[Magnetic resonance imaging could predict delayed encephalopathy after acute carbon monoxide intoxication].

OBJECTIVES: Some patients with acute carbon monoxide (CO) intoxication relapse into severe neuropsychiatric symptomes several weeks after the lucid interval. This serious neurological sequelae, delayed encephalopathy, is difficult to anticipate. Although magnetic resonance imaging (MRI) was reported to show characteristic findings, there has been few information on MRI during the lucid interval. We retrospectively reviewed MR images obtained within 15 days after the exposure, and analyzed whether MRI could predict delayed encephalopathy. DESIGN: Retrospective, single-center study. PATIENTS: Sixteen serial patients with severe CO intoxication, who were found unconscious and underwent hyperbaric oxygen therapy, and in whom MR-imagings were performed at least once within 15 days after the exposure. MEASUREMENTS AND MAIN RESULTS: Although all 16 patients recovered consciouness, six of them (37.5 %) went into delayed encephalopathy (DE group) while the others did not (non-DE group). FLAIR images of all patients in DE group showed bilateral diffuse high intensity in white matter of centrum semiovale after the relapse of neuropsychiatric symptomes. In 4 of them, the identical findings were recognized earlier during the lucid interval. In contrast, no MR images of patients in non-DE group showed white matter hyperintensity (4/6 vs 0/10, p < 0.01). T2-hyperintensities in basal ganglia were seen not only in DE group (3 of 6 patients) but also in non-DE group (2 of 10). Diffusion-weighted images (DWI) were obtained in 10 patients (5 in each group). Although white matter hyperintensities in DWI were positive in 4 patients in DE group (none in non-DE group), 3 of them showed negative findings during the lucid interval. CONCLUSIONS: Bilateral symmetric white matter hyperintensity in MRI (T2WI/FLAIR) could be a good predictor of delayed encephalopathy after acute CO intoxication.

Differences in antithrombin III activities by administration method in critical patients with disseminated intravascular coagulation: a pharmacokinetic study.

Pharmacokinetic (PK) data for antithrombin III (AT) are limited in the critical patients. We therefore performed PK analysis using a two-compartment model and also examined whether plasma AT activity would change depending on two administration methods, AT agent at 500 U/8 h (divided group) or 1,500 U/24 h (combined group) for 3 days, a regulated dosage for disseminated intravascular coagulation (DIC) treatment in Japan, in critical patients with DIC. Clinical prospective randomized study. A high care unit in a university hospital. Twenty-four consecutive critical patients with DIC. Ages ranged from 34 to 91 years. Acute physiology age and chronic health evaluation II scores were 25 to 35. Antithrombin III activities in the combined group caused remarkable transient increases but returned to near the preadministration level 24 h after the infusion. Antithrombin III level in the divided group showed small elevations on each session; therefore, steady increases were found after serial administrations of the agent. On the third day, AT trough activities in the divided group were significantly higher than those in the combined group (P = 0.005). However, peak AT activities in the combined group after AT administration were higher than those in the divided group throughout the study (P = 0.024). Aggravation of bleeding tendency occurred more frequently in the combined group (P = 0.03). Half-life times on the distribution phase in both groups were remarkably shorter than those of previously reported control in congenital AT deficiency. This suggests an increased vascular permeability in the critical patients in this study. Distribution volume in the patients here increased significantly as compared with the previous controls. This is the first PK report using a two-compartment model to demonstrate that remarkable increases in vascular permeability and distribution volume occur in critical patients with DIC, and if the same dose is administered intermittently in such PK situation, AT administration in divided manner can maintain plasma AT trough activity higher than that in the combined method.

Time related changes in reversible MRI findings after prolonged hypoglycemia.

Diffusion weighted magnetic resonance images (DWI) in hypoglycemic coma show more definite and earlier findings than do T1-weighted images, or even fluid-attenuated inversion recovery (FLAIR). However, there has been limited information on the time related changes of such MRI images. We report here the time related changes of MRI findings after prolonged hypoglycemia in a diabetic 62-year-old man without hypoxia. We found in the patient that hyperintensities in DWI, T2-weighted and FLAIR images disappeared on the 14th day along with normalization of the apparent diffusion coefficient (ADC). Single photon emission computed tomography (SPECT) showed no low perfusion findings throughout the course. Since the day when the hyperintensities disappeared, the patient became to open his eyes in response to verbal command. This paper demonstrates serial alterations in reversible DWI findings after prolonged hypoglycemia and we need to define its mechanisms in the future.

Elevated serum beta-D-glucan level and depressed neutrophil phagocytosis in a heatstroke patient.

