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Introduction: Subarachnoid haemorrhage (SAH) may damage the hypothalamo-pituitary-adrenal gland (HPA) axis and disturb cortisol metabolism. There are no available data that relates to the response of the HPA axis in the acute phase of SAH. We aimed to characterise the behavior of serum adrenocorticotropic hormone (ACTH), total cortisol, stimulated total cortisol and free cortisol concentrations in acute aneurysmal SAH., Methods: A prospective cohort study was conducted of patients with acute aneurysmal SAH (n = 30) admitted to a tertiary university hospital. Patients admitted for elective aneurysmal surgery (n = 16) served as the control group. An ACTH stimulation test was performed twice during the first week and at three months. The main outcome measure was description of the ACTH-cortisol response by calculating serum free cortisol and measuring total cortisol and ACTH concentrations. A mixed models method was used for testing between the groups, allowing heterogeneity between the groups., Results: Patients with SAH had higher initial serum total cortisol (mean +/- SD; 793 +/- 312 nmol/L) and free cortisol concentrations (83 +/- 55 nmol/L) than control patients (535 +/- 193 nmol/L, p = 0.001 and 33 +/- 18 nmol/L, p < 0.001, respectively). Thereafter, there were no differences in this respect. Serum free and total cortisol concentrations correlated but were unaffected by the severity of SAH. ACTH concentrations were comparable between SAH and control groups. Patients with Hunt-Hess grades IV to V had higher ACTH concentrations at day one (10.7 +/- 7.1 pmol/l/L) and day five (8.2 +/- 7.7 pmol/L) than patients with grade I-III (day one: 3.8 +/- 2.0 pmol/L, p = 0.002; day five: 4.7 +/- 1.8 pmol/L, p = 0.04)., Conclusions: Calculation of serum free cortisol concentration was not helpful in identifying patients with potential hypocortisolism. SAH severity did not affect cortisol concentrations, possibly indicating relative pituitary-adrenal insufficiency in patients with more severe bleeding., Trial Registration: ClinicalTrials.gov Identifier NCT00614887.

Introduction: Although classical asthma is associated with airway hyperresponsiveness (AHR), this condition is also present in many cardiopulmonary disorders undermining the rational basis of its measurement in the differential diagnosis of asthma. We have recently introduced a new method to investigate AHR, the hypertonic histamine challenge (HHC)., Objective: The aim of this study was to evaluate the differential diagnostic power of HHC in a clinically representative sample of 138 patients., Methods: Fifty-seven patients from the outpatient clinic of the authors' hospital with symptoms indicative of asthma were consecutively recruited. Asthma was confirmed in 31 subjects. The remaining 26 subjects formed the control group, in conjunction with seven patients with COPD, 15 patients with interstitial lung disease, 21 patients with rhinitis, 13 patients with heart failure and 25 healthy controls. Hypertonic histamine solution was administered with an ultrasonic nebuliser., Results: Only the PC(20) values of asthmatic subjects differed statistically significantly from those of the healthy group (P < 0.0001). The receiver operator characteristic curve indicated that a PC(20) value of 0.83 mg/mL would be the optimal cut-off point of HHC to separate the asthmatics from the symptomatic controls with a sensitivity of 81% and specificity of 70%. With the PC(20) values of 0.1 and 4.0 mg/mL, the sensitivities were 42% and 100%, and the specificities were 96% and 40%, respectively. In these limits, HHC either confirmed or excluded asthma in 64 out of 138 patients (46%)., Conclusion: The authors' attempt to improve the accuracy of the airway challenge test by combining direct and indirect challenges did not overcome the diagnostic limitations of previously utilised airway challenges.

