Hajime Takase

Postoperative Interleukin-6 and Cortisol Concentrations in Elderly Patients with Postoperative Confusion

Objective: To investigate changes in plasma interleukin (IL)-6, cortisol or noradrenaline concentrations after surgery in elderly patients with postoperative confusion. Methods: We studied 80 patients aged 70–90 years undergoing abdominal surgery and measured plasma IL-6, cortisol or noradrenaline concentrations before surgery, at the end of surgery, and 24 and 48 h after surgery. Results: Plasma IL-6 concentrations in elderly patients with postoperative confusion were 83.2 ± 30.5, 49.3 ± 14.1 and 42.9 ± 19.4 pg·ml–1 at the end of surgery, and 24 and 48 h after surgery, respectively, being significantly higher than in elderly patients without postoperative confusion (58.0 ± 37.5, 36.1 ± 20.0 and 28.2 ± 16.7 pg· ml–1). Plasma cortisol concentrations in elderly patients with postoperative confusion (42.2 ± 7.8, 38.3 ± 8.3 and 33.1 ± 8.4 µg·dl–1 at the end of surgery, and 24 and 48 h after surgery, respectively) were significantly higher than in elderly patients without postoperative confusion (32.9 ± 6.7, 30.4 ± 8.6 and 25.6 ± 6.5 µg·dl–1, respectively). There were no significant differences in plasma norepinephrine concentrations at all sampling points between elderly patients with and without postoperative confusion. However, plasma IL-6 and cortisol concentrations were related in elderly patients with postoperative confusion (at the end of surgery and 24 and 48 h after surgery). However, there was no relationship between plasma IL-6 and cortisol concentrations 24 and 48 h after surgery in elderly patients without postoperative confusion. Conclusion: Elderly patients with postoperative confusion had increased plasma IL-6 and cortisol concentrations. The interaction between IL-6 and cortisol after surgery is associated with developing postoperative confusion in the elderly patients.

Postoperative confusion increases in elderly long-term benzodiazepine users.

We investigated the relationship between postoperative confusion and duration of benzodiazepine exposure, preoperative anxiety, depressive state, and cognitive function in elderly patients regularly taking benzodiazepines. We studied 328 patients ranging in age from 65 to 80 yr who underwent orthopedic surgery. Information on benzodiazepine use was obtained by face-to-face interview and visual assessment of the patient’s medicine chest. Postoperative confusion was assessed by using a confusion-assessment method. The patients were divided into two groups: those who regularly took benzodiazepines and those who did not. Fifty-seven (17%) of 328 patients were treated with benzodiazepines. There were no significant differences in preoperative Mini-Mental State (MMS) scores, anxiety scores, or depression scores between benzodiazepine users and nonusers. Postoperative confusion occurred in 15 (26%) of 57 benzodiazepine users and in 34 (13%) of 271 nonusers (P < 0.01). The patients who had a score <23 on the MMS were 5 (9%) of 57 benzodiazepine users and 8 (3%) of 271 nonusers (P < 0.05). Postoperative confusion occurred in 13 (35%) of 37 long-term benzodiazepine users (daily use for >1 yr) and in 2 (10%) of 20 short-term users (daily use for <1 yr). The incidence of postoperative confusion was significantly more frequent in long-term than in short-term benzodiazepine users or nonusers of benzodiazepines. The patients who developed a score <23 on the MMS were 5 (14%) of 37 long-term benzodiazepine users and 0 (0%) of 20 short-term benzodiazepine users. In conclusion, the incidence of postoperative confusion was significantly more frequent in long-term benzodiazepine users.

Semiquantitative analysis using thallium-201 SPECT for differential diagnosis between tumor recurrence and radiation necrosis after gamma knife surgery for malignant brain tumors.

PURPOSE Semiquantitative analysis of thallium-201 chloride single photon emission computed tomography (201Tl SPECT) was evaluated for the discrimination between recurrent brain tumor and delayed radiation necrosis after gamma knife surgery (GKS) for metastatic brain tumors and high-grade gliomas. METHODS AND MATERIALS The medical records were reviewed of 75 patients, including 48 patients with metastatic brain tumor and 27 patients with high-grade glioma who underwent GKS in our institution, and had suspected tumor recurrence or radiation necrosis on follow-up neuroimaging and deteriorating clinical status after GKS. Analysis of 201Tl SPECT data used the early ratio (ER) and the delayed ratio (DR) calculated as tumor/normal average counts on the early and delayed images, and the retention index (RI) as the ratio of DR to ER. RESULTS A total of 107 tumors were analyzed with 201Tl SPECT. Nineteen lesions were removed surgically and histological diagnoses established, and the other lesions were evaluated with follow-up clinical and neuroimaging examinations after GKS. The final diagnosis was considered to be recurrent tumor in 65 lesions and radiation necrosis in 42 lesions. Semiquantitative analysis demonstrated significant differences in DR (P=.002) and RI (P<.0001), but not in ER (P=.372), between the tumor recurrence and radiation necrosis groups, and no significant differences between metastatic brain tumors and high-grade gliomas in all indices (P=.926 for ER, P=.263 for DR, and P=.826 for RI). Receiver operating characteristics analysis indicated that RI was the most informative index with the optimum threshold of 0.775, which provided 82.8% sensitivity, 83.7% specificity, and 82.8% accuracy. CONCLUSIONS Semiquantitative analysis of 201Tl SPECT provides useful information for the differentiation between tumor recurrence and radiation necrosis in metastatic brain tumors and high-grade gliomas after GKS, and the RI may be the most valuable index for this purpose.

