Increased IL-6 receptor expression and signaling in ageing cartilage can be explained by loss of TGF-ß-mediated IL-6 receptor suppression.

OBJECTIVE: Osteoarthritis (OA) development is strongly associated with ageing, possibly due to age-related changes in transforming growth factor-ß (TGF-ß) signaling in cartilage. Recently, we showed that TGF-ß suppresses interleukin (IL)-6 receptor (IL-6R) expression in chondrocytes. As IL-6 is involved in cartilage degeneration, we hypothesized that age-related loss of TGF-ß signaling results in increased IL-6R expression and signaling in ageing cartilage. DESIGN: Bovine articular cartilage was collected and immediately processed to study age-related changes in IL-6R expression using qPCR and IHC (age-range: 0.5-14 years). Moreover, cartilage from young and aged cows was stimulated with rhIL-6 and/or rhTGF-ß1 to measure IL-6-induced p-STAT3 using Western blot. Expression of STAT3-responsive genes was analyzed using qPCR. RESULTS: Expression of IL-6 receptor (bIL-6R) significantly increased in cartilage upon ageing (slope: 0.32, 95%CI: 0.20-0.45), while expression of glycoprotein 130 (bGP130) was unaffected. Cartilage stimulation with IL-6 showed increased induction of p-STAT3 upon ageing (slope: 0.14, 95%CI: 0.08-0.20). Furthermore, IL-6-mediated induction of STAT3-responsive genes like bSOCS3 and bMMP3 was increased in aged compared to young cartilage. Interestingly, the ability of TGF-ß to suppress bIL6R expression in young cartilage was lost upon ageing (slope: 0.21, 95%CI: 0.13-0.30). Concurrently, an age-related loss in TGF-ß-mediated suppression of IL-6-induced p-STAT3 and bSOCS3 expression was observed. CONCLUSIONS: Ageing results in enhanced IL-6R expression and subsequent IL-6-induced p-STAT3 signaling in articular cartilage. This is likely caused by age-related loss of protective TGF-ß signaling, resulting in loss of TGF-ß-mediated IL-6R suppression. Because of the detrimental role of IL-6 in cartilage, this mechanism may be involved in age-related OA development.

[Epidemiology of hallucinogenic drug use in the Netherlands]. / Epidemiologie van het gebruik van psychedelica in Nederland.

BACKGROUND: In recent years there was a renewed interest in psychedelic substances.
AIM: To present an overview of what is known about the use of classic psychedelic drugs and 'atypical' psychedelic drugs (i.e. entactogen/empathogenic drugs like mdma and dissociative drugs such as ketamine) in the Netherlands.
METHOD: Data from a Dutch adult general population survey from 2016 and 2018 and other surveys - mainly among nightlife attendees - were used to provide prevalence estimates and user characteristics. In addition to that, data from several Dutch monitoring systems were included for information on problematic psychedelic drug use, health emergencies and psychedelic drug markets.
RESULTS: The last year prevalence of ecstasy among Dutch adults was 2.9%, making it the most used psychedelic in the general population. For hallucinogenic mushrooms/truffles, lsd, 2C-B and ketamine, the last year prevalence estimate ranged between 0.2 and 0.6%. For all psychedelic substances, higher use rates were found among men, young adults between 20-29 years old, adults with higher education, and inhabitants of urban areas. In different groups of nightlife attendees, psychedelic substance use prevalence was greater than that of the general population. Data from various sources suggested an increase in the number of ketamine users.
CONCLUSION: Apart from ecstasy, the use of psychedelic substances is relatively low in the general population. In subgroups of the Dutch population, ketamine use increased in recent years. Further research is needed to gain a better understanding of the use of psychedelics in the Netherlands, particularly in subpopulations.

Clustering of health risk behaviours and the relationship with mental disorders.

