Pigs are not a reliable experimental model in the study of the haemodynamic and respiratory effects of CO2 pneumoperitoneum.

BACKGROUND: Haemodynamic and respiratory effects of a CO2 pneumoperitoneum (intra-abdominal pressure = 12 mmHg) associated to a head-up position(15 degrees ) were studied in 20 pigs using a Swan-Ganz catheter and the Single Breath Test for CO2. The pneumoperitoneum induced a moderate rise in mean arterial pressure (+17%) (P<0.001) without any variation in heart rate, cardiac output and systemic vascular resistances. RESULTS: The following respiratory effects were observed: an increase in PaCO2 (+20%) (P<0.001), PE'CO2 (+31%) (P<0.001), expired volume of CO2 (+28%) (P<0.001), arterial to end-tidal CO2 gradient (+80%) (P<0.001) and alveolar dead space (+40%) (P<0.001) occured. Alveolar ventilation remained stable. Finally and contrary to healthy human patient, intraperitoneal CO2 insufflation in pig induced slight haemodynamic changes and major respiratory modifications. CONCLUSION: Thus, our data do not support the conclusion that the pig is a reliable experimental model for studying the pathophysiology of CO2 pneumoperitoneum-induced changes in haemodynamic and respiratory parameters, in human patients.

Continuous versus non-nightly use of zolpidem in chronic insomnia: results of a large-scale, double-blind, randomized, outpatient study.

New treatment strategies are encouraged in insomnia and, in particular, discontinuous treatment. The aim of this double-blind study was to compare, in a large primary care population of chronic insomniacs (> 4 weeks duration) the efficacy and safety of zolpidem 10 mg 5 nights/week and placebo 2 nights/week, to that of nightly zolpidem. Seven hundred and eighty-nine drug-free insomniacs, with a Total Sleep Time (TST) of 3-6 h/night were enrolled in seven European countries. After a placebo run-in period, treatment lasted 14 days. The primary criterion was the Clinical Global Impression improvement score (CGI-II) which showed that 65.2% of patients in the continuous and 58.6% in the discontinuous groups were rated 'much' or 'very much' improved. Even though the non-inferiority test did not show the equivalence of both regimens, the difference of 7% in responder rates does not appear to be clinically relevant. Other sleep parameters such as TST, number of nocturnal awakenings and Quality of Life scales showed marked, not significantly different, improvements in both groups. Both regimens were well tolerated and no adverse event which could be related to non-treatment nights was reported in the discontinuous group. Non-nightly zolpidem appears to be a feasible and safe additional option for the management of chronic insomnia.

The use of actigraphy revised: the value for clinical practice in insomnia.

In the last years, actigraphy has been used more often for clinical research and research evaluation of sleep disorders. Compared to polysomnography, actigraphy is cheap and less time-consuming. Actigraphy provides more objective information about sleep than sleep logs. Although the algorithms to score sleep and wake based on motions measured by actigraphy are still being improved, we believe that the role of actigraphy in the clinical evaluation of sleep in insomnia is limited. Instead of using actigraphy to distinguish a wakeful state from sleep in insomnia, we might better use the activity plots which the actigraph provides to get more insight into the physiological hyperarousal or restfulness of insomnia patients.

[Anti-allergy therapy in children]. / Les thérapeutiques anti-allergiques chez l'enfant.

The discovery of the physiopathological mechanisms of asthma and the diseases of allergy has allowed the development of many symptomatic therapeutical perspectives. We review below the mechanisms of actions, routes of administration, secondary effects, dosages and indications for different commercialised anti-allergy medications. A better understanding of the pharmacology of the different medications should produce optimisation of the treatment of the allergic child.

Evaluation for sleep apnea in patients with Ehlers-Danlos syndrome and Marfan: a questionnaire study.

