Post-traumatic stress disorder in patients 3 years after aneurysmal subarachnoid haemorrhage.

BACKGROUND: Subarachnoid haemorrhage (SAH) from a ruptured intracranial aneurysm accounts for approximately 5% of all strokes. Post-traumatic stress disorder (PTSD) is common in the early phase after recovery from aneurysmal SAH. The aim of our study was to examine the prevalence of PTSD 3 years after SAH, its predictors, and relationship with health-related quality of life (HRQoL) in patients living independently in the community. METHODS: From a prospectively collected cohort of 143 patients with aneurysmal SAH who visited our outpatient clinic 3 months after SAH, 94 patients (65.7%) completed a mailed questionnaire 3 years after SAH. We assessed PTSD with the Impact of Event Scale and HRQoL with the Stroke-Specific Quality of Life Scale (SS-QoL). The χ(2) and t tests were used to investigate if patients who returned the questionnaires were different from those who did not reply. Non-parametric tests (χ(2) and Mann-Whitney tests) were used to test for differences between patients with and without PTSD. Relative risks and 95% confidence intervals were calculated. RESULTS: No relevant differences in demographic (age, sex, education) or SAH characteristics (clinical condition on admission, complication, location of aneurysm, Glasgow Outcome Scale score at 3 months) were seen between participants and drop-outs. In 24 patients (26%), Impact of Event Scale scores indicated PTSD. Passive coping style (relative risk, 5.7; 95% confidence interval, 2.1-15.3), but none of the demographic or SAH-related factors, predicted PTSD. The mean SS-QoL total score was 4.2 (SD 1.1), indicative of a relatively satisfactory HRQoL. PTSD was associated with lower HRQoL (p < 0.001), a mean SS-QoL score of 4.4 (SD 1.0) without PTSD, and a mean SS-QoL score of 3.5 (SD 1.1) with PTSD. CONCLUSIONS: Even 3 years after SAH, 1 out of 4 patients had PTSD, which was associated with reduced HRQoL. Passive coping style was the most important predictor. There is a need to organize SAH care with more attention to and treatment of PTSD. Strategies shown to reduce PTSD in other conditions should be tested for effectiveness in SAH patients.

Determinants of health-related quality of life after aneurysmal subarachnoid hemorrhage: a systematic review.

BACKGROUND AND PURPOSE: Many persons with subarachnoid hemorrhage (SAH) from a ruptured intracranial aneurysm recover to functional independence but nevertheless experience reduced quality of life (QoL). The aim of this study was to summarize the evidence on determinants of reduced QoL in this diagnostic group. METHODS: Databases PubMed, PsychINFO, and CINAHL were used to identify empirical studies reporting on quantitative relationships between possible determinants and QoL in persons with aneurysmal SAH and published in English. Determinants were classified using the International Classification of Functioning, Disability and Health (ICF). RESULTS: Twenty studies met the inclusion criteria for this review, in which 13 different HRQoL questionnaires were used. Determinants related to Body Structure & Function (clinical condition at admission, fatigue, and disturbed mood), Activity limitations (physical disability and cognitive complaints), and Personal factors (female gender, higher age, neuroticism, and passive coping) are consistently related to worse HRQoL after aneurysmal SAH. Treatment characteristics were not consistently related to HRQoL. CONCLUSION: This study identified a broad range of determinants of HRQoL after aneurysmal SAH. The findings provide clues to tailor multidisciplinary rehabilitation programs. Further research is needed on participation, psychological characteristics, and environmental factors as determinants of HRQoL after SAH.

The Self-Regulation Assessment (SeRA) questionnaire: development and exploratory analyses of a new patient-reported outcome measure for rehabilitation.

PURPOSE: To develop and explore underlying dimensions of the Self-Regulation Assessment (SeRA) and psychometric features of potential components. Further, to identify associations between the SeRA and disability-management self-efficacy, type of diagnosis, and type of rehabilitation. MATERIALS AND METHODS: Based on a previously developed model of self-regulation, expert and patient opinions, and cognitive interviews, a list of 22 items on self-regulation (the SeRA) was constructed. The SeRA was included in a cross-sectional survey among a multi-diagnostic group of 563 former rehabilitation patients. Exploratory analyses were conducted. RESULTS: Respondents had a mean age of 56.5 (SD 12.7) years. The largest diagnostic groups were chronic pain disorder and brain injury. Four components were found within the SeRA, labelled as "insight into own health condition," "insight into own capabilities," "apply self-regulation," and "organization of help." Cronbach's alpha was high (total scale: 0.93, subscales: range 0.85-0.89). Only scores on the first subscale showed a ceiling effect. Subscale three showed the highest correlation with a self-efficacy measure. Small differences in SeRA total scores (range 71.6-78.1) were found between different diagnostic groups. CONCLUSION: The SeRA is a new self-regulation measure with four subscales. Further research is needed to establish the validity and reliability of the SeRA. IMPLICATIONS FOR REHABILITATIONThe Self-Regulation Assessment (SeRA) was developed to provide a comprehensive measurement of self-regulation among rehabilitation populations.The SeRA could potentially be used to identify persons with self-regulation problems at the start of rehabilitation treatment and measure outcomes of rehabilitation for self-regulation.The SeRA could potentially be used to help analyse outcomes of rehabilitation practice as well as evaluate interventions on self-regulation.