Background: Plant stanol esters in spreads have demonstrated efficacy in reducing serum cholesterol. The cost-effectiveness of plant stanol esters in the prevention of coronary heart disease, however, has remained unevaluated., Design: A Bayesian modelling approach was applied to synthesize clinical evidence and evaluate the cost-effectiveness (Euro/quality-adjusted life years) of plant stanol esters in spread in the prevention of coronary heart disease based on published FINRISK and 4S risk functions., Results: The regular use of plant stanol esters reduced total serum cholesterol by -0.362 mmol/l [95% credibility interval (CrI) -0.31 to -0.41]. The corresponding placebo-adjusted reduction attributable to stanol esters when combined with statin was -0.385 mmol/l (95% CrI -0.18 to -0.61). The cost-effectiveness estimations were assessed for men and women separately at four different initial ages at which the regular use of stanol esters was assumed to be started. The base case cost per quality-adjusted life years gained by using stanol esters regularly ranged from 7436 to 20,999 Euro in men and from 34,327 to 112,151 Euro in women based on the initial starting age. According to uncertainty analysis, there is over a 90% probability that the use of plant stanol esters is cost-effective for men inclusively and for 60-year-old and older women assuming that decision-makers' maximum willingness to pay per quality-adjusted life year is 50,000 Euro., Conclusions: A recommendation that plant stanol ester-containing spreads be used as a part of daily diet replacing regular spread could be viewed as potentially cost-effective public health policy in the prevention of CHD in all adult men and in older age-groups of women with total serum cholesterol levels of 5 mmol/l or greater.

This study aimed to develop a theoretical basis for the promotion of school staff's occupational well-being. The 'Content Model for the Promotion of School Community Staff's Occupational Well-being' describes the four aspects of the promotion of occupational well-being ('working conditions', 'worker and work', 'working community' and 'professional competence') as well as the functionality and structure of the model. The content model was examined empirically by means of a structural equation model. The project was developed with school staff and occupational health nurses and implemented in 2001-2004. The target group consisted of the staff of 12 comprehensive schools in Eastern Finland in 2002 (n = 211) and 2004 (n = 266). The data were collected using a 'well-being at your work index' questionnaire at both times. A structural equation model for the school staff's occupational well-being, i.e. the 'Occupational Well-being of School Staff Model' (baseline OWSS Model: Study I in the year 2002), was produced. The model was tested with the 2004 data. Based on this, the model was further developed into the final OWSS Model (Study II). The theoretical Content Model for the Promotion of School Community Staff's Occupational Well-being can be used as a framework for planning, implementing and evaluating school staff's occupational well-being.

The working memory functions and processing speed of 35 adolescents born preterm (< or = 32 weeks of gestation) and those of 31 control adolescents were assessed at the age of 16 years. All study participants were free from major disabilities. There were no statistically significant differences in verbal IQ between the study groups. Adolescents born preterm performed less well in complex spatial span compared to their peers born full term, even when verbal IQ and processing speed were allowed to covary. Both groups performed equally well in other working memory tasks and processing speed. Gestational age was the primary contributor to spatial span performance. These results indicate a minor spatial working memory deficit in preterm born adolescents without major disability and with normal cognitive capacity. Our results are encouraging and indicate only minor neuropsychological consequences due to very preterm birth.

Background: The purpose of this study was to investigate, whether low vs. high absorption of cholesterol affects the postprandial lipid clearance (squalene as the surrogate marker) and postprandial cholesterol metabolism evaluated with plasma levels of cholesterol absorption (cholestanol and plant sterols) and synthesis markers (desmosterol and lathosterol)., Methods: Fifteen normo- or mildly hypercholesterolemic men were divided into low or high cholesterol absorbers on the basis of plasma cholestanol to cholesterol ratio and they volunteered to an oral fat load test containing fat 35 g/m(2) body surface., Results: Plasma squalene to cholesterol ratio did not differ between the groups throughout the postprandial follow-up of 8 h. The level differences in the plasma absorption and synthesis markers seen at baseline remained between the groups, so that in high absorbers the absorption markers remained high and synthesis markers low throughout the postprandial follow-up. The postprandial response curves of desmosterol (p<0.05) and lathosterol (p=0.052) to cholestanol decreased linearly in the low, but not in the high absorbers., Conclusions: Low vs. high absorption of cholesterol does not affect the first 8-h postprandial lipid clearance. The metabolic profile of cholesterol is maintained postprandially. The postprandial decrease in cholesterol synthesis differs in low vs. high absorbers especially through the desmosterol pathway.

