The traits of Autism Spectrum Disorder and bullying victimization in an epidemiological population.

Autistic children (Autism Spectrum Disorder, ASD) show an increased risk of bullying victimization and often face challenges in communication and peer relationships. However, it is unclear to what extent the amount and quality of ASD traits are associated with bullying victimization. This study examined the association of bullying victimization and ASD traits in an epidemiological population of 8-year-old children (n = 4408) using parent and teacher completed Autism Spectrum Screening Questionnaires (ASSQs), both separately and combined. The ASSQ items relating to loneliness and social isolation, lack of co-operating skills, clumsiness and lack of common sense were associated with victimization in the study population. The higher the ASSQ scores, the more the children were victimized: the ASSQ scores increased in parallel with victimization from 0 (0% victimized) to 45 (64% victimized). The victimization rate was 46% in ASD sample, 2% in the total population sample and 2% in the non-ASD population sample. The results enable more targeted means for recognizing potential victimization.

Association between body mass index and sperm quality and sperm DNA integrity. A large population study.

This study aimed to analyse whether the functional quality of spermatozoa is associated with body mass index (BMI). Semen samples were obtained from 1824 men undergoing fertility evaluation/treatment. Semen analysis was performed using World Health Organization (WHO) criteria, and morphology was evaluated with the motile sperm organelle morphology examination (MSOME). The percentages of sperm DNA fragmentation (using TdT (terminal deoxynucleotidyl transferase)-mediated dUTP nick-end labelling (TUNEL) assays), sperm chromatin packaging/underprotamination (using chromomycin A3/CMA3 ), mitochondrial damage (using MitoTracker Green) and apoptosis (using annexin V) were also assessed. At least 200 spermatozoa were examined in each evaluation. The following BMI values were used as cut-off points: ≤24.9 kg/m2 , 25-29.9 kg/m2 (overweight) and ≥30 kg/m2 (obese). High BMI negatively affects sperm concentration, vitality, motility and morphology (p < .05). Conversely, high BMI does not seem to be associated with impaired sperm DNA integrity, as assessed by DNA fragmentation, sperm protamination and sperm apoptosis (p > .05). However, increased BMI is associated with increased mitochondrial damage in spermatozoa (p < .05). In conclusion, given the adverse consequences of obesity and the possible effect of male BMI on assisted reproduction technology (ART) outcomes, the benefits of weight reduction should be discussed when counselling couples interested in fertility treatment.

Sense of coherence and health behaviour in adolescence.

AIM: To explore associations of Sense of coherence (SOC) with health behaviour and social competence among 15-year-old adolescents. METHODS: Study population is a prospective cohort of a randomized cluster sample of families and their first-born children from south-western Finland in 1986-1987. In this study, cross-sectional data of the 15-year-olds were used. The present data were based on mailed, pretested questionnaires. The outcome variable, SOC, was based on the 13-item scale of Antonovsky's Orientation to Life Questionnaire (OLQ). The principal explanatory variables were health behaviour, including experienced oral health, and social competence. The statistical analysis was performed using linear regression modelling. RESULTS: Strong SOC of adolescents associated significantly with lighter use of alcohol, being a non-smoker, better care of oral health and better social competence compared with the others. CONCLUSION: Sense of coherence is a useful tool for identifying adolescents in need of extra support and motivation for their health behaviour.

Sensory Abnormality and Quantitative Autism Traits in Children With and Without Autism Spectrum Disorder in an Epidemiological Population.

Sensory abnormalities (SAs) are recognized features in Autism Spectrum Disorder (ASD), and a relationship between SAs and ASD traits is also suggested in general population. Our aims were to estimate the prevalence of SAs in three different settings, and to study the association between SAs and quantitative autism traits (QAT) using the Autism Spectrum Screening Questionnaire (ASSQ) and a parental questionnaire. In an epidemiological population of 8-year-old children (n = 4397), the prevalence of SAs was 8.3%, in an ASD sample (n = 28), 53.6%, and in a non-ASD sample (n = 4369), 8.0%, respectively. Tactile and auditory hypersensitivity predicted an ASD diagnosis. The ASSQ was able to differentiate children with and without SA. In conclusion, QAT level and SAs were associated in all study samples.