Sleep complaints are frequently reported by patients with Marfan and Ehlers-Danlos syndrome (EDS). We examined the exact nature of sleep complaints in these patients. A representative sample of Marfan and EDS patients responded to a general sleep questionnaire, including the Epworth Sleepiness Scale (ESS) and the Medical Outcomes Study Short-Form 36 (SF-36) health-related quality of life (QOL) questionnaire. Fifteen Marfan patients and 9 EDS patients were evaluated and compared to 24 healthy controls, matched for age, sex and body mass index. Maintaining sleep was frequently disturbed in Marfan (40%, p < 0.04) as well as in EDS patients (56%, p < 0.01). Sleep apnea was exclusively reported by Marfan patients (27%, p = 0.03). Periodic limb movements were much more reported in EDS (67%, p = 0.02) than in Marfan (27%, p = 0.25) compared to controls (8%). Pain and back complaints were highly presented in both groups, but most pronounced in EDS patients (47% in Marfan versus 77% in EDS). No differences for the scores in the ESS were found. For all SF-36 questionnaire items, scores were much lower in patient groups, except for emotional problems. We found that sleep complaints were not rare in Marfan and EDS patients and correlated well with different QOL items. Our study calls for greater attention to the presence of apnea, pain and periodic limb movements in these patients.

[Gammahydroxybutyrate must remain available for patients with narcolepsy]. / Gammahydroxyboterzuur dient beschikbaar te blijven voor patiënten met narcolepsie.

There is growing public concern about the use of gamma-hydroxybutyrate (GHB) as a party drug. This justified concern about misuse, however, should not lead to prohibition of the drug as it is efficacious in narcolepsy.

Zolpidem, a valuable alternative to benzodiazepine hypnotics for chronic insomnia?

Sleep quality and anxiety levels were examined using questionnaires and polysomnographic recordings in 22 chronic insomnia patients who regularly used benzodiazepines to treat their sleeping problems. After abruptly discontinuing their benzodiazepine medication, patients were randomly allocated to receive either a placebo or zolpidem 10 mg for 1 week, after which they entered an open extension phase, receiving zolpidem 10 mg for 3 weeks. Subjectively, sleep quality was considered mediocre during the use of a benzodiazepine hypnotic. One week after the discontinuation, an increase in sleep latency was observed in the placebo group, whereas zolpidem induced a significant decrease in sleep latency. Deterioration of other sleep variables (probably rebound) was not suppressed by zolpidem. An explanation for this could be the selective pharmacological profile of zolpidem. Polysomnographic differences between placebo and benzodiazepine and between placebo and zolpidem were not reflected by the subjective data on sleep and anxiety. Changes of sleep structure caused by hypnotics seem not always to be felt as such by patients. After 3-4 weeks of zolpidem treatment, the percentage of non-rapid eye movement-4 sleep increased significantly, corresponding with a significant subjective improvement of sleep quality. This indicates that zolpidem may restore physiological sleep.

K-complexes: are they signs of arousal or sleep protective?

The number of K-complexes recorded at the central-temporal EEG derivation (C3-T3) during 5 min periods for both the ascending and descending phase of Stage 2 of NREM sleep for cycles 1, 2. etc. were counted in 10 subjects for each of the following five groups: normal persons, patients with a primary generalized form of epilepsy, narcolepsy, insomnia and obstructive sleep apnoea. The differences in time spent in different stages of sleep were as expected for these types of patients. A 2-within, 1-between factors, repeated measure ANOVA was applied to the data on K-complexes. Overall, there was no significant difference between the number of K-complexes observed during the ascending and descending phases of the different sleep cycles. Patients with a sleep disorder had significantly less well-defined K-complexes than the normals and the patients with a primary form of generalized epilepsy: for insomnia (P = 0.035), for apnoea (P = 0.011) and for narcolepsy (P = 0.001). There was a significant, but very low correlation coefficient between the number of K-complexes observed during Stage 2 of NREM sleep and the time spent during that stage for all groups combined (Rho 0.27, P = 0.002) and for the narcoleptic patients (Rho 0.44, P = 0.017). In all, the findings lend support to the hypothesis that a K-complex can be seen as a 'defensive response', or has a sleep protective function.

Septo-optic dysplasia.

