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OBJECTIVE: To assess the efficacy and safety of the dopamine agonist cabergoline in the treatment of patients with idiopathic restless legs syndrome (CATOR study). METHODS: Patients with moderate to severe restless legs syndrome (RLS) were randomly assigned to cabergoline (single evening dose: 2 mg) or placebo and treated for 5 weeks in a double-blind, multicenter polysomnography (PSG) trial. The primary efficacy measures were the periodic leg movements during sleep arousal index (PLMS-AI) and sleep efficiency. These and further PSG variables were monitored by centrally evaluated PSG. Severity of RLS was assessed using the International RLS Study Group Severity Scale (IRLS), the RLS-6 scales, the Sleep Questionnaire Form A (SF-A; quality of sleep), and the Quality of Life for RLS questionnaire. RESULTS: Forty-three patients were treated and 40 patients were evaluated with PSG (age 56 +/- 10 years, 73% women). Cabergoline was superior to placebo in terms of the PLMS-AI (-17.7 +/- 16.4 vs -4.5 +/- 20.0 placebo; p = 0.0024), sleep efficiency (+6.2 +/- 13.9% vs +3.3 +/- 11.7%; p = 0.0443), PLMS index (p = 0.0014), PLM index (p = 0.0012), and total sleep time (p = 0.0443). Improvements in IRLS total score (-23.7 +/- 11.2 vs -7.9 +/- 11.0 placebo; p = 0.0002), RLS-6 severity scales during the night (p = 0.0010) and during the day (p = 0.0018), Clinical Global Impressions severity item (p = 0.0003), sleep quality (p = 0.0180), SF-A sleep quality (p = 0.0371), and QoL-RLS (p = 0.0247) were larger in patients treated with cabergoline compared with the placebo group. Adverse events were only mild and well-known side effects of dopamine agonists. CONCLUSION: Single-evening cabergoline is an efficacious and well-tolerated short-term therapy for sensorimotor symptoms of restless legs syndrome and associated sleep disturbances.

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Low-temperature photolysis of phenyldiazirine, incarcerated inside a hemicarcerand which is built from two cavitands connected by four butane-1,4-dioxy linker groups, yields transient phenylcarbene; this carbene then undergoes ring photochemical expansion to cycloheptatetraene in low yield. Competitively, the transiently formed phenylcarbene reacts with the surrounding hemicarcerand. The yield of the photochemical ring expansion was increased when the photolysis was carried out inside a partially deuterated hemicarcerand. Two insertion products resulting from an intramolecular phenylcarbene insertion into an acetal C-H(D) bond or an alpha-C-H bond of a butane-1,4-dioxy linker group have been isolated and characterized. The measured isotope effect for insertion into an acetal C-H(D) bond at 15.5 K is consistent with a reaction of singlet phenylcarbene. Incarcerated cycloheptatetraene is stable for a limited time at 100 degrees C and almost infinitely stable at room temperature in the absence of oxygen. NOESY experiments provide the distance ratio r21/r23 = 1.134 +/- 0.01 between protons H1-H2 and H2-H3 of cycloheptatetraene which is consistent with its twisted structure. Low-temperature photolysis of phenyldiazirine, incarcerated inside a chiral hemicarcerand which is built from two cavitands connected with three butane-1,4-dioxy and one (S,S)-2,3-O-isopropylidene-2,3-dihydroxybutane-1,4-dioxy linker group yields two diastereomeric cycloheptatetraene hemicarceplexes in a 2:3 ratio (30% total yield). Variable temperature 1H NMR studies provided a lower limit of deltaG++ = 19.6 kcalmol(-1) for the enantiomerization barrier of cycloheptatetraene. Incarcerated cycloheptatetraene reacts rapidly with oxygen to yield benzene and carbon dioxide via the 1,2-dioxaspiro[2,6]nona-4,6,8-triene intermediate. Different mechanisms for the formation of this spirodioxirane intermediate are discussed based on the measured rate of the oxygen addition. The activation parameters for the decarboxylation of the spirodioxirane have been measured in different bulk solvents. The free energy of activation shows very little solvent dependency. However. a strong propensity for enthalpy-entropy compensation due to a solvent reorganization that accompanies the reaction coordinate is observed.

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Since Donald J. Cram's first synthesis of a carcerand, which permanently entrapped a single guest molecule, many other carcerands and hemicarcerands have been synthesized and studied. Slowly, we begin to understand the role of the template in the formation of hemicarceplexes and carceplexes, why some hemicarceplexes are more stable than others, and how guests enter and exit the inner phases of molecular containers. In this Account we discuss our new insight in the chemistry of molecular containers, as well as recent highlights in through-shell chemistry and in the inner-phase stabilization of reactive intermediates.

