Validation of the burns itch questionnaire.

Itch (pruritus) is a common multidimensional complaint after burn that can persist for months to years. A questionnaire able to investigate itch and its consequences is imperative for clinical and research purposes. The current study investigated the factor structure, internal consistency and construct validity of the Burns Itch Questionnaire (BIQ), a questionnaire particularly focusing on itch in the burns population. The BIQ was completed by 195 respondents at 3 months after burn. An exploratory factor analysis (EFA) was performed to investigate the factor structure. EFA showed the BIQ comprised three latent factors: itch severity, sleep interference and daily life interference. This was re-evaluated in a confirmatory factor analysis that yielded good fit indices after removing two items. The three subscales showed to have high internal consistency (.89) and were able to distinguish between patients with severe and less severe complaints. In conclusion, the BIQ showed to be useful in persons suffering from itch following burns.

Exploring stress-induced cognitive impairment in middle aged, centrally obese adults.

Extensive research has shown that psychosocial stress can induce cognitive impairment. However, few studies have explored impairment following acute stress exposure in individuals with central obesity. Central obesity co-occurs with glucocorticoid excess and can lead to elevated cortisol responses to stress. It is not clear whether centrally obese individuals exhibit greater cognitive impairment following acute stress. Cortisol responses to stress versus no-stress control were compared in 66 high- and low waist to hip ratio (WHR) middle-aged adults (mean age of 46 ± 7.17 years). Cognitive performance post exposure was assessed using Cambridge Automated Neuropsychological Test Battery. It was hypothesised that high WHR would exhibit greater cortisol in response to stress exposure and would show poorer cognitive performance. Males, particularly of high WHR, tended to secrete greater cortisol during stress exposure. Exposure to stress and increasing WHR were specifically associated with poorer performance on declarative memory tasks (spatial recognition memory and paired associates learning). These data tentatively suggest a reduction in cognitive performance in those with central obesity following exposure to acute stress. Further research is needed to elucidate the effects of stress on cognition in this population.

Behavioural modification of the cholinergic anti-inflammatory response to C-reactive protein in patients with hypertension.

OBJECTIVES: A central hypothesis of the cholinergic anti-inflammatory reflex model is that innate immune activity is inhibited by the efferent vagus. We evaluated whether changes in markers of tonic or reflex vagal heart rate modulation following behavioural intervention were associated inversely with changes in high-sensitivity C-reactive protein (hsCRP) or interleukin-6 (IL-6). DESIGN: Subjects diagnosed with hypertension (n = 45, age 35-64 years, 53% women) were randomized to an 8-week protocol of behavioural neurocardiac training (with heart rate variability biofeedback) or autogenic relaxation. Assessments before and after intervention included pro-inflammatory factors (hsCRP, IL-6), markers of vagal heart rate modulation [RR high-frequency (HF) power within 0.15-0.40 Hz, baroreflex sensitivity and RR interval], conventional measures of lipoprotein cholesterol and 24-h ambulatory systolic and diastolic blood pressure. RESULTS: Changes in hsCRP and IL-6 were not associated with changes in lipoprotein cholesterol or blood pressure. After adjusting for anti-inflammatory drugs and confounding factors, changes in hsCRP related inversely to changes in HF power (ß = -0.25±0.1, P = 0.02), baroreflex sensitivity (ß = -0.33±0.7, P = 0.04) and RR interval (ß = -0.001 ± 0.0004, P = 0.02). Statistically significant relationships were not observed for IL-6. CONCLUSIONS: Changes in hsCRP were consistent with the inhibitory effect of increased vagal efferent activity on pro-inflammatory factors predicted by the cholinergic anti-inflammatory reflex model. Clinical trials for patients with cardiovascular dysfunction are warranted to assess whether behavioural interventions can contribute independently to the chronic regulation of inflammatory activity and to improved clinical outcomes.

Cortisol awakening rise in middle-aged women in relation to psychological stress.