The authors present three patients with the diagnosis of septo-optic dysplasia or 'de Morsier' syndrome. They stress the important role of the ophthalmologist in the diagnosis. With the advent of MRI, subtle central nervous system abnormalities have been recognized. A close ophthalmological and endocrinological follow-up is necessary.

Is "poor sleep" too vague a concept for rational treatment?

Poor sleep is a common complaint, accounting for 4-5% of all general practitioner consultations. Disorders of initiating sleep are overrated by patients compared with disorders of maintaining sleep, despite the greater effect of the latter on daytime performance. There is frequently a discrepancy between subjective observations and objective measurements of sleep. General practitioners should pay attention to sleep disorders lasting more than three weeks and should bear in mind that poor sleep is a symptom, the underlying cause of which needs to be determined. Good coordination of endogenous biorhythms and external life and working circumstances can positively influence sleeping patterns. Sleep onset latency determines the amount of deep sleep and, thus, the duration and stability of core sleep. General practitioners usually prescribe a single type of benzodiazepine drug with a half-life of 5-10 h for sleep disorders. Such drugs cause the patient to fall asleep quickly, to have a considerable period of uninterrupted sleep with little waking and to wake in the morning with a subjective feeling of having slept well. A number of less desirable changes can occur, however, that may produce, for example, anxiety dreams, increased snoring and sleep apnoea periods at night, and weakness of muscles during the day. The third generation of hypnotic agents produce less undesirable changes than the second generation. Zolpidem (an imidazoypridine), one such agent, seems to provide an effective treatment for insomnia without inducing undesirable side-effects.

Shifts and awakenings: valuable indicators of the quality of sleep: do these parameters react differently to hypnotics?

In order to test the assumption that the sleep stability increases as the number of shifts and awakenings decreases, all-night sleep recordings (registered at home) were reanalyzed. The registrations belong to 10 young good sleepers, 10 adult good sleepers, 10 insomnia patients without treatment, 10 treated with a benzodiazepine and 10 treated with a nonbenzodiazepine hypnotic, 10 patients with proven narcolepsy, and 10 with obstructive sleep apnea syndrome (OSAS). For each of the categories NREM-1-2, NREM 3-4, and REM sleep, indices were defined as the number of shifts and awakenings that occurred per hour. Our results show that the indices of awakenings for the good as well for the bad sleepers were similar, whereas the indices of awakenings were very group dependent. We interpreted these results as showing that awakenings are valuable indicators for studying the quality of sleep, whereas shifts are not.

Gammahydroxybutyrate and narcolepsy: a double-blind placebo-controlled study.

We treated 24 patients with narcolepsy for 4 weeks with gammahydroxybutyrate (GHB), 60 mg/kg/night, in a randomized double-blind placebo-controlled cross-over trial. Both clinical and polysomnographic criteria were used to assess the results. Compared to placebo, GHB reduced the daily number of hypnagogic hallucinations (from 0.87 to 0.28; p = 0.008), daytime sleep attacks (from 2.27 to 1.40; p = 0.001) and the severity of subjective daytime sleepiness (from 1.57 to 1.24 on a 0-4 scale; p = 0.028). The number of daily cataplexy attacks was reduced from 1.26 at baseline to 0.56 after 4 weeks of GHB intake. This reduction, however, was not statistically significantly different from the difference between baseline and placebo. GHB stabilized nocturnal rapid eye movement (REM) sleep, i.e. it reduced the percentage of wakefulness during REM sleep (p = 0.007) and the number of awakenings out of REM sleep (p = 0.016), and tended to increase slow wave sleep (p = 0.053). Adverse events were few and mild. We conclude that GHB is an effective and well-tolerated treatment for narcolepsy.

Value of the electroencephalogram in adult patients with untreated idiopathic first seizures.