BACKGROUND: Health risk behaviours tend to co-occur and are found to be related to mental health symptoms. This is the first study to identify health behaviour clusters in relation to mental disorders. METHODS: Data were used from the second wave of the Netherlands Mental Health Survey and Incidence Study (NEMESIS-2), a nationally representative sample of adults (n=5303). Latent class analysis was performed to identify clusters based on four health risk behaviours (smoking, heavy drinking, physical inactivity, and unhealthy diet). Concurrently, we examined the relationship between the identified clusters and a range of DSM-IV diagnoses, assessed with the Composite International Diagnostic Interview 3.0. RESULTS: Four distinct health behaviour clusters were identified: most healthy (mainly non-smokers, moderate drinkers, active, healthy diet; class 1: 79.3%); smokers, moderate drinkers, inactive, unhealthy diet (class 2: 13.2%); smokers, heavy episodic drinkers, active, unhealthy diet (class 3: 3.8%); Smokers, frequent heavy drinkers, active, low fruit (class 4: 3.6%). Despite their different lifestyles, individuals in all three unhealthy clusters had double the risk of depression. Unhealthy behaviour clusters were strongly associated with drug dependence (classes 2 and 3), alcohol abuse and dependence (classes 3 and 4), and social phobia (class 4). LIMITATIONS: Due to the cross-sectional design, no conclusions about the causality of the relationship between HRB clusters and mental disorders can be drawn from the current study. CONCLUSIONS: Health behaviour clusters are strongly associated with mental disorders. This co-existence of behaviours and disorders emphasises the importance of an integrative approach in the prevention of mental illnesses.

Cardiovascular sequelae in long-term survivors of young peoples' cancer: a linked cohort study.

BACKGROUND: We aimed to define the incidence and risk of cardiovascular late effects (LEs) identified from inpatient hospital episode statistics (HES) among long-term survivors of cancer in young people by age at diagnosis (0-14 and 15-29 years). METHODS: Records from the Yorkshire Specialist Register of Cancer in Children and Young People (1991-2006) were linked to inpatient HES data (1996-2011) to assess rates of cardiovascular LEs. Rates were compared with the general population in Yorkshire using age-sex-matched HES records for the entire region. RESULTS: Of 3247 survivors of cancer, 3.6% had at least one cardiovascular LE. Overall, cardiovascular hospitalisations for the childhood cohort were threefold higher compared with the general population, but did not differ for young adults. For young adults, increased rates were limited to pericardial disease, cardiomyopathy and heart failure, pulmonary heart disease, hypertension and conduction disorders. CONCLUSIONS: Survivors of childhood and young adult cancer remain at increased risk of cardiovascular LEs compared with the general population.

Does referral to specialist paediatric palliative care services reduce hospital admissions in oncology patients at the end of life?

BACKGROUND: Despite advances in the treatment of childhood cancer, some children continue to die from their disease. This study aimed to assess the impact of specialist paediatric palliative care services (SPPCSs) on the number of hospital admissions in children who subsequently died from cancer in Yorkshire, UK. METHODS: An extract of patients aged 0-19 years from the Yorkshire Specialist Register of Cancer in Children and Young People (YSRCCYP) diagnosed from 1990 to 2009 were linked to inpatient hospital episodes data and a SPPCS database. Deaths were included if they occurred before 31 August 2011. Differences in hospital admission patterns were assessed using negative binomial regression and presented as incidence rate ratios (IRRs). RESULTS: Of 2508 children on the YSRCCYP, 657 (26%) had died by the censoring date. A total of 211 children had been referred to the local SPPCS, of whom 182 (86%) had subsequently died. Referral to SPPCS was associated with a significant reduction in the rate of planned hospital admissions (IRR=0.60, 95% CI 0.43-0.85). Central nervous system tumours showed significant decreases for all planned and emergency admissions compared with all other diagnostic groups. CONCLUSION: Referral to SPPCS significantly reduced the number of planned hospital admissions for children and young people with cancer before their death, which are often integral to paediatric oncology treatment regimens. Overall, our findings show that SPPCS have a role in reducing hospital admissions during end of life care of paediatric cancer patients with potential personal, social and economic benefits.