OBJECTIVES: The cortisol awakening rise (CAR) is defined as cortisol secretory activity in the first 45-60 min immediately post-awakening. It has been suggested that psychological factors may disrupt the normal awakening rise. Recent research has shown that psychological stress may influence the magnitude of the CAR, however the findings have been mixed. This study examined the impact of stress on the CAR and the diurnal mean in a sample of middle-aged women. METHOD: One hundred and eighteen healthy female participants who reported experiencing high or low stress were recruited. Salivary cortisol levels were measured immediately upon awakening (at 0, 15, 30, and 45 min) and at 3, 6, 9 and 12 h on two consecutive days. A number of metabolic and inflammatory biomarkers were also assessed together with measures of mood disturbance and health behaviour. RESULTS: The magnitude of the CAR, assessed by the area under the response curve (AURC) estimate, was significantly lower in the high stress group compared to the low stress group indicating that participants who experienced high stress secreted lower levels of cortisol. The effect was largely accounted for by differences 30 min after waking. The diurnal mean was also lower for the high stress group. Although participants in the high stress group had a slightly worse inflammatory profile, only low-density lipoprotein levels were found to be significantly higher, compared to the low stress group. Lifestyle indicators and mood were also found to be significantly poorer in the high stress group. CONCLUSIONS: The results suggest that psychological stress may be associated with a smaller cortisol awakening rise, a lower diurnal mean, poor lifestyle choices and high levels of psychological distress. These findings may have broader implications for future health risk and for an individual's ability to cope with imminent daily stressors and demands.

Exploration of basal diurnal salivary cortisol profiles in middle-aged adults: associations with sleep quality and metabolic parameters.

The use of saliva samples is a practical and feasible method to explore basal diurnal cortisol profiles in free-living research. This study explores a number of psychological and physiological characteristics in relation to the observed pattern of salivary cortisol activity over a 12-h period with particular emphasis on sleep. Basal diurnal cortisol profiles were examined in a sample of 147 volunteers (mean age 46.21+/-7.18 years). Profiles were constructed for each volunteer and explored in terms of the area under the curve (AUC) of the cortisol-awakening response with samples obtained immediately upon waking (0, 15, 30 and 45 min post waking) and at 3, 6, 9 and 12h post waking to assess diurnal decline. Diurnal mean of cortisol was based on the mean of cortisol at time points 3, 6, 9 and 12h post waking. Psychological measures of perceived stress and sleep were collected with concurrent biological assessment of fasting plasma glucose, insulin, blood lipids and inflammatory markers. Blunted cortisol profiles, characterised by a reduced AUC, were observed in the majority (78%) of a middle-aged sample and were associated with significantly poorer sleep quality and significantly greater waist-hip ratio (WHR). Blunted cortisol profiles were further associated with a tendency to exhibit a less favourable metabolic profile. These findings suggest that reduced cortisol secretion post waking may serve as an additional marker of psychological and biological vulnerability to adverse health outcomes in middle-aged adults.

Neither extended sequential nor simultaneous feature positive training result in modulation of evaluative flavor-flavor conditioning in humans.

In previous attempts to induce Pavlovian modulation of human evaluative flavor-flavor associations, the recurrent finding was that exposure to a Feature Positive (FP) schedule (XA+/A-), in which flavor A was reinforced by the aversive flavor Tween20 if and only if it was accompanied by a feature stimulus X, did not result in the expected X-modulated dislike for target A, but in simple unconditional A-US associations. The first experiment reported here investigated if more extended training results in a shift from simple A-US learning to the development of X-modulated A-US associations. Participants were exposed to a 32-trial, 4-session sequential FP schedule using flavors both for feature and target stimuli. The modulatory and/or excitatory power of the stimuli was assessed after each training session. After initial training, participants again acquired a simple unmodulated target A-US association. Contrary to expectations, the additional training sessions did not result in participants gradually learning the XA+/A- discrimination, but rather seemed to corroborate the already established A-US association. This was true whether or not participants acquired valid explicit knowledge about the conditional X-->(A-US) relation. The second experiment tested the hypothesis that what can be described as conditional flavor preferences may actually be based on a configural learning process. Participants were exposed to a single-session, eight-trial XA+/A- simultaneous discrimination schedule, the parameters of which were selected so as to enhance the probability of configuring XA, while simultaneously making it likely to observe a pattern of evaluations similar to an X-modulated dislike for A (X was less salient than A). Even though there was good evidence that participants noticed flavor X, they again failed to solve the XA+/A- discrimination and most probably acquired an association between the more salient flavor A and the US. The possibility is discussed that evaluative learning, unlike expectancy learning, might ultimately prove not to be subject to modulation.

Evaluative learning with "subliminally" presented stimuli.

