Animal models for viral haemorrhagic fever.

Viral haemorrhagic fever can be caused by one of a diverse group of viruses that come from four different families of RNA viruses. Disease severity can vary from mild self-limiting febrile illness to severe disease characterized by high fever, high-level viraemia, increased vascular permeability that can progress to shock, multi-organ failure and death. Despite the urgent need, effective treatments and preventative vaccines are currently lacking for the majority of these viruses. A number of factors preclude the effective study of these diseases in humans including the high virulence of the agents involved, the sporadic nature of outbreaks of these viruses, which are typically in geographically isolated areas with underserviced diagnostic capabilities, and the requirements for high level bio-containment. As a result, animal models that accurately mimic human disease are essential for advancing our understanding of the pathogenesis of viral haemorrhagic fevers. Moreover, animal models for viral haemorrhagic fevers are necessary to test vaccines and therapeutic intervention strategies. Here, we present an overview of the animal models that have been established for each of the haemorrhagic fever viruses and identify which aspects of human disease are modelled. Furthermore, we discuss how experimental design considerations, such as choice of species and virus strain as well as route and dose of inoculation, have an influence on animal model development. We also bring attention to some of the pitfalls that need to be avoided when extrapolating results from animal models.

A comprehensive hip fracture program reduces complication rates and mortality.

OBJECTIVES: To evaluate the rate of postoperative complications, length of stay, and 1-year mortality before and after introduction of a comprehensive multidisciplinary fast-track treatment and care program for hip fracture patients (the optimized program). DESIGN: Retrospective chart review with historical control. SETTING: Orthopedic ward (110 beds) at a university hospital (700 beds). PARTICIPANTS: Five hundred thirty-five consecutive patients aged 40 and older (94%>or=60) hospitalized for hip fracture between January 1, 2003, and March 31, 2004. Three hundred and thirty-six patients (70.3%) were community dwellers before the fracture and 159 (29.7%) were admitted from nursing homes. INTERVENTION: The fast-track treatment and care program included a switch from systemic opiates to a local femoral nerve catheter block; an earlier assessment by the anesthesiologist; and a more-systematic approach to nutrition, fluid and oxygen therapy, and urinary retention. RESULTS: In the intervention group, the rate of any in-hospital postoperative complication was reduced from 33% to 20% (odds ratio=0.61, 95% confidence interval=0.4-0.9; P=.002). Rates of confusion (P=.02), pneumonia (P=.03), and urinary tract infection (P<.001) were lower in the intervention group than in the control group, and length of stay was 15.8 days in the control group, versus 9.7 days in the intervention group (P<.001). For community dwellers, 12-month mortality was 23% in the control group versus 12% in the intervention group (P=.02). Overall 12-month mortality was 29% in the control group and 23% in the intervention group (P=.2). CONCLUSION: The optimized hip fracture program reduced the rate of in-hospital postoperative complications and mortality. Randomized clinical trials are needed to confirm these results and elucidate the elements of the program that have the greatest effect on clinical outcomes and mortality.

Pulse oximetry for perioperative monitoring: systematic review of randomized, controlled trials.

Monitoring with pulse oximetry might improve patient outcome by enabling an early diagnosis and, consequently, correction of perioperative events that might otherwise cause postoperative complications or even death. The aim of the study was to clarify the effect of perioperative monitoring with pulse oximetry and to identify the adverse outcomes that might be prevented or improved by its use. Trials were identified by computerized searches of the Cochrane Library, MEDLINE, EMBASE, and by checking the reference lists of trials and review articles. All controlled trials that randomized patients to either pulse oximetry or no pulse oximetry during the perioperative period, including in the operating and recovery room, were included in the study. The search identified six reports. Of these 6 reports, 4 studies with data from 21,773 patients were considered eligible for analysis. Two studies specifically addressed the outcomes in question; both found no effect on the rate of postoperative complications using perioperative pulse oximetry. Hypoxemia was reduced in the pulse oximetry group both in the operating room and in the recovery room. During observation in the recovery room, the incidence of hypoxemia in the pulse oximetry group was 1.5-3 times less. There were postoperative complications in 10% of the patients in the oximetry group and in 9.4% in the control group. The duration of hospital stay was a median of 5 days in both groups, and an equal number of in-hospital deaths was registered in both groups. The studies confirmed that pulse oximetry could detect hypoxemia and related events. However, given the relatively small number of patients studied and the rare events being sought, the studies were not able to show an improvement in various outcomes.