Initial distribution volume of glucose can be approximated using a conventional glucose analyzer in the intensive care unit

IntroductionWe previously reported that initial distribution volume of glucose (IDVG) reflects central extracellular fluid volume, and that IDVG may represent an indirect measure of cardiac preload that is independent of the plasma glucose values present before glucose injection or infusion of insulin and/or vasoactive drugs. The original IDVG measurement requires an accurate glucose analyzer and repeated arterial blood sampling over a period of 7 min after glucose injection. The purpose of the present study was to compare approximated IDVG, derived from just two blood samples, versus original IDVG, and to test whether approximated IDVG is an acceptable alternative measure of IDVG in the intensive care unit.MethodsA total of 50 consecutive intensive care unit patients were included, and the first IDVG determination in each patient was analyzed. Glucose (5 g) was injected through the central venous line to calculate IDVG. Original IDVG was calculated using a one-compartment model from serial incremental arterial plasma glucose concentrations above preinjection using a reference glucose analyzer. Approximated IDVG was calculated from glucose concentrations in both plasma and whole blood, using a combined blood gas and glucose analyzer, drawn at two time points: immediately before glucose injection and 3 min after injection. Subsequently, each approximated IDVG was calculated using a formula we proposed previously.ResultsThe difference (mean ± standard deviation) between approximated IDVG calculated from plasma samples and original IDVG was -0.05 ± 0.54 l, and the difference between approximated IDVG calculated from whole blood samples and original IDVG was -0.04 ± 0.61 l. There was a linear correlation between approximated and original IDVG (r2 = 0.92 for plasma samples, and r2 = 0.89 for whole blood samples).ConclusionOur findings demonstrate that there was good correlation between each approximated IDVG and original IDVG, although the two measures are not interchangeable. This suggests that approximated IDVG is clinically acceptable as an alternative calculation of IDVG, although approximated and original IDVGs are not equivalent; plasma rather than whole blood measurements are preferable.

Flat electroencephalogram caused by carbon dioxide pneumoperitoneum.

Hypercapnia during laparoscopy with CO2 is predicted in the following situations: compromised pulmonary function, retroperitoneal insufflation, and subcutaneous emphysema. We present a case of sudden electroencephalogram (EEG) depression in response to severe hypercapnia during laparoscopic ureteronephrectomy in a 77-yr-old patient with chronic pulmonary emphysema. During intraperitoneal and retroperitoneal insufflation, subcutaneous emphysema and difficult ventilation occurred. Severe hypercapnia ensued, with pH = 6.94, and Paco2 = 137 mm Hg. Subsequent EEG activity was markedly depressed with a minimum Bispectral Index of 4, accompanied by an increase in arterial blood pressure and heart rate. Termination of the laparoscopic procedure improved ventilation, EEG, and hemodynamics. These EEG changes may result from the narcotic properties of CO2 or hypercapnia-induced neurological abnormalities.

Increased cortisol response to surgery in patients with alcohol problems who developed postoperative confusion.

BACKGROUND Patients with alcohol problems often develop postoperative confusion and have impaired cortisol, ACTH, and norepinephrine. However, the relationship between neuroendocrine responses to surgical stress and postoperative confusion remains unclear in patients with alcohol problems. METHODS Plasma cortisol, ACTH, and norepinephrine concentrations during and after surgery in 30 patients with alcohol problems and 30 control patients who underwent lower abdominal surgery were measured before the induction of anesthesia, 15 and 60 min after skin incision, 60 min after the end of surgery, the next day, and the second day after the operation. RESULTS Plasma cortisol concentrations (21.2 +/- 4.7 microg x dl) of patients with alcohol problems before anesthesia were significantly higher than 15.6 +/- 4.8 microg x dl(-1) of control patients. Plasma cortisol and ACTH responses to surgery in patients with alcohol problems were not significantly increased compared with preoperative values. The incidence of postoperative confusion was significantly higher in patients with alcohol problems than that of control patients (33% vs. 3%). Plasma cortisol concentrations (29.7 +/- 7.0, 31.2 +/- 6.6, 30.3 +/- 8.0, and 28.4 +/- 6.2 microg x dl(-1)) 15 and 60 min after the skin incision, 60 min after the end of surgery, and the next day after operation in postoperatively confused patients with alcohol problems were significantly higher than those of nonconfused patients with alcohol problems (23.0 +/- 5.8, 22.7 +/- 4.1, 22.4 +/- 7.2, and 21.9 +/- 5.5 microg x dl(-1)). CONCLUSION The cortisol response to surgical stress increases in patients with alcohol problems who develop postoperative confusion, although cortisol response to surgical stress decreases in patients with alcohol problems without postoperative confusion.