Assessment of the bronchodilation response to short-acting beta2-adrenoreceptor agonists on pharmacologically induced bronchoconstriction has often been used to investigate airway smooth muscle beta2-adrenoreceptor function. However, little is known about factors affecting this response. In the present study, the bronchodilation response to 0.2 mg of salbutamol on histamine-induced bronchoconstriction was assessed in 101 steroid-naïve asthmatic subjects. The associations of the response with a wide range of challenge procedure-related variables, clinical asthma severity indicators, and blood markers of airway inflammation were investigated. The response was re-assessed after 6 and 12 weeks' therapy with inhaled budesonide. Baseline FEV1, final histamine concentration, and the maximal fall in FEV1 explained 35-59% of the total variation in the response to salbutamol, depending on the index chosen to express the response. Serum concentration of myeloperoxidase, an index of neutrophilic inflammation, was associated with a poor response. The preceding week daily PEF variation, rescue bronchodilator use, severity of asthmatic symptoms, blood eosinophil count, and serum eosinophilic cationic protein and eosinophilic protein X concentrations were not associated with the response. The salbutamol response seemed to diminish during budesonide treatment but when adjusted by the challenge procedure-related variables the treatment effect vanished. In conclusion, the bronchodilation response to salbutamol on histamine-induced bronchoconstriction is largely determined by challenge procedure-related variables. It seems to be unrelated to the clinical severity of asthma and is not affected by treatment with inhaled corticosteroids. Neutrophilic airway inflammation may be associated with a poor response.

We studied the association between environmental stress and epidermal papillomatosis of roach Rutilus rutilus L. in Finnish waters using a 'matched pairs' design. Populations impacted by industrial and/or sewage effluents were compared to reference populations from pristine sites. We examined both the prevalence (proportion of diseased fish) and intensity (number of scales covered by tumors) of the disease. Results of Generalized Linear Mixed Models (GLMM) indicated that the risk of papillomatosis was 7.5 times higher in males than females, and increased 1.3 times for every 10 mm increment in fish length. We controlled for the possible effects of fish size, sex and temporal variation through sampling procedures and statistical analyses. Mean prevalence of epidermal papillomatosis was 16.6 and 5.8% in impact and reference populations, respectively (10 population pairs; nfish = 1714). Results of GLMM suggested that the risk of being diseased was 2.7 times higher in the impact than reference populations. Thus, the prevalence of epidermal papillomatosis in roach can be used as an indicator of environmental stress. Results of Linear Mixed Models indicated no difference in the intensity of the disease between impact and reference populations (5 population pairs; nfish = 73; mean+/-SE 10.7+/-1.8 and 11.7+/- 2.9 scales, respectively), although prevalence was higher in impact populations in those 5 population pairs. The possible relationship between environmental stress and intensity of epidermal papillomatosis in natural roach populations remains to be demonstrated.

Many doctors consider wheezing infants and young children who respond to beta-adrenergic agents to be asthmatics, or at least at risk for later asthma. The aim of this study was to compare responses to inhaled albuterol and racemic epinephrine in infancy between children with and without asthma later in childhood. In a crossover study setting, 100 acutely wheezing infants aged less than 24 months were randomized to receive inhalations of either racemic epinephrine and placebo, or albuterol and placebo. Clinical evaluation consisted of measurements of respiratory rate, heart rate, and oxygen saturation, and clinical assessment of the respiratory distress assessment instrument (RDAI) score, consisting of wheezing and chest indrawings. The asthma status of the children was evaluated at three clinical follow-up visits, at 4.0, 7.2, and 12.3 (median) years of age. Responses to bronchodilating agents, when respiratory rates and RDAI scores were used as outcome measures, were not different in future asthmatics compared to nonasthmatics. However, oxygen saturation was significantly higher after albuterol inhalation in children who had asthma at all three visits (92.67% confidence interval (CI), 91.39-93.96) than in those without asthma at these visits (92.52% CI, 91.79-93.25), but lower, correspondingly, after racemic epinephrine (91.97% CI, 90.74-93.19 vs. 93.04% CI, 92.29-93.79) and placebo (91.38% CI, 90.49-92.28 vs. 93.12% CI, 92.60-93.65) inhalations (P = 0.04). In conclusion, we were not able to confirm that future asthmatics respond better than future nonasthmatics to bronchodilating agents during wheezing in infancy. More studies are needed to characterize the subset of infants who benefit from bronchodilating treatment in infancy.