Key performance indicators score (KPIs-score) based on clinical and laboratorial parameters can establish benchmarks for internal quality control in an ART program.

OBJECTIVE: KPIs have been employed for internal quality control (IQC) in ART. However, clinical KPIs (C-KPIs) such as age, AMH and number of oocytes collected are never added to laboratory KPIs (L-KPIs), such as fertilization rate and morphological quality of the embryos for analysis, even though the final endpoint is the evaluation of clinical pregnancy rates. This paper analyzed if a KPIs-score strategy with clinical and laboratorial parameters could be used to establish benchmarks for IQC in ART cycles. METHODS: In this prospective cohort study, 280 patients (36.4±4.3years) underwent ART. The total KPIs-score was obtained by the analysis of age, AMH (AMH Gen II ELISA/pre-mixing modified, Beckman Coulter Inc.), number of metaphase-II oocytes, fertilization rates and morphological quality of the embryonic lot. RESULTS: The total KPIs-score (C-KPIs+L-KPIs) was correlated with the presence or absence of clinical pregnancy. The relationship between the C-KPIs and L-KPIs scores was analyzed to establish quality standards, to increase the performance of clinical and laboratorial processes in ART. The logistic regression model (LRM), with respect to pregnancy and total KPIs-score (280 patients/102 clinical pregnancies), yielded an odds ratio of 1.24 (95%CI = 1.16-1.32). There was also a significant difference (p<0.0001) with respect to the total KPIs-score mean value between the group of patients with clinical pregnancies (total KPIs-score=20.4±3.7) and the group without clinical pregnancies (total KPIs-score=15.9±5). Clinical pregnancy probabilities (CPP) can be obtained using the LRM (prediction key) with the total KPIs-score as a predictor variable. The mean C-KPIs and L-KPIs scores obtained in the pregnancy group were 11.9±2.9 and 8.5±1.7, respectively. Routinely, in all cases where the C-KPIs score was ≥9, after the procedure, the L-KPIs score obtained was ≤6, a revision of the laboratory procedure was performed to assess quality standards. CONCLUSION: This total KPIs-score could set up benchmarks for clinical pregnancy. Moreover, IQC can use C-KPIs and L-KPIs scores to detect problems in the clinical-laboratorial interface.

Gelatine matrix with human thrombin decreases blood loss in adolescents undergoing posterior spinal fusion for idiopathic scoliosis: a multicentre, randomised clinical trial.

AIMS: In a multicentre, randomised study of adolescents undergoing posterior spinal fusion for idiopathic scoliosis, we investigated the effect of adding gelatine matrix with human thrombin to the standard surgical methods of controlling blood loss. PATIENTS AND METHODS: Patients in the intervention group (n = 30) were randomised to receive a minimum of two and a maximum of four units of gelatine matrix with thrombin in addition to conventional surgical methods of achieving haemostasis. Only conventional surgical methods were used in the control group (n = 30). We measured the intra-operative and total blood loss (intra-operative blood loss plus post-operative drain output). RESULTS: Each additional hour of operating time increased the intra-operative blood loss by 356.9 ml (p < 0.001) and the total blood loss by 430.5 ml (p < 0.001). Multiple linear regression analysis showed that the intervention significantly decreased the intra-operative (-171 ml, p = 0.025) and total blood loss (-177 ml, p = 0.027). The decrease in haemoglobin concentration from the day before the operation to the second post-operative day was significantly smaller in the intervention group (-6 g/l, p = 0.013) than in the control group. CONCLUSION: The addition of gelatine matrix with human thrombin to conventional methods of achieving haemostasis reduces both the intra-operative blood loss and the decrease in haemoglobin concentration post-operatively in adolescents undergoing posterior spinal fusion for idiopathic scoliosis. TAKE HOME MESSAGE: A randomised clinical trial showed that gelatine matrix with human thrombin decreases intra-operative blood loss by 30% when added to traditional surgical haemostatic methods in adolescents undergoing posterior spinal fusion for idiopathic scoliosis.