Evaluative learning refers to the change in the affective evaluation of a previously neutral stimulus (NS) that occurs after the stimulus has been associated with a second, positive or negative, affective stimulus (AS). Four experiments are reported in which the AS was presented very briefly. Significant evaluative learning was observed in participants who did not notice the presentation of the affective stimuli (ASi) (Experiment 2) or could not discriminate between the briefly presented positive and negative ASi when asked to do so (Experiment 3). In two other experiments (Experiments 1 and 4), no significant learning effect was obtained. A meta-analysis performed on the present and previously reported results (De Houwer, Baeyens, & Eelen, 1994) gave evidence for a small, though statistically reliable evaluative learning effect when ASi are presented "subliminally." This finding supports the hypothesis that evaluative associations can be learned implicitly.

Tumor-cell lysis by in-situ-activated human peripheral-blood mononuclear cells.

A heteroconjugate (HC) was synthesized between OKT3 and monoclonal antibody (MAb) 7E8, which specifically reacts with the tumor marker placental alkaline phosphatase (PLAP). Similarly to OKT3, in vitro, the HC induced a dose-dependent proliferation response of human peripheral-blood mononuclear cells (PBMCs) and, in concert with rIL-2, it progressively activated T cells over a 4-day period. In co-cultures of continuously activated PBMCs and MO4 tumor cells (non-MHC-restricted mouse fibroblasts transfected with the cDNA for PLAP), the HC (25 ng/ml), again acting in concert with rIL-2, induced specific lysis of the MO4 cells. This process occurred progressively over 2 to 3 days and was monitored from the release in the supernatant fluid of cellular 3H-L-leucine, but also from analyses involving the remaining non-lysed cancer cells, i.e., by estimates of their protein content, by measurements of their viability, and most accurately by determinations of their PLAP content. Antibody 7E8 by itself induced a weak tumor-cell lysis (ADCC), potentiated by the addition of rIL-2. However, after 7 days of PBMC-preactivation with the HC and rIL-2, antibody 7E8 no longer mediated any ADCC, whereas the HC-dependent lysis was further potentiated. The observed proliferation of T cells and development of cytotoxicity at low concentrations of HC and rIL-2 support the idea that a moderate but continuous T-cell activation combined with T-cell targeting is sufficient for the induction of progressive and efficient tumor-cell lysis.

Delayed recovery of behavior after anesthesia in rats.

UNLABELLED: Early, complete recovery from general anesthesia is of importance for outpatients, in resuscitation research and in behavior testing of neonates. A model was designed to study behavior during the first week of recovery from anesthesia in rats, using two methods: spontaneous and unrestrained locomotor activity was tested and passive avoidance of electroshock was studied in a two session, one trial model. Neurologic deficit and ease of handling were also tested. After anesthesia with halothane 1-2% in N2O/O2 for 30 min, spontaneous activity was reduced, compared with unanesthetized rats, for up to at least 48 h. On day 6 post-anesthesia, locomotor activity was recovered, and, on days 4 and 5, passive avoidance was unchanged. Neurologic deficits were absent after the first hour of recovery and ease of handling was unchanged. CONCLUSION: Halothane and nitrous oxide have prolonged effects on locomotor behavior beyond the immediate post-anesthesia recovery period, at a time when neurologic deficit testing does not reveal any abnormalities. The model is suitable for the comparison of recovery from different anesthesia techniques in rats.

Effect of orientational order on the decay of the fluorescence anisotropy in membrane suspensions. Experimental verification on unilamellar vesicles and lipid/alpha-lactalbumin complexes.

Various models for the analysis of time-dependent fluorescence anisotropy measurements were evaluated. The discussion was based on the analysis of pulsed experiments with 1,6-diphenyl-1,3,5-hexatriene embedded in small unilamellar vesicles of dimyristoylphosphatidylcholine or dipalmitoylphosphatidylcholine and in dimyristoylphosphatidylcholine/alpha-lactalbumin complexes. It was shown that a recently proposed model (Van der Meer, W., H. Pottel, W. Herreman, M. Ameloot, H. Hendrickx, H. Schröder, 1984, Biophys. J., 46:515-523) described the data better than did the earlier suggested cone model (Kinosita K., Jr., S. Kawato, and A. Ikegami, 1977, Biophys. J., 20:289-305). This permitted the use of the new model for the estimation of the second- and fourth-rank order parameters on nonoriented systems. The results indicated that a fraction of the probes was oriented perpendicularly to the preferred direction of the lipids. An increase of the rotational correlation times of the fluorescent probe and a higher order of its environment were detected after the interaction of alpha-lactalbumin with the dimyristoylphosphatidylcholine vesicles at acidic pH at 24.2 degrees C.