Prevalence and determinants of cognitive complaints after aneurysmal subarachnoid hemorrhage.

BACKGROUND: To investigate the prevalence of cognitive complaints after subarachnoid hemorrhage (SAH) and the relationships between cognitive complaints and cognitive impairments, disability and emotional problems. METHODS: Cognitive complaints were assessed with the Checklist for Cognitive and Emotional Consequences following stroke (CLCE-24) in 111 persons who visited our outpatient clinic 3 months after SAH. Associations between cognitive complaints and cognitive functioning, demographic characteristics, disability and emotional problems were examined using Spearman correlations and linear regression analysis. RESULTS: In this study group, 105 patients (94.6%) reported at least one cognitive or emotional complaint that hampered everyday functioning. The most frequently reported cognitive complaints were mental slowness, short-term memory problems and attention deficits. All cognitive domains, disability, depressive symptoms and feelings of anxiety were significantly associated with the CLCE-24 cognition score. In the final regression model, memory functioning (beta value -0.21), disability (-0.28) and depressive symptoms (0.40) were significant determinants of cognitive complaints, together explaining 35.4% of the variance. CONCLUSION: Cognitive complaints are common after SAH and associated with memory deficits, disability and depressive symptoms. Rehabilitation programs should focus on these symptoms and deficits.

Pharmacodynamic and pharmacokinetic effects of the intravenously administered CB1 receptor agonist Org 28611 in healthy male volunteers.

CB1/CB2 agonists are reported to have sedative, amnestic, analgesic and anti-emetic properties, which would make them ideal drugs for outpatient treatments under conscious sedation. The main objective of this in human study was to assess the sedative properties of Org 28611, a potent water-soluble CB1 agonist. Single ascending doses were administered during a slow 25 min infusion and after a 1 min bolus administration to healthy male volunteers. In addition, the pharmacokinetics, amnestic properties, postural stability, electro-encephalography, behavioural and cardiovascular effects were studied. Midazolam 0.1 mg/kg was used as a positive control. The pharmacokinetic parameters were proportional to dose. No effects were observed after intravenous administration of doses up to Org 28611 1 microg/kg. Dose-related effects were observed at higher doses. Although subjects reported subjective sedation after administration of Org 28611 3-10 microg/kg, the observed sedation was considerably less than after midazolam. Org 28611 is, therefore, not suitable for providing sedation for outpatient surgical procedures and doses above the maximum tolerated dose of 3 microg/kg (either administered as a slow infusion or a bolus dose) can cause untoward psychotropic effects.

Isolation and characterization of an adipokinetic hormone release-inducing factor in locusts: the crustacean cardioactive peptide.

A methanolic extract of 7000 desert locust (Schistocerca gregaria) brains contains several factors that stimulate the in vitro release of adipokinetic hormone (AKH) by glandular cells of locust (Locusta migratoria and Schistocerca gregaria) corpora cardiaca. The most potent one has now been fully identified. Matrix-assisted laser desorption ionization mass spectrometry-time of flight analysis revealed a mass of 954.6 Da. The primary structure of the peptide, Pro-Phe-Cys-Asn-Ala-Phe-Thr-Gly-Cys-NH2, appeared identical to that of a previously identified crustacean cardioactive peptide. This myotropin was first isolated from the shore crab, Carcinus maenas, and later from several insect species, but was never reported in the context of AKH release. The present study shows that synthetic crustacean cardioactive peptide induces the release of AKH from corpora cardiaca in a dose-dependent manner when tested in concentrations ranging from 10(-5)-10(-9) M. This is the first demonstration in invertebrates of a peptide neurohormone controlling the release of a second peptide hormone.

Trehalose inhibits the release of adipokinetic hormones from the corpus cardiacum in the African migratory locust, Locusta migratoria, at the level of the adipokinetic cells.