[Electroencephalographic correlates of vigilance: methods and examples]. / Elektroenzephalographische Vigilanzbestimmungen: Methoden und Beispiele.

Quantitative methods for electroencephalographic assessment of vigilance must be oriented along certain principal sign patterns on the one hand, and must also take into account the dynamics of vigilance on the other. The more differentiated the approach, the more efficient will the determination be. Such quantitative methods can supply us with on-target and detailed information on the structure and dynamics of the neural processes involved in the regulation of vigilance, over and above the information supplied via visual analyses.

[Changes in the electric organization of the brain in visual search and discrimination processes of different degrees of difficulty]. / Veränderungen der hirnelektrischen Organisation bei visuellen Suchund Diskriminationsprozessen unterschiedlichen Schwierigkeitsgrades.

EEG activity during visual search processes with different degrees of discrimination difficulty was investigated in 13 male subjects. In accordance with the paradigm used by Neisser, 17 corresponding lists of rounded or angular letters were displayed. The task was to select the target letter Z from each list. The discrimination of the letter Z out of the lists of angular letters is the more difficult task. Spectral analysis shows a significant change in alpha-frequency structure during the more difficult search process. There is a shift of the dominant alpha-frequency from 11.5 to 10 Hz with a significant increase and concentration of power in the dominant frequency. This concentration of alpha-power around 10 Hz is more pronounced in the right occipital region than in the left. Concomitantly, there is a significant increase of power in subharmonic theta-frequencies. By consecutive principal analysis of spectral data these results were further differentiated and confirmed. The changes in the alpha- and theta-band during the more difficult search process are the expression of a complex transformation of EEG-frequency structure and patterning which cannot be interpreted by the usual concepts based on the theory of activation. Moreover, they seem to be the neurophysiological correlate of the accommodation (Piaget) of the neurodynamic processes to the altered perceptual conditions and to their effects on the internal matching process.

[Factor analysis of spectral EEG-data. Models of application in pharmaco-elektroencephalography (author's transl)]. / Die faktorenanalytische Verarbeitung spektraler EEG-Daten: Auswertungsstrategien und pharmakoelektroenzephalographische Anwendungsbeispiele.

The factor analysis of spectral EEG values is a data-reducing and also a structural analytical procedure. This procedure enables the numerous frequency variables obtained by spectral analysis to be replaced by a more clearly arranged system of independent complex spectral variables (spectral or frequency factors), while at the same time the interrelations which exist between the individual frequency variables are taken into consideration. The use of this information elucidates the substantial dimensions of spectral configurations, the relationship of the frequency components which constitute them and their factor scores under various conditions. We have used several application models obtained in the course of pharmacoencephalographical examinations which are based on the procedure of a not fully developed multi-model factor analysis; on the basis of these models we have shown how, in a problem-orientated application of the factor analysis, well interpretable information can be gained on the relevant dimensions of the pattern of the brain electric activity, their dynamics and their topical localisation.

Vigilance and evaluation of psychotropic drug effects on EEG.

Dynamics and structure of EEG-patterning are highly sensitive indicators of psychotropic drug effects on the regulation of vigilance. Methodological requirements for an adequate evaluation of these effects and appropriate procedures for their measurement are discussed. The kind of information to be obtained by using these strategies is illustrated by the results of comparative investigations concerning the action of Viloxazine, a new antidepressant drug, on the resting activity and on the waking EEG during performance of various tracking tasks.

[Quantitative EEG examinations on the vigilance stabilizing effect of nicergoline / Results of a double blind study with gerontopsychiatric patients (author's transl)]. / Quantitative EEG-Untersuchungen zur vigilanzfördernden Wirkung von Nicergolin. Ergebnisse einer Doppelblindstudie bei gerontopsychiatrischen Patienten.

A randomized, double blind, cross-over study was carried out on long-term gerontopsychiatric patients. The aim of the study was to compare the EEG effects of a four weeks' treatment with 10-methoxy-1,6-dimethyl-ergoline-8 beta-methanol-(5-bromonicotinate) (nicergoline, Sermion) with those of dihydroergotoxin-mesylate (DHETM) and a four weeks' placebo period. The results of the power spectrum analysis with a consecutive factor analysis of the spectral data show that nicergoline and DHETM have a vigilance stabilizing effect which is characterized by a decrease in the relative power of slow delta-theta frequencies and an increase in the alpha power. As opposed to DHETM, for which this effect could not be proved, nicergoline produces a significant increase in power of the fast alpha frequencies as well as of the beta 1, beta 2, and beta 3 band.