The impact of a managed transition of care upon psychosocial characteristics and patient satisfaction in a cohort of adult survivors of childhood cancer.

OBJECTIVE: Many adult survivors of childhood cancer receive care in paediatric departments, despite national policy to transition their care to adult services. When long-term follow-up care for survivors of childhood cancer in our region moved from a paediatric to an adult environment in 2009, we prospectively assessed the impact of this change on patient satisfaction. METHODS: Questionnaire data were collected in paediatric and adult clinical environments regarding the level of satisfaction with care and potential mediators: quality of life, psychological health and social difficulties. Predictors of satisfaction and optimum longitudinal risk-based care were described using path analysis and compared with previously described models. RESULTS: There was no significant difference in satisfaction between the paediatric and adult settings. Short waiting times and increased understanding of the purpose of follow-up were significantly associated with increased satisfaction. Those with a higher perception of health problems and those that were older were more likely to not attend all of their clinic appointments. CONCLUSIONS: Within our service, transition to adult care did not impact significantly upon patient satisfaction. Shorter waits and knowing why participants were attending the clinic increased satisfaction. Joint working between adult and paediatric cancer professionals enabled adult survivors of childhood cancer to receive highly satisfactory care in adult services.

Changes in the patterns of care of central nervous system tumours among 16-24 year olds and the effect on survival in Yorkshire between 1990 and 2009.

AIM: There is a paucity of work documenting the influence of patterns of care on survival for teenagers and young adults with primary central nervous system tumours. Therefore, the aim of this study was to undertake a detailed assessment examining any changes in the patterns of care over time and how these related to survival outcomes for 16-24 year olds diagnosed with a primary central nervous system tumour between 1990 and 2009. MATERIALS AND METHODS: We used high-quality data from one population-based cancer registry in Yorkshire, UK to describe primary central nervous system tumours in teenagers and young adults (16-24 years) diagnosed between 1990 and 2009. The Birch classification scheme was used to identify differences by tumour subgroup. Incidence, patterns of care and survival trends were described using Poisson and Cox regression. RESULTS: There were 163 cases comprising 98 astrocytomas, 17 'other gliomas', 14 ependymomas, 11 medulloblastomas and 23 'other intracranial and intraspinal neoplasms' yielding an overall incidence of 18.1 million person-years. Care varied significantly over time and by principal treatment centre (Leeds 77%, Hull 23%), co-ordinating specialty (neurosurgery 53%, clinical oncology 22%, paediatrics 17%, other adult services 8%) and treatment received. Cox regression showed no significant difference in survival by age, gender, treatment centre, level of deprivation, year of diagnosis or co-ordinating specialty, but a significant difference by tumour grade and diagnostic group. Survival improved for all diagnostic groups except astrocytoma, although only the medulloblastoma group showed a significant change over time. CONCLUSION: The lack of any significant improvement in survival over time in most diagnostic groups warrants further investigation and provides justification for a more collaborative regional approach to the care of central nervous system tumours, perhaps through the development of regional guidelines for this unique population. More detailed analysis of relapse patterns and prediagnostic symptoms would also be informative for this cohort.

Survival trends of cancer amongst the south Asian and non-south Asian population under 30 years of age in Yorkshire, UK.

INTRODUCTION: Several studies have shown differences in survival trends between ethnic groups across adults with cancer in the UK. It is unclear whether these differences exist exclusively in the older adult population or whether they begin to emerge in children and young adults. METHODS: Subjects (n=3534) diagnosed with cancer under 30 years of age in Yorkshire between 1990 and 2005 were analysed. Differences in survival rates for diagnostic subgroups were estimated by ethnic group (south Asian or not) using Kaplan-Meier estimation and Cox regression. RESULTS: When compared to non-south Asians (all other ethnic groups excluding south Asians) a significant increased risk of death was seen for south Asians with leukaemia (hazard ratio (HR)=1.75; 95% confidence interval (CI)=1.11-2.76) and lymphoma (HR=2.05; 95% CI=1.09-3.87), whereas south Asians with solid tumours other than central nervous system tumours had a significantly reduced risk of death(HR=0.50; 95% CI=0.28-0.89). This was independent of socioeconomic deprivation. CONCLUSION: We found evidence of poorer survival outcomes for south Asians compared to non-south Asian children and young adults with leukaemia and lymphoma, but better outcomes for south Asian children and young adults with other solid tumours. This needs to be explained, and carefully addressed in the on-going development of cancer services.

