically applied estriol. Long-term results in the treatment of hereditary hemorrhagic telangiectasia of the nasal mucosa]. / Argonplasmachirurgie und topische Estriolapplikation. Langzeitergebnisse in der Behandlung von hereditären hämorrhagischen Teleangiektasien der Nasenschleimhaut.

BACKGROUND AND OBJECTIVE: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant fibrovascular dysplasia with the main symptom of recurrent epistaxis. At present, only limited data are available on long-term results in the treatment of epistaxis. A part from the surgical treatment of the bleeding telangiectasia with argon plasma, an additional postoperative long-term treatment with estriol nose-ointment was performed and the results were analysed. PATIENTS AND METHODS: 69 patients with HHT were treated with APC and estriol nose ointment. 43 patients could be examined over a follow-up period of more than 20 months. The bleeding frequency and intensity as well as the patient's satisfaction with the treatment result were evaluated and the serum estriol level determined. RESULTS: After more than 20 months, the bleeding frequency and intensity were reduced in 95% of the patients compared to their preoperative findings. Under the influence of estriol, former berry-like telangiectasias became flatter and more even. Neither systemic side effects under topically applied estriol nor a relevant increase of serum estriol levels were observed. CONCLUSION: The combined treatment regimen with APC and topically applied estriol provides a new treatment concept of epistaxis in HHT.

Tonsillectomy with argon plasma coagulation (APC): evaluation of pain and hemorrhage.

OBJECTIVE: Argon plasma coagulation (APC) offers a new possibility for tonsillectomy (TE) because of its effective hemostasis and limited penetration depth of the coagulation zone. The APC dissector allows dissection and hemostasis in a one-step procedure. The aim of this prospective, randomized, single-blinded study was the evaluation of pain and hemorrhage of the "hot" argon-plasma-coagulation tonsillectomy (TE(APC)) compared with a conventional "cold" non-electrosurgery tonsillectomy (TE(Conv)). METHODS: Two hundred one consecutive patients undergoing tonsillectomy were included in a single-blinded, randomized, prospective study with stratification in two age groups. RESULTS: There was no statistical significant difference between TE(APC) and TE(Conv) in the intensity of postoperative pain and primary or secondary hemorrhage in both age groups. In the TE(APC) group, the mean duration of tonsillectomy was significantly reduced by more than 50% in both age groups (P <.01). The blood loss was 90% decreased in the TE(APC) compared with the TE(Conv) in both age groups (P <.01). CONCLUSIONS: The APC technique does not face the general problem of electrosurgery or thermal coagulation techniques in which the postoperative pain is often increased compared with conventional cold techniques. It offers an innovative new tonsillectomy method with significant reduced blood loss and surgical time.

Long-term results of inferior turbinate reduction with argon plasma coagulation.

OBJECTIVES: Surgical reduction of the inferior turbinates is a commonly used therapy in patients with hyperplastic inferior turbinates when medical management remains ineffective. Current surgical methods have disadvantages (e.g., necessity of nasal packing, extended postoperative swelling, and high costs). Theoretical considerations render argon plasma coagulation (APC) a promising new therapeutic approach. STUDY DESIGN: In a prospective study, 121 patients with chronic nasal obstruction were treated for inferior turbinate reduction with APC. Hyperplasia of the nasal turbinates was diagnosed rhinoscopically and endoscopically and confirmed rhinomanometrically. The mean follow-up period was 12 months, ranging from 10 to 16 months. The treatment results were evaluated by a questionnaire, rhinomanometric findings, and electron microscopic studies of the nasal mucosa. In 50 patients a ciliary function test was performed preoperatively and postoperatively. METHODS: Argon plasma coagulation, a high-frequency electrosurgery, has been used for volume reduction of the inferior turbinate in local anesthesia. RESULTS: Seventy-six percent of the patients reported an improvement of the postoperative swelling within the first week. After 6 weeks, macroscopically the turbinates were re-epithelialized by normal mucosa in 63% of the patients. Electron microscopic studies after 3 months verified normal cilia. After 12 months, 83% of the patients stated that they had a better nasal airflow than preoperatively. Crust formation was minimal. No bleeding or impaired ciliary function occurred. Ninety-five percent of the patients were willing to undergo the same operation again. CONCLUSION: The long-term results have proved APC to be an effective and easy-to-perform alternative for inferior turbinate reduction with comparable results to other established surgical methods.

High-dose intravenous paraoxon exposure does not cause organophosphate-induced delayed neuropathy (OPIDN) in mini pigs.

