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Biomedical subjects

M Barreto

Publications and source records attributed to M Barreto.

At least 19 recordsLinked to original sources
PubMed2006

The prevalence of atopy in asthmatic children correlates strictly with the prevalence of atopy among nonasthmatic children.

BACKGROUND: Because asthma preferentially burdens persons with atopy, atopy is simplistically considered a primary 'cause' of asthma. Yet at the population level, the percentage of asthma cases 'attributable' to atopy ranges from less than 10% to more than 60%. Seeking to understand the rationale for the variability of atopy-attributable cases of asthma, we systematically reviewed the results of our own previous epidemiological studies and several studies conducted by others in children. METHODS: From each of the 37 random pediatric populations selected by a Medline search combining the key words 'IgE or skin tests or hypersensitivity, immediate' with 'epidemiological studies, cross-sectional, case-control, prevalence, longitudinal, epidemiology of asthma' (12 from our previous pediatric surveys and a further 25 reported from 19 studies in children), we extracted the population prevalence of asthma and atopy among asthmatic subjects and among the nonasthmatic part of the population. RESULTS: No correlation was found between the prevalence of asthma (range 1.8-44.1%) and atopy (range 5.8-63.9%) in these 37 populations of children (r = 0.052, p = 0.761). Nevertheless, the prevalence of atopy among asthmatics strictly correlated with the prevalence of atopy in nonasthmatics (r = 0.900, p < 0.001, slope 1.364). CONCLUSION: The prevalence of asthma and atopy varies worldwide and at various time points and independently undergoes the influence of powerful environmental factors. The almost perfect correlation we found between atopy in asthmatics and atopy in the nonasthmatic part of the childhood population shows that the prevalence of atopy in asthma depends on environmental factors that simultaneously induce atopy in asthmatic and nonasthmatic subjects.

Asthma↗
PubMed2005

Allergen skin weal/radioallergosorbent test relationship in childhood populations that differ in histamine skin reactivity: a multi-national survey.

BACKGROUND: Histamine skin reactivity (HSR, the dimension of the skin weal elicited by histamine 10 mg/mL) is a variable that differs in children from different European countries and increases over time in the same place (Italy). OBJECTIVE: In this epidemiologic study, we investigated to what extent differences in HSR influence the relationship between positive allergen skin prick tests (ASPTs) and serum-specific IgE concentrations. METHODS: Between October 2001 and February 2002, 591 unselected 9-10-year-old schoolchildren drawn from five small towns in central Poland (Starachowice), central Italy (Ronciglione, Guardea) and Libya (Al-Azyzia, near the Mediterranean sea and Samno, 900 km south of the coast) were analysed for histamine, common ASPT and for serum total and specific IgE. RESULTS: HSR differed markedly in children from the three countries (Libya>Italy>Poland) whereas serum total IgE concentrations remained the same. The prevalence of children with measurable serum specific IgE (> or = 0.35 kU) or with a positive ASPT for five common allergens was high in Italy, lower in Poland and far lower in Libya. A 3-mm ASPT weal corresponded to a serum-specific IgE concentration that was two to threefold higher in children with low HSR compared with children with high HSR (P = 0.008). CONCLUSION: These findings suggest that HSR--a variable that differs in schoolchildren populations from the three countries studied--independently influences the results of ASPT and its influence should be considered when ASPT are assessed in international studies. The HSR differences found in the populations reported here probably reflect a complex, dynamic, environmental interaction that should be monitored in the different parts of the world.

Analysis of Variance↗
PubMed2004

Diffusing capacity for carbon monoxide in children with type 1 diabetes.