The effect of trehalose at various concentrations on the release of adipokinetic hormones (AKHs) from the adipokinetic cells in the glandular part of the corpus cardiacum of Locusta migratoria was studied in vitro. Pools of five corpora cardiaca or pools of five glandular parts of corpora cardiaca were incubated in a medium containing different concentrations of trehalose in the absence or presence of AKH-release-inducing agents. It was demonstrated that trehalose inhibits spontaneous release of AKH I in a dose-dependent manner. At a concentration of 80 mM, which is the concentration found in the hemolymph at rest, trehalose significantly decreased the release of AKH I induced by 100 microM locustatachykinin 1, 10 microM 3-isobutyl-1-methylxanthine (IBMX) or high potassium concentrations. The specificity of the effect of trehalose was studied by incubating pools of corpora cardiaca with the non-hydrolyzable disaccharide sucrose or with glucose, the degradation product of trehalose, both in the presence and absence of 10 microM IBMX. Sucrose had no effect at all on the release of AKH I, whereas glucose strongly inhibited its release. The results point to the inhibitory effect of trehalose on the release of AKH I being exerted, at least partly, at the level of the adipokinetic cells, possibly after its conversion into glucose. The data presented in this study support the hypothesis that in vivo the relatively high concentration of trehalose (80 mM) at rest strongly inhibits the release of AKHs. At the onset of flight, the demand for energy substrates exceeds the amount of trehalose that can be mobilized from the fat body and consequently the trehalose concentration in the hemolymph decreases. This relieves the inhibitory effect of trehalose on the release of AKHs, which in turn mobilize lipids from the fat body.

Evidence that locustatachykinin I is involved in release of adipokinetic hormone from locust corpora cardiaca.

The glandular cells of the corpus cardiacum of the locust Locusta migratoria, known to synthesize and release adipokinetic hormones (AKH), are contacted by axons immunoreactive to an antiserum raised against the locust neuropeptide locustatachykinin I (LomTK I). Electron-microscopical immunocytochemistry reveals LomTK immunoreactive axon terminals, containing granular vesicles, in close contact with the glandular cells cells. Release of AKH I from isolated corpora cardiaca of the locust has been monitored in an in vitro system where the amount of AKH I released into the incubation saline is determined by reversed phase high performance liquid chromatography with fluorometric detection. We could show that LomTK I induces release of AKH from corpora cardiaca in a dose-dependent manner when tested in a range of 10-200 microM. This is thus the first clear demonstration of a substance inducing release of AKH, correlated with the presence of the substance in fibers innervating the AKH-synthesizing glandular cells, in the insect corpora cardiaca.

A novel approach to identify responder subgroups and predictors of response to low- and high-dose capsaicin patches in postherpetic neuralgia.

BACKGROUND: Treatment of chronic pain conditions is commonly assessed at specific endpoints at preset times during or after treatment by analysis of the total study population. An alternative approach is the identification of specific patient subgroups characterized by differential response patterns in their analgesic response and to determine the presence of significant predictors of effect. METHODS: Data from four double-blind, randomized controlled trials on the efficacy of topical capsaicin 8% (Qutenza) versus an active control (capsaicin 0.04%) in patients with postherpetic neuropathic pain were combined. Longitudinal pharmacodynamic, mixture and covariate analyses were performed on the pooled dataset. RESULTS: Data from 1248 patients treated with Qutenza (n = 722) or topical low-dose capsaicin 0.04% (n = 526) were successfully analysed. Five distinct response subgroups were detected with different treatment efficacies, including a group of non-responders, a group showing partial analgesic effect and a group showing full analgesic effect. Active control and Qutenza had similar response profiles, but the proportional distribution of patients among the five response groups was in favour of Qutenza, with 40% less non-responders and 25% more patients showing a full analgesic response. For Qutenza, important predictors of efficacy were efficacy of lidocaine pretreatment and greater pretreatment pain score variability. CONCLUSIONS: The analyses indicate the existence of different response groups to treatment with Qutenza and an active control patch that may possibly be related to different pain mechanisms among these groups, despite a presumed common underlying disease process, and that require different treatment approaches among subgroups.

