Modulation of nociceptive withdrawal reflexes evoked by single and repeated nociceptive stimuli in conscious dogs by low-dose acepromazine

OBJECTIVES: To investigate the modulation of the nociceptive withdrawal reflex (NWR) and temporal summation (TS) by low-dose acepromazine (ACP) in conscious dogs. To assess the short- and long-term stability of the reflex thresholds. STUDY DESIGN: Randomized, blinded, placebo-controlled cross-over experimental study. ANIMALS: Eight adult male Beagles. METHODS: The NWR was elicited using single transcutaneous electrical stimulation of the ulnar nerve. Repeated stimuli (10 pulses, 5 Hz) were applied to evoke TS. The responses of the deltoideus muscle were recorded and quantified by surface electromyography and the behavioural reactions were scored. Each dog received 0.01 mg kg(-1) ACP or an equal volume saline intravenously (IV) at 1 week intervals. Measurements were performed before (baseline) and 20, 60 and 100 minutes after drug administration. Sedation was scored before drug administration and then at 10 minutes intervals. Data were analyzed with Friedman repeated measures analysis of variance on ranks and Wilcoxon signed rank tests. RESULTS: Acepromazine resulted in a mild tranquilization becoming obvious at 20 minutes and peaking 30 minutes after injection. Single (I(t)) and repeated stimuli (TS(t)) threshold intensities, NWR and TS characteristics and behavioural responses were not affected by the ACP at any time point. Both I(t) and TS(t) were stable over time. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, 0.01 mg kg(-1) ACP IV had no modulatory action on the NWR evoked by single or repeated stimuli, suggesting no antinociceptive activity on phasic nociceptive stimuli. The evidence of the stability of the NWR thresholds supports the use of the model as an objective tool to investigate nociception in conscious dogs. A low dose of ACP administered as the sole drug, can be used to facilitate the recordings in anxious subjects without altering the validity of this model.

Plasma levels of a low-dose constant-rate-infusion of ketamine and its effect on single and repeated nociceptive stimuli in conscious dogs

This study quantitatively investigated the analgesic action of a low-dose constant-rate-infusion (CRI) of racemic ketamine (as a 0.5 mg kg(-1) bolus and at a dose rate of 10 microg kg(-1) min(-1)) in conscious dogs using a nociceptive withdrawal reflex (NWR) and with enantioselective measurement of plasma levels of ketamine and norketamine. Withdrawal reflexes evoked by transcutaneous single and repeated electrical stimulation (10 pulses, 5 Hz) of the digital plantar nerve were recorded from the biceps femoris muscle using surface electromyography. Ketamine did not affect NWR thresholds or the recruitment curves after a single nociceptive stimulation. Temporal summation (as evaluated by repeated stimuli) and the evoked behavioural response scores were however reduced compared to baseline demonstrating the antinociceptive activity of ketamine correlated with the peak plasma concentrations. Thereafter the plasma levels at pseudo-steady-state did not modulate temporal summation. Based on these experimental findings low-dose ketamine CRI cannot be recommended for use as a sole analgesic in the dog.

Prevalence and predictors of suicide attempt in an incidence cohort of 661 young people with first-episode psychosis

Studies investigating suicidal behaviour in psychosis rarely focus on incidence cohorts of first-episode patients. This is important, because patients who refuse study participation have higher rates of comorbid substance use disorders and longer duration of untreated psychosis as well as worse course illness, variables potentially linked to higher prevalence of suicidal behaviour. The aims of the present study were therefore to examine the prevalence and predictors of suicide and suicide attempt before and during the first 18-24 months of treatment.

