Snoring noise pollution--the need for objective quantification of annoyance, regulatory guidelines and mandatory therapy for snoring.

Habitual snoring without episodes of apnea or hypoventilation and without respiratory related arousals is considered to be annoying and without any need for treatment. However, studies seem to suggest an enormous psychosocial impact of annoyance for the bed partner. Apart from subjective questionnaires there still exists no generally accepted mode of measurement that can describe snoring objectively. We therefore adapted methods developed for environmental medicine and established a new snore score using psycho-acoustic parameters. For quantification of snoring noise we conducted nocturnal measurements in 19 habitual snorers. Free-field snore sounds were acquired with two low-cost non-contact microphones and transferred to a PC (sampling frequency 11 kHz). The data were recorded, analysed and stored automatically using a MATLAB script. Following the analysis of sound characteristics and levels, the score was computed from relevant parameters containing the rating level (L(R)), maximum level, two percentile levels for frequent maxima (L(5)S; L(1)) and snoring time. The determined values substantially exceeded the prescribed limits defined by WHO noise guidelines, and mainly affected the equivalent continuous sound exposure level, rating level and the immission standard values of brief noise peaks, whose maximum was exceeded by up to 32 dB(A). The Berlin snore score illustrated the objective acoustic annoyance on a scale from 0 to 100. It allows inter-individual comparison and objectifies the need for therapy. The clinical applicability of evaluating the reduction of snoring after surgical therapy is discussed exemplarily. The presented measuring method was found to be suitable for quantifying snoring noise and can be easily integrated into existing polysomnographic applications. In the case of habitual snoring with objective evidence of psychosocially disturbing acoustic annoyance, health fund providers should assume the costs of mandatory medical therapy.

[Integrated intensive treatment of tinnitus: method and initial results]. / Integrierte Tinnitusintensivbehandlung: Konzept und erste praktische Erfahrungen.

In recent years, no major advances have been made in understanding the mechanisms underlying the development of tinnitus. Hence, the present therapeutic strategies aim at decoupling the subconscious from the perception of tinnitus. Mindful of the lessons drawn from existing tinnitus retraining and desensitisation therapies, a new integrated day hospital strategy of treatment lasting 7-14 days has been developed at the Charité Hospital and is presented in the present paper. The strategy for treating tinnitus in the proximity of patient domicile is designed for patients who feel disturbed in their world of perception and their efficiency due to tinnitus and give evidence of mental and physical strain. In view of the etiologically non-uniform and multiple events connected with tinnitus, consideration was also given to the fact that somatic and psychosocial factors are equally involved. Therefore, therapy should aim at diagnosing and therapeutically influencing those psychosocial factors that reduce the hearing impression to such an extent that the affected persons suffer from strain. The first results of therapy-dependent changes of 46 patients suffering from chronic tinnitus are presented. The data were evaluated before and after 7 days of treatment and 6 months after the end of treatment. Immediately after the treatment, the scores of both the tinnitus questionnaire (Goebel and Hiller) and the subscales improved significantly. These results were maintained during the 6-month post-treatment period and even improved.

Combined intratumor cisplatinum injection and Nd:YAG laser therapy.

OBJECTIVES/HYPOTHESIS: Interstitial laser therapy (ILT) has become useful for tumor palliation in patients with advanced head and neck cancer. Cisplatinum chemotherapy also is a frequent adjuvant treatment for recurrent tumors, but systemic toxicity limits application. Intratumor cisplatinum injection combined with ILT may improve therapy of these recurrent tumors with reduced toxicity. STUDY DESIGN: Prospective. Tumor transplants were injected with cisplatinum in a gel implant before ILT to evaluate treatment response and toxicity in a preclinical study. METHODS: UCLA-P3 human squamous cell carcinoma tumors were grown as subcutaneous transplants in nude mice and treated by intratumor injection of 2 mg/mL cisplatinum in a slow-release, collagen-based gel carrier 4 hours before interstitial implantation of Nd:YAG laser fiberoptics to induce local tumor hyperthermia. Treatment efficacy and toxicity were followed for 12 weeks after combined drug and laser therapy compared with ILT alone. RESULTS: Combined cisplatinum gel and ILT was a significant improvement (P < .01 by chi-square test) and induced 57% complete responses without regrowth in 21 transplanted tumors compared with only 24% in 21 tumors after ILT alone during 12-week follow-up. Recurrences in both cases appeared to result from nonuniform laser energy delivery within tumors via the implanted fiberoptic tip. CONCLUSIONS: The results of this experimental combined cisplatinum and ILT study suggest it may be possible to improve treatment of advanced head and neck cancer by intratumor injection of gel implants containing the drug followed by interstitial Nd:YAG laser hyperthermia.

Experimental studies on the suitability of the erbium laser for stapedotomy in an animal model.

Animal experiments in mature guinea pigs were devised to determine whether and to what extent inner ear damage can be caused by in vivo use of the erbium laser for stapedotomy. The present study examined the laser effect in connection with perforation of the basal convolution of the cochlea and subsequent application in the opened cochlea. Acoustic evoked potentials as compound action potentials (CAP) were recorded for changes in inner ear function. Findings demonstrated that five applications of the erbium:YSGG (yttrium-scandium-gallium-garnet) laser (energy, 85 mJ/pulse; energy density, 36 J/cm2) were needed to create a footplate perforation of 500-600 microns and did not lead to CAP alteration in any animal (n = 20). An increase of the repetition rate from 1 to 5 Hz likewise caused no CAP alteration (n = 17). Application of high total energies in the open cochlea (n = 5) to determine the safety of the laser system for stapedotomy revealed that a 10-fold increase in the total energy required for adequate perforation led to irreversible CAP alterations and no CAP could be recorded at a 15-fold increase in total energy. In contrast, a 5-fold maximum increase in total energy caused no CAP alterations. These results demonstrate the safety of the Er:YSGG laser comparable to that of the CO2 laser for stapedotomy, supporting its utility as an alternative method for surgery.