Organophosphorus compounds are inhibitors of serine hydrolases. Some of these compounds produce, in addition to their high acute toxicity, a more persistent effect: organophosphate-induced delayed neuropathy (OPIDN). The putative molecular entity whose inhibition is thought to be responsible for OPIDN is the neuropathy target esterase (NTE). Although in vitro NTE is resistant to paraoxon (PX), occasional case reports have associated PX with OPIDN. To assess clinically whether or not high-dose i.v. PX causes OPIDN in mini pigs, 14 mini pigs were anaesthesized, intubated and mechanically ventilated. In a first set of experiments eight pigs received 1 mg PX kg(-1) body weight (BW) dissolved in alcohol. Two control animals received alcohol in a corresponding amount. After infusion of PX, survival of the animals during the acute phase of intoxication was achieved by intensive-care support, using appropriate drugs and fluids according to a pre-established protocol. The mini pigs were extubated 1036 +/- 363 min later (mean +/- SD). The pigs were observed prior to PX application and for 6 weeks thereafter for any abnormalities and/or signs of OPIDN, such as leg weakness, ataxia and paralysis. Observations were graded on a scale for three categories (position, motor deficiency, reaction), with a maximal cumulative score of 9. In a second set of experiments (four additional pigs) larger PX doses were used (3, 9, 27 and 81 mg kg(-1) BW). After recovering from general anaesthesia/surgery, within 2 weeks all animals reached the initial score on the scale. It can be concluded that high-dose i.v. PX exposure does not induce OPIDN in mini pigs during the 6-week observation period.

Paraoxon sensitive phenylvalerate hydrolase in assessing the severity of acute paraoxon poisoning.

INTRODUCTION: Intoxications with organophosphorous compounds, especially paraoxon, are frequent. Organophosphorous compounds inhibit serine hydrolases such as acetylcholine, butyrilcholine, and carboxyl esterases although acetylcholine and butyrylcholine are too sensitive to paraoxon to be useful markers of severity. They cannot show a dose-dependent inhibition during an acute organophosphorous compounds exposure because maximal enzyme inhibition is reached at very low organophosphorous compounds concentrations. PURPOSE: To determine in vitro the dose-effect relationship between the activity of the paraoxon-sensitive phenylvalerate hydrolase, a member of the carboxvl esterases family, and the paraoxon dose, and to assess its utility as a putatively less sensitive enzyme marker to monitor the severity of an acute paraoxon intoxication. MATERIALS AND METHODS: Phenylvalerate hydrolase and butyrylcholine activities were determined in serum of nine healthy human volunteers before and after addition of different concentrations of paraoxon. The determination of phenyl-valerate hydrolase activity was carried out using a modification of the method described by Johnson. A commercially available kit was used to measure butyrylcholine activity. RESULTS: Paraoxon inhibits phenyl-valerate hydrolase activity at concentrations above 10 M. Maximal inhibition (approximately 50% of baseline) is achieved at concentrations above 2.5 x 10(-7) M. The IC50 value of paraoxon for phenyl-valerate hydrolase is 34+/-2 nM. The uninhibited phenyl-valerate hydrolase activity is due to paraoxon-resistent isoforms. Paraoxon begins inhibiting butyrylcholine activity at concentrations above 10(-9) M. At concentrations above 5 x 10(-5) M, no butyrylcholine activity is measulrable. The IC50 value of paraoxon for butyrylcholine is 150+/-23 nM. CONCLUSION: The paraoxon-sensitive subunit of phenyl-valerate hydrolase shows dose-dependent inhibition when exposed to paraoxon in vitro, but it is even more sensitive than butyrylcholine to paraoxon inhibition. Determinations of phenyl-valerate hydrolase activity to assess the severity of an acute organophosphorous compounds poisoning cannot be recommended, but phenyl-valerate hydrolase may have utility in worker surveillance.

Inverse correlation of apoptotic and angiogenic markers in squamous cell carcinoma of the head and neck.

