Rapid improvement of diffusion-weighted imaging abnormalities after glucose infusion in hypoglycaemic coma.

Diffusion-weighted imaging (DWI) may detect hyperintense lesions in patients with transient hypoglycaemia-induced hemiparesis or coma, which are completely reversible after glucose infusion.1(-)3 In vivo animal studies have documented the visualisation of such hypoglycaemia-induced changes of signal intensity and the reversal by glucose intake in detail.4 However, the time necessary for hyperintense lesions on DWI to disappear after glucose infusion in humans is still unclear. A 54 year old woman presented comatose with brain stem signs and severe hypoglycaemia. DWI demonstrated hyperintense lesions in the corpus callosum and internal capsules. She was treated with IV glucose. These lesions had resolved significantly on imaging 2 hours later and completely resolved on repeat imaging 2 days later. This report documents the time course of recovery of neurological lesions induced by hypoglycaemia after treatment with IV glucose.

Effects of repeated maternal stress on FOS expression in the hypothalamic paraventricular nucleus of fetal rats.

The effects of repeated prenatal stress with different severity (restraint and immobilization) on Fos expression in the maternal and fetal hypothalamic paraventricular nucleus (PVN) were examined in rats. Acute stress treatment was performed for 30 min on gestational day 21, and repeated stress treatment for 30 min daily for 5 days from gestational days 17-21. In the parvocellular region of the maternal PVN, the stress-induced increases in the number of Fos-immunoreactive neurons were smaller in the repeated stress groups than the acute stress groups, indicating an adaptation of Fos expression to repeated stress. The attenuated Fos expression observed in the maternal PVN following repeated mild stress did not occur in the fetal PVN. In contrast, repeated immobilization stress caused a much smaller increase in Fos expression in the fetal PVN than did acute immobilization stress. The reduced Fos expression in the fetal PVN following repeated severe stress was thought to be due to cell death, since the fetal PVN in the chronic immobilization group revealed a reduction in the total number of cells and an increase in the number of apoptotic cells. In the female but not male fetuses, repeated restraint stress induced a significant increase in the number of apoptotic cells in the PVN. These findings suggest that the fetal PVN shows no adaptation of Fos expression to repeated maternal stress, but great vulnerability to cell death, including apoptosis. In addition, stress-induced apoptosis may more easily occur in the fetal PVN in females than males.

Caspase-like activity in programmed nuclear death during conjugation of Tetrahymena thermophila.

Apoptosis, or programmed cell death, is common in a variety of eucaryotes, from unicellular protozoa to vertebrates. The ciliated protozoan Tetrahymena thermophila has a unique apoptosis-like nuclear death during conjugation, called programmed nuclear death. This death program involves nuclear condensation (pyknosis) and oligonucleosomal DNA fragmentation in the parental macronucleus. Subsequently, the condensed nucleus is entirely resorbed in the autophagosome. Here we demonstrate that caspase-8- and -9-like activity was detected, but no caspase-3-like activity, by in vitro assay during the nuclear resorption process, suggesting that caspase-like activity is associated with both programmed cell death and apoptosis-like nuclear death in Tetrahymena. The use of indicator dye to detect the loss of mitochondrial membrane potential suggested the uptake of mitochondria and the degenerating macronucleus by the autophagosome. An involvement of mitochondria in the programmed nuclear death is discussed.

Materno-fetal coordination of stress-induced Fos expression in the hypothalamic paraventricular nucleus during pregnancy.

This study investigates whether maternal stress during pregnancy induces maternal and fetal hypothalamic paraventricular nucleus (PVN) neuronal activation and the effects of maternal stress on fetal hypothalamic and PVN brain-derived neurotrophic factor (BDNF) expression. Pregnant rats were exposed to three types of maternal stress with varying severity (restraint, forced walking and immobilization) for 30 min on gestational day 21. Severity of stress was assessed by measurement of maternal plasma corticosterone 30 min following the stimulus. Maternal plasma corticosterone increased in each stress response group (immobilization>forced walking>restraint). Further, the expression of Fos protein, a marker of neuronal activation, increased in the fetal and maternal PVN in direct relation to the severity of stress treatments. Forced walking and immobilized stress, but not restraint stress, significantly increased BDNF expression in the fetal hypothalamus.These findings suggest that the fetal hypothalamic-pituitary-adrenal (HPA) response following maternal stress mirrors maternal HPA activation. In addition, BDNF may play a role in protecting fetal brain neurons from damage caused by severe stress.

