Evaluation of combination therapy using aciclovir and corticosteroid in adult patients with herpes simplex virus encephalitis.

OBJECTIVE: Herpes simplex virus encephalitis (HSVE) is associated with significant morbidity and mortality, even with appropriate antiviral therapy. In the present investigation, the first to assess efficacy of corticosteroid treatment with aciclovir therapy in HSVE, multiple logistic regression analysis was performed of predictors of outcome in adult patients with HSVE. METHODS: A non-randomised retrospective study of 45 patients with HSVE treated with aciclovir was conducted. The patients were divided into poor and good groups based on outcome at three months after completion of aciclovir treatment. The variables evaluated were: clinical variables (sex, age, days after onset at initiation of aciclovir, Glasgow Coma Scale (GCS) at initiation of aciclovir, initial and maximum values for the cell numbers and protein concentration in the cerebrospinal fluid, and corticosteroid administration); neuroradiological variables (detection of lesions by initial cranial computed tomography and by initial magnetic resonance imaging); and one neurophysiological variable (detection of periodic lateralised epileptiform discharges on the initial electroencephalogram). Single variable logistic regression analysis was performed followed by multiple logistic regression analysis. The best set of predictors for the outcome of HSVE was estimated by stepwise logistic regression analysis. RESULTS: A poor outcome was evident with older age, lower GCS score at initiation of aciclovir, and no administration of corticosteroid. Patient age, GCS at initiation of aciclovir, and corticosteroid administration were found to be significant independent predictors of outcome on multiple logistic regression analysis, and these three variables also formed the best set of predictors (R(2) = 0.594, p<0.0001). CONCLUSION: Combination therapy using both aciclovir and corticosteroid represents one of the predictors of outcome in HSVE.

Autonomic nervous activity and stress hormones induced by hyperbaric saturation diving.

This study describes the changes in autonomic nervous activity and stress hormones during a hyperbaric saturation dive up to 4.1 MPa in six subjects. Their autonomic nervous activity was assessed by a power spectrum analysis of heart rate variability (HRV). The levels of plasma epinephrine (E) and norepinephrine (NE), and those of salivary chromogranin A and cortisol, were compared with the pre-dive control levels. Restrained activity of the cardiac vagal nerve was recognized in the early post-dive period by a decrease in high frequency power and by the standard deviation of the HRV. By contrast, enhanced activity of sympathetic nerve was recognized in the early post-dive period by an elevated plasma E, and also in the late 3.1 MPa, 4.1 MPa, and post-dive periods by elevated plasma NE. The levels of plasma E and NE were the most sensitive indicators of sympathetic nervous activity. A joint utilization of HRV parameters with stress hormones may be an effective means of estimating the adaptive responses between hyperbaric and normobaric environments.

Alterations of quantitative EEG and mini-mental state examination in interferon-alpha-treated hepatitis C.

We have recently observed a diffuse slowing of brain waves using serial quantitative electroencephalographic (qEEG) examinations in interferon (IFN)-alpha-treated chronic hepatitis C patients. However, it remains unclear how this alteration could be assessed. We evaluated the correlation between the qEEG changes and three tests of mental status, including the Mini-Mental State Examination (MMSE), in such patients. This is the first study to undertake a clinical evaluation of the adverse effects on brain function due to IFN. We undertook blind, prospective and serial qEEG examinations on 56 chronic hepatitis C patients at three independent hospitals. IFN-alpha was administered intramuscularly at a dose of 9 x 10(6) IU daily for the first 4 weeks and then 3 times/week for the next 20 weeks. Serial EEGs were obtained before, at 2 and 4 weeks of treatment, and after the IFN-alpha treatment. The absolute power values of each frequency band in each patient at different stages of treatment were recorded by qEEG. Each patient was assessed by the MMSE, Hamilton Rating Scale for Depression (HSD), and Hamilton Rating Scale for Anxiety (HSA). We statistically evaluated the correlations between the changes in power values and alterations of scores on the mental status tests during IFN-alpha treatment. The decreased scores observed on the MMSE ranged from 2 to 5 points at both 2 and 4 weeks of IFN-alpha treatment. There were no significant differences in age distribution for each decreased score on the MMSE. As the alteration in MMSE score during IFN treatment increased, the alteration in absolute power values for the slow waves during IFN treatment increased significantly, while that for the alpha 2 and fast waves during treatment decreased significantly. However, the changes in the HDS and HSA revealed no significant correlations. The alteration of the qEEG was reversible after the treatment. MMSE scores represent one screening method for the clinical assessment of IFN-alpha-induced alterations of brain function.