FGF-8b increases angiogenic capacity and tumor growth of androgen-regulated S115 breast cancer cells.

Fibroblast growth factor 8 (FGF-8) is a secreted heparin-binding protein, which has transforming potential. Alternative splicing of the mouse Fgf-8 gene potentially codes for eight protein isoforms (a-h) which differ in their transforming capacity in transfected cells. S115 mouse mammary tumor cells express a transformed phenotype and secrete FGF-8 in an androgen-dependent manner. In order to study the role of FGF-8 isoforms in the induction of transformed phenotype of breast cancer cells, we over-expressed FGF-8 isoforms a, b and e in S115 cells. Over-expression of FGF-8b, but not FGF-8a or FGF-8e, induced androgen and anchorage independent growth of S115 cells. FGF-8b-transfected S115 cells formed rapidly growing tumors with increased vascularization when injected s.c. into nude mice. FGF-8a also slightly increased tumor growth and probably tumor vascularization but FGF-8e was not found to have any effects. The angiogenic activity of FGF-8b and heparin-binding growth factor fraction (HBGF) of S115 cell conditioned media was tested in in vitro and in vivo models for angiogenesis using immortomouse brain capillary endothelial cells (IBEC) and chorion allantoic membrane (CAM) assays. Recombinant FGF-8b protein was able to stimulate proliferation, migration, and vessel-like tube formation of IBECs. In addition, stimulatory effect of S115-HBGF on IBE cell proliferation was evident. A positive angiogenic response to FGF-8b was also seen in CAM assay. The results demonstrate that the expression of Fgf-8b is able to promote vessel formation. Angiogenic capacity probably markedly contributes to the ability of FGF-8b to increase tumor growth of androgen-regulated S115 mouse breast cancer cells.

Clomipramine and doxepin in depressive neurosis. Plasma levels and therapeutic response.

The therapeutic efficacy, plasma levels, and psychomotor effects of tryptophan (L-tryptophan), clomipramine hydrochloride, and doxepin were investigate in "neurotically" depressed outpatients. The tricyclic antidepressants were significantly more efficacious than tryptophan in inducing remission. The alleviation of depression was preceded by an improvement of the initially slow information-processing rates in the depressed patients. The plasma levels of the tricyclics that were associated with a therapeutic response were significantly lower than those reported in "endogenously" depressed inpatients.

Neuropeptide Y in the noradrenergic neurones induces obesity and inhibits sympathetic tone in mice.

AIM: Neuropeptide Y (NPY) co-localized with noradrenaline in central and sympathetic nervous systems seems to play a role in the control of energy metabolism. In this study, the aim was to elucidate the effects and pathophysiological mechanisms of increased NPY in catecholaminergic neurones on accumulation of body adiposity. METHODS: Transgenic mice overexpressing NPY under the dopamine-beta-hydroxylase promoter (OE-NPY(DßH) ) and wild-type control mice were followed for body weight gain and body fat content. Food intake, energy expenditure, physical activity, body temperature, serum lipid content and markers of glucose homoeostasis were monitored. Thermogenic and lipolytic responses in adipose tissues, and urine catecholamine and tissue catecholamine synthesizing enzyme levels were analysed as indices of sympathetic tone. RESULTS: Homozygous OE-NPY(DßH) mice showed significant obesity accompanied with impaired glucose tolerance and insulin resistance. Increased adiposity was explained by neither increased food intake or fat absorption nor by decreased total energy expenditure or physical activity. Adipocyte hypertrophy and decreased circulating lipid levels suggested decreased lipolysis and increased lipid uptake. Brown adipose tissue thermogenic capacity was decreased and brown adipocytes filled with lipids. Enhanced response to adrenergic stimuli, downregulation of catecholamine synthesizing enzyme expressions in the brainstem and lower adrenaline excretion supported the notion of low basal catecholaminergic activity. CONCLUSION: Increased NPY in catecholaminergic neurones induces obesity that seems to be a result of preferential fat storage. These results support the role of NPY as a direct effector in peripheral tissues and an inhibitor of sympathetic activity in the pathogenesis of obesity.

