Prognostic value of cerebrospinal fluid cytokine changes in herpes simplex virus encephalitis.

A recent trial suggested that corticosteroid was beneficial in herpes simplex virus encephalitis (HSVE), but that precise role remains unclear. We assessed the differences of cerebrospinal fluid (CSF) cytokine changes between different outcomes and between patients with and without corticosteroid administration at the acute stage of HSVE. Interleukin (IL)-1beta, IL-2, IL-6, IL-10, interferon (IFN)-gamma, and tumor necrosis factor-alpha were measured in 56 serial CSFs taken from 20 adult HSVE patients. Their outcomes were poor in 7 and good in 13 patients, and corticosteroid was administered in 10. The differences in the initial and maximum cytokine values were assessed among the different outcomes. The decline rate of cytokine values between the initial and second CSF samples was also assessed between patients with and without corticosteroid. The initial IFN-gamma and maximum IL-6 with a poor outcome were higher than those with a good outcome (p=0.019 for IFN-gamma and p=0.013 for IL-6). The decline rate of IL-6 in patients with corticosteroid was higher than that without corticosteroid (p=0.034). The initial IFN-gamma and maximum IL-6 CSF values represented prognostic biomarkers in HSVE. One pharmacological mechanism related to corticosteroid in HSVE is apparently inhibition of pro-inflammatory cytokines such as IL-6.

Executive dysfunction using behavioral assessment of the dysexecutive syndrome in Parkinson's disease.

The objective of this study was to evaluate the executive dysfunction (ExD) in Parkinson's disease (PD) using the Behavioral Assessment of the Dysexecutive Syndrome (BADS), which provides a wide-range assessment of ExD. The BADS and the Unified Parkinson's Disease Rating Scale (UPDRS) were investigated in 63 nondemented PD patients who revealed scores of >or=24 points on the Mini-Mental State Examination based on the DSM-IV. Multiple logistic regression analysis was performed to evaluate the predisposing factors to ExD, which was defined as <70 points on the age-controlled standardized score. The total score on the UPDRS was a significant independent predisposing factor to ExD. Among the various parts of the UPDRS, part II was the significant factor for ExD. The profile scores of all subtests on the BADS in patients with ExD were significantly lower than those of patients without ExD. All profile scores decreased with severity of PD, but the changes among these scores differed. ExD in nondemented PD predisposed to a greater severity of PD, particularly as regards the activity of daily living impairment. Nondemented PD revealed wide-range components of ExD. All components of ExD were impaired with severity of PD, but the patterns of each component exhibited variety.

Correlation between quantitative-EEG alterations and age in patients with interferon-alpha-treated hepatitis C.

The authors recently observed alterations in the quantitative EEG findings in patients with chronic hepatitis C who were treated with interferon-alpha (IFN-alpha). However, the factors that influenced such EEG alterations remain unclear. The authors evaluated the correlation between QEEG alterations that occurred during IFN-alpha treatment and the age of 98 patients with chronic hepatitis C. These patients underwent blind, prospective, and serial quantitative EEG examinations. IFN-alpha was administered intramuscularly at 9 x 10 IU daily for the first 4 weeks and then three times per week for the next 20 weeks. Serial EEGs were obtained before, at 2 and 4 weeks, and at 2 to 3 days after the treatment. The absolute powers of each frequency band at different stages of the treatment were determined by QEEG. The ages of the patients were classified into five groups: 20 to 29, 30 to 39, 40 to 49, 50 to 59, and > or =60 years. The relationship between the alterations in power values and age was statistically evaluated. As the age of the patients increased, the alterations in power values for the slow waves, alpha 2, and fast waves during IFN-alpha treatment became more remarkable, and significant (repeated-measure analysis of variance; P < 0.0001). The alterations of EEG occurring during IFN-alpha treatment were marked in older patients.

Autonomic cardiovascular changes during and after 14 days of head-down bed rest.