Transcranial Doppler enhanced thrombolysis for embolic occlusion of major cerebral arteries.

SUMMARY: For the treatment of 11 patients with hyperacute embolic occlusion of major cerebral arteries (ten with occlusion of middle cerebral artery and one with occlusion of basilar artery), TCDenhanced thrombolysis (TCDET) was performed in combination with ultrasound irradiation, using diagnostic transcranial Doppler (TCD) (TC2-64B: 2MHz, 100mW/cm(2), pulsed wave) (TCDET group), and the effectiveness of this procedure was compared with that of local intra-arterial fibrinolysis (LIF) in 45 patients with embolic occlusion of the middle cerebral artery (LIF group). Regarding dose of TPA, the LIF group used 1046.7 +/- 607.8 units and the TCDET group 700.0 +/- 431.3 units (p < 0.05). Regarding time technically required to attain recanalization, the LIF group required 68.2 minutes, and the TCDET group 28.6 minutes. A good outcome was noted in 60.8% of the LIF group and 64% of the TCDET group. Haemorrhagic transformation was observed in 7.8% of the LIF group and in 0% of the TCDET group. No complications due to TCD irradiation were observed in the TCDET group. These findings suggest that TCDET can be an effective method of achieving recanalization.

Morphological changes in the rat exocrine pancreas after pancreatic duct ligation.

In the present study, morphological changes of the exocrine pancreas in rats after pancreatic duct ligation were examined with light microscopy (hematoxylin-eosin, TUNEL, and PCNA staining) and scanning electron microscopy in order to elucidate the effects of increased pancreatic duct pressure. On the fifth day after pancreatic duct ligation, ductular proliferation, periductal fibrosis, and disappearance of acini were observed. TUNEL and PCNA staining demonstrated many apoptotic acinar cells and proliferating ductal cells immediately after ligation, which reached a maximal number on the 2nd or 3rd day. Tortuous or helical interlobular pancreatic ducts with inner surfaces containing many crater-like depressions and long cilia were found after ligation. These changes were almost identical to those observed in the pancreatic tissue of model chronic pancreatitis rats, WBN/Kob rats, and stroke-prone spontaneously hypertensive (SHRSP) rats. In summary, the morphological changes observed after pancreatic duct ligation were similar to those of chronic pancreatitis, therefore, the characteristic changes of pancreatic ducts observed in chronic pancreatitis may be caused by increased pancreatic duct pressure.

[Multimodal treatment including intraoperative irradiation for advanced pancreatic cancer with extended metastasis].

From January 1987 to December 1999, we treated 11 advanced pancreatic cancer patients with extended metastasis with multimodal treatment. Two patients received external radiation therapy (ERT) and systemic chemotherapy, 1 received intraoperative radiation therapy (IORT) and ERT and arterial infusion chemotherapy (AIC), 2 received IORT and AIC, 4 received only IORT, 2 received only AIC, and 15 did not receive any of these treatments. There was a significant difference in the survival rate between treatment and no treatment cases (median survival of 177 days and 109 days, respectively) (p = 0.04). A significant difference in the survival rate was also observed between IORT cases and no treatment cases (median survival of 212 days and 109 days, respectively) (p = 0.02). However, there was no significant difference in the survival rate between AIC cases and no treatment cases (median survival of 177 days and 109 days, respectively) (p = 0.10). Therefore, our experience suggests that multimodal treatment including intraoperative irradiation is effective for advanced pancreatic cancer patients with extended metastasis.

Selective coactivation of estrogen-dependent transcription by CITED1 CBP/p300-binding protein.