AIMS/HYPOTHESIS: Few data are available on lung dysfunction in children with diabetes. We studied the association of pulmonary function variables (flows, volumes and alveolar capillary diffusion) with disease-related variables in children with type 1 diabetes mellitus. METHODS: We studied 39 children with type 1 diabetes (mean age 10.9+/-2.6 years, disease duration 3.6+/-2.4 years, insulin.kg(-1).day(-1) 0.77+/-0.31) and 30 healthy control children (mean age 10.4+/-3.0 years). Pulmonary function tests included spirometry, N(2) wash-out and the single-breath diffusing capacity for carbon monoxide (DL(CO)) corrected for the alveolar volume (DL(CO)/V(A)). Glycaemic control was assessed on the basis of HbA(1)c, with HbA(1)c values of 8% or less considered to indicate good glycaemic control, and HbA(1)c values of 8% or more considered to indicate poor control. RESULTS: Children with poor glycaemic control had comparable percentage values for predicted flows and volumes but lower DL(CO)/V(A) values than children with good glycaemic control and healthy control children (86.7+/-12.6 vs 99.8+/-18.4 and 102.0+/-15.7; p<0.05). The predicted DL(CO)/V(A) percentages correlated with HbA(1)c levels (r=-0.39, p=0.013). A multiple regression analysis (stepwise model) controlling for HbA(1)c levels and other disease-related variables (age of disease onset, disease duration, daily insulin dose/kg, sex) identified HbA(1)c levels as the sole predictor of DL(CO)/V(A) in percent. CONCLUSIONS/INTERPRETATION: In children with type 1 diabetes, the diffusing capacity diminishes early in childhood and is associated with poor metabolic control. Although low DL(CO)/V(A) levels in these children probably reflect pulmonary microangiopathy induced by type 1 diabetes, other factors presumably influencing CO diffusion capacity measurements (e.g. a left shift in HbA(1)c resulting in high O(2) binding and low CO binding) could explain the apparent capillary and alveolar basal membrane dysfunction.

Adolescent↗
PubMed2004

[Childhood asthma].

The concept of chronicity in asthma, as emphasized by recent definitions of the disease, rests on the major characteristics of inflammatory response of the airways and progressive development of irreversible structural and functional alterations, or so-called airway remodeling. In childhood, however, such characteristics as chronicity and irreversibility are debatable. Various clinical phenotypes with variable degrees of severity of persistence are found in children. Furthermore, many patients with a history of recurrent wheezing in early infancy do not develop asthma later in life. The prevalence of asthma, especially in its mild forms, has increased markedly in recent years. Although the trend has stabilized in Italy, it continues to rise in other Western countries. Our research has shown that increased cutaneous response to histamine determines a major prevalence of positive skin tests. The rise in clinical forms of the disease accompanied by gastrointestinal symptoms is partly attributable to the dietary intake of food and beverages processed from environmentally engineered products. The features of the new forms of asthma demand accurate clinical and functional assessment. In addition to pulmonary function tests, determinations for eosinophils and inflammation markers in the blood and sputum, noninvasive methods have recently become available to assess airway inflammation. Among these, particularly useful studies include test for nitric oxide in exhaled air, along with tests for other markers of allergic inflammation and oxidative stress in the droplets of the exhaled air. Because in paediatric age, prolonged use of inhaled steroids increase the risk of growth impairment, asthma therapy should be guided by clinical criteria and examinations, rather than by rigid treatment guidelines. Moreover, to secure successful treatment, the parents and the child as well should be involved in monitoring the course of the disease.

Asthma↗
PubMed2003

Immediate skin reactivity to histamine and to allergens in cohorts of 9-year-old schoolchildren studied 16 years apart.

BACKGROUND: Differing or increasing prevalence of positive allergen skin-prick tests observed in Europe could at least in part be explained by population changes in histamine skin reactivity. These changes would also alter the relationship between positive allergen skin-prick tests and serum IgE. OBJECTIVE: To assess changes in histamine reactivity, allergen skin-prick tests and serum IgE in our geographical setting. METHODS: We compared the outcome of two epidemiological surveys conducted 16 years apart in unselected 9-year-old schoolchildren (170 in 1983 and 176 in 1999) from a semi-rural region in central Italy. Outcome measures were skin-prick tests with two histamine concentrations (10 and 1 mg/mL) and 11 locally relevant allergens; serum total and specific IgE for positive allergens. RESULTS: The two histamine concentrations induced significantly larger mean weal diameters in 1999 than in 1983 (10 mg/mL: 5.28+/-0.82 mm vs. 3.25+/-0.97 mm; P<0.001). Whereas the prevalence of subjects with at least one positive allergen-induced weal reaction (>or=3 mm) increased over the 16 years (from 15.3% in 1983 to 25.6% in 1999), the prevalence of positive skin-prick tests, expressed as the allergen/ histamine weal ratio, remained almost unchanged. A given allergen weal diameter yielded less total (P<0.05 by Student's t-test for cumulative weals <8 mm) and specific (P<0.01 by Student's t-test for weals <3 mm, P<0.05 by Kruskal-Wallis test) serum IgE in 1999 than in 1983. CONCLUSIONS: Although the causes and mechanisms remain unclear, the increased histamine skin reactivity over time is associated with an increase in positive allergen skin-prick tests. In the presence of increased tissue and organ susceptibility to histamine, minute amounts of specific IgE could have important biological consequences.