Cancer incidence among the south Asian and non-south Asian population under 30 years of age in Yorkshire, UK.

BACKGROUND: Few studies have examined epidemiological differences between ethnic groups for children and young adults with cancer. METHODS: Subjects aged 0-29 years, diagnosed between 1990 and 2005 in the former Yorkshire Regional Health Authority, were included in the analysis. Ethnicity (south Asian or not) was assigned using name analysis program and Hospital Episode Statistics data. Differences in incidence (per 1,000,000 person-years) rates and trends were analysed using joinpoint and Poisson regression analysis. RESULTS: Overall cancer incidence was similar for south Asians (12.1, 95% CI: 10.7-13.5; n=275) and non-south Asians (12.6, 95% CI: 12.2-13.1; n=3259). Annual incidence rates increased significantly by 1.9% per year on average (95% CI: 1.2-2.6%), especially for south Asians (7.0%; 95% CI: 4.2-9.9%). CONCLUSION: If present trends continue, the higher rate of increase seen among south Asians aged 0-29 years in Yorkshire will result in three times higher cancer incidence than non-south Asians by 2020.

An atomic force microscope operating at hypergravity for in situ measurement of cellular mechano-response.

We present a novel atomic force microscope (AFM) system, operational in liquid at variable gravity, dedicated to image cell shape changes of cells in vitro under hypergravity conditions. The hypergravity AFM is realized by mounting a stand-alone AFM into a large-diameter centrifuge. The balance between mechanical forces, both intra- and extracellular, determines both cell shape and integrity. Gravity seems to be an insignificant force at the level of a single cell, in contrast to the effect of gravity on a complete (multicellular) organism, where for instance bones and muscles are highly unloaded under near weightless (microgravity) conditions. However, past space flights and ground based cell biological studies, under both hypogravity and hypergravity conditions have shown changes in cell behaviour (signal transduction), cell architecture (cytoskeleton) and proliferation. Thus the role of direct or indirect gravity effects at the level of cells has remained unclear. Here we aim to address the role of gravity on cell shape. We concentrate on the validation of the novel AFM for use under hypergravity conditions. We find indications that a single cell exposed to 2 to 3 x g reduces some 30-50% in average height, as monitored with AFM. Indeed, in situ measurements of the effects of changing gravitational load on cell shape are well feasible by means of AFM in liquid. The combination provides a promising technique to measure, online, the temporal characteristics of the cellular mechano-response during exposure to inertial forces.

[Morbidity due to smoking in The Netherlands: an estimated 90,000 clinical hospital admissions in 2005]. / Ziekte door roken in Nederland: naar schatting 90 duizend klinische ziekenhuisopnamen in 2005.

OBJECTIVE: To estimate the number of hospital admissions due to smoking tobacco. DESIGN: Theoretical study based on data from the Dutch National Medical Registration. METHOD: Attributive fractions were determined based on the percentages of smokers and ex-smokers and the relative risks for certain diseases. Applying the attributive fractions to the number of hospital admissions provided an estimation of the number of tobacco-related hospital admissions. RESULTS: In 2005, there were 89,800 clinical hospital admissions in the Netherlands that could be attributed to smoking in the age group 35 years or more. This amounts to 7.5% of all hospital admissions in this age group. CONCLUSION: A large number of hospital admissions can be attributed to smoking.

Monitoring of alcohol and drugs under scrutiny: output and shortcomings.