Combined effects of buspirone and diazepam on objective and subjective tests of performance in healthy volunteers.

The combined effects on performance of two anxiolytics with different mechanisms of action were evaluated double-blind and crossover in 12 healthy students. Objective (tracking, divided attention, Maddox wing, etc.) and subjective (visual analogue scales and questionnaires) tests were done before and twice after single oral doses. Diazepam (0.15 and 0.30 mg/kg) impaired performance dose relatedly and rendered the subjects drowsy, calm, mentally slow, and clumsy. Buspirone (15 mg) proved inactive in objective tests but matched diazepam (0.30 mg/kg) subjectively. In combinations, buspirone added to the effects of diazepam in Maddox wing and letter cancellation but tended to counteract diazepam effects on divided attention and learning acquisition. Subjectively buspirone prolonged diazepam-induced sedation. Increased calmness caused by diazepam was not affected by concomitant buspirone. It is suggested that combining small doses of buspirone to diazepam does not cause any additional decrement in psychomotor performance. Possible advantages of the diazepam-buspirone combination in therapeutic use are discussed.

Oral activated charcoal and dapsone elimination.

The effect of orally given activated charcoal on the elimination of therapeutic and toxic doses of dapsone was studied in 5 healthy subjects and in 2 intoxicated patients. In a randomized crossover study the subjects took a total dose of 500 mg dapsone over 4 days; 10 hr after the last 100-mg dose of dapsone 50 gm activated charcoal as a water suspension (or water) was taken, followed by 4 consecutive doses of 17 gm at 12-hr intervals. The half-life (t 1/2) of serum dapsone was 20.5 +/- 2.0 hr during the control period and 10.8 +/- 0.4 hr during the charcoal period (p less than 0.01). The t 1/2 on serum monoacetyldapsone (MADDS) was shortened from 19.3 +/- 1.2 hr to 9.5 +/- 0.7 hr (p less than 0.01) by charcoal. The t 1/2s of dapsone and MADDS, calculated on the basis of urinary excretion rate, were shortened by charcoal; Two patients had taken large doses of dapsone in suicide attempts. The use of activated charcoal, 80 gm/day for 1 or 2 days, increased (3 to 5 times) the rate of elimination of both dapsone and MADDS, as reflected in serum concentration and urinary excretion data. The use of multiple doses of charcoal seems to be indicated as supplementary treatment of certain intoxications during the postabsorption phase if the drugs have a long t 1/2 and if they are secreted into the gut with subsequent reabsorption.

Effect of tricyclic antidepressants and alcohol in psychomotor skills related to driving.

Twenty healthy subjects took amitriptyline, doxepin, and placebo for 2 wk each in a double-blind crossover trial, and another 20 subjects similarly took nortriptyline, chlorimipramine, and placebo. The antidepressants were given three times daily in doses generally used for neurotic patients. The presence of antidepressants in tissues was checked with the tyramine pressor test. On the seventh and fourteenth days of each period, psychomotor skills (choice reaction, coordination, and attention) were measured after the administration of drugs in combination with an alcoholic or placebo drink. Dose-response graphs for the tyramine pressor effect were shifted to the right during the antidepressant treatment, indicating a blockade of the membrane pump in peripheral sympathetic terminals. This antityramine effect of antidepressants did not correlate with their psychomotor effects. No drug alone importantly impaired psychomotor skills. Amitriptyline in combination with alcohol increased cumulative choice reaction times, and doxepin in combination with alcohol increased both cumulative choice reaction times and inaccuracy of reactions. Coordination was impaired after both of these combinations on the seventh day. It seems as if doxepin and amitriptyline but not nortiriptyline or chlorimipramine, in combination with 0.5 gm/kg of alcohol, may be especially dangerous in driving.