Allergens↗
PubMed2001

Off-line exhaled nitric oxide measurements in children.

The concentration of exhaled nitric oxide (eNO) is a useful marker of asthmatic bronchial inflammation. eNO can now be measured away from the laboratory (off-line), even in children. Short exhalation maneuvers (8 sec) and small samples (1 L) of exhaled gas are probably sufficient in children, but more information is needed about the effect of different measurement conditions. As a preliminary step before conducting epidemiological studies in schoolchildren, we investigated the effects of expiratory flow, dead space, and expiratory time on eNO concentrations collected in 1-L mylar collection bags. We studied 101 cooperative subjects (62 males) aged 5-18 years (30 healthy volunteers, 51 asthmatics, and 20 children with various other respiratory diseases) in our pulmonary function laboratory. On-line and off-line eNO were compared in a single session, and analyzed with a Sievers NOA 280 nitric oxide analyzer. For both methods of collecting expired gas, subjects did a single exhalation without breath-holding against an expiratory pressure 10 cm H(2)O. We investigated the effects of expiratory flow, dead space, and exhalation time on eNO; we also compared on-line and off-line eNO measurements, and the repeatability of both techniques at a given flow rate. Expiratory flows of 58 mL/sec provided more reproducible data than lower flows (coefficient of repeatability 1.1 ppb for 58 mL/sec vs. 2.8 for 27 mL/sec vs. 5.7 for 18 mL/sec). eNO concentrations were about 25% higher in off-line than in on-line recordings if the initial 250 mL of exhaled gas were not eliminated, and 37% higher if exhalation lasted longer (16 sec vs. 8 sec). Eliminating 250 mL of dead space and shortening the filling time to 8 sec yielded off-line eNO values close to those on-line (geometric mean off-line eNO 14.4 ppb, 95% confidence interval: 12.2-17.0) vs. on-line eNO 13.8 ppb (95% confidence interval: 11.6-16.5). On-line and off-line results were highly correlated (r = 0.996, P = 0.000) and had similar coefficients of variation (on-line eNO 2.6%, off-line 2.8%). Neither agreement nor repeatability of eNO measurements were affected by disease status or baseline FEV(1) (% predicted values). Once standardized, the off-line eNO technique using 1-L gas collection bags will provide results similar to those recorded on-line.

Adolescent↗
PubMed2001

Changes over 13 years in skin reactivity to histamine in cohorts of children aged 9-13 years.

BACKGROUND: Several studies report substantial differences in the prevalence of skin test reactivity to allergens in children from adjacent geographic areas; others report an increased prevalence over time. To find out whether these differences depend on variations in skin reactivity to histamine, we determined the time trend of histamine wheal sizes in successive cohorts of unselected children living in the same area (Viterbo, Italy). METHODS: We conducted three epidemiologic surveys, each including children aged 9 and 13 years. The 1983-7 study investigated 170 children (150 were tested twice); the 1992 study, 158 children; and the 1996 study, 208 children. RESULTS: In both age groups, the mean diameter of the wheal induced by histamine skin prick tests (10 mg/ml) increased significantly over time (9-year-olds: 3.25 mm in 1983, 4.68 in 1992, and 5.89 in 1996; 13-year-olds: 3.89 mm in 1987, 5.18 in 1992, and 6.50 in 1996) (P < 0.001 between subsequent studies). The distribution of the wheal diameters for both ages showed a trend to a right shift in the three successive studies (P < 0.001). The dose-response curves for three histamine concentrations (0.2, 1, and 10 mg/ml) had significantly steeper slopes in 1996 than in 1983-7 (P < 0.001). CONCLUSION: The marked time-related increase in the size of the histamine wheals could help to explain the trend toward an increased prevalence of positive allergen skin test reactions reported during the past years. The causes of increased skin reactivity to histamine remain conjectural.

Adolescent↗
PubMed2001

Exhaled nitric oxide in asthmatic and non-asthmatic children: influence of type of allergen sensitization and exposure to tobacco smoke.