Angiogenesis is essential for tumour growth and metastasis. The induction of tumour vascularization is mediated by the release of angiogenic peptides. Among these factors, basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) are thought to be the most important. Previous experimental studies indicate that the process of apoptosis, the programme of cell death, may be related to angiogenesis in head and neck carcinogenesis. Therefore, cryostat sections of 49 head and neck squamous cell carcinomas (HNSCC) were investigated immunohistochemically for pro-apoptotic factors caspase-3 and Fas ligand (FasL) using a standard streptavidin-biotin complex procedure. Expression of bFGF, VEGF and MMP-9 served as angiogenic markers. Additionally, intratumoral microvascular density (MVD) was counted by immunostaining of endothelial cells using anti-vWF antibody. Comparing the expression of apoptotic and angiogenic factors, a statistically significant inverse correlation of caspase-3 expression and VEGF and MMP-9 expression was found. Concerning FasL, the correlation of its expression with expression of VEGF, bFGF and MMP-9 was inversely correlated. With respect to vWF-immunostaining, statistical analysis gave a clear inverse correlation between the tumour vascularity and the expression of FasL (p = 0.0008) and caspase-3 (p = 0.0068). Our results suggest that HNSCC tumour angiogenesis contributes to a reduction of apoptosis in tumour cells. This may be explained by the activation of pro-apoptotic factors caused by hypoxia.

Pralidoxime and l-lactate effects in vitro on the inhibition of acetylcholinesterase by paraoxon: pralidoxime does not confer superior protection.

Intoxication with the organophosphorus compound paraoxon (POX), an inhibitor of serine hydrolases, is frequent. Although oximes are the only enzyme reactivators presently available, clinical experience with their use was rather disappointing. Recent work has shown that under certain conditions l-lactate is also able to reduce in vitro the POX inhibition of butyrylcholine- and acetylcholineesterase (BChE and AChE). To assess the practical relevance, if any, of these findings, the protective effects of pralidoxime (PRX) and those of lactate had to be compared in the same in vitro model. Effects of PRX on the inhibition of AChE by POX were assessed in vitro in plasma of 12 (six male and six female) healthy human volunteers. The determinations were repeated using different oxime and different POX concentrations. The AChE activity determinations were performed using the following sampler: sample BL-baseline (or untreated plasma); sample a-after addition of POX to plasma (pl + POX); sample b-after POX and plasma were incubated and then oxime was added (pl + POX/PRX); sample c-after addition of oxime to plasma (pl + PRX); sample d-after oxime and plasma were incubated and then POX was added (pl + PRX/POX); sample e-after oxime and POX were incubated and then added to plasma (PRX + POX/pl). Results were corrected for spurious enzyme 'pseudo-activity' due to interaction between PRX and substrate (acetylthiocholine) in the absence of enzyme. In the micro- and millimolar ranges, PRX is able to protect in vitro AChE from inhibition by POX when added to human plasma prior to POX or when incubated with POX prior to addition to plasma. Adding PRX to plasma after POX has no protective effect. The PRX results were compared statistically with historical lactate data (obtained under identical conditions) using the Wilcoxon matched pairs test, with significance assumed for p = 0.01. No difference between PRX and lactate's protective effect on the AChE inhibition by POX was found in the in vitro model used. We therefore conclude that in vivo testing of lactate as a POX protective agent is warranted.

[Nitinol stent implantation in benign esophagotracheal fistula]. / Nitinolstentimplantation bei benigner ösophagotrachealer Fistel.

The self-expanding nitinol stent is easy to handle and well tolerated. It offers an improved method in the treatment of perforations of the upper aerodigestive tract. It is easily implantable with rigid and flexible endoscopes. A 45-year-old female patient developed a tracheal necrosis after polytrauma and protracted intubation and ventilation. The permanent cuff pressure caused a 5-cm long fistula located at the posterior trachea 3 cm above the carina. After stabilization of the general condition and spontaneous reduction of the fistula length to 2 cm, we implanted the silicon-covered esophageal stent. Daily bronchoscopic examination was done before and after implantation of the stent. Two days after implantation, we were able to remove the blocked tracheostomy tube. Immediately oral nutrition was possible without complications. Because of its easy and fast application without any complications, the new type of nitinol stent is a promising alternative for ear, nose, and throat patients in bad general condition to provide fast and safe treatment in benign tracheoesophageal fistulas.

[Emergency tracheotomy in Göttingen minipigs. Comparison: standard technique versus Nu-Trake cricothyrotomy set]. / Nottracheotomie bei Göttinger Miniaturschweinen. Vergleich: Konventionelle Technik gegenüber Nu-Trake Koniotomie Set.