Usefulness of daily +2Gz load as a countermeasure against physiological problems during weightlessness.

UNLABELLED: Adaptation to head-down-tilt bed rest as a simulated microgravity leads to an abnormality of reflex control of circulation, hypovolemia and reduction of exercise capacity. We hypothesized that this cardiovascular deconditioning and reduction of exercise capacity could be prevented by a daily 1 hr centrifugation at +2Gz. To test this hypothesis, twenty healthy male subjects underwent 4 day of 6 degrees head-down-tilt bed rest. Ten of them were exposed to a +2Gz load for up to 30 min twice per day (the Gz group). The remaining 10 were not exposed to a Gz load (the no-Gz group). We estimated autonomic cardiovascular control by power spectral analysis of blood pressure and R-R interval variability, and baroreflex regulation by the transfer function analysis and the sequence method, before and after bed rest. Further, we measured hematocrit as an index of changes in plasma volume and maximal oxygen consumption as an index of exercise capacity, before and after bed rest. RESULT: In the no-Gz group, heart rate increased after bed rest. The high frequency power of R-R interval variability as an index of cardiac parasympathetic nervous activity, baroreflex gains estimated by transfer function analysis and the sequence method as index of the integrated arterial-cardiac baroreflex function decreased significantly. Associated with these changes, the ratio of low to high frequency power of R-R as an indicator of cardiac sympathovagal balance tended to increase after bed rest in the no-Gz group. However, those showed no significant changes after bed rest in the Gz group. Hematocrit increased after bed rest in the no-Gz group. It also tended to increase in the Gz group, however it did not achieve statistical significance. Maximal oxygen consumption decreased significantly to similar extent in both the groups. CONCLUSION: This result suggested that 1) a daily 1hr +2Gz load produced by a centrifuge might eliminate the changes in autonomic cardiovascular control during simulated weightlessness; 2) furthermore, it might partly reverse hypovolemia induced by bed rest; 3) however, it could not prevent the decreases in exercise capacity.

Can daily centrifugation prevent the haematocrit increase elicited by 6-degree, head-down tilt?

A measure to counteract the effects of low or zero gravity is required for long-term space flight, such as the manned Mars mission scheduled by the National Aeronautics and Space administration (NASA) for 2014. We conducted a series of centrifugation experiments with humans, using a short-arm centrifuge (radius 1.8 m, made by First Medical Co., Tokyo, Japan). We employed 6-degree, head-down tilt (HDT) for 4 days to simulate space flight. Ten healthy male volunteers underwent 4-day HDT and a 2-G daily centrifuge load for 60 min in the +Gz direction and measurements, such as haematocrit, 24-h urine volume, body weight and electrocardiogram (ECG) were made. There was no significant increase in the haematocrit during the HDT period, although our previous studies had shown a significant increase during HDT. A 60-min daily load of +2 Gz appears to be effective in reversing the haematocrit increase due to 4-day HDT.

Effects of skin surface cooling and heating on autonomic nervous activity and baroreflex sensitivity in humans.

The influence of skin surface cooling and heating on heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS) were studied in 11 healthy supine volunteers in air temperatures of 18 degrees C (cool), 24 degrees C (mild), 48 degrees C (warm), and 60 degrees C (hot) in a styrene foam chamber. The high-frequency component of HRV (HFRR) decreased and the ratio of low- to high-frequency components, LFRR/HFRR, increased with skin surface heating. Therefore, a suppression of cardiac vagal nervous activity and an enhancement of cardiac sympathetic nervous activity can be caused by skin surface heating. The low-frequency component of BPV (LFSBP), i.e. the fluctuations of the Mayer waves, increased with skin surface heating. The responses between the very low-frequency components of HRV (VLFRR) and systolic BPV (VLFSBP) to thermal skin stimulation were different, although these variables both were considered to be indicators of the thermoregulatory vasomotor control or renin-angiotensin system. Baroreflex sensitivity (BRS) did not increase with skin surface heating, at least in humans.

Non-invasive assessment of human baroreflex during different body positions.