CITED1, a CBP/p300-binding nuclear protein that does not bind directly to DNA, is a transcriptional coregulator. Here, we show evidence that CITED1 functions as a selective coactivator for estrogen-dependent transcription. When transfected, CITED1 enhanced transcriptional activation by the ligand-binding/AF2 domain of both estrogen receptor-alpha (ERalpha) and ERbeta in an estrogen-dependent manner, but it affected transcriptional activities of other nuclear receptors only marginally. CITED1 bound directly to ERalpha in an estrogen-dependent manner through its transactivating domain, and this binding activity was separable from its p300-binding activity. CITED1 was strongly expressed in nulliparous mouse mammary epithelial cells and, when expressed in ER-positive MCF-7 breast cancer cells by transduction, exogenous CITED1 enhanced sensitivity of MCF-7 cells to estrogen, stabilizing the estrogen-dependent interaction between p300 and ERalpha. The estrogen-induced expression of the transforming growth factor-alpha (TGF-alpha) mRNA transcript was enhanced in the CITED1-expressing MCF-7 cells, whereas estrogen-induced expression of the mRNA transcripts for progesterone receptor or pS2 was not affected. Chromatin immunoprecipitation assay revealed that endogenous CITED1 is recruited to the chromosomal TGF-alpha promoter in MCF-7 cells in an estrogen-dependent manner but not to the pS2 promoter. These results suggest that CITED1 may play roles in regulation of estrogen sensitivity in a gene-specific manner.

The influence of nitroglycerin and prostaglandin E1 on dynamic cerebral autoregulation in adult patients during propofol and fentanyl anaesthesia.

We investigated dynamic cerebral autoregulation in 24 normocapnic adult patients during propofol and fentanyl anaesthesia. Hypotension was induced, to a mean arterial pressure (MAP) of 60-65 mmHg, using nitroglycerin or prostaglandin E1. Time-averaged mean cerebral blood flow velocity in the right middle cerebral artery was measured continuously using transcranial Doppler sonography. Dynamic autoregulatory response was activated by a sudden decrease in MAP following release of bilateral thigh cuffs (thigh cuff test) and evaluated as a dynamic rate of autoregulation (dRoR in % x s(-1)). The cuff test was repeated to obtain two values of dRoR during baseline and during induced hypotension; the data were then averaged. The mean value of dRoR during baseline and during induced hypotension was 14.2 (2.9) and 14.2 (1.6) % x s(-1), respectively, in the nitroglycerin group, and 14.6 (2.6) and 14.4 (2.4) % x s(-1), in the prostaglandin E1 group. We were unable to demonstrate significant between- or within-group differences in dRoR. Thus, we conclude that nitroglycerin and prostaglandin E1 do not attenuate dynamic cerebral autoregulation.

Continuous intra-jugular venous blood-gas monitoring with the Paratrend 7 during hypothermic cardiopulmonary bypass.

We measured the accuracy of the continuous intra-vascular blood-gas monitoring system (Paratrend 7, PT7) placed in the jugular venous bulb in 18 adult patients having cardiac or aortic surgery with hypothermic cardiopulmonary bypass (CPB). After induction of anaesthesia, a PT7 sensor was inserted through a 20-gauge venous catheter into the right jugular venous bulb. Blood samples were drawn from the venous catheter and measured with a blood gas analyser (BGA). Five to eight paired measurements using the PT7 and blood samples were made per patient, and bias and precision were calculated for each patient using the Bland-Altman method. The ranges for the blood sample measurements were: pH 7.12 to 7.59, PCO(2) 3.7 to 9.6 kPa, PO(2) 3.5 to 16.0 kPa, oxygen saturation 40 to 99%, bicarbonate 18.6 to 34.4 mmol l(-1), and base excess -7.8 to 12.5 mmol l(-1). Bias and precision values were 0.014/0.071 for pH, 0/0.90 kPa for PCO(2), and -0.16/1.18 kPa for PO(2). These values were comparable with those previously made on arterial blood. However, precision for oxygen saturation in each patient varied 2.3 to 23.6% (95% CI: 6.3 to 12.9%), which was unsatisfactory for clinical measurements. Deep hypothermia ( approximately 19.6 degrees C) and marked haemodilution ( approximately 13.5%) during CPB did not influence the reliability of the PT7 sensor. Thus, we concluded that continuous intra-jugular venous blood-gas monitoring is clinically feasible using the PT7 and may provide valuable information during CPB.