Asthmatic bronchial inflammation is associated with increased nitric oxide concentrations in exhaled air (eNO). Recent data suggest that this effect arises from atopy. Our aim in this study was to find out whether atopy and sensitization to particular allergens influences eNO levels. A total of 213 subjects (41 asthmatics and 172 controls) (96 boys and 117 girls, 7.3-14 years of age) were studied. Parents completed a questionnaire that sought information on their children's respiratory symptoms and exposure to tobacco smoke. Subjects underwent skin-prick tests for the following common allergens: Dermatophagoides pteronyssinus (Dpt), cat fur, Aspergillus fumigatus, Alternaria tenuis, mixed grass, mixed tree pollen, Parietaria officinalis, egg, and cow's milk. eNO was collected in 1-l mylar bags (exhaled pressure 10 cmH2O, flow 58 ml/s) and analyzed by using chemiluminescence. Atopic and non-atopic children without a history of chronic respiratory symptoms had a similar geometric mean eNO (atopics, n = 28, 11.2 p.p.b.; non-atopics, n = 96, 10.0 p.p.b.; mean ratio 1.1, 95% confidence interval [CI]: 0.7-1.6). Conversely, atopic asthmatic subjects had significantly higher eNO values than non-atopic asthmatic subjects (atopics, n = 25, 24.8 p.p.b.; non-atopics, n = 16, 11.4 p.p.b.; mean ratio 2.2, 95% CI: 1.2-3.9, p= 0.000). In children with rhinitis alone (n = 15) and those with lower respiratory symptoms other than asthma (n = 33), eNO increased slightly, but not significantly, with atopy. eNO levels correlated significantly with Dpt wheal size (r = 0.51) as well with the wheal size for cat, mixed grass, and Parietaria officinalis (r = 0.30-0.29), and with the sum of all wheals (r = 0.47) (p= 0.000). Subjects sensitized only for Dpt (but not those subjects sensitized only for grass pollen or other allergens) showed significantly higher eNO levels than non-atopic subjects (16.4 p.p.b. vs. 10.2 p.p.b., mean ratio 1.6, 95% CI: 1.1-2.3, p= 0.002). In asthmatic subjects, Dpt sensitization markedly increased eNO levels (Dpt-sensitized subjects: 28.0 p.p.b.; Dpt-unsensitized subjects: 12.2 p.p.b.; mean ratio 2.3, 95% CI: 1.5-3.5, p= 0.000). Non-asthmatic Dpt-sensitized subjects also had significantly higher eNO values than non-asthmatic, non-Dpt-sensitized subjects (14.2 p.p.b. vs. 10.1 p.p.b.; mean ratio 1.4, 95% CI: 1.1-1.9, p= 0.008). No difference was found between eNO levels in asthmatic subjects and control subjects exposed or unexposed to tobacco smoke. In conclusion, eNO concentrations are high in atopic asthmatic children and particularly high in atopic asthmatics who are sensitized to house-dust mite allergen.

Allergens↗
PubMed2001

Is the increase in childhood asthma coming to an end? Findings from three surveys of schoolchildren in Rome, Italy.

Time trends in the prevalence of asthma, family history of asthma and atopy in Roman schoolchildren were assessed. The study population consisted of all children (aged 6-14 yrs) attending two primary schools in Rome, situated in urban areas that differed markedly in socioeconomic conditions and environmental pollution. Three questionnaire-based surveys were conducted in 1974, 1992 and 1998 in 2,259, 1,229 and 1,139 children. The prevalence of asthma in males and females increased significantly during 1974-1992 and remained stable from 1992-1998. In age groups born in the subsequent 4-yr periods it increased almost linearly, for children born from 1962-1965 to 1982-1985 (4.4%-12.5%), and remained remarkably stable in children born after 1985. Because the prevalence of asthma had a steeper trend in males than in females (approximately 0.55% x yr(-1) versus 0.25% x yr(-1)), the male:female asthma ratio increased (1:38 in 1974; 1:84 in 1992 and 1:62 in 1998). No single environmental factor, including area of residence, seemed to influence the prevalence of asthma. Family history of asthma and atopy also increased steadily (0.72% x yr(-1) and 0.30% x yr(-1) respectively) more than doubling during the 24-yr study period. The strong relationship between asthma and a family history of atopy not only persisted but also strengthened over time (23.3% of asthmatic children belonged to families with atopic illnesses in 1974 but 44.2% in 1998). The environmental factors that might explain the almost three-fold rise in childhood asthma between 1974 and 1992 remain unknown but the genetic background of the disease has presumably remained unchanged since the early 1970s. The fact that the prevalence of asthma increased no further during the past 6 yrs suggests that the progressive induction of asthma symptoms in genetically predisposed subjects is a self-limiting process that has probably come to an end in the authors' study area.