Predictors of long-term health-related quality of life in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To determine the predictive value of physical and psychological factors assessed three months after aneurysmal subarachnoid hemorrhage (SAH) for health-related quality of life (HRQoL) one year after the SAH. DESIGN: Prospective cohort study. SUBJECTS: Patients with SAH (n=113) who visited our SAH-outpatient clinic three months after SAH and who were living independently in the community one year after SAH. METHODS: HRQoL was evaluated using the Stroke Specific Quality of Life scale (SS-QoL). We used Spearman correlations, Somers'd, and linear regression analyses. Independent variables were demographic and SAH characteristics, cognitive and emotional complaints, depressive symptoms, anxiety, cognitive functioning, and passive coping style. RESULTS: In the regression analysis, female gender (beta value -0.17), cognitive complaints (-0.31 ), cognitive functioning (0.40) and passive coping style (-0.23) were independent predictors, and together explained 45.9% of the variance of the SS-QoL total score. CONCLUSION: Female gender, cognitive complaints, cognitive functioning and passive coping style assessed at 3 months after SAH are important predictors of HRQoL 1 year after SAH. Early interventions to improve cognitive and emotional functioning should be evaluated for their ability to improve long-term HRQoL after SAH.

Predicting fatigue 1 year after aneurysmal subarachnoid hemorrhage.

Fatigue is an important contributor to quality of life in patients who survive aneurysmal subarachnoid hemorrhage (SAH), but the determinants of this fatigue are unclear. We assessed the occurrence of fatigue 1 year after SAH and its relation to physical or cognitive impairment, passive coping, and emotional problems, measured 3 months after SAH. This was a prospective cohort study of 108 patients who visited our SAH outpatient clinic 3 months after SAH and who were living independently in the community 1 year after SAH. Fatigue was evaluated using the Fatigue Severity Scale (FSS). Analysis of variance was used to analyze the data. Fatigue (FSS ≥ 4) was present in 77 patients (71%). Mean FSS scores were 4.1 (SD 1.6) in the group of patients having 'neither physical nor cognitive impairment,' 5.2 (1.4) having 'either physical or cognitive impairment,' and 5.9 (0.9) having 'both physical and cognitive impairments.' Mean FSS scores were higher in patients scoring high on passive coping (85 vs. 58%; RR 1.46, 95% CI 1.13-1.87), anxiety (84 vs. 55%; RR 1.53, 95% CI 1.17-2.02), or depression (85 vs. 62%; RR 1.36, 95% CI 1.08-1.72) than in patients without these complaints. Relationships between these complaints and FSS scores were higher in patients having neither physical nor cognitive impairments than in patients having physical or cognitive impairments. Fatigue is common after SAH and is related to physical and cognitive impairments. In patients with neither physical nor cognitive impairments, passive coping style and emotional problems are important predictors of fatigue.

Prevalence of silicosis in the Dutch fine-ceramic industry.

In the nineteen-seventies a cross-sectional survey was conducted in the Dutch fine-ceramic industry. Workers employed in the ceramic industry (n = 3258) were examined for the presence of silicosis. In this article the results are reported for the area of Gouda and Maastricht. In Gouda the fine-ceramic industry consists of small workshops. The Maastricht working population comprises workers of two large, mechanized companies. The survey indicated that silicosis is still commonly present in Gouda (total prevalence of 13.3%), but is relatively rare in Maastricht (total prevalence of 1.7%). A clear dose-response relationship was found in both areas between duration of exposure to quartz-containing dust and the prevalence of silicosis. Furthermore it was noted that smoking was a risk factor for silicosis. However, this was restricted to workers who were heavy smokers and had had an occupational history of 20 years or more of exposure to quartz-containing dust. In this exposure category the prevalence of silicosis among heavy smokers was 50% higher than in light smokers and non-smokers.

Modulatory effects of biogenic amines on adipokinetic hormone secretion from locust corpora cardiaca in vitro.

The control of the release of adipokinetic hormones from neurosecretory cells within the glandular lobes of the corpus cardiacum involving axons running through the paired nervus corporis cardiaci II is unclear. Cyclic-AMP (cAMP) is clearly a second messenger. The effects of four biogenic amines (octopamine, dopamine, tyramine, and serotonin) on the release of adipokinetic hormone-I were investigated in vitro. None had an effect on its own; they all potentiated the hormone release induced by cAMP-activating agents. Dopamine and serotonin were only present in the neurohemal part of the corpus cardiacum. Octopamine and tyramine were not detectable in the corpus cardiacum.

Basilar migraine with severe EEG abnormalities.

We report a patient suffering from a series of attacks fulfilling the criteria of basilar migraine. During the attack there was no normal EEG background pattern and the EEG showed predominantly delta activity. After the attack the EEG returned to (nearly) normal in a very short time. Up to now no such EEG findings have been reported in basilar migraine.