A 14-day, 6 degrees head-down bed rest (HDBR) study was conducted with 12 healthy young men to determine whether there are transient responses of the cardiovascular autonomic regulatory system including cardiovascular, autonomic nervous, and cardiac baroreceptor reflex functions in the acute phases of HDBR and post-HDBR. Compared with the supine position before bed rest, the high-frequency band power (HF(RRI)) of RR intervals (RRIs) decreased significantly at 3, 6, and 24 h of HDBR. This tendency went on until 24 h post-HDBR. Three kinds of cardiac baroreceptor reflex sensitivity (BRS) were estimated from closed-loop approaches to simultaneously recorded spontaneous RRI and systolic arterial pressure (SAP) fluctuations. BRSsequence is based on the simultaneous changes between RRI and SAP. alphaLF and alphaHF are based on a cross-spectrum analysis for low- and high-frequency bands of RRI and SAP. Although BRSsequence decreased significantly at acute phases of both HDBR and post-HDBR, neither alphaLF nor alphaHF decreased significantly at any of the acute phases of HDBR and post-HDBR. Our results suggest that HF(RRI) and BRSsequence can be used effectively to reveal reductions in cardiac vagal nervous modulation on the sinus node and cardiac BRS within 24 h of both HDBR and post-HDBR.

Parasympathetic nervous activity after administration of atropine and neostigmine using heart rate spectral analysis.

Recently, heart rate spectral analysis has become recognized as a powerful tool for quantitatively evaluating autonomic nervous system activity. The purpose of this study was to analyze parasympathetic nervous activity by heart rate spectral analysis after administration of atropine and neostigmine for reversal of residual neuromuscular blockade. For our study, 36 female patients (26-37 years of age), ASA physical status (PS) I, who were scheduled for laparoscopic examination, were randomly allocated to one of the following four groups: In group A (1∶1), 9 patients received 1.0mg atropine followed 4 min later by 1.0 mg neostigmine. In group B (1∶2), 9 patients received 0.5 mg atropine followed 4 min later by 1.0 mg neostigmine. In group C (1∶2.5), 9 patients received 1.0 mg atropine followed 4 min later by 2.5 mg neostigmine. In group D (1∶2 mix), 9 patients received a mixed solution of atropine 0.5 mg and neostigmine 1.0mg. After finishing the laparoscopic examination, additional anesthesia was maintained with 70% nitrous oxide, 30% oxygen, and 0.5% isoflurane. The control data were obtained 10 min after finishing the laparoscopic examination. After that, the data on atropine were obtained between 2 and 4min after administration of atropine, and the data on neostigmine were obtained between 5 and 7 min after administration of neostigmine. We selected power spectral density of the high-frequency component (HF-p) in heart rate spectral analysis as an index to assess parasympathetic activity. In groups A, B, and C, the HF-p decreased after administration of atropine. In groups B and C, the HF-p increased after administration of neostigmine as compared to the control. In group A, the HF-p increased after neostigmine but did not differ from the control. The difference between groups D and B was not statistically significant. From the results of this study, we concluded that the muscarinic effect of neostigmine could not be sufficiently blocked by atropine at 1/2 dosages of neostigmine, but could be sufficiently blocked by atropine at equivalent dosages of neostigmine, under light isoflurane anesthesia.

High TSC22D3 and low GBP1 expression in the liver is a risk factor for early recurrence of hepatocellular carcinoma.