[Synopsis of psychopathological, electroencephalographical, and pharmacokinetic variables during antidepressive treatment with viloxazine (author's transl)]. / Synopsis psychopathologischer, elektroenzephalographischer und pharmakokinetischer Parameter unter einer antidepressiven Therapie mit Viloxazin.

In order to achieve a more differentiated assessment of the profile and time course of treatment with a new antidepressant drug, several psychiatric, neurophysiological, and biochemical parameters were examined in a double-blind study (viloxazine versus amitriptyline). Special attention was directed to the use of a time-blind audiovisual technique. The TV technique allowed to demonstrate an earlier onset of the therapeutic effect under viloxazine, which is in good agreement with the cross-sectional and longitudinal profile of viloxazine as regards pharmacokinetics and EEG.

[Piracetam and vigilance. A study of EEG changes and clinical effects in gerontopsychiatric patients (author's transl)]. / Piracetam und Vigilanz. Elektroenzephalographische und klinische Ergebnisse einer Langzeitmedikation bei gerontopsychiatrischen Patienten.

The electroencephalographic and clinical effects of piracetam were studied in a group of 11 hospitalized gerontopsychiatric patients treated with a daily dosage of 4.8 g for 8--13 months. The EEG was evaluated by power spectral analysis, followed by a principal component analysis of frequency parameters. The statistical analysis of the resulting factor scores shows that piracetam induces significant EEG changes: decrease of slow frequencies, augmentation and acceleration of alpha-activity and increase of beta-activity. These EEG changes, indicating an increase in vigilance, correspond clinically to an improvement of communicative behavior and cognitive functioning.

[On the effect of the antidepressant viloxazin on EEG and optimization of the system driver-vehicle-road (author's transl)]. / Zur Wirkung des Antidepressivums Viloxazin auf das hirnelektrische Verhalten und die Optimierung des Systems Fahrer-Fahrzeug-Strasse.

The effects of a single dose of 100 mg 2-[(o-ethoxyphenoxy)-methyl]-morpholine hydrochloride (viloxazin) on EEG and optimizing control behaviour of drivers were investigated under double-blind conditions in 5 male subjects with many years' driving experience. The study was carried out on a special test course using a car equipped with measuring devices. The following signals were recorded: EEG and EOG, driving speed, steering torque, steering angle and angle rate, longitudinal and lateral acceleration, and yaw rate. As evaluated by means of spectral analysis with a subsequent principal component analysis the EEG showed an increase of the power in alpha- and beta-frequencies indicating a drug induced decrease of EEG vigilance. In correspondence the optimization of the system driver-vehicle-road was reduced indicating an impairment of the driver's control behaviour.

[Psychophysiological studies of EEG, operational performance and the dynamics of vigilance regulation. I. The EEG during performance of Brickenkamp's attention-concentration test (test d 2) (author's transl)]. / Psychophysiologische Studien zum Verhalten der hirnelektrischen Wachaktivität bei definierter Vigilanzbeanspruchung. 1. Mitteilung: d2-Aufmerksamkeits-Belastungs-Test und EEG-Verhalten

During the performance of the d 2 test developed by Brickenkamp (standardized test of attention and concentration), occipital EEG activity was registered telemetrically in 10 male students aged 25 to 32 years. Simultaneously, the pencil markings performed by the subjects, indicating the time course of their pattern recognition and discrimination, were recorded by means of a piezo-electrical transducer. The EEG behavior during test performance was evaluated by serial spectral analysis. The analysis of the EEG parameters derived from it (total power, absolute and relative alpha-power) showed that there is a relationship between these EEG measures reflecting the regulation of cortical vigilance and the error rate in the concentration test. While subjects with low error rate present a heightening of cortical arousal focused in the right occipital area, subjects with higher error rate tend to have a higher degree of general cortical activation.