A major focus of Dutch addiction policy is to improve the monitoring of substance use and addiction - which surveys and registrations are important for the monitoring of alcohol and drugs problems, and what information is generated or needs to be generated by these monitors? Three methods were used: an inventorisation of existing monitoring projects, a survey among experts in the field of alcohol and drugs to study the information needs, and a study on the output and shortcomings of the existing monitors. Sixty monitors and 13 'umbrella' monitors were found. Experts formulated the needs of 11 topics which were matched with the output of the monitors. Coverage of the nature and extent of use in general is good. Shortcomings apply to the use and accessibility of the monitors, as well as to their completeness, standardisation and content. Especially questions with respect to problem use, treatment demand/need of help and user careers cannot be answered sufficiently with the existing information.

Dose related risk of motor vehicle crashes after cannabis use.

The role of Delta(9)-tetrahydrocannabinol (THC) in driver impairment and motor vehicle crashes has traditionally been established in experimental and epidemiological studies. Experimental studies have repeatedly shown that THC impairs cognition, psychomotor function and actual driving performance in a dose related manner. The degree of performance impairment observed in experimental studies after doses up to 300 microg/kg THC were equivalent to the impairing effect of an alcohol dose producing a blood alcohol concentration (BAC) >/=0.05 g/dl, the legal limit for driving under the influence in most European countries. Higher doses of THC, i.e. >300 microg/kg THC have not been systematically studied but can be predicted to produce even larger impairment. Detrimental effects of THC were more prominent in certain driving tasks than others. Highly automated behaviors, such as road tracking control, were more affected by THC as compared to more complex driving tasks requiring conscious control. Epidemiological findings on the role of THC in vehicle crashes have sometimes contrasted findings from experimental research. Case-control studies generally confirmed experimental data, but culpability surveys showed little evidence that crashed drivers who only used cannabis are more likely to cause accidents than drug free drivers. However, most culpability surveys have established cannabis use among crashed drivers by determining the presence of an inactive metabolite of THC in blood or urine that can be detected for days after smoking and can only be taken as evidence for past use of cannabis. Surveys that established recent use of cannabis by directly measuring THC in blood showed that THC positives, particularly at higher doses, are about three to seven times more likely to be responsible for their crash as compared to drivers that had not used drugs or alcohol. Together these epidemiological data suggests that recent use of cannabis may increase crash risk, whereas past use of cannabis does not. Experimental and epidemiological research provided similar findings concerning the combined use of THC and alcohol in traffic. Combined use of THC and alcohol produced severe impairment of cognitive, psychomotor, and actual driving performance in experimental studies and sharply increased the crash risk in epidemiological analyses.

Differential effects of amitriptyline, nefazodone and paroxetine on performance and brain indices of visual selective attention and working memory.

RATIONALE: Antidepressants may vary widely in their potential to impair cognitive and psychomotor functions. Little is known about their effects on event-related brain potentials (ERPs).OBJECTIVES. To compare the effects of three pharmacologically different antidepressants on performance and ERPs in tasks of selective attention and working memory. METHODS: Subjects were treated for 8 days with amitriptyline (sedative/anticholinergic TCA), nefazodone (5-HT(2) receptor antagonist), paroxetine (SSRI) and placebo, in a double-blind, crossover design. Measurements were carried out on day 1 and 8 of each treatment period. A task was used in which memory load (two and four items) and attention (focused, divided) were orthogonally varied. RESULTS: On day 1 amitriptyline increased reaction times (focused attention) and the percentage of misses (load 4>load 2) and false alarms. Sensitivity (A') was reduced as a function of memory load. Effects were greatly diminished on day 8. The ERP analysis yielded a reduced early frontal positive difference wave related to memory load (day 1). Attention-related search negativity was slightly prolonged. P3 latency (stimulus evaluation time) was prolonged. P3 amplitude was reduced (mainly on day 8) suggesting diminished attention capacity. Nefazodone increased reaction times and miss rates and reduced sensitivity (A') on day 8 only. Paroxetine speeded responses on day 1 and slightly increased miss rates on day 8. Performance effects of nefazodone and paroxetine did not interact with the task factors. Search negativity and P3 measures were not affected. CONCLUSIONS: The results suggest that the pharmacologically selective serotonergic antidepressants lack the specific memory and attention deficits seen with amitriptyline. Both performance and ERP data suggest that paroxetine and nefazodone may influence response-related processes, while for nefazodone an effect on other processes cannot be excluded.