Recurrence after liver resection for hepatocellular carcinoma (HCC) is a major clinical problem, and prognostic markers for recurrence are urgently required. For 390 HCC cases, segmented linear regression analysis with two segments was performed, and the interval for the early and late recurrence groups was partitioned at the crosspoint (676 days). We investigated whether gene expression in non-tumorous tissues of remnant liver from 39 hepatitis C virus-positive HCC cases may be associated with early recurrence of this disease. By microarray analysis, 21 genes were identified as candidate recurrence-associated genes. Further gene expression analysis was performed, and the localization and expression of the gene products of these candidate genes were immunohistochemically evaluated. Low expression of the GBP1 gene and high expression of the TSC22D3 gene were significantly (both P=0.04) associated with the risk of early recurrence. Through backward step-wise multivariate logistic regression analysis for the 21 candidate genes, high expression of GBP1 reduced [odds ratio (OR)=0.20; 95% confidence interval (CI) 0.06-0.73, P=0.02] and high expression of TSC22D3 increased the risk of early recurrence (OR=19.6; 95% CI 1.14-337.2; P=0.04). Immunohistochemical analysis revealed that hepatocytes showed strong membranous expression for GBP1 in the late recurrence group, but weak membranous expression for GBP1 in the early recurrence group. TSC22D3 was frequently expressed in lymphocytes and in a few hepatocytes in tissues of the early recurrence group. Our observations suggest that the combination of the high expression of the TSC22D3 gene and low expression of the GBP1 gene in the non-tumorous tissue of the remnant liver is significantly associated with early recurrence after surgical resection of HCC.

Quantitative EEG analysis of executive dysfunction in Parkinson disease.

Quantitative EEG evaluation in Parkinson disease (PD) reveals diffuse slowing. This is the first quantitative EEG evaluation of the differences between PD with and without executive dysfunction (ExD). The subjects were 32 PD patients without remarkable dementia. The lack of ischemic lesions was confirmed by magnetic resonance imaging. ExD was defined as <70 points on the age-controlled standardized score of the Behavioral Assessment of the Dysexecutive Syndrome. Absolute power was measured for four frequency bands from delta to beta. Electrodes were placed at frontal pole, frontal, central, parietal, occipital, and temporal locations. Spectral ratio was calculated as the sum of power values for alpha and beta waves divided by the sum of values for the slow waves. In multiple logistic regression analysis of each electrode location, the dependent variable was ExD or not, and the independent variables were spectral ratio, age, and Unified Parkinson Disease Rating Scale. The only significant predictor of ExD was spectral ratio at the frontal pole (P = 0.031) and frontal (P = 0.048) locations. PD with ExD exhibited an increase in slow wave activity and a decrease in alpha and fast wave activities in these locations. These findings indicated that the ExD in PD was caused by frontal dysfunction.

Relationships between quantitative electroencephalographic alterations and the severity of hepatitis C based on liver biopsy in interferon-alpha treated patients.

OBJECTIVE: We have observed alterations of quantitative (q)-EEG findings occurring in interferon (IFN)-alpha treated chronic hepatitis C (CH-C) patients, and found patient's age to be one factor influencing such EEG alterations. In the present study we evaluated the correlation between q-EEG alterations during IFN-alpha treatment and the severity of hepatitis based on liver biopsies. METHODS: A total of 102 CH-C patients underwent blind, prospective and serial q-EEG examinations. The IFN-alpha was administered under the same therapeutic regimen to all patients. Serial EEGs were obtained before, at 2 and 4 weeks, and at 2-3 days after the conclusion of treatment. The absolute powers of each frequency band in different periods were determined by q-EEG. Staging (of fibrosis) and grading (of inflammatory cell infiltration) were scaled according to Desmet's classification. We evaluated the relationship between q-EEG and scales of staging or grading. RESULTS: Age distributions did not differ significantly among stages or grades. As the stage or grade increased, the alterations of EEG during IFN-alpha treatment became more pronounced, and significant (repeated-measures analysis of variances; both, p<0.0001). CONCLUSION: Alterations of the EEG occurring during IFN-alpha treatment became pronounced with more severe pathological findings for CH-C. Alterations in the EEGs during IFN-alpha treatment should be carefully monitored in CH-C patients with severe pathological findings.

Comparison of quantitative EEGs between Parkinson disease and age-adjusted normal controls.