We prospectively studied the reliability and accuracy of the electroencephalogram as a predictor of the risk of recurrence within 2 years in 157 patients with untreated idiopathic first seizures. In all patients, a standard electroencephalogram and, if necessary, an electroencephalogram after partial sleep deprivation were obtained. All electroencephalograms were scored by one observer according to a fixed protocol. The finding of epileptic discharges was associated with a risk of recurrence of 83% (95% confidence interval, 69% to 97%) vs 41% (95% confidence interval, 29% to 53%) in patients with nonepileptic abnormalities and 12% (95% confidence interval, 3% to 21%) in patients in whom both electroencephalograms were normal. The sensitivity proved to be 48%. Interobserver agreement among four neurologists, who independently read 50 electroencephalograms, was found to be moderate. Predictive value for each observer, however, was good. We conclude that electroencephalogram findings may play a role in the decision to initiate or delay treatment after an idiopathic first seizure.

Effects of zolpidem and flunitrazepam on nocturnal sleep of women subjectively complaining of insomnia.

Eighteen non-pregnant woman complaining about insomnia were polysomnographically investigated for 3 nights with weekly intervals. They received placebo, 2 mg flunitrazepam or 10 mg zolpidem according to a cross-over double blind design. The patients were selected by general practitioners on the basis of subjective complaints. Zolpidem is a recently introduced short-acting imidazopyridine hypnotic, binding to a subunit of the benzodiazepine 1 receptor. Flunitrazepam is a well-known hypnotic, binding to both the benzodiazepine 1 and 2 receptor subtypes. Objective recording did not substantiate the subjective complaint of insomnia. Sleep patterns during placebo differed only little from that expected from age matched healthy persons. Both flunitrazepam and zolpidem significantly shortened sleep onset (5 min of continuous sleep beginning with NREM 1 sleep). The sleep composition following flunitrazepam was characterized by an increase in NREM 2, a prolongation of the time of REM sleep, a reduction of REM sleep and an increase in NREM 3-4 sleep during the first 2 h of sleep. The sleep composition following zolpidem resembled more than seen in persons without sleep complaints. However, as compared to placebo, there was a decrease of the time spent awake during sleep and an increase in NREM 3-4 during the first 2 of sleep.

Disturbances in time estimation during absence seizures in children.

In the present study children suffering from primary generalized absence epilepsy were asked to estimate time under EEG monitoring. They were asked to press a button when they thought that a fixed period of time had elapsed. Only the first response after the passage of the interval was reinforced. The dependent variable was the duration of the interval between the start of the trial and the first response, the post-reinforcement time. This parameter was used as an index for the accuracy of time estimation. The performance of the subjects in trials with and without spike wave discharges was compared. Short spike wave discharges (less than 3 s) prolonged the duration of the post-reinforcement pause while longer ones reduced its duration. The prolongation was longer than could be anticipated from the duration of the spike wave discharge. It was also found that the time between the end of an EEG paroxysm and the first response was significantly shorter in trials with long spike wave discharges than in trials with short spike wave discharges. There were no differences between subjects with and without spike wave discharges. It was concluded that this type of time estimation task is sensitive in detecting cognitive disturbances induced by both short and long spike wave discharges. Moreover, it seems that after long spike wave discharges patients behave differently and are perhaps more severely disturbed.(ABSTRACT TRUNCATED AT 250 WORDS)

Ritanserin, a 5-HT2 receptor blocker, as add-on treatment in narcolepsy.

In a double-blind placebo-controlled trial, ritanserin (a 5-HT2 receptor blocker) 5 mg/day or placebo was added to the usual medication in 28 patients with narcolepsy during 4 wk. The effect was assessed by means of polysomnography, daily and weekly subjective evaluations, and Multiple sleep latency tests (MSLT). During the night ritanserin increased the amount of nonrapid eye movement slow wave sleep and reduced wakefulness after sleep onset. It improved the feeling of being refreshed in the morning after awakening and reduced subjective daytime sleepiness. The drug did not significantly influence sleep latency in the MSLT.

Measuring sleep (dys)function by polysomnography.

A vigilance state is characterized by a particular activity state of the motorIautonomic and psychiclcognitive functional systems. S-W screening is possible through poly graphic monitoring of physiological variables and signals. Quantification of these signals introduces a set of parameters allowing the characterisation of the sleep (dys)function. There is no consensus regarding the choice or definition of these parameters. A particular cluster is presented and their informative value with respect to clinical practice and research is discussed.