BACKGROUND: Caspase-3 exists in normal cell in form of zymogen and is capable of stimulating cell apoptosis after activated by apoptosis inducing factors.OBJECTIVE: To observe the activity of caspase-3 in hippocampal cytosolic S-100 and neuronal apoptosis in hippocampal regions, so as to discuss the relationship between hippocampal neuronal apoptosis and caspase3 activity during the whole brain ishcemic-reperfuasional injury.DESIGN: Randomized controlled experiment.SETTING: Emergency Department of Southwest Hospital Affiliated to the Third Military Medical University of Chinese PLA.MATERIALS: This experiment was carried out at Southwest Hospital Affiliated to the Third Military Medical University of Chinese PLA from January to April 1999. Totally 182 male Wistar rats were randomly divided into 3 groups: namely sham operation group of 14 rats, cerebral IR group of 84, rats acetyl-asp-glu-val-asp-aldehyde (AC-DEVD-CHO) treatment group of 84 rats, rats in the latter two groups were then subdivided into IR 8, 24, 48, 72, 120 and 168 hours time points subgroups with 14 rats in each.METHODS: The whole brain ischemia 20 minutes and reperfusional model was established on rats in brain IR group and Ac-DEVD-CHO treatment group, and rats were executed separately at post-reperfusional 8, 24,48, 72, 120 and 168 hours for obtaining hippocampal specimen; rats in sham operation group were only underwent anesthesia and operation without common carotid arterial occlusion and burns of vertebral artery, they were executed at 72 hours after operation and hippocampal specimen was obtained. The quantity of amino-methylcoumarin that was produced from the same mass of specimen within same decomposition time was used to reflect the activity of caspase-3. Brain slices that were obtained from different time points were stained and embedded for observing the hippocampal cell apoptosis under fluorescence microscope at 330-350 nm.MAIN OUTCOME MEASURS: ① The caspase-3 activity in hippocampal S-100 in different post-IR time point groups. ② The hippocampal cell apoptosis in different post-IR time point groups. ③ relationship between caspase-3 activity and neuronal apoptosis in hippocampal regions.RESULTS: Totally 182 rats were enrolled in this experiment, 14 rats got lost, thereby date of 168 rats was entered the result analysis. ① The changes of caspase-3 activity in hippocampal S-100 in different post-IR time point groups: There was no change in sham operation group at postoperative 72 hours. In contrast with cerebral IR group, there were obvious reduction in Ac-DEVD-CHO treatment group at post-reperfusional 24, 48,72, 120 and 168 hours [(1.71±0.03, 1.22±0.03; 2.77±0.09, 1.59±0.7;5.54±0.51, 2.3±0.19, 6.28±1.71, 3.43±0.46; 3.11±1.21, 1.73±0.14) nkat/kg;P ＜ 0.05 or 0.01]. ② The hippocampal cell apoptosis in different post-IR time point groups: Under 400× field of vision, the number of apoptotic cells in sham operation group was 1.2±0.4 cells at postoperative 72 hours.It was lower in Ac-DEVD-CHO treatment group at post-reperfusional 24,48, 72, 120 and 168 hours than cerebral IR group [(6.4±1.7, 2.8±0.8;11.8±1.3, 5.8±1.9; 19.8±3.1, 10.0±1.9; 31.2±5.9, 16.4±2.4; 19.8±2.3, 9.0±2.3)cells/400× field of vision; P ＜ 0.01]. ③ Relationship between caspase-3activity and neuronal apoptosis in hippocampal regions: It was proved of linear correlation in cerebral IR group and Ac-DEVD-CHO treatment group,displaying significantly positive correlation r= 0.935 6 or 0.980 0, P ＜ 0.01).CONCLUSION: Caspase-3 activation is one of the major inducer for hippocampal neuronal apoptosis, playing important role in hippocampus neuronal apoptosis in rats during IR injury.

OBJECTIVE To evaluate the efficacy and safety of meropenem as first choice for hospital acquired pneumonia(HAP) treatment in intensive care units(ICU) in Southwest Hospital. METHODS The usage of meropenem for the patients with HAP in ICU was studied by a prospective,open,and non-comparative trial.Prior to the clinical trial,the preliminary experiment on etiologic investigation was done through bronchoalveolar lavage and blood cultures.In the trial,all patients were treated intravenously with meropenem at a dose of 1g every 8 hours and(3 to 7 days) were established as a treatment duration period. RESULTS After the meropenem therapy,35 patients(66%) showed either cure or improvement.Mortality was 11% at the end of therapy.Clinical complications were observed in 11 patients(21%),with none of them definitely related to the study drug. CONCLUSIONS Meropenem is effective and well-tolerated as monotherapy for most HAP patients in our ICU.The low mortality rate in this study might have been attributed to the first choice use of this drug.