Thrombotic thrombocytopenic purpura in autoimmune hepatitis.

A 19-year-old woman presented with clinical manifestations of sudden, fulminant thrombotic thrombocytopenic purpura associated with autoimmune hepatitis and autoimmune thrombocytopenic purpura. Although thrombotic thrombocytopenic purpura may, rarely, be associated with systemic lupus erythematosus and other autoimmune diseases, to our knowledge, the syndrome has never been described in association with autoimmune hepatitis. In this patient, too, the etiology of thrombotic thrombocytopenic purpura associated with autoimmune disease remains elusive. The patient was treated with corticosteroid, which brought about no improvement in her condition, and she died of multiorgan failure. Diagnosis is challenging, but prompt diagnosis is necessary because thrombotic thrombocytopenic purpura is a life-threatening syndrome whose prognosis has been improved significantly by early plasmapheresis treatment.

Naloxone improves arterial blood pressure and hypoxic ventilatory depression, but not survival, of rats during acute hypoxia.

OBJECTIVE: To investigate the effects of naloxone and morphine during acute hypoxia. DESIGN: Prospective, randomized animal study. SETTING: University laboratory. SUBJECTS: Twenty-eight adult male Sprague Dawley rats, weighing 300-350 g. INTERVENTIONS: The rats were implanted with a femoral catheter and subcutaneous electrodes for electrocardiogram recording and were randomly assigned to receive morphine (5 mg/kg), naloxone (5 mg and 10 mg/kg), or normal saline (control) (n = 7 in each). Fifteen minutes after intraperitoneal injection of the drug, each rat was exposed to hypoxic gas (5% oxygen, 95% N2) for 70 mins. Hypoxic survival time was measured. Mean arterial pressure (MAP), arterial pH, Paco2, Pao2, and base excess were measured before injection (baseline), 14 mins after injection (H0), and 6 mins (H1), 33 mins (H2), and 48 mins (H3) after exposure to hypoxia. MEASUREMENTS AND MAIN RESULTS: Hypoxic survival was similar between the naloxone 5 mg/kg and control groups (p = .183), significantly lower in the naloxone 10 mg/kg group (p < .01), and significantly higher in the morphine 5 mg/kg group (p < .05) compared with controls. MAP significantly decreased in all groups. However, at H2-H3, MAP was better preserved in both naloxone groups and was lower in the morphine group compared with controls. Paco2 was maintained higher at H0-H3 in the morphine group and lower at H2-H3 in both naloxone groups compared with controls. CONCLUSION: During acute hypoxia, naloxone preserves arterial blood pressure and attenuates hypoxic ventilatory depression by antagonizing endogenous opiates, but it does not improve hypoxic survival. In contrast, morphine, which enhances the action of endogenous opiates, does improve hypoxic survival. The acute hypoxic tolerance of morphine may be partly attributable to a depression of oxygen consumption, increased cerebral blood flow secondary to high Paco2, and protective actions mediated by delta-opioid receptors.

[Cerebral autoregulation during sevoflurane or isoflurane anesthesia: evaluation with transient hyperemic response].

We investigated dynamic cerebral autoregulation during N2O-O2/fentanyl anesthesia (baseline) plus 1.0 and 2.0 minimum alveolar anesthetic concentrations (MAC) of sevoflurane or isoflurane anesthesia in 14 patients undergoing non-neurosurgical operation. Cerebral blood flow velocity in the right middle cerebral artery (Vmca) was measured continuously using transcranial Doppler ultrasonography. At normocapnia, dynamic cerebral autoregulation was tested by transient hyperemic response (a response of Vmca after a brief compression of the ipsilateral common carotid artery). For quantitative comparisons, ratio of systolic Vmca before, to immediately after compression (THRR) was calculated. Values of THRR were 1.14 +/- 0.03 (mean +/- SD), 1.15 +/- 0.04, and 1.12 +/- 0.03 during baseline, 1.0, and 2.0 MAC sevoflurane anesthesia, respectively. THRR was not significantly different among the 3 conditions. In contrast, THRR values were 1.17 +/- 0.03, 1.07 +/- 0.02, and 1.01 +/- 0.01 during baseline, 1.0, and 2.0 MAC isoflurane anesthesia, respectively. THRR was significantly attenuated in a dose dependent manner during isoflurane anesthesia. These results indicate that dynamic cerebral autoregulation is preserved during 2.0 MAC sevoflurane anesthesia, but not during 1.0 MAC isoflurane anesthesia.