In 40-60% of cases with interictal activity in EEG, fMRI cannot locate any focus or foci with simultaneous EEG/fMRI. In experimental focal epilepsy, a priori knowledge exists of the location of the epileptogenic area. This study aimed to develop and to test an experimental focal epilepsy model, which includes dynamic induction of epileptic activity, simultaneous EEG/fMRI, and deep anesthesia. Reported results are from seven pigs (23 +/- 2 kg) studied under isoflurane anesthesia (1.2-1.6 MAC, burst-suppression EEG) and muscle relaxant. Hypo- and hypercapnia were tested in one pig. Penicillin (6000 IU) was injected via a plastic catheter (inserted into the somatosensory cortex) during fMRI (GRE-EPI, TE = 40 ms, 300 ms/two slices, acquisition delay 1700 ms) in 1.5 T (N = 6). Epileptic spikes between acquisition artifacts were reviewed and EEG total power calculated. Cross-correlation between voxel time series and three model functions resembling induced spike activity were tested. Activation map averages were calculated. Development of penicillin induced focal epileptic activity was associated with linear increase and saturation up to approximately 10-20%, in BOLD activation map average. Its initial linear increase reached 2.5-10% at the appearance of the first distinguished spike in ipsilateral EEG in all six animals. Correlated voxels were located mainly in the vicinity of the penicillin injection site and midline, but few in the thalamus. In conclusion, development of focal epileptic activity can be detected as a BOLD signal change, even preceding the spike activity in scalp EEG. This experimental model contains potential for development and testing different localization methods and revealing the characteristic time sequence of epileptic activity with fMRI during deep anesthesia.

Objective: The effect of glioma removal on blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) activation has not been widely documented. The aim of this preliminary study was to observe the effect of tumor resection on BOLD fMRI of the auditory and motor cortices., Methods: Seven patients with gliomas underwent preoperative and early postoperative BOLD fMRI, and five of them underwent additional late postoperative BOLD fMRI. The auditory and motor cortices were localized with activation studies. A hemispheric activation index was used to quantify the relative extent of BOLD activation., Results: The resection of a glioma with preoperative edema resulted in an increase from the preoperative to the early postoperative fMRI on auditory BOLD activation on the side of the tumor compared with the contralateral side. The same phenomenon was observed in one patient with motor BOLD activation. However, when no preoperative edema was present, a transient decrease in relative auditory BOLD activation was found., Conclusion: The results of this study suggest that the resection of a glioma with preoperative edema affecting the auditory and/or motor cortex may cause a transient increase in the BOLD response ipsilateral to the tumor. It seems that when the tumor is resected, the pressure on the brain, specifically on the affected auditory and/or motor cortex, decreases and the functional cortex becomes more easily detectable in BOLD fMRI.

Anesthetized children have dominant blood-oxygen-level-dependent (BOLD) signal sources presenting high-power fluctuations at very low frequencies (VLF <0.05 Hz). Aliasing of frequencies higher than critically sampled has been regarded as one probable origin of the VLF fluctuations. Aliased signal frequencies change when the sampling rate of the data is altered. In this study, the aliasing of VLF BOLD signal fluctuation was analysed by switching the repetition time (TR) of magnetic resonance (MR) images. Eleven anesthetized children were imaged at 1.5 T using TRs of 500 and 1200 ms. The BOLD signal sources were separated with independent component analysis (ICA). Occipital cortex signal sources had nonaliased VLF fluctuation ( approximately 0.03 Hz) in 9 of 11 subjects. Arterial signal sources failed to present stable power peaks at frequencies lower than 0.42 Hz presumably due to aliasing. Cerebrospinal fluid (CSF)-related signal sources showed nonaliased VLF in four subjects. In conclusion, the VLF BOLD signal fluctuation in the occipital cortex is a true physiological fluctuation, not a result of signal aliasing.