Objective To investigate the roles of Caspase 3 in neuron apoptosis following cerebral ischemia/reperfusion in the rat hippocampus. Methods A model of rats with global ischemia induced by occlusion of the four vessels according to the method by Pulsinelli et al was used in this study. A total of 182 Wistar rats [(220?20) g] were divided randomly into three groups: control group ( n =14), cerebral ischemia group ( n =84), and cerebral ischemia group treated with acetyl asp glu val asp aldehyde (Ac DEVD CHO, n =84). Time points for observation included 8, 24, 48, 72, 120, and 168 h in the latter two groups. Caspase 3 activity in cytosolic extracts (S 100) of hippocampus and apoptotic neurons in hippocampus following cerebral ischemia/reperfusion were observed at the above mentioned time points, respectively. Results (1) No caspase 3 activity was detected in S 100 from the control group. In S 100 from the ischemia group, weak caspase 3 activity was detected at 8 h, but it increased gradually and peaked at 120 h, and then decreased apparently at 168 h after reperfusion. After treatment with Ac DEVD CHO following cerebral ischemia/ reperfusion, caspase 3 activity was inhibited to some extent at each time point. (2) Apoptotic cells were occasionally observed in hippocampus in the control group, but the apoptotic cells increased apparently at 24 h, peaked at 120 h, and decreased a few at 168 h after reperfusion in ischemia group. After treatment with Ac DEVD CHO following cerebral ischemia/reperfusion, apoptosis decreased to some extent at each time point (except 8 h following cerebral ischemia/ reperfusion). (3) Caspase 3 activity in S 100 from hippocampus was positively correlated with apoptotic neurons in hippocampus following cerebral ischemia/reperfusion at each time point ( r =0.9356 in ischemia group, r =0.980 0 in treatment group). Conclusion Caspase 3 may be one of the key causes resulting in neuron apoptosis in rat hippocampus after cerebral ischemia/reperfusion. It may play an important role in ischemia reperfusion brain injury.

Objective To evaluate the efficacy and safety of itraconazole injection in treatment of invasive fungal infection in the patients with multiple organ dysfunction syndrome.Methods Invasive fungal infection in 15 patients with multiple organ dysfunction syndrome was treated with 200 mg itraconazole injection,twice a day on the first two days,then once a day,for 8 to 14 days.During the treatment,the symptoms and signs,the results of chemical detection were recorded.Everyday fungus,sputum,stool smear or culture were performed.Results The recovery rate,effective rate,and fungal clearance in this trial with itraconazole injection were 80%(12/15),86.7%(13/15),and 86.7%(13/15) respectively.The side effect was not found.Conclusion Itraconazole injection is an effective and safe drug against invasive fungal infection in patients with multiple organ dysfunction syndrome.

ObjectiveTo evaluate whether the human patient simulator-based training would improve the leadership and management skills in critical care unit physicians.MethodsThe 40 physicians was completed 1/2 day of training on the human patient simulator. Each subject participated in four scenarios in the rescue team and two experts scored emergency care skills and teamwork leadership/interpersonal skills. A multiple choice question examination and training effectiveness questionnaire were completed before and after training.ResultsThe training effectiveness had more advantages than traditional teaching.Improvement was seen in participants' scores in leadership skills ( 34.8％ ),interpersonal ability ( 36.5％ ) and self-confidence ( 29.9％ ).ConclusionHuman patient simulator training may be useful for leadership,teamwork,and self-confidence skills in critical care unit physicians.

Objective To investigate the effects of sustained inflation (SI) combined with small tidal volume ventilation on lung recruitment and hemodynamics in patients with acute lung injury (ALI). Methods Patients with severe trauma followed by ALI were selected for this study. Patients underwent small tidal volume ventilation (baseline) for 1 h and then SI with 20 cm H 2O?30 s(SI 1), 30 cm H 2O?30 s(SI 2), 40 cm H 2O?30 s(SI 3) and 50 cm H 2O?30 s(SI 4) for 1 h, respectively. Parameters of pulmonary mechanics and hemodynamics were measured at 1 h after baseline, SI and returning baseline, respectively. Results Compared with those of the baseline, no changes of parameters were found after SI 1 and SI 2, but EELV and Cst increased significantly after SI 3 and SI 4. Paw, PAP and PVRI decreased significantly after SI 3 and SI 4. After SI interruption, all the physiological variables returned to baseline. SI had no significant effect on HR, AP and CI. Conclusion Treatment with SI combined with small tidal volume ventilation in patients with ALI can provide lung recruitment and improve lung compliance, but it has no significant side effect on hemodynamics.

Objective To observe the regulative effect of high dose of glucocorticoid (GC) on protein synthesis and mRNA transcription of corticotropin-releasing hormone (CRH) in paraventricular hypothalamic nucleus (PVN) so to ascertain whether there exists difference upon effect of GC either at high dose or at normal dose. Methods A total of 60 Wistar rats were divided into five groups, ie, blank control group, 10 -6 mol/L dexamethasone (DEX) group, 10 -9 mol/L DEX group, 9 g/L saline group and group that was treated with 10 -4 mol/L RU486 first and then with 10 -6 mol/L DEX. The drugs were given through femoral vein. CRH protein expression was measured by means of immunohistochemistry and laser confocal scanning microscophy (LCSM); CRH mRNA transcription level was investigated by in situ hybridization. Results There appeared positive CRH mRNA granules in cytoplasm of PVN after administration with 10 -6 mol/L DEX for 20 minutes but could be seen positive fluorescent granules of CRH protein 30 minutes later, which was reversed at an in advance blockage of GR, as was free in 10 -9 mol/L DEX group, 9 g/L saline group and blank control group. Conclusions High dose of GC can up regulate CRH gene expression in PVN and differs much from the traditional effect of GC at normal dose, as may be due to that high dose of GC exerts effects depending on membrane glucocorticoid receptor but normal dose of GC dose via iGR.