Two techniques for evaluating human baroreflex sensitivity (BRS), i.e. the sequence technique and the cross-spectral technique, were compared during the following four different body positions; 6 degrees head-down tilt (HDT), supine (Sup), 60 degrees head-up tilt (HUT) and upright (Upr). The sequence technique is based on the slope of linear regression between beat-to-beat RR intervals and systolic blood pressures. The cross-spectral technique is based on the cross-spectral analysis of RR interval and systolic blood pressure variabilities, and the estimates of BRS were computed separately for the low-frequency region (0.04-0.15 Hz) and the high-frequency region (0.15-0.5 Hz). The BRS obtained by the sequence technique had a significant correlation to that obtained by the cross-spectral technique for the low-frequency region in HDT, Sup and HUT, but not in Upr. There was a significant correlation between the BRS obtained by the sequence technique and that obtained by the cross-spectral technique for the high-frequency region in every body position. It became clear that the sequence technique is mutually related to the cross-spectral technique for the high-frequency region, but not necessarily identical to the cross-spectral technique for the low-frequency region. Moreover, a comparison was also made between the baroreceptor activating sequence and the deactivating sequence in the sequence technique during the four different body positions. Although the estimates of BRS of the activating sequence and the deactivating sequence were similar in every body position, the numbers of their sequences were progressively separated in the order of HDT, Sup, HUT and Upr. The numbers of the activating sequence and the deactivating sequence in the sequence technique were found to be separated in a sympathetically dominant condition.

Sensitivity analyses of heart rate variability variables by an incremental, passive head-up tilt.

We analyzed the sensitivity of heart rate variability (HRV) variables as an index of autonomic nervous activity by an incremental, passive head-up tilt (HUT). Twelve healthy male volunteers, mean age 20.5 years +/- 2.1 SD, were subjected, after a horizontal (0 degrees) supine posture period, to an incremental, passive HUT of 14.5, 30, 48.6, 61 and 90 degrees. The tested HRV variables were: heart rate (HR), standard deviation of the RR interval (SD(RR)), coefficient of variance of the RR interval (CV(RR)), low-frequency band [0.04-0.15 Hz] power spectrum (P(LF)), high-frequency band [0.15-0.4 Hz] power spectrum (P(HF)), the ratio of P(LF) to P(HF) (P(LF)/P(HF)), coefficients of low-frequency and high-frequency component variance (C-CV(LF), C-CV(HF)), percentages of P(LF) and P(HF) in total power spectrum (%LF, %HF), and normalized units of low frequency and high frequency band power spectra (NU(LF), NU(HF)). The SD(RR), CV(RR), P(LF) and C-CV(LF) were not sensitive to the sine of the tilt angles, i.e., the body-axis component of gravity (+Gz), in the incremental HUT. Therefore, these variables may be less suitable as indices of autonomic nervous activity. The P(LF)/P(HF), NU(LF), and NU(HF) appear to be useful as indices of sympathovagal balance. Both the NU(LF) and NU(HF) (both are equivalent and inversely related) are suitable for the comparison of sympathovagal balance between subjects of different ages and levels of physical fitness because they are not significantly influenced by age and physical fitness. The HR and HRV variables represent quite different characteristics of autonomic nervous activity, according to the Rosenblueth Simeone model. Therefore, the HR appears to be effective for combined assessment of sympathovagal balance. These results provide information useful in the selection of HRV variables while estimating autonomic nervous activity from short-term HRV.

Effects of daily 2-Gz load on human cardiovascular function during weightlessness simulation using 4-day head-down bed rest.

An onboard short arm human centrifuge has been proposed as a countermeasure against physiological problems during long exposure to weightlessness in space and during extra planetary exploration. However, there are few studies on the effects of intermittent application of a Gz load via centrifuge during weightlessness. The present study evaluated the effects of a daily 2-Gz load on cardiovascular function during simulated weightlessness using a 4-day head-down bed rest (HDBR) period. Twelve young male subjects were exposed a HDBR period. Eight of them were exposed to a Gz load for up to 30 min twice per day (the Gz group). The remaining 4 were not exposed to a Gz load; they served as controls (the no-Gz group). Compared with the pre-HDBR period, the no-Gz group showed percent changes in the RR interval, the standard deviation (SD) of the RR interval, parasympathetic nervous activity, and baroreflex sensitivity (BRS) that progressively decreased and reached significance at the end of the HDBR period (-5.96 +/- 2.60%, -33.82 +/- 9.60%, -46.3 +/- 12.7% and -30.9 +/- 7.2%, respectively). In the Gz group, however, the percent changes in the RR interval, the SD of the RR interval, parasympathetic nervous activity, and BRS showed no significant changes throughout the HDBR period. At the end of the HDBR period, these indexes were 2.22 +/- 2.21%, -2.31 +/- 12.28%, 5.08 +/- 14.82% and 10.6 +/- 12.5%, respectively, and significantly greater than those of the no-Gz group. Sympathovagal balance indicators showed no significant change in the Gz and no-Gz groups (5.17 +/- 12.85% and 18.5 +/- 10.7%, respectively). These results indicate that a daily load of 2-Gz eliminates reduction of the RR interval, the SD of the RR interval, parasympathetic nervous activity, and BRS, and that it can maintain autonomic cardiovascular function in short-term weightlessness.

