Objective To systemically review the effectiveness and safety of human recombinant activated protein C (rhAPC) for severe sepsis. Methods Such databases as MEDLINE, EMbase, The Cochrane Library, VIP, CNKI and CBM were electronically searched for comprehensively collecting randomized controlled trials (RCTs) on the effectiveness and safety of human recombinant activated protein C (rhAPC) for severe sepsis from inception to July 2012. References of included studies were also retrieved. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of included studies. Then, meta-analysis was performed using RevMan 5.0 software. Results Totally, five RCTs involving 6 307 patients were included. The results of meta-analysis showed that, no significant difference was found in 28-day mortality (RR=1.00, 95%CI 0.84 to 1.19, P=1.00) and 90-day mortality (RR=1.00, 95%CI 0.87 to 1.14, P=0.96) between the rhAPC group and the placebo group. The results of subgroup analysis showed that, the two groups were similar in the 28-day mortality of patients with different Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (APACHE II scorelt;25: RR=1.06, 95%CI 0.93 to 1.21, P=0.37; APACHE II score≥25: RR=0.93, 95%CI 0.69 to 1.24, P=0.60), and in the 28-day mortality by protein C deficiency class (APC deficiencylt;80%: RR=0.96, 95%CI 0.56 to 1.65, P=0.89; APC deficiencygt;80%: RR=0.61, 95%CI 0.34 to 1.08, P=0.09). Besides, bleeding risk in the rhAPC group was 1.62 fold more than that in the placebo group (RR=1.62, 95%CI 1.17 to 2.23, P=0.004). No significant difference was found in the incidence of adverse reaction (RR=1.04, 95%CI 0.92 to 1.18, P=0.53). Conclusion Current evidence suggests that, rhAPC could not improve the prognosis of patients with severe sepsis, but it significantly increases bleeding risk.
Objective To systematically review the effectiveness and safety of alanyl-glutamine dipeptide for severe acute pancreatitis (SAP). Methods Such databases as MEDLINE, EMbase, CENTRAL, VIP, WanFang Data, CBM and CNKI were electronically searched from inception to October, 2012 for randomized controlled trials on alanyl-glutamine dipeptide for SAP. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality. Then, meta-analysis was performed using RevMan 5.2. Results Five trials were included involving a total of 227 patients. The results of meta-analysis showed that: compared with the control group, the alanyl-glutamine dipeptide group had the lower incidence of SAP complications (RR=0.41, 95%CI 0.20 to 0.82), the lower incidence of infected pancreatic necrosis (RR=0.12, 95%CI 0.02 to 0.89), less time for alleviating bellyache (MD= –0.90, 95%CI –1.72 to –0.08). There was a tendency in decreasing SAP mortality (RR=0.15, 95%CI 0.02 to 1.19) and lessening the recovery time of blood amylase (SMD=0.37, 95%CI –0.04 to 0.79). Conclusion Current evidence shows that, alanyl-glutamine dipeptide can lower the incidence of complications and the incidence of infected pancreatic necrosis, and shorten the time for alleviating bellyache in SAP patients. Due to the limited quality of the included studies, the above conclusion needs to be verified by more high quality studies.
Objective To investigate the quality of the randomized controlled trials (RCTs) of traditional Chinese medicine (TCM) integrated with western medicine for severe acute respiratory syndrome (SARS). Method All the randomized controlled trials of traditional Chinese medicine integrated with western medicine for SARS worldwide were gained by electronic searching and hand searching. The quality of the RCTs was analyzed by the quality grade evaluation used in Cochrane handbook.The sample size, the baseline data, the results indexes were also analyzed. Results Seven RCTs included 501 SARS cases were identified. The quality grade of one RCT is B, the other six RCTs were graded C. None pre-specified sample size. One RCT tested the differences of the baseline data by statistic method. One RCT reported quality of life as result index. None reported the adverse events.Conclusions Current RCTs of TCM integrated with western medicine can’t provide b evidence for clinical practice because of the poor quality.
Objective To study the epidemic and clinical characteristics of three clusters of early cases of severe acute respiratery syndrome (SARS) in Shenzhen. Methods To retrospectively investigate three clusters of patients. To extract data on clinical presentation and laboratory studies. Results In the first cluster, one patient with SARS in Shenzhen had visited Hong Kong twice in one week. He had felt initial cold and fever in Hong Kong on January 14, while the second case had been onset of SARS when he had been back from Hong Kong. There were 5 people infected in the second cluster at the same time 1 week after they visited their father in a hospital in GuangZhou. Among the three clusters, two clusters had not been infected in ShenZhen, they are inputted, and another cluster is not clear, but it maybe inputted. Three clusters are distributed, they all had high fever. Among them, five had total body muscular soreness and unproductive cough, four with headache, three chill, and two dizziness and pharyngalgia. Three cases had asthma and diarrhea 1 week after the onset of SARS, and progressed to ARDS. The six patients with SARS in Shenzhen People’s Hospital tested positive for coronavirus-related anti-body (IgG) in their plasma 10-15 d after the onset. This IgG titres in one patient remained high (1∶640) 120 days after the onset. Neutrophilia and lymphopenia occurred in patients who died. The more severe the patients’condition was, the higher was the level of LDH increased. Conclusion In three clusters, most patients had not infected in Shenzhen, they are inputted and distributed. That patients with SARS tested positive for coronavirus-related IgG in their plasma.