Effect of orientational order on the decay of the fluorescence anisotropy in membrane suspensions. A new approximate solution of the rotational diffusion equation.

We discussed the time-dependence of fluorescent emission anisotropy of a cylindrical probe in membrane vesicles. We showed that, if the motion of the probe were described as diffusion in an anisotropic environment, it would be possible to determine not only the second-rank but also the fourth-rank orientational order parameter from the decay of the fluorescence anisotropy. The approximations involved were based on an interpolation of short-time and long-time behavior of the relevant correlation functions. A general expression was derived for the time dependence of the fluorescence anisotropy in closed form, which applies to any particular distribution model. It was shown to be in good agreement with previously reported results for the cone model and the Gaussian model. Finally, the applicability of the theory to time-resolved and differential phase fluorescence depolarization experiments was discussed.

Brain lactate and alanine-glutamate ratios during and after asphyxia in rats.

Recently, Conger, Garcia, Kauffman, Lust, Murakami and Passonneau, (1981) proposed the use of brain alanine-glutamate ratios (A:G) for the prediction of outcome after brain ischemia. This study evaluates this parameter and brain lactate concentration during and after asphyxial insults in rats. During the first 15 min of asphyxial death in rats (n = 37), lactate increased sharply from mean values of 1.48 to 18.06 mumol g-1 wet brain, and thereafter to 19.44 mumol g-1 wet brain at 180 min. During total body asphyxia (n = 38) and recovery after resuscitation, brain lactates increased to mean values of 15 and 17.5 mumol g-1 wet brain at 5 and 10 min, respectively, to recover after 30-60 min to baseline. The alanine-glutamate ratios did not rise during the insult; however, after restoration of circulation, the ratios rose to peak at about 15 min post-restoration of circulation and recovered slowly during the next 165 min to still slightly increased levels. During intermittent asphyxia (n = 15), lactate and alanine-glutamate ratios followed the same patterns as found before except at lower levels. The conclusions of this study are: (1) brain lactate concentrations had no value in predicting the potential of recovery; (2) increased lactate concentrations during recovery indicated secondary insult; (3) brain A:G's did not increase during asphyxiation; (4) brain alanine-glutamate ratios increased after restoration of circulation and may have reflected the quality of reflow; (5) increased ratios during recovery beyond 20 min indicated secondary insult. Brain alanine-glutamate ratios could not be used for prediction of outcome in asphyxial insults in rats.

[Short-term transtracheal jet for reversible support of respiration in the rat]. / Zeitlicher transtrachealer Jet für die reversible Unterstützung der Atmung bei Ratten.

A method is described for reversible controlled ventilation of rats by transtracheal catheter (20 or 22 G). A small rodent ventilator is used, rather then a jet ventilator, because the former enables the mixing of inhalation anesthetics with the carrying gas mixture. The method proved to be the most successful one for weaning from controlled ventilation after cardiac arrest and resuscitation of rats. In general, the method can be considered as an alterative to oral intubation and tracheotomy for controlled ventilation in rats.

Asphyxia, cardiac arrest and resuscitation in rats. II. Long term behavioral changes.

This study in 53 rats was conducted to investigate a mild insult, sensitive parameter model in contrast to a severe insult, severe damage model of brain resuscitation. Up to now, the latter approach, which causes neuropathologic changes and neurological abnormalities, has not provided unequivocal data on pharmacological measures to ameliorate post-anoxic brain damage, because of logistical difficulties and many extracranial complicating factors. As tracheotomy and oral intubation in rats proved impractical in studies on recovery from asphyxia, transtracheal jet ventilation was tested in 14 rats as a measure for effective prolonged and reversible control of airway and ventilation. Subsequently, in 37 other rats we studied, during the first post-insult week, the effects of anesthesia, with or without 6 min asphyxia, on behavior, i.e. unrestrained spontaneous locomotor activity and two sessions of one-trial passive avoidance. Transtracheal jet ventilation proved a reliable method for reversible and prolonged controlled ventilation in rats. Spontaneous locomotor activity was affected for at least 48 h after anesthesia and differently so after asphyxia. Passive avoidance was affected only after asphyxia. The recovery of behavior was delayed for days, whereas the recovery of neurologic deficits was only delayed for several post-asphyxia hours. The asphyxiated rats showed hyper-excitability for at least 2 weeks. The existence of abnormal behavior during recovery from mild anoxic-ischemic insults to the brain provides parameters for evaluation of therapies of the post-resuscitation disease in a model without the difficulties encountered in models with severe insults, which made post-insult intensive care necessary. The mild insult, sensitive parameter model is promising and further work in this direction is indicated.