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The sleep apnea syndrome is often associated with the syndromes of daytime exhaustion and involuntary daytime sleeping fits. The cause is assumed to be fragmentary sleep resulting from night-time arousal. The central nervous activation reactions caused by apnea or hypopnea, respectively, and not the movement arousal determine the sleep structure. We have examined 10 male patients in the age range 40-55 years (48 +/- 6 SD) before and during the first 3 nights of CPAP therapy. Cardiorespiratory polysomnography was performed in all four nights. Sleep way analyzed visually and differentiation was made between respiratory (RA) and movement arousal (MA). All 10 patients had a pronounced sleep apnea syndrome. Deep and dream sleep were reduced, significantly more respiratory arousals occurred than movement arousals. The SWS latency was shortened in the first therapy night, the deep and dream sleep proportions increased and the RA decreased significantly. No further significant changes in the sleep parameters occurred during the second and third nights. We found that the number of apnea/hypopnea was not equal to the number of RA. When less arousal was recognized it was suggestive of a deficit of the diversion function while more RA was indicative of additional respiratory events, e.g. pharyngeal obstructions and hyperventilations which were not recognized as apnea or hypopnea. In addition to its role in the differential diagnosis of sleeping disorders, in particular sleep apnea, arousal differentiation is also an important criterion for estimating the efficiency of CPAP therapy.

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Obstructive snoring belongs to the sleep-related breathing disorders. The characteristics of this disorder is described, following the case report about two young snorers, complaining of excessive day-time sleepiness, involuntary falling asleep in monotoneous situations. Ambulatory monitoring using the four-channel system MESAM-IV showed a Respiratory Disturbance Index of < 5 during a predominantly continuous snoring episode without significant drops in oxygen saturation. Clinical cardio-respiratoric polysomnographic monitoring showed a normal architecture of sleep interrupted by respiratory arousals. Under nasal CPAP treatment these arousals, as well as the complained excessive daytime sleepiness disappeared. The latter fact becomes evident, when comparing the sleep latencies before therapy to those under CPAP-treatment, estimated by the Multiple Sleep Latency Test (MSLT). Thus, this therapy proved to be very effective in patients suffering from obstructive snoring.

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The therapeutical strategy of the obstructive sleep apnoea syndrome depends on the differential diagnosis of the sleep disorder, the subjective complaints and the patients' individual cardiopulmonary risk profile. Basic requirements for a successful treatment are stepped concepts for therapy. Initial therapeutical methods are preventive measures such as adequate sleep hygiene, weight loss, and reduction of alcoholic intake. We investigated the effectiveness of following therapeutical methods: drug treatment, nasal CPAP therapy and surgical approach. We present the results of the first 151 treated patients aged between 15 and 88 years (mean: 50.8 +/- 11.5 SD). 20 patients with an apnoea index below 20 per hour were treated with theophylline. After 4 weeks with theophylline there were no significant changes in apnoea index, O2 saturation and snoring level. 24 patients themselves preferred the Uvulopalatopharyngoplasty (UPPP). 8 weeks after surgical approach we couldn't find significant changes in the apnoea index although 11 of these patients reported on a better sleep quality. 107 patients were treated with nasal CPAP. The effective CPAP pressures were between 6 and 14.5 mbar. Long term compliance with CPAP was studied in a survey of 70 patients who underwent a CPAP trial. After 6 months 97% were complaint, 17% of them additionally were using a humidifier. Our data show that effective therapy can be achieved with nCPAP objectively and subjectively. Other methods--theophylline and UPPP--are less successful. CPAP is likely to remain the first choice for treatment of sleep related breathing disorders and it should be applied more generously.

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The outpatient measurement with the ME-SAM IC system, including the analysis of heart rate, respiration sounds, continuous oxygen saturation and body position, is an important part in a stepped concept for diagnosis and therapy of patients with an obstructive sleep apnea syndrome (OSAS). We investigated the importance of these parameters as well as age and Broca in relation to the continuous positive airway pressure determined in the sleep laboratory. In this study we present the first 60 patients (56 m, 4 f) treated successfully with nCPAP. The mean age was 53.1 +/- 8.6 years, the Broca Index 133.6 +/- 22.9, the respiratory disturbance index (RDI, apnea + hypopnea index) 48.1 +/- 22.7, the mean nocturnal oxygen saturation 90.4 +/- 3.8% and the mean minimal oxygen saturation 84.4 +/- 4.2%. We found positive significant correlation between Broca, RDI and oxygen saturation as well as between Broca and age. The mean effective continuous positive airway pressure was 9.7 +/- 2.1 cm H2O in our group of OSAS patients. With an increase in RDI and with a decrease in age and oxygen saturation we found an significant increase in the effective continuous positive airway pressure. A positive correlation between Broca and air pressure could be seen, but was not significant. Our data show that there is a strong correlation between constitution, the outpatient measurement with MESAM-system and the effective positive airway pressure in patients with a pronounced obstructive sleep apnea syndrome (RDI > 15 and marked clinical symptoms). The knowledge about these relationships should be considered in the nCPAP therapy and during the long term medical care of treated patients.

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Equilibrium binding studies have been carried out by spectrofluorometric precision titrations on FITC-Na,K-ATPase and employing the styryl dye RH-421 to obtain equilibrium constants and stoichiometric coefficients together with information related to competition between different binding equilibria. A new interpretation concerning the assignment of spectral properties and cation complex formation equilibria, as well as the involvement of conformational transitions, is suggested, based on a differentiation between selective and unselective alkali ion binding. The kinetics of K+ binding to the FITC-enzyme have been studied by employing a new microvolume technique consisting of flash photolysis of caged-K+.

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