Subchronic effects of the GABA-agonist lorazepam and the 5-HT2A/2C antagonist ritanserin on driving performance, slow wave sleep and daytime sleepiness in healthy volunteers.

RATIONALE: Lorazepam, a benzodiazepine anxiolytic, may increase daytime sleepiness and impair psychomotor performance, which is hazardous for patients engaging in daily activities such as car driving. Given current prescription practice, information on the repeated dose effects is required. The 5-HT2A/2C antagonist ritanserin was originally developed as a safer alternative to the benzodiazepines, yet having limited clinical efficacy. 5HT2A/2C receptors have been implicated in regulating slow-wave sleep but little is known about their role in human performance. OBJECTIVE: The present study investigated the subchronic effects of the benzodiazepine anxiolytic lorazepam and the 5-HT2A/2C antagonist ritanserin on actual driving performance, objective and subjective sleepiness, and nocturnal slow wave sleep. METHODS: Eighteen healthy volunteers were treated twice daily for 7 days with ritanserin 5 mg, lorazepam 1.5 mg or placebo. Treatments were administered according to a double-blind, cross-over design. Tests were performed on day 7 of each treatment week. Sleep EEG was recorded during the preceding night. RESULTS: Lorazepam had a pronounced impairing effect on lateral position control and induced daytime sleepiness, while having no effect on other parameters. In contrast, ritanserin did not impair driving performance or affect objectively measured daytime sleepiness, while subjects reported to feel more alert during daytime. Moreover, consistent with its effects on 5-HT2 receptors, ritanserin increased the amount of nocturnal slow wave sleep. There were no relationships between changes in slow wave sleep and performance parameters. CONCLUSIONS: Lorazepam administered for 7 consecutive days may be hazardous for patients who engage in driving activities. Antagonism of 5-HT2A/2C receptors, as accomplished by ritanserin, increases slow wave sleep and is devoid of effects on objective sleepiness and driving behaviour. Whether this extends to other cognitive and psychomotor domains remains to be established.

Chronic congestive heart failure is associated with a phenotypic shift of intramyocardial endothelial cells.

BACKGROUND: There is evidence that patients with chronic congestive heart failure have endothelial cell-related abnormalities of the peripheral circulation and the coronary microvasculature. For that reason, we have studied the phenotypic expression of endothelial cells in hearts of patients with congestive heart failure. METHODS AND RESULTS: We studied cardiac explants (n = 19) and autopsy hearts (n = 5) of patients with chronic congestive heart failure caused by either a dilated cardiomyopathy (n = 12) or ischemic heart disease (n = 12) and compared them with normal hearts (n = 12). The antigenic expression obtained with several endothelial cell markers (factor VIII-related antigen, EN-4, Ulex europaeus agglutinin-1 (UEA-1), PAL-E, endoglin, and endothelin) and adhesion molecules (intercellular adhesion molecule [ICAM], vascular cell adhesion molecule [VCAM], or E-selectin) was compared by use of immunohistochemical techniques. On the basis of the initial findings, the number of PAL-E- and EN-4-positive vessels was counted. The incidence of PAL-E-positive vessels per area was quantified and related to the percentage of heart muscle cells and the total number of vessels per area. In control hearts, endothelial cells rarely were positive for PAL-E. In hearts of patients with ischemic cardiomyopathies, there was distinct staining with this marker. Hearts of patients with dilated cardiomyopathies showed a marked increase in the number of PAL-E-positive endothelial cells. Vessels with a muscular media were PAL-E-negative. Two-sample analysis revealed a statistically significant difference between hearts with dilated cardiomyopathies and ischemic cardiomyopathies (P < .01), between hearts with dilated cardiomyopathies and control hearts (P < .01), and between hearts with ischemic cardiomyopathies and control hearts (P < .01). Endoglin and ICAM were positive but nondiscriminating. Endothelin, VCAM, and E-selectin were negative. CONCLUSIONS: A phenotypic shift in endothelial antigen expression of the coronary microvasculature occurs in both ischemic hearts and hearts with dilated cardiomyopathies, as revealed by PAL-E, compared with control hearts. The change may relate to compensatory mechanisms in long-standing chronic heart failure.