Spin trapping agent, phenyl N-tert-butylnitrone, reduces nitric oxide production in the rat brain during experimental meningitis.

Phenyl N-tert-butylnitrone (PBN) is a spin trapping agent previously shown to exert a neuroprotective effect in infant rat brain during bacterial meningitis. In the present study, we investigated the effect of systemic PBN administration on nitric oxide (NO) production in a rat model of experimental meningitis induced by lipopolysaccharide (LPS). We assessed the NO concentration in rat brain tissues with an electron paramagnetic resonance (EPR) NO trapping technique. In this model, rats receiving intracisternal LPS administration showed symptoms of meningitis and cerebrospinal fluid (CSF) pleocytosis. The time course study indicated that the concentration of NO in the brain reached the maximum level 8.5 h after injection of LPS, and returned to the control level 24 h after the injection. When various doses of PBN (125-400 mg/kg) were injected intraperitoneally 30 min prior to LPS, NO production in the brain was reduced with increasing PBN dose (250 mg/kg suppressed 80% at 8.5 h after LPS injection), and white blood cells (WBC) in CSF were significantly decreased. We concluded that reduction of NO generation during bacterial meningitis contributes to the neuroprotective effect of PBN in addition to its possible direct scavenging of reactive oxygen intermediate (ROI).

Diagnosis of chest wall invasion by lung cancer: useful criteria for exclusion of the possibility of chest wall invasion with MR imaging.

PURPOSE: To compare the accuracy of thin-section CT, conventional static MR imaging (conventional MRI), and breathing dynamic echo planar magnetic resonance imaging (BDEPI) in evaluating lung cancer invasion to the chest wall. MATERIALS AND METHODS: Thin-section CT, conventional MRI, and BDEPI were performed preoperatively in 20 patients suspected of having primary lung cancers adjacent to the chest wall on conventional CT. The results of imaging findings were compared with those of surgical and histopathological findings. RESULTS: All patients were confirmed to have no chest wall invasion after surgery. By thin-section CT, 10 of 20 patients were correctly diagnosed as having no chest wall invasion (50% specificity). Two of the 20 patients were incorrectly diagnosed as having chest wall invasion by conventional MRI and BDEPI (90% specificity). CONCLUSION: When chest wall invasion is suspected on CT scans, static and breathing dynamic MRI are recommended to avoid false positive interpretations.

Improved cardiac contractile functions in hypoxia-reoxygenation in rats treated with low concentration Co(2+).

An intracellular mechanism that senses decreases in tissue oxygen level and stimulates hypoxia-related gene expression has been reported in various cell types including the cardiac cell. The mechanism can also be activated by Co(2+) in normoxia. Thus we investigated the effects of prior chronic oral CoCl(2) on mechanical functions of isolated, perfused rat hearts in hypoxia-reoxygenation. In normoxic rats, 43 days of Co(2+) administration increased hematocrit from 45 +/- 0.3% (control, n = 18) to 51 +/- 0.6% (n = 19). In hypoxia and reoxygenation, Co(2+)-pretreated hearts exhibited a significantly higher rate-pressure product (267 and 163%, respectively) and coronary flow (127 and 118%, respectively) and lower end-diastolic pressure (72 and 60%, respectively) compared with the control hearts. Although the oral Co(2+) administration significantly raised myocardial Co(2+) concentration, it did not affect mitochondrial respiration, tissue glycogen concentration, or myocardial tissue histology. The levels of vascular endothelial growth factor, aldolase-A, and glucose transporter-1 mRNA were significantly elevated in the Co(2+)-treated myocardium. We conclude that cardiac contractile functions would gain hypoxic tolerance when the endogenous cellular oxygen-sensing mechanism is activated.