Quantitative EEG (qEEG) findings in Parkinson disease (PD) have been reported in only five previous studies. In these studies, the sample size was small and the distribution of qEEG changes was not estimated. This is the first qEEG evaluation not only employing multiple logistic regression analysis but also estimating the distribution of qEEG changes. The subjects comprised 45 PD patients without remarkable dementia and 40 age-adjusted normal controls. The lack of ischemic lesions in all subjects was confirmed by MRI. Absolute power values were measured for four frequency bands from delta to beta. The electrodes were divided into six, viz. frontal pole, frontal, central, parietal, temporal, and occipital locations. We calculated the spectral ratio, i.e., the sum of the power values in the alpha and beta waves divided by the sum of the values in the slow waves. The dependent variable was either PD or normal control; the independent variables were the spectral ratios, age, sex, and Mini-Mental State Examination score. The significant predictive variables in PD were the spectral ratios at all electrode locations except for the frontal pole (frontal location: P = 0.025, other locations: P < 0.01). PD presented diffuse slowing in the qEEG when compared with age-adjusted normal controls.

Relationship between the plasma levels of brain natriuretic peptide and left ventricular ejection fraction in asymptomatic patients with previous myocardial infarction.

While the usefulness of measuring the plasma levels of brain natriuretic peptide (BNP) in cases with worsening heart failure and severe heart failure has already been established, the benefits of evaluation of this parameter in asymptomatic stable patients with left ventricular dysfunction is still under debate. Left ventricular function was evaluated in 141 ambulatory outpatients with a previous history of myocardial infarction not associated with symptoms of heart failure for at least one year. The plasma BNP level was also determined in these patients for comparative study. No correlation between the plasma level of BNP and EF was noted in the normal-EF group, while a negative correlation between the two parameters was observed in the low-EF group (Y = 0.439 - 0.000266X) (R2 = 0.244, P < 0.0001). The sensitivity was 91.5%, specificity 56.3%, positive predictive accuracy value 61.9%, and negative predictive accuracy value 83.8% for a plasma BNP cut-off level of 89.0 pg/mL. The results suggested that it might be meaningful to measure the plasma BNP level, especially in asymptomatic patients with a previous history of myocardial infarction having a low-EF.

Alternations of static cerebral and systemic circulation in normal humans during 14-day head-down bed rest.

BACKGROUND: There have so far been few reports on the static regulations of cerebral and systemic circulation during prolonged head-down bed rest (HDBR). Our aim was to investigate the time course changes in static cerebral and systemic circulation during 14 days of 6 degrees HDBR. MATERIAL/METHODS: Sixteen subjects participated in the HDBR study. The systolic, mean, and diastolic cerebral blood flow velocities (CBFVs) of the middle cerebral artery were measured using a transcranial Doppler technique. Cerebrovascular bed resistance indices, i.e., resistance index (RI), pulsatility index (PI), and estimated regional cerebrovascular resistance (CVRest) were calculated. The systemic cardiovascular functions, i.e, heart rate (HR), mean arterial pressure (MAP), left ventricular ejection time (LVET), stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) were measured or calculated. RESULTS: All CBFVs consistently showed significant decreases from the 2nd day to the last day of the HDBR. The RI and PI showed a rising tendency throughout the HDBR. The CVRest showed significantly higher levels in the later half of the HDBR. The HR and MAP did not change during the HDBR. CONCLUSIONS: The adaptive process of cerebral circulation triggered by HDBR begins very early and leads to a new equilibrium within few days after the onset of HDBR. The alteration of static cerebral circulation with prolonged HDBR, i.e., lowered CBFVs and somewhat higher cerebrovascular bed resistance implies a reduction in the cerebral circulation, but it does not necessarily imply the impaired regulation of cerebral circulation.

Hypergravity exercise against bed rest induced changes in cardiac autonomic control.

