Long-term therapy with trandolapril, a new nonsulfhydryl ACE inhibitor, in hypertension : a multicenter international trial

An international trial recruited 1,049 patients from 122 investigators. After a 2- to 4-week, single-blind placebo run-in, patients were treated unblinded for 1 year. Therapy was started with trandolapril 2 mg once daily. The dose was increased to 4 mg/day if, after 1 month, blood pressure was not normalized, and then was combined with diuretics and/or calcium antagonists in increasing doses if necessary. At the cutoff point for this interim analysis, 481 patients had been treated for over 12 months and 960 for 3 months. At end point, trandolapril produced a significant decrease in blood pressure (-14 mm Hg for mean supine diastolic blood pressure). Blood pressure was normalized in 60% of the population with monotherapy. Trandolapril, alone or in combination with diuretics or calcium antagonists, was well tolerated clinically and biochemically. Only 3.9% patients reported dry cough. Withdrawals of patients from the study for treatment related reasons were 3.8%. Trandolapril had also an excellent antihypertensive effect and was well tolerated in elderly patients, in patients with glucose intolerance, and in patients with renal dysfunction

Modifications of sleep structure induced by increasing levels of acoustic perturbation in normal subjects.

In each non-REM (NREM) sleep stage, the aggregation of the arousal-related phasic events permits identification of periods of arousal fluctuation (cyclic alternating pattern or CAP) and periods of long-lasting arousal stability (non-CAP or NCAP). As the ratio CAP time to NREM sleep time (CAP/NREM) measures the instability of arousal during sleep, any perturbing event determines an increase of CAP/NREM. On the basis of these premises, 6 healthy volunteers underwent 5 sleep recordings at increasing intensities of sound pressure level (basal condition followed by continuous white noise at 45 dBA, 55 dBA, 65 dBA and 75 dBA, respectively). Besides a remarkable enhancement of CAP/NREM (P less than 0.00001), acoustic perturbation induced a significant linear increase of waking time after sleep onset, stage 2, NREM sleep, stage shifts and a significant linear decrease of stage 4, deep sleep, REM sleep and total sleep time. At each step of environmental disturbance, the values of the CAP ratio were consistent with the gradual changes of sleep organization. Although the Multiple Sleep Latency Test was unremarkable during the day following the sleep recording, CAP/NREM was significantly correlated with the personal evaluation of sleep quality (P less than 0.01). Through this model of transient situational insomnia it was possible to outline different degrees of subjective complaint depending on 3 ranges of CAP/NREM. A crucial role of CAP in the pathophysiological mechanisms of clinical insomnia is hypothesized

[Cyclic alternating pattern. A new approach to the pharmacology of sleep disorders].

The Cyclic Alternating Pattern (CAP) is an intrinsic component of normal NREM sleep. This periodic activity is organized in biphasic 40-sec cycles clustered in sequences. CAP sequences are functionally correlated to long lasting arousal instability. CAP is induced by endogenous stimuli (change in sleep stage, body movements) but it is considerably increased by exogenous impulses (noise). CAP rate (CAPR) is a novel polysomnographic variable that measures the amount of CAP during sleep, and it may be calculated for total sleep time and total NREM sleep. We demonstrated that all-night exposure to a 45 dB(A) white noise induced a significant CAPR increase, correlated with impaired sleep quality, even without changes in sleep architecture. We hypothesized that administration of an hypnotic should attenuate this CAPR rise. This hypothesis was verified in a double-blind placebo study, in which 12 healthy young adults received zolpidem, a new imidazopyridine hypnotic. During the noise perturbed nights, zolpidem clearly demonstrated a protective effect on CAPR (mainly during slow wave sleep) and on sleep quality. CAPR appears to be a sensitive indicator of sleep quality, and the cumulative distribution of CAPR throughout the night represents a new method to evaluate the effects of an hypnotic in sleep

French approaches to accreditation of prior learning : practices and research

The French experience of validating the knowledge, skills and competences acquired through informal and non-formal learning is unique in the world. In this chapter, we argue for the singularity of this experience in France. We first review the beginnings of accreditation of prior learning (APL) movement, from the early experiments until its current modes of functioning. We show in particular how the implementation of APL introduced a significant break in the French educational model that attaches great importance to diplomas obtained within the school system. APL radically transformed the landscape of classic means of certification. It established a strong distinction between diplomas and other pathways to gain certification, by recognising the formative dimension of work experience. The issue which then arises is not so much the recognition of knowledge, skills and competences that have been acquired at work, but the means by which the recognition can be operationalised. We focus, therefore, on the methodological resources provided to support candidates and to assist the complex process by which they are expected to put into words their work experience. To do so, we discuss recent research conducted in France in the field of psychology and educational sciences that investigate the counsellors' activities. This research, we argue, opens up interesting perspectives in terms of training and professionalisation in the field of APL