Endothelial Progenitor Cell Secretome and Oligovascular Repair in a Mouse Model of Prolonged Cerebral Hypoperfusion

Background and Purpose— Endothelial progenitor cells (EPCs) have been extensively investigated as a therapeutic approach for repairing the vascular system in cerebrovascular diseases. Beyond vascular regeneration per se, EPCs may also release factors that affect the entire neurovascular unit. Here, we aim to study the effects of the EPC secretome on oligovascular remodeling in a mouse model of white matter injury after prolonged cerebral hypoperfusion. Methods— The secretome of mouse EPCs was analyzed with a proteome array. In vitro, the effects of the EPC secretome and its factor angiogenin were assessed on primary oligodendrocyte precursor cells and mature human cerebral microvascular endothelial cells (hCMED/D3). In vivo, mice were subjected to permanent bilateral common carotid artery stenosis, then treated with EPC secretome at 24 hours and at 1 week, and cognitive outcome was evaluated with the Y maze test together with oligodendrocyte precursor cell proliferation/differentiation and vascular density in white matter at 4 weeks. Results— Multiple growth factors, cytokines, and proteases were identified in the EPC secretome, including angiogenin. In vitro, the EPC secretome significantly enhanced endothelial and oligodendrocyte precursor cell proliferation and potentiated oligodendrocyte precursor cell maturation. Angiogenin was proved to be a key factor since pharmacological blockade of angiogenin signaling negated the positive effects of the EPC secretome. In vivo, treatment with the EPC secretome increased vascular density, myelin, and mature oligodendrocytes in white matter and rescued cognitive function in the mouse hypoperfusion model. Conclusions— Factors secreted by EPCs may ameliorate white matter damage in the brain by boosting oligovascular remodeling.

Oligodendrogenesis after traumatic brain injury

White matter injury is an important contributor to long term motor and cognitive dysfunction after traumatic brain injury. During brain trauma, acceleration, deceleration, torsion, and compression forces often cause direct damage to the axon tracts, and pathways that are triggered by the initial injury can trigger molecular events that result in secondary axon degeneration. White matter injury is often associated with altered mental status, memory deficits, motor or autonomic dysfunction, and contribute to the development of chronic neurodegenerative diseases. The presence and proper functioning of oligodendrocyte precursor cells offer the potential for repair and recovery of injured white matter. The process of the proliferation, maturation of oligodendrocyte precursor cells and their migration to the site of injury to replace injured or lost oligodendrocytes is know as oligodendrogenesis. The process of oligodendrogenesis, as well as the interaction of oligodendrocyte precursor cells with other elements of the neurovascular unit, will be discussed in this review.

LOTUS overexpression accelerates neuronal plasticity after focal brain ischemia in mice

Nogo receptor-1 (NgR1) and its ligands inhibit neuronal plasticity and limit functional recovery after brain damage such as ischemic stroke. We have previously shown that lateral olfactory tract usher substance (LOTUS) antagonizes NgR1-mediated signaling. Here, we investigated whether LOTUS enhances neuronal plasticity and functional recovery after brain focal ischemia in adult mice. Focal ischemic infarcts were induced in wild-type and LOTUS-overexpressing transgenic mice via middle cerebral artery occlusion. Endogenous LOTUS expression was increased in brain and cervical spinal cord of the contralateral side of ischemia in the chronic phase after brain ischemia. LOTUS overexpression accelerated midline-crossing axonal sprouting from the contralateral side to the ipsilateral side of ischemia in the medullar reticular formation and gray matter of denervated cervical spinal cord. Importantly, LOTUS overexpression improved neurological score highly correlated with laterality ratio of corticoreticular fibers of the medulla oblongata, indicating that LOTUS overexpression may overcome the inhibitory environment induced by NgR1 signaling for damaged motor pathway reconstruction after ischemic stroke. Thus, our data suggest that LOTUS overexpression accelerates neuronal plasticity in the brainstem and cervical spinal cord after stroke and LOTUS administration is useful for future therapeutic strategies.

Protective effects of a radical scavenger edaravone on oligodendrocyte precursor cells against oxidative stress

Oligodendrocyte precursor cells (OPCs) play critical roles in maintaining the number of oligodendrocytes in white matter. Previously, we have shown that oxidative stress dampens oligodendrocyte regeneration after white matter damage, while a clinically proven radical scavenger, edaravone, supports oligodendrocyte repopulation. However, it is not known how edaravone exerts this beneficial effect against oxidative stress. Using in vivo and in vitro experiments, we have examined whether edaravone exhibits direct OPC-protective effects. For in vivo experiments, prolonged cerebral hypoperfusion was induced by bilateral common carotid artery stenosis in mice. OPC damage was observed on day 14 after the onset of cerebral hypoperfusion, and edaravone was demonstrated to decrease OPC death in cerebral white matter. In vitro experiments also confirmed that edaravone reduced oxidative-stress-induced OPC death. Because white matter damage is a major hallmark of many neurological diseases, and OPCs are instrumental in white matter repair after injury, our current study supports the idea that radical scavengers may provide a potential therapeutic approach for white matter related diseases.