Endotoxemia has been reported as a mechanism for the fatal sequela after heatstroke. Subsequent disseminated fungal infection in a heatstroke patient has been also described. Beta-D-glucan, a constituent of the fungal cell wall, is an early diagnostic measure for fungal infection. In a heatstroke case, we examined for the first time levels of serum beta-d-glucan and endotoxin. A 34-year-old man with a body temperature of 43.5 degrees C was admitted in a state of shock. Prior to the development of disseminated intravascular coagulopathy (DIC), a remarkable elevation of serum beta-D-glucan level to 116 pg/mL (normal level<6.0 pg/mL) was revealed on the first day of admission. However, serum endotoxin was not detected when using a method that excluded beta-D-glucan contamination from endotoxin measurement (normal level<1.0 pg/mL). This change of beta-D-glucan level was accompanied by a depressed neutrophil function, especially in phagocytosis of 34% (normal range 70-90%) but not in bacterocidal function (81% versus a normal range of 70-100%). After intensive care including continuous hemodiafiltration, the patient regained consciousness but remained ataxic due to cerebellar infarction, which might have resulted from DIC, and subsequent bilateral fungal oculitis were revealed 45 days after admission. This case report demonstrates the elevation of serum beta-D-glucan but normal endotoxin levels after heatstroke, which may prompt further study to re-examine the serum levels of endotoxin in such catastrophic insults.

Differential effects of lowering culture temperature on mediator release from lipopolysaccharide-stimulated neonatal rat microglia.

OBJECTIVE: Therapeutic moderate hypothermia has the potential for neuronal protection against brain injury. Microglia, a type of immune-related cell in the brain, may play a certain role in neuronal damage subsequent to injury. We examined the effects of culture temperature changes from 37 degrees C to 33 degrees C or 30 degrees C on mediator release, including nitric oxide, interleukin-6, and tumor necrosis factor-alpha from lipopolysaccharide-stimulated microglia harvested from neonatal rats. DESIGN: Laboratory study. SETTING: University medical school. SUBJECTS: Microglial cells isolated from primary cultures of rat brains. INTERVENTIONS: The production of nitric oxide was measured by a nitrite accumulation method in a culture medium, whereas cytokines, interleukin-6, and tumor necrosis factor-alpha were measured by enzyme-linked immunosorbent assay. MEASUREMENT AND MAIN RESULTS: At 30 degrees C and 33 degrees C, nitric oxide production stimulated by lipopolysaccharide decreased to 10 and 30% of control (37 degrees C), respectively, 24 hrs after the stimulation, and the decrease was sustained for 48 hrs. Interleukin-6 production at 30 degrees C and 33 degrees C was also reduced to 30% of control 6 hrs after the activation. Such responses lasted throughout the study. However, tumor necrosis factor-alpha release at 30 degrees C and 33 degrees C was depressed for only 6 hrs after stimulation, followed by subsequent elevation to concentrations similar to those at 37 degrees C. Microglial morphologic activation, showing changes from round to bipolar, reached a peak at 6 hrs in the 37 degrees C group, returning to round 12 hrs after lipopolysaccharide application. In 30 degrees C and 33 degrees C, the zenith was detected at 6 hrs, with activation remaining even 12 hrs after the stimulation, suggesting prolongation of the microglial response to lipopolysaccharide, which was inconsistent with changes in tumor necrosis factor release. CONCLUSIONS: Decreasing culture temperature inhibits the production of nitric oxide and interleukin-6 from activated microglia. Differences were found in the degree or time course change between tumor necrosis factor-alpha and the other mediators. Also, the time course of morphologic changes in microglia was dependent on culture temperature. Further studies are required to define the mechanisms for such differences in mediator release from cooled microglia and also to clarify the inconsistency between morphologic change and its function in the cell.

[A case of fluvoxamine overdose].

Selective serotonin reuptake inhibitors (SSRI) are newly developed-antidepressants authorized in 1999 in Japan. We experienced a case of drug poisoning including fluvoxamine, one of SSRI. A comatose nineteen-year-old girl was transported to our ER in the morning on July 25, 2000. There remained many empty packages of fluvoxamine and several sorts of tranquilizers in the room. Her consciousness became alert over the next morning. HPLC analysis revealed fluvoxamine, chlorpromazine, promethazine, biperiden, phenobarbital, and zopiclone in her blood and that serum concentrations of the first three were above the therapeutic ranges. The peak values of fluvoxamine, chlorpromazine, and promethazine were 1,343 ng/ml (6.7 times of the upper limit), 861 ng/ml (2 times), and 529 ng/ml (1.3 times), respectively. Fluvoxamine must be a main cause of her toxic symptoms although other CNS-depressing drugs might work jointly.