Incidence and risk factors of homicide-suicide in Swiss households: National Cohort study

BACKGROUND Homicide-suicides are rare but catastrophic events. This study examined the epidemiology of homicide-suicide in Switzerland. METHODS The study identified homicide-suicide events 1991-2008 in persons from the same household in the Swiss National Cohort, which links census and mortality records. The analysis examined the association of the risk of dying in a homicide-suicide event with socio-demographic variables, measured at the individual-level, household composition variables and area-level variables. Proportional hazards regression models were calculated for male perpetrators and female victims. Results are presented as age-adjusted hazard ratios (HR) with 95% confidence intervals (95%CI). RESULTS The study identified 158 deaths from homicide-suicide events, including 85 murder victims (62 women, 4 men, 19 children and adolescents) and 68 male and 5 female perpetrators. The incidence was 3 events per million households and year. Firearms were the most prominent method for both homicides and suicides. The risk of perpetrating homicide-suicide was higher in divorced than in married men (HR 3.64; 95%CI 1.56-8.49), in foreigners without permanent residency compared to Swiss citizens (HR 3.95; 1.52-10.2), higher in men without religious affiliations than in Catholics (HR 2.23; 1.14-4.36) and higher in crowded households (HR 4.85; 1.72-13.6 comparing ≥2 with <1 persons/room). There was no association with education, occupation or nationality, the number of children, the language region or degree of urbanicity. Associations were similar for female victims. CONCLUSIONS This national longitudinal study shows that living conditions associated with psychological stress and lower levels of social support are associated with homicide-suicide events in Switzerland.

Religion and suicide in patients with mental illness or cancer

In Switzerland, the highest rates of suicide are observed in persons without religious affiliation and the lowest in Catholics, with Protestants in an intermediate position. We examined whether this association was modified by concomitant psychiatric diagnoses or malignancies, based on 6,909 suicides (ICD-10 codes X60-X84) recorded in 3.69 million adult residents 2001-2008. Suicides were related to mental illness or cancer if codes F or C, respectively, were mentioned on the death certificate. The protective effect of religion was substantially stronger if a diagnosis of cancer was mentioned on the death certificate and weaker if a mental illness was mentioned.

Euthanasia and assisted suicide in selected European countries and US states: systematic literature review

BACKGROUND Legal in some European countries and US states, physician-assisted suicide and voluntary active euthanasia remain under debate in these and other countries. OBJECTIVES The aim of the study was to examine numbers, characteristics, and trends over time for assisted dying in regions where these practices are legal: Belgium, Luxembourg, the Netherlands, Switzerland, Oregon, Washington, and Montana. DESIGN This was a systematic review of journal articles and official reports. Medline and Embase databases were searched for relevant studies, from inception to end of 2012. We searched the websites of the health authorities of all eligible countries and states for reports on physician-assisted suicide or euthanasia and included publications that reported on cases of physician-assisted suicide or euthanasia. We extracted information on the total number of assisted deaths, its proportion in relation to all deaths, and socio-demographic and clinical characteristics of individuals assisted to die. RESULTS A total of 1043 publications were identified; 25 articles and reports were retained, including series of reported cases, physician surveys, and reviews of death certificates. The percentage of physician-assisted deaths among all deaths ranged from 0.1%-0.2% in the US states and Luxembourg to 1.8%-2.9% in the Netherlands. Percentages of cases reported to the authorities increased in most countries over time. The typical person who died with assistance was a well-educated male cancer patient, aged 60-85 years. CONCLUSIONS Despite some common characteristics between countries, we found wide variation in the extent and specific characteristics of those who died an assisted death.

Suicide assisted by right-to-die associations: a population based cohort study

Background: In Switzerland, assisted suicide is legal but there is concern that vulnerable or disadvantaged groups are more likely to die in this way than other people. We examined socio-economic factors associated with assisted suicide. Methods: We linked the suicides assisted by right-to-die associations during 2003–08 to a census-based longitudinal study of the Swiss population. We used Cox and logistic regression models to examine associations with gender, age, marital status, education, religion, type of household, urbanization, neighbourhood socio-economic position and other variables. Separate analyses were done for younger (25 to 64 years) and older (65 to 94 years) people. Results: Analyses were based on 5 004 403 Swiss residents and 1301 assisted suicides (439 in the younger and 862 in the older group). In 1093 (84.0%) assisted suicides, an underlying cause was recorded; cancer was the most common cause (508, 46.5%). In both age groups, assisted suicide was more likely in women than in men, those living alone compared with those living with others and in those with no religious affiliation compared with Protestants or Catholics. The rate was also higher in more educated people, in urban compared with rural areas and in neighbourhoods of higher socio-economic position. In older people, assisted suicide was more likely in the divorced compared with the married; in younger people, having children was associated with a lower rate. Conclusions: Assisted suicide in Switzerland was associated with female gender and situations that may indicate greater vulnerability such as living alone or being divorced, but also with higher education and higher socio-economic position.