Effects of repeated long duration +2Gz load on man's cardiovascular function.

Usefulness of a short-arm human centrifuge is expected when it is used in space as a countermeasure against cardiovascular deconditioning, problem of bone-calcium metabolism, etc. However, nothing is solidly established regarding the most desirable program for artificial G application. Accordingly, this study was designed to analytically evaluate the effects of repeated long duration +Gz load on human cardiovascular function. Recently heart rate spectral analysis has been recognized as a powerful tool for quantitatively evaluating parasympathetic and sympathetic activity separately in human. It is reported that power of the high frequency component (HF-p) is mediated selectively by parasympathetic activity and the power ratio of low to high frequency components(LF/HF) is indicative of cardiac sympathetic activity or cardiac sympathovagal balance. Sequence method is developed to examine spontaneous baroreceptor reflex sensitivity (BRS). We studied cardiovascular control function by using these methods in 9 healthy men before and after 7 days of daily repeated 1hour +2Gz load. When compared with the data of pre-G load period, post-G load period, decrease of HR, increases of HF-p and BRS were statistically significant. SBP, DBP and LF/HF tended to decrease, however, these changes were not statistically significant. This results indicate that repeated +2Gz load increases parasympathetic activity and arterial baroreceptor-cardiac reflex sensitivity. In recent years, many investigators suggest that space flight and head-down bedrest leads to impaired baroreceptor-cardiac reflex responses and decrease of parasympathetic activity, which may contribute to orthostatic intolerance. So our results suggest that daily repeated 1hour +2Gz load would be useful in preventing post-flight orthostatic intolerance.

Comparison of gradual and rapid onset runs in a short-arm centrifugation.

A gradual onset run (GOR) in a short-arm centrifugation was performed on ten healthy students. The centrifuge had a 1.8 m radius, and the subjects sat on a chair in a cabin. The Gz force increased to 2.2 Gz at 0.1 degree/sec2 for 32 min. and the same Gz-level was maintained for 20 min. Three out of ten subjects completed the whole protocol; the load on the others was terminated because of symptoms or increased heart rate. There were few symptoms such as vertigo, that was a common problem with a rapid onset run (ROR) in former experiments, due to the short-arm centrifugation. The changes of the flicker test after the load were much less in the GOR protocol than in the ROR protocol, even in the terminated group. GOR seemed preferable to ROR in preventing vertigo even though it took longer to reach the necessary G load.

[Estimation of location and size of myocardial infarction from body surface potentials using the ECG inverse solution method].

This paper describes a non-invasive mathematical method for estimating the locations and sizes of myocardial infarction using body surface electrocardiographic mappings. The inverse calculation is the theoretical basis of our method of estimation. First, the boundary integral equations were used to relate body surface and epicardial potential distributions. Next, a spherical harmonic expansion was used to solve the equations in order to obtain the epicardial potentials from the body surface potentials. The validity of the method was assessed by animal experiments and the clinical application. Body surface potentials were recorded using a 128 channel electrocardiographic mapping device equipped with a 16 bit microprocessor. In the animal study, the epicardial potentials were recorded by another potential mapping device simultaneously with body surface potential recordings. In the animal study, 60 epicardial electrodes and a freezing unit were mounted on a elastic fabric sack and attached to the heart. After completion of open chest surgery, freezing myocardial injury was incurred by perfusing -50 degrees C acetone-dry ice cryogen into the freezing unit. Twenty minutes after the start of freezing, ST elevations of the body surface and epicardial potentials were simultaneously recorded. An ST subtraction map was compiled as the difference between the maps before and after the myocardial freezing injury. Then, an inverse calculation was applied to the ST subtraction potentials to estimate the epicardial ST elevation. The geometric parameters of each electrode were determined from stereometry using two-dimensional X-ray images. In the clinical study, the body surface potentials of a patient with old myocardial infarction were recorded. The abnormal Q subtraction map was calculated as the difference between the measured and standard potentials of a normal subject. In the inverse calculation, the geometric shape of the heart and the body surface were determined from cross-sectional body images of computed tomography. The location of the infarction was estimated independently using coronary arteriography and left ventriculography. The results obtained were as follows: Experimentally, the estimated epicardial ST elevations correlated well with the measured ones. The area of estimated ST elevation included the portion of the myocardial injury produced by the freezing procedure, although the area estimated was relatively small compared with the actual one. Clinically, the estimated abnormal Q area correlated well with the area of the left anterior descending artery in which severe stenosis was detected by coronary arteriography.(ABSTRACT TRUNCATED AT 400 WORDS)