[Psychophysiological studies of EEG, operational performance and the dynamics of vigilance regulation. II. EEG activity and reactivity during tracking performance in a control loop with varying degrees of difficulty (author's transl)]. / Psychophysiologische Studien zum Verhalten der hirnelektrischen Wachaktivität bei definierter Vigilanzbeanspruchung. 2. Mitteilung: Das hirnelektrische Verhalten bei visuomotorischen Regelaufgaben steigenden Schwierigkeitsgrades

In ten male students the EEG occipital activity was recorded during a visuo-motor task consisting of pursuit-tracking. The degree of task difficulty varied systematically depending on the modification of the transfer function of control element dynamics. The EEG data were evaluated by serial spectral analysis. The distribution functions of the total power estimates and their minima and maxima reflect the dynamics of the regulation of cortical vigilance and permit to differentiate the degree of effort which corresponds to the varying degree of task difficulty. The study of task-irrelevant acoustically evoked potentials showed that with increasing cortical activation the amplitudes of N1-P2 and P2-N2 are diminished. These results might suggest that evoked potentials induced by task-irrelevant stimuli can serve as indicators of the neuronal capacity available for information processing that is not task-oriented.

[EEG aspects of waking-sleep behaviour and the chronophysiology of endogenous depressions]. / Elektroenzephalographische Gesichtspunkte zum Wach-Schlaf-Verhalten und zur Chronophysiologie endogener Depressionen

1. The resting EEG in endogenous depressions, characterized by an increase of slow alpha- and subalphacomponents and a change of spatial organization of background activity, indicates a lowered level of vigilance, If the physiological diurnal increase of the dominant alpha-frequency compensates the described slowing of alpha-rhythm, the typical daily mood fluctuation of endogenous depressions will result. 2. Changes in the resting activity occurring during arousal are probably related to the functional alteration of the EEG-sleep activity, especially to the diminishing of phasic REM-activity. 3. It is suggested that the alterations in EEG pattern during sleep and wakeful state, indicating a dissolution of slow sleep activity and a deficiency of the arousal functions, represent a regression towards an immature functioning of the vigilance regulation.

[Signal analysis of EEG-changes induced by nomifensin - a new antidepressant (author's transl)]. / Signalanalytische Untersuchungen zur Wirkung des Antidepressivums Nomifensin auf das EEG gesunder Probanden

Ten healthy volunteers received a single oral dose of 100 mg nomifensive, a new antidepressant (tetragtdriusiqyubikube deruvatuve; Hoe 36-984). The drug-induced effects on the EEG were compared with those of placebo. The statistically proved results show that nomifensine causes a distinct shift in vigilance with two different partial processes. After an initially occurring stabilization of the dominant alpha-frequency there appears a polyrhythmic disintegration of the alpha-rhythm with increase of slower and faster frequencies. At the same time a shifting takes place within the beta-range with increasing of 23.5-32.0 Hz-components. Accordingly it is evident that nomifensine results in a typical pharmaco-electroencephalographic profile.

Mianserin versus amitriptyline. A double-blind-trial evaluated by the AMP system.

Amitriptyline and mianserin were compared in a double-blind trial. Most of the depressive symptoms were influenced by both drugs, though quantitative and qualitative differences became evident. Amitriptyline predominantly influenced anxiety, despair and suicidal tendencies, while mianserin was particularly effective in psychomotor inhibition and the reduction of vegitative complaints. Mianserin did not show anticholinergic side effects.

[Clinical effects of moderate and high doses of carpipramine (author's transl)]. / Das klinische Wirkungsspektrum mittlerer und hoher Dosen von Carpipramin

An open trial of Carpipramine which chemically is a synthesis of a tricyclic antidepressant and the side chain of a butyrophrenone has been performed in 75 acute and chronic schizophrenics over a period of 30 days. The daily dose was 400-800 mg exeeding the recommendations of the manufacturer. The psychopathological changes were documented and evaluated by means of the AMP and the AMPAS-system. In 50 of the patients the trial could be completed. Only the productive symptoms and disturbance of sleep showed a significantly decreased frequency before day 10. It seems remarkable that the symptom of somatic hallucinations responded very rapidly under treatment with Carpipramine. Significant sedative or extrapyramidal side-effects were not observed; anticholinergic effects were moderate. There seems to be evidence of a slight centrally stimulating component. The substance cnnot be classified as a typical neuroleptic nor as an antidepressant drug. A differential action depending on the initial syndrome constellation is discussed.