Role of fatty acid-binding protein in lipid metabolism of insect flight muscle.

Since insect flight muscles are among the most active muscles in nature, their extremely high rates of fuel supply and oxidation pose interesting physiological problems. Long-distance flights of species like locusts and hawkmoths are fueled through fatty acid oxidation. The lipid substrate is transported as diacylglycerol in the blood, employing a unique and efficient lipoprotein shuttle system. Following diacyglycerol hydrolysis by a flight muscle lipoprotein lipase, the liberated fatty acids are ultimately oxidized in the mitochondria. Locusta flight muscle cytoplasm contains an abundant fatty acid-binding protein (FABP). The flight muscle FABP of Locusta migratoria is a 15 kDa protein with an isoelectric point of 5.8, binding fatty acids in a 1:1 molar stoichiometric ratio. Binding affinity of the FABP for long-chain fatty acids (apparent dissociation constant Kd = 5.21 +/- 0.16 microM) is however markedly lower than that of mammalian FABPs. The NH2-terminal amino acid sequence shares structural homologies with two insect FABPs recently purified from hawkmoth midgut, as well as with mammalian FABPs. In contrast to all other isolated FABPs, the NH2 terminus of locust flight muscle FABP appeared not to be acetylated. During development of the insect, a marked increase in fatty acid binding capacity of flight muscle homogenate was measured, along with similar increases in both fatty acid oxidation capacity and citrate synthase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

A possible role of SchistoFLRFamide in inhibition of adipokinetic hormone release from locust corpora cardiaca.

The distribution and actions of FMRFamide-related peptides (FaRPs) in the corpora cardiaca of the locust Locusta migratoria were studied. Antisera to FMRFamide and SchistoFLRFamide (PDVDHVFLRFamide) label neuronal processes that impinge on glandular cells in the glandular lobe of the corpora cardiaca known to produce adipokinetic hormones. Electron microscopic immunocytochemistry revealed that these FaRP-containing processes form synaptoid contacts with the glandular cells. Approximately 12% of the axon profiles present in the glandular part of the corpus cardiacum contained SchistoFLRFamide-immunoreactive material. Retrograde tracing of the axons in the nervus corporis cardiaci II with Lucifer yellow revealed 25-30 labelled neuronal cell bodies in each lateral part of the protocerebrum. About five of these in each hemisphere reacted with the SchistoFLRFamide-antiserum. Double-labelling immunocytochemistry showed that the FaRP-containing processes in the glandular lobe of the corpora cardiaca are distinct from neuronal processes, reacting with an antiserum to the neuropeptide locustatachykinin. The effect of the decapeptide SchistoFLRFamide and the tetrapeptide FMRFamide on the release of adipokinetic hormone I (AKH I) from the cells in the glandular part of the corpus cardiacum was studied in vitro. Neither the deca- nor the tetrapeptide had any effect on the spontaneous release of AKH I. Release of AKH I induced by the phosphodiesterase inhibitor IBMX, however, was reduced significantly by both peptides. These results point to an involvement of FaRPs as inhibitory modulators in the regulation of the release of adipokinetic hormone from the glandular cells.

Several isoforms of locustatachykinins may be involved in cyclic AMP-mediated release of adipokinetic hormones from the locust Corpora cardiaca.

Four locustatachykinins (LomTK I-IV) were identified in about equal amounts in extracts of corpora cardiaca of locusts, using reverse-phase high-performance liquid chromatography and radioimmunoassay with synthetic LomTK I-IV as standards. Brain extracts also contained the four isoforms in roughly equimolar concentrations. Retrograde tracing of the nervi corporis cardiaci II (NCC II) in vitro with Lucifer yellow in combination with LomTK immunocytochemistry revealed that about half of the secretomotor neurons in the lateral part of the protocerebrum projecting into the glandular lobe of the corpora cardiaca (CCG) contain LomTK-immunoreactive material. Since the four LomTKs are present in the CCG, these four or five neurons in each hemisphere are likely to contain colocalized LomTK I-IV. The role of two of the LomTKs in the regulation of the release of adipokinetic hormones (AKHs) from the adipokinetic cells in the CCG in the locust was investigated. Experiments performed in vitro showed that LomTK I and II induced release of AKH in a dose-dependent manner. These peptides also rapidly and transiently elevated the cyclic AMP-content of the CCG. The peak level of cyclic AMP occurred about 45 seconds after stimulation with LomTK. These results support the proposal that LomTKs are involved in controlling the release of the adipokinetic hormones and suggest that all LomTK isoforms may participate in this cyclic AMP-mediated event.