Hypoxia refines plasticity of mitochondrial respiration to repeated muscle work.

PURPOSE We explored whether altered expression of factors tuning mitochondrial metabolism contributes to muscular adaptations with endurance training in the condition of lowered ambient oxygen concentration (hypoxia) and whether these adaptations relate to oxygen transfer as reflected by subsarcolemmal mitochondria and oxygen metabolism in muscle. METHODS Male volunteers completed 30 bicycle exercise sessions in normoxia or normobaric hypoxia (4,000 m above sea level) at 65% of the respective peak aerobic power output. Myoglobin content, basal oxygen consumption, and re-oxygenation rates upon reperfusion after 8 min of arterial occlusion were measured in vastus muscles by magnetic resonance spectroscopy. Biopsies from vastus lateralis muscle, collected pre and post a single exercise bout, and training, were assessed for levels of transcripts and proteins being associated with mitochondrial metabolism. RESULTS Hypoxia specifically lowered the training-induced expression of markers of respiratory complex II and IV (i.e. SDHA and isoform 1 of COX-4; COX4I1) and preserved fibre cross-sectional area. Concomitantly, trends (p < 0.10) were found for a hypoxia-specific reduction in the basal oxygen consumption rate, and improvements in oxygen repletion, and aerobic performance in hypoxia. Repeated exercise in hypoxia promoted the biogenesis of subsarcolemmal mitochondria and this was co-related to expression of isoform 2 of COX-4 with higher oxygen affinity after single exercise, de-oxygenation time and myoglobin content (r ≥ 0.75). Conversely, expression in COX4I1 with training correlated negatively with changes of subsarcolemmal mitochondria (r < -0.82). CONCLUSION Hypoxia-modulated adjustments of aerobic performance with repeated muscle work are reflected by expressional adaptations within the respiratory chain and modified muscle oxygen metabolism.

Repeated measurements of cerebral blood flow in the left superior temporal gyrus reveal tonic hyperactivity in patients with auditory verbal hallucinations: a possible trait marker

Background: The left superior temporal gyrus (STG) has been suggested to play a key role in auditory verbal hallucinations (AVH) in patients with schizophrenia. Methods: Eleven medicated subjects with schizophrenia and medication-resistant AVH and 19 healthy controls underwent perfusion magnetic resonance (MR) imaging with arterial spin labeling (ASL). Three additional repeated measurements were conducted in the patients. Patients underwent a treatment with transcranial magnetic stimulation (TMS) between the first 2 measurements. The main outcome measure was the pooled cerebral blood flow (CBF), which consisted of the regional CBF measurement in the left STG and the global CBF measurement in the whole brain. Results: Regional CBF in the left STG in patients was significantly higher compared to controls (p < 0.0001) and to the global CBF in patients (p < 0.004) at baseline. Regional CBF in the left STG remained significantly increased compared to the global CBF in patients across time (p < 0.0007), and it remained increased in patients after TMS compared to the baseline CBF in controls (p < 0.0001). After TMS, PANSS (p = 0.003) and PSYRATS (p = 0.01) scores decreased significantly in patients. Conclusions: This study demonstrated tonically increased regional CBF in the left STG in patients with schizophrenia and auditory hallucinations despite a decrease in symptoms after TMS. These findings were consistent with what has previously been termed a trait marker of AVH in schizophrenia.