Differences in the blood oxygen level dependent (BOLD) signal changes were studied during voluntary hyperventilation (HV) between young healthy volunteer groups, (1) with intermittent rhythmic delta activity (IRDA) (N = 4) and (2) controls (N = 4) with only diffuse arrhythmic slowing in EEG (normal response). Subjects hyperventilated (3 min) during an 8-min functional MRI in a 1.5-T scanner, with simultaneous recording of EEG (successful with N = 3 in both groups) and physiological parameters. IRDA power and average BOLD signal intensities (of selected brain regions) were calculated. Hypocapnia showed a tendency to be slightly lighter in the controls than in the IRDA group. IRDA power increased during the last minute of HV and ended 10-15 s after HV. The BOLD signal decreased in white and gray matter after the onset of HV and returned to the baseline within 2 min after HV. The BOLD signal in gray matter decreased approximately 30% more in subjects with IRDA than in controls, during the first 2 min of HV. This difference disappeared (in three subjects out of four) during IRDA in EEG. BOLD signal changes seem to depict changes, which precede IRDA. IRDA due to HV in healthy volunteers represent a model with a clearly defined EEG pattern and an observable BOLD signal change.

Functional MR imaging (fMRI) has been used in detecting neuronal activation and intrinsic blood flow fluctuations in the brain cortex. This article is aimed for comparing the methods for analyzing the nondeterministic flow fluctuations. Fast Fourier Transformation (FFT), cross correlation (CC), spatial principal component analysis (sPCA), and independent component analysis (sICA) were compared. 15 subjects were imaged at 1.5 T. Three quantitative measures were compared: (1) The number of subjects with identifiable fluctuation, (2) the volume, and (3) mean correlation coefficient (MCC) of the detected voxels. The focusing on cortical structures and the overall usability were qualitatively assessed. sICA was spatially most accurate but time consuming, robust, and detected voxels with high temporal synchrony. The CC and FFT were fast suiting primary screening. The CC detected highest temporal synchrony but the subjective detection for reference vector produced excess variance of the detected volumes. The FFT and sPCA were not spatially accurate and did not detect adequate temporal synchrony of the voxels.

Neuronal activation can be separated from other signal sources of functional magnetic resonance imaging (fMRI) data by using independent component analysis (ICA). Without deliberate neuronal activity of the brain cortex, the fMRI signal is a stochastic sum of various physiological and artifact related signal sources. The ability of spatial-domain ICA to separate spontaneous physiological signal sources was evaluated in 15 anesthetized children known to present prominent vasomotor fluctuations in the functional cortices. ICA separated multiple clustered signal sources in the primary sensory areas in all of the subjects. The spatial distribution and frequency spectra of the signal sources correspond to the known properties of 0.03-Hz very-low-frequency vasomotor waves in fMRI data. In addition, ICA was able to separate major artery and sagittal sinus related signal sources in each subject. The characteristics of the blood vessel related signal sources were different from the parenchyma sources. ICA analysis of fMRI can be used for both assessing the statistical independence of brain signals and segmenting nondeterministic signal sources for further analysis.

Signal intensity changes in fMRI during rest caused by vasomotor fluctuations were investigated in this work. Resting-state baseline fluctuations were evaluated in 12 children anesthetized with thiopental. Five subjects had fluctuations related to subvoxel motion. In seven subjects without significant motion, slow signal fluctuation at 0.025-0.041 Hz near one or more primary sensory cortices was observed. In each subject the amplitude and frequency of the fluctuations were stable. It is hypothesized that thiopental, which reduces blood pressure and flow in the cortex, alters the feedback in neurovascular coupling leading to an increase in the magnitude and a reduction in the frequency of these fluctuations. The use of anesthesia in fMRI may provide new insight into neural connectivity and the coupling of blood flow and neural metabolism.

Background and Aims: [corrected] To evaluate the outcome of transverse distal metatarsal osteotomies for intractable plantar callosity without hammer toe deformity and associated toe corns., Material and Methods: Twenty-five plantar callosities were treated in 19 feet of 13 patients (mean age 48 years, 5 male, 8 female) with transverse distal metatarsal osteotomy., Results: Twenty-four of the osteotomies united primarily, one after revision. After a 7-year follow-up, 23 of the callosities had healed, two of them after an oblique reosteotomy. Eight hammer toe deformities had developed in the involved rays of four feet. Eight plantar callosities had developed outside the operated rays in five feet. Hallux valgus was a frequent finding in both operated and non-operated feet., Conclusion: It seems that transverse distal metatarsal osteotomy is an effective treatment of intractable plantar callosities. Harmful hammer toe deformities and transfer lesions below adjacent metatarsal heads tend to develop over time.