Effects of alcohol on buspirone and lorazepam actions.

Psychomotor and psychologic effects of single doses of buspirone (10 and 20 mg) and lorazepam (2.5 mg) alone or combined with alcohol (1 gm/kg) were investigated in 12 healthy young men (crossover study). Lorazepam alone impaired psychomotor skills (tracking, body balance, extraocular muscle balance, and flicker recognition), the effects being maximal at 180 min. This impairment was not subjectively perceived by the subjects. Neither dose of buspirone alone impaired objective measurements, although buspirone, especially in the 20-mg dose, was felt to cause drowsiness, weakness, and faintness. Lorazepam, but not buspirone, interacted with alcohol.

Coffee and caffeine and alcohol effects on psychomotor function.

Interactions of alcohol and caffeine were studied in two double-blind and crossover trials in which several psychophysiologic functions and subjective effects were measured in healthy men. The effects of alcohol (1 gm/kg) with and without caffeine (200 or 500 mg) were measured in 10 subjects. Two doses (0.7 or 1.5 gm/kg) of alcohol alone and in combination with caffeine (250 + 250 mg) were similarly studied in another 10 subjects. Alcohol impaired psychomotor functions to an extent dependent on dose whereas caffeinated and decaffeinated coffee did not. Both kinds of coffee also failed to modify alcohol effects. Subjectively, caffeine was indistinguishable from placebo and no particular interaction of alcohol and caffeine was detected. Alcohol did elevate serum caffeine concentrations. We conclude that coffee does not counteract alcohol inebriation.

Pharmacokinetics of oxicam nonsteroidal anti-inflammatory agents.

Oxicam nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of structurally closely related substances with anti-inflammatory, analgesic and antipyretic activities. They have a weakly acidic character and are extensively bound to plasma proteins. Piroxicam, the most widely used oxicam, is well absorbed after oral administration. Peak plasma concentrations (Cmax) of the drug are reached within 2 to 4 hours. Piroxicam has a small volume of distribution and a low plasma clearance. It undergoes hepatic metabolism and only 5 to 10% is excreted unchanged in urine. The elimination half-life varies between 30 and 70 hours. Age of the patient and renal or hepatic dysfunction do not seem to have any major effect on the pharmacokinetics of piroxicam. The drug reduces the renal excretion of lithium to a clinically significant extent, but the clinical significance of piroxicam-aspirin (acetylsalicylic-acid) and piroxicam-acenocoumarol interaction has not been established. Ampiroxicam, droxicam and pivoxicam are prodrugs of piroxicam that have been synthesised to reduce piroxicam-related gastrointestinal irritation. All prodrugs are well absorbed, but Cmax values are reached later than those following administration of piroxicam. Tenoxicam is used in the management of rheumatic and inflammatory diseases. Mean Cmax values are achieved 2 hours postdose. Food reduces the rate but not the extent of absorption. The oral bioavailability of tenoxicam is 100% and rectal bioavailability is 80%. Like piroxicam, tenoxicam has a low volume of distribution and low plasma clearance. It is eliminated through hepatic metabolism. The mean elimination half-life is 60 to 75 hours. The pharmacokinetics of tenoxicam are independent of patient age, or concurrent liver or renal diseases. High doses of aspirin have been shown to increase the elimination of tenoxicam, but this has little clinical significance. Isoxicam was in widespread clinical use until its worldwide marketing was suspended because of fatal skin reactions. Isoxicam is completely absorbed, but Cmax values are not reached until 10 hours postdose. It has a low plasma clearance, approximately 5 ml/min (0.3 L/h), and low volume of distribution. The mean elimination half-life is 30 hours and does not appear to be affected by the age of the patient. Isoxicam potentiated the anticoagulant effect of warfarin, necessitating a 20% dosage reduction. Lornoxicam differs from other oxicam NSAIDs because it has a short elimination half-life of 3 to 4 hours. On the basis of limited data, some individuals seem to eliminate lornoxicam very slowly, suggesting the presence of polymorphic metabolism. The pharmacokinetics of cinnoxicam and sudoxicam have not been studied thoroughly.(ABSTRACT TRUNCATED AT 400 WORDS)

Modification by betamethasone of the effects of bronchodilator drugs on cholinergic bronchoconstriction in rats.