Repeated and predictable patterns of ecotypic differentiation during a biological invasion: lake-stream divergence in parapatric Swiss stickleback

The relative importance of ecological selection and geographical isolation in promoting and constraining genetic and phenotypic differentiation among populations is not always obvious. Interacting with divergent selection, restricted opportunity for gene flow may in some cases be as much a cause as a consequence of adaptation, with the latter being a hallmark of ecologi- cal speciation. Ecological speciation is well studied in parts of the native range of the three-spined stickleback. Here, we study this process in a recently invaded part of its range. Switzerland was colonized within the past 140 years from at least three different colonization events involving differ- ent stickleback lineages. They now occupy diverse habitats, ranging from small streams to the pelagic zone of large lakes. We use replicated systems of parapatric lake and stream populations, some of which trace their origins to different invasive lineages, to ask (i) whether phenotypic divergence occurred among populations inhabiting distinct habitats, (ii) whether trajec- tories of phenotypic divergence follow predictable parallel patterns and (iii) whether gene flow constrains divergent adaptation or vice versa. We find consistent phenotypic divergence between populations occupying distinct habitats. This involves parallel evolution in several traits with known eco- logical relevance in independent evolutionary lineages. Adaptive divergence supersedes homogenizing gene flow even at a small spatial scale. We find evidence that adaptive phenotypic divergence places constraints on gene flow over and above that imposed by geographical distance, signalling the early onset of ecological speciation.

Change in suicide rates in Switzerland before and after firearm restriction resulting from the 2003 “Army XXI” reform

Objective: Firearms are the most common method of suicide among young men in Switzerland. From March 2003 through February 2004, the number of Swiss soldiers was halved as a result of an army reform (Army XXI), leading to a decrease in the availability of guns nationwide. The authors investigated the patterns of the overall suicide rate and the firearm suicide rate before and after the reform. Method: Using a naturalistic study design, the authors compared suicide rates before (1995–2003) and after the intervention (2004–2008) in the affected population (men ages 18–43) and in two comparison groups (women ages 18–44 and men ages 44–53). Data were received from the Swiss Federal Statistical Office. Interrupted time series analysis was used to control for preexisting temporal trends. Alternative methods (Poisson regression, autocorrelation analysis, and surrogate data tests) were used to check validity. Results: The authors found a reduction in both the overall suicide rate and the firearm suicide rate after the Army XXI reform. No significant increases were found for other suicide methods overall. An increase in railway suicides was observed. It was estimated that 22% of the reduction in firearm suicides was substituted by other suicide methods. The attenuation of the suicide rate was not compensated for during the follow-up years. Neither of the comparison groups showed statistically significant changes in firearm suicide rate and overall suicide rate. Conclusions: The restriction of firearm availability in Switzerland resulting from the Army XXI reform was followed by an enduring decrease in the general suicide rate.

Smoking behaviour, former quit attempts and intention to quit in urban adolescents and young adults: A five-year longitudinal study

OBJECTIVES: To examine smoking behaviour, former quit attempts and intention to quit among Swiss adolescents and young adults over five year's time. STUDY DESIGN: five-year longitudinal study (2003, 2005 and 2008) based on a random urban community sample (N = 1345 complete cases). METHODS: Data were collected by computer-assisted telephone interviews with adolescents (16-17) and young adults (18-24). Main outcome measures included self-reported smoking behaviour, former quit attempts, smoking cessation methods and current intentions to quit smoking. RESULTS: Adolescents were more often non-smokers and less often daily smokers when compared to young adults at baseline (χ(2)(4) = 28.68, P < .001). Their smoking behaviour increased significantly from baseline to follow-up (T = 1445.50, r = .20, P < .001) in contrast to the stable smoking behaviour in young adults (χ(2)(2) = .12, n.s.). In longitudinal analyses young adults were also more stable in their smoking status at the later measurement points. In comparison adolescents changed their smoking status more often being non-smokers at baseline and smokers later on. Independently of the age group, the majority of smokers already had previously attempted to quit (65%) or intended to give up smoking at some point (72%). However only 17% were motivated to make the quit attempt within the next 6 months. Self-quitting was the preferred method, and 25% of the self-quitters had been successful. CONCLUSION: This study illustrates that different developments in smoking behaviour exist in adolescents and young adults. Our study reveals that a majority of smokers are willing to quit but often fail. Furthermore, the data indicates that for adolescents the focus should lie on primary prevention.