STUDY OBJECTIVE: To compare the time required, success rate and complication rate of the standard surgical approach for cricothyrotomy versus a prepacked kit in regard to the experience of the surgeon. METHODS: The cricothyrotomies were performed in Goettingen mini-pigs (n = 14) under general anaesthesia. 7 different surgeons (2 Otorhinolaryngologists, 2 Emergency Physicians, 3 medical students) used each technique (standard surgical approach and Nu-Trake device) once to perform the cricothyrotomy without prior practice. RESULTS: The fastest time to do the cricothyrotomy with Nu-Trake was 40 s, the slowest 93 s and the mean time of all 7 surgeons was 58 +/- 18 s. Using the standard approach it took 42 s up to 154 s until ventilation with a mean time of 106 +/- 48 s. The use of Nu-Trake was significantly faster than the standard surgical approach (p < 0.05, t-test). Otorhinolaryngologists were quicker using the standard technique (46 s versus 58 s with Nu-Trake), whereas each surgeon of the other two groups (emergency physicians and medical students) was quicker with the Nu-Trake Set (58 +/- 21 s) than with the conventional method (135 +/- 18 s). The number of complications was similar with both methods, but a difference was detected in the type and severity of the complication: An injury of the posterior tracheal wall was observed twice with Nu-Trake. CONCLUSIONS: Experienced personnel should maintain the standard surgical approach for cricothyrotomy. Inexperienced personnel can use the Nu-Trake device which was found to be quicker as it facilitates the procedure, but causes more severe complications. We recommend to practise cricothyrotomy regularly in human cadavers, in the animal model if possible or on mannequins to be sufficiently trained in advanced airway management.

Expression of 92-kDa type IV collagenase correlates with angiogenic markers and poor survival in head and neck squamous cell carcinoma.

MMP-9, which degrades extracellular matrix, is believed to play a crucial role in tumor invasion and metastasis. Angiogenesis is also perceived as an important step in tumor growth and metastasis. The aim of this study was to investigate the expression of MMP-9 in tumor samples of HNSCC patients and to study a possible correlation to angiogenic markers. Cryostat sections of 52 HNSCC tumors were immunostained for MMP-9, bFGF and VEGF using a standard streptavidin-biotin complex procedure for light microscopic investigation. Microvessel density (MVD) was determined by staining of endothelial cells immunohistochemically using anti-vWF monoclonal antibody. MMP-9 positive staining was detected in 27/52 (52%) of the tumors. MMP-9 immunoreactivity did not correlate with the main clinicopathological characteristics of the patients (localisation, T-stage, N-stage, histological grading), but correlated with worse survival of the patients. MMP-9 negative tumors showed a significant lower mean MVD per microscopic field than MMP-9 positive tumors (p<0. 001). There was a significant association of MMP-9 and VEGF expression (p<0.05). The presence of MMP-9 in HNSCC cancer and the positive correlation with MVD and VEGF expression supports the theory that MMP-9 functions as a regulator of tumor angiogenesis supporting endothelial cell invasion. MMP-9 and VEGF might act co-operatively in the process of neovascularization in human head and neck cancer.

Argon plasma coagulation for inferior turbinate reduction.

Surgical reduction of the inferior turbinate remains a widely used therapy for nasal obstruction caused by hyperplastic turbinates. Current methods are costly and time-consuming, require nasal packing, and cause extended postoperative swelling. Argon plasma coagulation (APC) is a new, innovative technique in otorhinolaryngological surgery that is based on high-frequency electrical current. The current is transmitted through ionized argon gas (plasma) contact-free to the tissue surface and creates a coagulation and devitalization zone with limited penetration. Forty-five patients with nasal obstruction were treated under local anesthesia for reduction of the inferior turbinates with APC. Seventy-six percent of the patients reported an improvement of postoperative swelling within the first week. After 3 months, 86% reported having better nasal airflow than they had before the operation. Macroscopically, after 4 weeks the turbinate was covered by normal mucosa in 51% of the patients. Crust formation was minimal, and no bleeding occurred. Turbinate reduction with APC is an alternative technique with many advantages, and the results are comparable to those of standard techniques. Ninety-five percent of the patients were satisfied with the operation.

Serum levels of vascular endothelial growth factor in patients with head and neck cancer.