Effects of betamethasone (BM), a long-acting glucocorticoid, given alone and in combination with bronchodilator drugs, terbutaline (Ter), theophylline (Theo), or ipratropium bromide (Ipra), were studied on dose-related methacholine (MeCh 2, 3, and 4.5 micrograms i.v.)-induced bronchoconstriction in anaesthetized rats. BM (0.4 or 2 mg kg-1) was given intraperitoneally 24 h before the experiment followed by a similar dose intravenously, 12 min before MeCh challenge. The bronchodilator drugs were given i.v. as acute single doses. BM 0.4 mg kg-1 counteracted significantly MeCh-induced bronchoconstriction without modifying MeCh-induced transient bradycardia and hypotension. BM 2 mg kg-1 failed to improve that response. A time interval of 24 h after pretreatment proved mandatory to produce these effects. Combined treatment with BM 0.4 mg kg-1 + Ter 20 micrograms kg-1 antagonized the MeCh-induced bronchoconstriction in an additive manner at 2 and 3 micrograms of MeCh, but a synergistic interaction was found at the largest MeCh dose. The effects of the other combinations (BM 0.4 mg kg-1 + Theo 20 mg kg-1 and BM 0.4 mg kg-1 + Ipra 0.5 microgram kg-1) on airways failed to exceed the expected sum of the individual drugs. The combination of BM + Ter was selective to the airways only, whereas BM + Theo also counteracted MeCh-induced bradycardia and BM + Ipra counteracted both hypotension and bradycardia. It is concluded that combined treatment with glucocorticoid and beta 2-adrenoceptor agonist may result in a synergistic interaction on severe airway obstruction without significant influence on cardiovascular system.

Flunitrazepam: a review of its pharmacological properties and therapeutic use.

Flunitrazepam is a benzodiazepine derivative whose hypnotic effect predominates over the sedative, anxiolytic, muscle-relaxing and anticonvulsant effects characteristic of benzodiazepines. Thus, it is used as a night-time hypnotic and in anaesthesiology: due to the pronounced hypnotic effect it is not appropriate as a daytime sedative. As a hypnotic for insomnia its effect is usually characterised by a very fast onset of action and quiet sleep without interruptions. On the morning after a hypnotic dose some residual psychomotor impairment does occur, which is comparable to that with usual doses of nitrazepam or flurazepam, but clinically apparent 'hangover' occurs infrequently. There is no pronounced cumulative effect with chronic use. In anaesthesiology it has proven to be useful as a hypnotic on the night before operation, as an oral, intramuscular or intravenous premedication, in induction and as a supplement to other anaesthetics. Its sedative and amnesic properties can also be beneficial in intensive care patients. Much of the usefulness of flunitrazepam in anaesthesia relates to its synergistic effect with other anaesthetics, to its effective amnesic action and its acceptable effects on circulation and respiration. Possible drawbacks include a somewhat unusual course of induction (when used for this purpose) and an often prolonged recovery. Although the safe dosage range is wide with flunitrazepam, its effective application both as a hypnotic for insomnia and in anaesthesiology is dependent upon use of the optimal dosage, and adequate knowledge of its pharmacokinetic properties.

Drug interactions with alcohol.