Asphyxia, cardiac arrest and resuscitation in rats. I. Short term recovery.

This study was conducted to investigate the degree of insult from asphyxia leading to total body circulatory arrest, as a model for brain resuscitation studies in rats. Of 78 male rats, 68 were anesthetized with halothane in O2/N2O, controlled ventilated, paralyzed with pancuronium and asphyxiated, 5, 7.5, 10, 12.5 and 15 min, respectively. Asphyxiation led to circulatory arrest in 244 +/- 22 s (mean +/- S.E.M.). Resuscitation was successful in 65% within 60 s using controlled ventilation with 100% O2, extrathoracic compressions and epinephrine intravenously. Subsequent intensive care to 6, 12 or 24 h was successful in 50% of resuscitated rats. At 6, 12 and 24 h of recovery, neurologic deficit scores and light microscopic neuropathology scores of the brain after in vivo fixation of the total body with intraventricular paraformaldehyde 3%, revealed a large scatter variability without a clear pattern. Lesions were located mostly in the frontal cortex and hippocampus (footplate) with ischemic neuronal change as the most frequent structural change. Brain cell necrosis was not seen after successful resuscitation. It seems that both scores were influenced by post-insult stress, as indicated by paroxysmal hypertension and motor activity, by complications, such as obstruction of the tracheotomy cannula by abundant sputum production, and by partial sedation with N2O and paralysis with pancuronium. This study indicates the feasibility of an asphyxial insult in rats for use in resuscitation studies of short duration. Although 24 h post-insult recovery is possible, up to 6 h seems most practical, with asphyxia of 7.5-10 min most successful and controllable. Questions are raised about the effects of irritation during the post-insult intensive care on both neurological deficit and neuropathology scores.

Thiopental treatment after global brain ischemia in pigtailed monkeys.

The authors investigated the value of high-dose thiopental (TH) therapy after 16-min complete global brain ischemia (GBI) in three groups of pigtailed monkeys, using a neck cuff model of GBI with 96 h intensive care postischemia (PI). Control group (n18): Normotension was restored within 2 min PI; paralysis/controlled ventilation was maintained for 48 h PI with 50% N2O/O2. Thiopental loading group (n13): Control treatment plus TH-loading with 90 mg/kg iv given from 5 to 65 min PI (mean peak TH plasma level 130 micrograms/ml). Thiopental anesthesia group (n14): Control treatment plus TH anesthesia with 90 mg/kg iv given over 12 h PI (sustained TH plasma levels of 25-35 micrograms/ml and EEG burst suppression). Norepinephrine requirement for blood pressure control PI was greater in the TH groups than in the control group (P less than 0.05). Lidocaine was needed for control of arrhythmias in the TH loading group. There was no significant difference in mortality or neurologic outcome between the groups. At 96 h PI seven of 11 animals were awake in the control group, compared with seven of 12 and six of 12 in the two TH groups. Neurologic deficit scores (NDS) for the survivors at 96 h PI were 23 +/- 6% (mean +/- SD) (n10) in the control group, compared with 25 +/- 9% (n11) and 26 +/- 12% (n10) in the two TH groups (NDS 100% = brain death, 0% = normal). Seizures PI (in 1-2 of each group) were associated with worse neurologic deficits.(ABSTRACT TRUNCATED AT 250 WORDS)

Extension of the performance of Laplace deconvolution in the analysis of fluorescence decay curves.

The original Laplace deconvolution of luminescence data, obtained with pulsed systems, is reviewed. The system of equations from which the luminescence parameters can be determined is generalized for the case that describes the relaxation by a sum of exponentials. Artifacts such as scatter and time-shift can be taken into account. A modification of the original method that eliminates the iterative procedure in the estimation of the cut-off correction is suggested. This modified Laplace method is no longer restricted to the cases where the cut-off error is rather small and the exciting flash has a low tail. The possibility of the combination of several discrete experiments in a single Laplace deconvolution, without introducing new parameters or normalization factors, is shown. The merits of this combination method are demonstrated on a time-resolved depolarization experiment.