Angiogenesis is now considered to be crucial for tumor growth and metastasis. In several tumors, microvascular density has been shown to be correlated with metastasis and aggressiveness. Vascular endothelial growth factor (VEGF) is a secreted endothelial cell-specific mitogen, which is induced by hypoxia and is angiogenic in vivo. VEGF has been identified in a wide variety of malignancies including head and neck squamous cell carcinomas (HNSCC). We investigated the circulating level of VEGF in sera from patients with various head and neck squamous cell carcinomas (n = 71) as well as from healthy normal controls (n = 47). Serum VEGF concentrations were determined as serum immunoreactivity by using a quantitative sandwich enzyme immunoassay technique. For statistical analysis, the Wilcoxon 2-sample test and Kruskal-Wallis test were performed. The majority of the patients with HNSCC were found to have high concentrations of serum VEGE The levels of VEGF in the sera of patients with cancer ranged from below the detection limit to 937.1 pg/ml (mean, 144.5 pg/ml). In contrast, the VEGF serum levels in 47 healthy individuals ranged from below the detection limit to 168.1 pg/ml (mean, 32.7 pg/ml), VEGF serum concentration being significantly higher in HNSCC patients (P = < 0.001). These findings indicate that a positive angiogenesis regulator such as VEGF might function as an endocrine growth factor, particularly for solid HNSCC tumors and may be a useful marker for clinical monitoring.

Current advances in the basic research and clinical management of juvenile-onset recurrent respiratory papillomatosis.

Juvenile-onset recurrent respiratory papillomatosis is a relatively uncommon disease that presents clinically with symptoms ranging from hoarseness to severe dyspnea. Human papilloma viruses type 6 and 11 are important in the etiology of the papillomata and are most probably transmitted from mother to child during childbirth. Although spontaneous remission is frequent, a rare fatal course because of pulmonary spread or malignant transformation has occurred. CO2 laser evaporation of papillomas and adjuvant drug therapy using lymphoblastoid alpha-interferon are the most common treatment modalities at present. However, several other treatment modalities have been tried with varying success. Recent advances in basic research and different therapeutic approaches are reviewed.

L-lactate protects in vitro acetylcholinesterase (AChE) from inhibition by paraoxon (E 600).

Intoxication with the organophosphorus compound paraoxon (POX), an inhibitor of serine hydrolases, is frequent. Oximes are the only enzyme reactivators clinically available. Recent work has shown that lactate is able to reduce in vitro the POX effects on butyrylcholinesterase (BChE). Most of the acute clinical symptoms, however, are caused by inhibition of acetylcholinesterase (AChE). Effects of lactate on the inhibition of AChE by POX were assessed in vitro in plasma of 12 (six male, six female) healthy human volunteers. The determinations were repeated using different lactate and different POX concentrations. The AChE activity determinations were performed in the following settings: (BL) baseline (untreated plasma); (a) after addition of POX to plasma (pl + POX); (b) after POX and plasma were incubated and then lactate was added (pl + POX/lact); (c) after addition of lactate to plasma (pl + lact); (d) after lactate and plasma were incubated and then POX was added (pl + lact/POX); (e) after lactate and POX were incubated and then added to plasma (lact + POX/pl). In the micro- and millimolar ranges, lactate is able to protect in vitro AChE from inhibition by POX when added to human plasma prior to POX or when incubated with POX prior to addition to plasma. Lactate added to plasma after POX has no protective effect. In a second set of experiments, the effect of lactate on AChE activity was determined. At high millimolar concentrations, lactate itself inhibits AChE non-competitively (mixed inhibition) to an extent comparable to POX (inhibition constant K(I) = 254 mM).

Characterization of the expanded T cell population in infectious mononucleosis: apoptosis, expression of apoptosis-related genes, and Epstein-Barr virus (EBV) status.

Infectious mononucleosis (IM), a manifestation of primary infection with EBV, is characterized by a massive expansion of the T cell population. In this study we examined this expanded T cell population regarding its EBV status, its proliferative and apoptotic activity, and its expression of apoptosis-related genes. Whereas previous studies were performed on ex vivo cultures or on peripheral blood, our investigations included in vivo analysis of IM tonsillectomy specimens (14 cases) by in situ hybridization for viral RNA (EBERs) combined with immunohistochemistry (IHC; CD3, CD45RO, CD20, CD79a, Ki-67, Bcl-2, Bax, Fas, FasL) and the TUNEL method. Of the EBER+ cells 50-70% showed expression of the B cell markers CD20/CD79a. The remainder of the EBER+ cells expressed neither B nor T cell antigens. No co-expression of EBERs and T cell antigens was detected in any of the specimens. In accordance with a high rate of apoptosis (up to 2.37%) within the expanded T cell population, Bcl-2 expression was drastically reduced and FasL expression remarkably increased. The levels of Bax and Fas expression showed no or moderate up-regulation. In conclusion, the massive expansion of IM T cells is not caused by EBV infection of these cells but merely represents an intense immune reaction. Through altered expression of Bcl-2/Bax and Fas/FasL, the activated T cells are subject to enhanced apoptosis while residing within the lymphoid tissue, which eventually allows the efficient silencing of this potentially damaging T cell response.