Adolescent↗
PubMed2000

Comparative physiology and biochemistry of rat and rabbit urinary bladder.

OBJECTIVE: To compare directly the biochemistry and contractile responses of rat and rabbit bladder to different stimuli. Materials and methods Sexually mature male New Zealand White rabbits and Sprague Dawley rats were compared. Each bladder was excised while the animal was anaesthetized; longitudinal bladder strips were cut and then mounted in an organ bath. Tension (2 g) was placed on all strips and each underwent field stimulation (FS) for a total of 20 s at 1-32 Hz, 1 ms and 80 V and was exposed to carbachol (100 micromol/L), ATP (2 mmol/L) and KCl (120 mmol/L). The tension was monitored continually using a polygraph and data stored digitally in a computer. The responses to each stimulus were determined as the maximum tension generated, maximum rate of tension generation and duration to a maximum response. The Ca2+- ATPase activity of the rat and rabbit bladder was determined. Bladder pressures were then predicted from the strip data using Laplace's law and compared with published values. RESULTS: Contractile responses (per unit tissue mass) of rat bladder strips were significantly greater than those of rabbit bladder strips at all frequencies of FS and to carbachol, KCl and ATP. The rate of contractile force generated by rat bladder strips in response to all stimuli were significantly greater than that generated by rabbit strips. Rabbit bladder strips took significantly longer to generate maximum tension than did rat bladder strips in response to pharmacological stimuli. In response to FS, rat strips took significantly longer than rabbit strips to generate maximum tension. Although the predicted rat bladder pressures were significantly greater than those for rabbit, the predicted pressures for both the rat and rabbit were significantly lower than the pressure responses of the isolated whole bladder model. The contractile data correlated well with the Ca2+-ATPase activity data; rat bladder had seven times the enzyme activity of rabbit bladder. CONCLUSION: Per unit mass, rat bladder is capable of generating more than five times the tension of rabbit bladder. Similarly, the rate of tension generation by rat bladder is three to five times greater than that by rabbit bladder. The duration to maximum tension generated in response to FS compared with pharmacological stimuli was affected by the inherent difference in the rate of contractile response to electrical activation compared with agents which diffuse through tissue, and by the difference in size between rat and rabbit bladder smooth muscle cells.

Adenosine Triphosphate↗
PubMed1999

Rabbit versus rat urinary bladder: effects of in vitro hypoxia.

PURPOSE: Studies indicate that bladder hypoxia may be an etiological factor for lower urinary tract dysfunction. Rat and rabbit are two species of experimental animals used frequently to study lower urinary tract function and dysfunction. The objective of this study was to compare directly effects of in vitro hypoxia on contractile responses of rat and rabbit urinary bladder to different forms of stimulation. METHODS: Sexually mature male New Zealand White rabbits and Sprague-Dawley rats were compared. Each bladder was excised while the animal was anesthetized, and longitudinal bladder strips were cut, then mounted in organ baths. A tension of 2 g was placed on all strips. Effects of 1, 2, 3 and 4 h hypoxia followed by 1 h of reoxygenation on contractile responses of bladder strips to field stimulation (FS), carbachol (100 micromol/l), ATP (1 mmol/l) and KCl (120 mmol/l) were determined. RESULTS: Contractility, per unit tissue mass, of rat bladder strips was significantly greater than that of rabbit bladder strips in response to FS (all frequencies), carbachol, KCl and ATP. Hypoxia (followed by reoxygenation) resulted in time-dependent progressive reduction in contractile responses of bladder strips to all stimuli. Rat bladder was significantly more sensitive to hypoxia than rabbit bladder in response to FS and carbachol. Hypoxia induced similar effects on rat and rabbit bladder responses to ATP and KCl. CONCLUSION: Rat bladder neurogenic and cholinergic responses are significantly more sensitive to hypoxia than are those of rabbit bladder, which may be due to the rat bladder's greater contractile force generation and previously reported higher Ca2+-ATPase activity.

Animals↗
PubMed1995

Biochemical systematics and population genetic structure of Anopheles pseudopunctipennis, vector of malaria in Central and South America.