Ethanol and drugs can affect each other's absorption, distribution, metabolism, and excretion. When ingested together, ethanol can increase drug absorption by enhancing the gastric solubility of drugs and by increasing gastrointestinal blood flow. However, high concentrations of ethanol induce gastric irritation causing a pyloric spasm which in turn may delay drug absorption and/or reduce bioavailability. The 'quality' of the alcoholic beverage, independent of its ethanol content, can contribute to altered absorption of a drug. Ethanol is not bound to plasma proteins extensively enough to modify drug distribution. However, serum albumin levels in chronic alcoholics may be abnormally low so that some drugs, e.g. diazepam, have an increased volume of distribution. In addition to the amount ingested, the duration of regular intake determines the effect of ethanol on drug metabolism. Acute intake of ethanol inhibits the metabolism of many drugs but long term intake of ethanol at a high level (greater than 200g of pure ethanol per day) can induce liver enzymes to metabolise drugs more efficiently. At the present time there are no accurate means, with the possible exception of liver biopsy, to clinically predict the capacity of an alcoholic to metabolise drugs. Several drugs can inhibit the metabolism of ethanol at the level of alcohol dehydrogenase. Individual predisposition determines the severity of this drug-ethanol interaction. During its absorption phase, ethanol inhibits the secretion of antidiuretic hormone and is also able to induce increased excretion of a drug through the kidneys. However, chronic alcoholics with water retention may show reduced excretion of drugs via this route. At the pharmacodynamic level, ethanol can enhance the deleterious effects of sedatives, certain anxiolytics, sedative antidepressants and antipsychotics and anticholinergic agents, on performance. Mechanisms of lethal interactions between moderate overdoses of ethanol and anxiolytics/opiates/sedatives are poorly understood. On the other hand, certain peptides, 'nonspecific' stimulants, dopaminergic agents and opiate antagonists can antagonise alcohol-induced inebriation to a significant degree.

Drugs, alcohol and driving.

Driving a car is a complex psychomotor and perceptual task which is subject to impairment by many factors. Several workers have studied the potential effects of drugs and alchol in crash production by epidemiological and laboratory studies. Both types of studies have yielded useful data but their limitations must be borne in mind when applying the results in pratice. Alcohol is obviously the most common single cause of traffic accidents. A progessively increased risk with increasing blood alcohol levels is well documented; fatigue and/or drugs increase this risk. Drugs are related much more infrequently to traffic accidents although on the basis of statistics, there is a potential risk with drug use. However, drugs alone are not as important as alcohol. The most significant drugs as regards driving risk are obviously certain antianxiety agents, hypnotics, stimulants, hallucinogens, marihuana, lithium and narcotic analgesics, as well as ganglionic blocking agents, insulin and sulphonylurea derivates. Patients should not drive after taking these drug until they are objectively fully alert and capable. Anticholinergics, antihistamines, antidepressants, antipsychotics, phenybutazone, indomethacin, alpha-methyldopa, and beta-blockers may in some cases cause central side effects (e.g. drowsiness) strong enough to affect driving performance. After starting therapy with these drugs, or after a significant change in dose, driving should be avoided until it is known that unwanted effects do not occur. Psychotropic drugs may enhance the deleterious effect of alcohol, and with most hypnotics there is still an effect the next morning. Some drugs (e.g. anticonvulsants or antiparkinsonian drugs) may make driving safer, but the disease (epilepsy, Parkinsonism, cardiovascular diseases, psychic disorders, etc.) ofter precludes driving. Clinicians should warn their patients about an impairment of driving skills if this is likely to occur due to the drug or the illness concerned.

Acute effects of sertraline, amitriptyline, and placebo on the psychomotor performance of healthy subjects over 50 years of age.

A double-blind, placebo-controlled, crossover study in 12 subjects (greater than or equal to 50 years) compared the effects of single oral doses of sertraline (100 mg) and amitriptyline (50 mg) with placebo as assessed by psychomotor function testing. Unlike sertraline and placebo, amitriptyline increased tracking error severity and impaired digit/symbol substitution. Sertraline slightly improved flicker frequency recognition. Both active drugs caused subjective drowsiness, although amitriptyline's effect was greater and of longer duration. Both drugs impaired subjectively assessed performance. Sertraline caused nausea, and amitriptyline, dry mouth; sertraline tended to increase supine systolic blood pressure. The authors conclude that sertraline has a considerably less detrimental effect on psychomotor performance and may have a slight activating effect not found with amitriptyline.