An intermittent exposure to artificial hypergravity with physical exercise by a human centrifuge may provide a countermeasure against various physiological problems after space flight. To test the effects of hypergravity with ergometric exercise on dynamic regulation of heart rate during weightlessness, we quantified autonomic cardiovascular control before and after head-down-tilt bed rest (HDBR) with and without the countermeasure. Twelve male subjects underwent a 14-day period of HDBR. Six of them were exposed to a hypergravity (+1.2 Gz acceleration at heart level) for 30 min with ergometric exercise (60 W, n=4; 40 W, n=2) as a countermeasure on day 1, 2, 3, 5, 7, 9, 11, 12, 13 and 14, during HDBR (CM group). The remaining six were not exposed to a hypergravity exercise during HDBR (control group). Blood pressure and ECG were recorded at a supine position before and after HDBR. The high frequency power of R-R interval (HFRR; 1,008+/-238 to 353+/-56 ms(2) P<0.05) as an index of cardiac parasympathetic activity, and transfer function gain between BP and R-R interval in the high frequency range (GainHF; 21.9+/-5.4 to 14.5+/-4.2 ms/mmHg, P<0.01) as an index of vagally mediated arterial-cardiac baroreflex, decreased significantly after HDBR in the control group. However, these changes were not statistically significant in the CM group (HFRR, 1,150+/-344 to 768+/-385 ms(2); GainHF, 21.5+/-3.3 to 18.6+/-3.4 ms/mmHg). Moreover, baroreflex gain by sequence analysis showed similar results. This observation suggests that the intermittent exposure to hypergravity with ergometric exercise may attenuate the decreases in the parasympathetic activity and the spontaneous arterial-cardiac baroreflex function after weightlessness.

Functional changes in autonomic nervous system and baroreceptor reflex induced by 14 days of 6 degrees head-down bed rest.

We studied the effects of 14 days of 6 degrees head-down bed rest (HDBR) in 16 healthy male subjects to examine the functional changes in the autonomic nervous system and cardiac baroreceptor reflex response with an emphasis on dynamic changes during HDBR. Beat-by-beat RR intervals (RRIs) and systolic arterial pressures (SAPs) were measured non-invasively from simultaneous, continuous recordings of ECG and arterial pressure waves in supine resting postures. A power spectrum analysis by the fast Fourier transform was applied to a data set composed of interpolated 512 RRIs and 512 SAPs (256 s in duration). Three indices of cardiac baroreceptor reflex sensitivity (BRS) were obtained by applying a sequence technique and a cross-spectrum analysis technique to the spontaneous RRIs and SAPs. The high-frequency band power of RRI variability (HF(RRI)) decreased significantly in the latter part of HDBR and persisted until the initial stage of the post-HDBR period (POST). The low-frequency band power of SAP variability decreased significantly only during the mid-part of HDBR. The BRS(sequence) obtained by the sequence technique showed a significant increase temporarily on the initial day of HDBR. The BRS(sequence) and the estimate of BRS obtained by the cross-spectrum analysis handling the high-frequency band were both significantly decreased on the initial day of POST. Each of the BRS estimates correlated negatively with heart rate and positively with HF(RRI) during HDBR and POST. These results suggest the following: (1) cardiac spontaneous baroreceptor reflex sensitivity might be transiently increased at the initial stage of HDBR, (2) the reduction in vagal modulation on the sinus node occurs from the latter part of HDBR to the initial stage of POST, (3) sympathetic vasomotor control is probably slightly inhibited during the mid-part of HDBR, and (4) the enhancement in cardiac sympathetic modulation and the impairment in cardiac spontaneous baroreceptor reflex sensitivity may occur in the initial stage of POST.

Effect of centrifuge-induced artificial gravity and ergometric exercise on cardiovascular deconditioning, myatrophy, and osteoporosis induced by a -6 degrees head-down bedrest.

We have reported that centrifuge-induced artificial gravity with ergometric exercise could reduce developing cardiovascular deconditioning in humans. In the present study, we examined this load could prevent the myatrophy and osteoporosis induced by head-down bedrest for 20 days. Subjects were ten healthy male volunteers with informed consent. They were requested to lie down at -6 degrees for 20 days, and evaluation for cardiovascular deconditioning, myatrophy, and osteoporosis. As the result, high G-load with low intensity exercise suppressed the orthostatic intolerance and increase in serum osteoporotic marker, whereas low G-load with high intensity ergometric exercise maintained the maximal oxygen intake, heart dimension, and prevented myatrophy. The combination of high/low G-load with low/high intensity exercise will determine the optimal protocol for prevention of cardiovascular deconditioning, myatrophy, and osteoporosis.