Acute and subchronic effects of nefazodone and imipramine on highway driving, cognitive functions, and daytime sleepiness in healthy adult and elderly subjects.

The acute and subchronic effects of two dosages of a new serotonergic antidepressant, nefazodone, and those of the tricyclic imipramine were examined in a double-blind, crossover, placebo-controlled study. Twenty-four healthy subjects from two age groups (12 adults and 12 elderly from both sexes) received the four treatments (nefazodone, 100 and 200 mg twice daily; imipramine, 50 mg twice daily; and placebo) for 7 days with a 7-day washout period. Measurements were performed after the morning doses on day 1 and day 7. These included a standard over-the-road highway driving test, a psychomotor test battery, and sleep latency tests. Blood samples were taken on both days and analyzed to determine concentrations of parent drugs and their major metabolites. The main results showed that the reference drug, imipramine, had a detrimental effect after a single dose on lateral position control in the driving test, primarily in the adult group, that diminished after repeated dosing. Minor impairment on psychomotor test performance was found with both days. On the other hand, a single administration of both doses of nefazodone did not impair highway driving performance (even showed some improvement) and had no or only minor effects on psychomotor performance. After repeated dosing, nefazodone 200 mg twice daily (but not the 100-mg dose) produced slight impairment of lateral position control; dose-related impairment of cognitive and memory functions was found. The effects of nefazodone were generally in the same direction in both age groups. Significant correlations were found between steady-state concentrations of nefazodone in plasma (200-mg, twice-daily condition) as well as imipramine, and reaction time changes in a memory scanning task. Neither drug appeared to induce daytime sleepiness as measured by the sleep latency tests.

A cetirizina pertence à nova geraçåo de anti-histamínicos?: uma investigaçåo de seus efeitos agudos e subcrônicos sobre a conduçåo de veículo em rodovia, o desempenho em testes psicométricos e a sonolência diurna / Does cetirizine belong to the new generation of antihistamines?: an investigation into its acute and subchronic effects on highway driving, psychometric test performance and daytime sleepiness

Vinte e sete voluntários saudáveis do sexo masculino participam deste ensaio duplo-cego cruzado em cinco etapas, que foi realizado para comparar um novo antagonista seletivo dos receptores de H1 - a cetirizina (10 mg q.d.) - e a terfenadina (60 mg b.i.d. e 120 mg q.d.) a um antagonista dos receptores de H1 mais tradicional, a tripolidina (5 mg b.i.d.), e a placebo. Os medicamentos foram administrados durante quatro dias consecutivos e os participantes foram testados no 1§ e no 4§ dias. No teste, os participantes já dirigiram um veículo equipado com instrumentos de mediçåo em uma rodovia de 100 Km, tentando manter uma velocidade constante (90 km/h) e um posionamento lateral estável na faixa de trafégo da direita. A seguir, foram submetidos a três testes computadorizados da memória. No 4§ dia de tratamento, a latência do sono foi medida antes e após o teste de direçåo. Em ambos os dias, a triprolidina comprometeu significativamente o desempenho dos participantes nos testes de direçåo e psicométricos, além de reduzir a latência, em comparaçåo com placebo, no 4§ dia de tratamento. A administraçåo de 60 m g b.i.d. de terfenadina comprometeu o desempenho psicométrico após o tratamento subcronico. Conclui-se que a cetirizina, com a terfenadina, pertence å classe mais recente de antihistamínicos e pode ser administrada com segurança a pacientes que continuam suas atitudes diárias