Chemical modification of prostaglandin endoperoxide synthase by N-acetylimidazole. Effect on enzymic activities and EPR spectroscopic properties.

Prostaglandin H synthase apoprotein, without its prosthetic heme group, was inactivated by N-acetylimidazole under conditions typical for the O-acetylation of tyrosyl residues. A spontaneous reactivation occurred above pH 7.5 at 22 degrees C, which indicated spontaneous hydrolysis of acetylated residues. Below pH 7.5, where stable inactivation was observed, reactivation was achieved by reaction with hydroxylamine. Both enzymic activities of prostaglandin H synthase, cyclooxygenase and peroxidase, were inactivated and reactivated simultaneously and to the same extent. In contrast to the apoprotein, the holoenzyme with heme was not inactivated by N-acetylimidazole. The number of acetyl groups, as determined as hydroxamate after the reaction with hydroxylamine at pH 8.2, was 2.5 +/- 0.4 for the apoprotein and 1.0 +/- 0.24 for the holoenzyme. The specific binding of heme as the prosthetic group was no longer observed by EPR (signals at g = 6.7 and 5.3) when hemin was added to the N-acetylimidazole-reacted apoprotein. Treatment of N-acetylimidazole-reacted apoprotein with hydroxylamine restored the specific binding of heme. The N-acetylimidazole-reacted apoprotein supplemented with hemin and reacted with hydroperoxides, neither showed electronic absorption spectra of higher oxidation states nor an EPR doublet signal due to a tyrosyl radical. These results demonstrate that heme protects against the inactivating modification by N-acetylimidazole and that this modification prevents binding of the prosthetic heme group necessary for both enzymic activities. The absence of the prosthetic heme group explains the concomitant loss of cyclooxygenase and peroxidase activities, as well as the absence of higher oxidation states and the tyrosyl radical. We suggest that the acetylation of a residue in the heme pocket, most probably a tyrosine, although a histidine cannot be definitely disproved, exerts the inhibiting effects. This residue could be the axial ligand of the heme or in close contact to the heme. The results also show that the inhibition by N-acetylimidazole does not involve the acetylation of Ser530 which causes the inhibition by acetylsalicylic acid of cyclooxygenase. [The numbering of amino acids in ovine prostaglandin H synthase is according to DeWitt, D. L. and Smith, W. L. (1988) Proc. Natl Acad. Sci. USA 85, 1412-1416 including a signal peptide of 24 residues which is missing in the processed protein.

31P nuclear magnetic resonance spectroscopy, histology and cytokinetics of a xenografted hypopharynx carcinoma following treatment with cisplatin: comparison in three sublines with increasing resistance.

The changes in the phosphorus metabolism of a xenografted hypopharynx carcinoma (Hyp 1), sensitive to cisplatin (CDDP), were compared to those occurring in two sublines of the tumour, characterised by moderate or high resistance to CDDP (Hyp 1/H and Hyp 1/R) following, i.p. administration of 4, 8 or 12 mg CDDP/kg-1. The investigations were performed by in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. Parallel to the NMR experiments, the cytokinetic and histological alterations in the tumours were studied under the same experimental conditions. No mentionable differences in the levels of the main phosphorus-containing metabolites could be detected between the three tumour lines before treatment. Following application of CDDP, the alterations in the NMR spectra were clearly related to the degree of tumour response. The most sensitive and earliest marker of tumour regression was a decrease in the phosphomonoester/phosphodiester ratio, parallelled by a gradual increase in the phosphocreatine/inorganic phosphorus quotient. In the resistant tumour lines Hyp 1/H and Hyp 1/R non-responding tumours showed alterations in the 31P NMR spectrum which were similar to those observed during uninfluenced tumour growth. Marked changes in the 31P NMR spectrum were always associated with severe cytotoxic lesions following therapy. The results suggest that the changes detected by 31P NMR spectroscopy following chemotherapy with CDDP are response-specific.

The anti-motion sickness mechanism of ginger. A comparative study with placebo and dimenhydrinate.

A controlled, double-blind study was carried out to determine whether nystagmus response to optokinetic or vestibular stimuli might be altered by some agent contained in powdered ginger root (Zingiber officinale). For comparative purposes, the test subjects were examined after medication with ginger root, placebo and with dimenhydrinate. Eye movements were recorded using standard ENG equipment and evaluation was performed by automatic nystagmus analysis. It could be demonstrated that the effect of ginger root did not differ from that found at baseline, or with placebo, i.e. it had no influence on the experimentally induced nystagmus. Dimenhydrinate, on the other hand, was found to cause a reduction in the nystagmus response to caloric, rotatory and optokinetic stimuli. From the present study it can be concluded that neither the vestibular nor the oculomotor system, both of which are of decisive importance in the occurrence of motion sickness, are influenced by ginger. A CNS mechanism, which is characteristic of the conventional anti-motion sickness drugs, can thus be excluded as regards ginger root. It is more likely that any reduction of motion-sickness symptoms derives from the influence of the ginger root agents on the gastric system.