An electrophoretic survey of 42 populations of Anopheles pseudopunctipennis collected throughout its known geographic distribution was performed to clarify the taxonomic status of this important malaria vector species. The results indicated strong differences in the allele frequencies of three enzyme loci (glycerol dehydrogenase, 6-phosphogluconate dehydrogenase, and phosphoglucomutase) of the 33 loci analyzed. No fixed electromorphic differences separate the populations of An. pseudopunctipennis. The populations of An. pseudopunctipennis showed little genetic divergence, with Nei distances ranging from 0 to 0.079. A comparison of An. pseudopunctipennis data with either one of three other Anopheles species showed a high genetic distance of 0.335 with a closely related species, An. franciscanus; 0.997 with An. crucians, and 2.355 with An. (Nyssorhynchus) albimanus. Geographic populations of An. pseudopunctipennis were classified into three clusters; one cluster included populations collected in North America (United States and Mexico) and Guatemala, one cluster included populations from Belize and South America (Colombia, Ecuador, Peru, Chile, and Argentina); and one cluster was represented by populations from the Island of Grenada (type-locality of An. pseudopunctipennis). Based on our isozyme analyses, we defined these clusters as three geographic populations of An. pseudopunctipennis. Of the two mainland populations, one extends from the southern United States south through Mexico and Guatemala, and the other extends north from southern South America through Central America to Belize. These two geographic populations converge in southern Mexico and northern Central America. One part of the convergence zone was identified in the area of eastern Guatemala and southern Belize.

Alleles↗
PubMed1994

The effect of transfusion on pulmonary function in patients with thalassemia major.

Pulmonary involvement has been documented in thalassemia major (TM). We studied 12 patients with TM before and 24 hr after transfusion to evaluate the effect of transfusion on baseline lung function. Personal and family histories of respiratory illnesses were obtained by a questionnaire. Spirometry and carbon monoxide diffusion capacity (KCO) measurements were made. Blood gases (PO2 and SO2) were determined on arterialized samples. Baseline expiratory volumes and flows were within normal range in all patients. Transfusion resulted in a significant reduction of forced expiratory volume in 1 sec (FEV1) and forced expiratory flow between 25 and 75% vital capacity (FEF25-75%). In two subgroups of patients identified by the questionnaire, those with no history of airway disease had normal baseline flows and no posttransfusion changes; those with history of airway obstruction had lower pretransfusion flows and significantly decreased posttransfusion FEV1 and FEF25-75%. The mean pretransfusion KCO value of 80% predicted for the whole group, significantly increased after transfusion (P < 0.05). Blood gases also significantly increased after transfusion (P < 0.05). When tested for the spirometric response to albuterol, patients with a history of asthma had a slightly greater increase in FEV1 and FEF25-75% than those who had never had asthma. We conclude that in our small study group, transfusion resulted in improved gas exchange and lung perfusion. The effect on flow limitation evident in some patients could, in part, be related to a preexisting bronchial hyperreactivity. Accurate evaluation of pulmonary function and of bronchial reactivity is advisable for patients with TM.

Adolescent↗
PubMed1990

Binding of [3H]cytochalasin B to tumoral islet cells.

Tumoral pancreatic islet cells of the RINm5F line are equipped with two classes of [3H]cytochalasin B binding sites with respective Kd of 0.4 and 7 microM. The binding of the fungal metabolite and its dissociation from the binding sites display rapid time courses. The binding is inhibited by D-glucose, more than by L-glucose, by phlorizin and by cytochalasin E. These findings are considered in the light of the dual action of cytochalasin B upon hexose transport and motile activity in islet cells.

Adenoma, Islet Cell↗
PubMed1990

A comparison of the efficacy, tolerance and residual effects of zopiclone, flurazepam and placebo in insomniac outpatients.

A double-blind randomized parallel group design was used to compare the tolerance and efficacy of zopiclone 7.5 mg, flurazepam 30 mg and placebo taken each night for 3 weeks in a group of 24 out-patients complaining of sleep disturbance. Analogue rating scales were used to assess the efficacy of the treatments while tolerance and residual effects were measured weekly using a battery of performance tests (Critical Flicker Fusion Threshold, Choice Reaction Time, Letter Cancellation and Digit Span). Physical and clinical examinations, including ECG and EEG, were conducted before and after the experimental period and spontaneously reported side-effects were recorded. Analysis of variance on 24 completed cases (8 patients in each treatment group) showed both active treatments to be significantly better than placebo in shortening sleep onset latency. Flurazepam increased the duration of sleep and produced a "hangover" of impaired psychomotor function. Zopiclone had no observable effect on early morning performance and was free from residual sedative activity. The lack of residual effects with zopiclone 7.5 mg, at a dose shown to be clinically effective, suggests its use in ambulant or out-patient populations where daytime sedation could interfere with every day activities.

Adolescent↗