Objective To establish a stable and reliable lung injury model caused by severe acute pancreatitis（SAP）in rats， which is helpful to study the acute lung injury （ALI）and acute respiratory distress syndrome （ARDS） induced by SAP.Methods Sixty Sprague-Dawley rats were randomized into ligature group （n=20）， traditional group （n=20），and sham operation group （n=20）. SAP model was established through retrograde injection of 5% taurocholic acid. After injection， the pancreatic duct of rats was ligated in ligature group， but not in traditional group. The lung damage and edema at 24 h after operaton and natural course of rats were observed.Results The ALI model of rats induced by SAP was established successfully in ligature group. The rats died of acute respiratory failure within 48 h in ligature group， the mortality was significantly higher than that in traditional group （100% vs.20%），P＜0.05. Pleural effusion occurred in four rats in ligature group， while no pleural effusion was found in rats in other two groups. The volume of ascites of rats in ligature group was （21.15±5.33） ml， which was more than that in traditional group 〔（7.75±2.66） ml〕，P＜0.05， while no ascites was found in rats in sham operation group. The level of serum amylase of rats in ligature group was （2 470.70±399.73） U/L，which was significantly higher than that in traditional group 〔（1 528.40±289.54） U/L〕 and sham operation group 〔（831.10±93.26） U/L〕，P＜0.001. The level of serum albumin of rats in ligature group was （6.90±1.66）g/L， which was significantly lower than that in traditional group 〔（13.10±0.99） g/L〕 and sham operation group 〔（16.20±0.92） g/L〕，P＜0.001.The lung wet-to-dry weight ratio （W/D） of rats in ligature group was 6.50±0.23， which was greater than that in traditional group （4.92±0.18） and sham operation group （4.61±0.16）， P＜0.001. The score of lung histopathologic of rats in ligature group was 29.25±1.07， which was significantly higher than that in traditional group （12.65±1.98） and sham operation group （0），P＜0.001. The score of pancreas histopathologic of rats in ligature group was 15.95±0.15，which was significantly higher than that in traditional group （13.75±0.66） and sham operation group （0.13±0.29），P＜0.001. Under transmission electron microscope， basement membrane of pulmonary capillary of rats in ligation group was destructive， the nuclei was dissolved， endothelial pinocytotic vesicles was functional active， and tight junctions between capillary endothelial cells were blurred and even ruptured. Moreover， tight junctions between alveolar epithelial cells were destructive. Pathological changes of lung ultrastructure of rats in ligation group were more severe than that in traditional group， while no pathological change of lung ultrastructure was observed in rats in sham operation group. Conclusions Injury process and pathogenesis of ALI or ARDS clinically caused by acute gallstone pancreatitis can be reproduced in this animal model， which is suitable to explore the related mechanisms of ALI caused by SAP and provides good animal model for the study of ALI caused by SAP.
ObjectiveTo study the effects of continuous regional arterial infusion (CRAI) of dexamethasone on plasma inflammatory factors of severe acute pancreatitis (SAP) rabbits. MethodsTwentyfour rabbits were randomly divided into sham operation group, SAP group, intravenous infusion of dexamethasone group and CRAI of dexamethasone group (each group 6 rabbits) by random number table. The serum tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and amylase (AMY) levels in rabbits were tested at hour 0.5, 3, 6, 9, and 12 after modeling succeed. The pathological changes of pancreas and the survival were observed on day 3 after modeling succeed. ResultsCompared with the sham operation group, the serum levels of IL-6 significantly increased at 3 h and reached the peak at 6 h, decreased at 9 h (all Plt;0.05); levels of IL-10 significantly increased at 6 h, continuously elevated at 9 h and 12 h (all Plt;0.001); levels of TNF-α significantly increased at 0.5 h (Plt;0.001), reached the peak at 6 h (Plt;0.001) and decreased at 9 h (Plt;0.05); levels of AMY significantly increased at 9 h, continuously elevated at 12 h (all Plt;0.05) in the SAP group. Compared with the SAP group, the serum levels of IL-6 and IL-10 in the CRAI of dexamethasone group all significantly decreased at 6 h, 9 h, and 12 h (Plt;0.001); levels of IL6 significantly decreased only at 6 h in the intravenous infusion of dexamethasone group; levels of TNF-α in the CRAI of dexamethasone group significantly decreased at 3 h, 6 h, 9 h, and 12 h (all Plt;0.001), which in the intravenous infusion of dexamethasone group significantly decreased only at 6 h (Plt;0.05); levels of AMY in the CRAI of dexamethasone group and intravenous infusion of dexamethasone group all significantly decreased at 12 h (Plt;0.05). Compared with the intravenous infusion of dexamethasone group, the serum levels of IL-6 and IL-10 in the CRAI of dexamethasone group all significantly decreased at 6 h (Plt;0.05) and 12 h (Plt;0.001); levels of TNF-α all significantly decreased at 3 h, 6 h, 9 h, and 12 h (all Plt;0.001); levels of AMY were not significantly different (Pgt;0.05). The pathological changes of pancreas in the CRAI of dexamethasone group were obvious, the death of rabbits reduced on day 3 after modeling succeed. ConclusionCRAI dexamethasone can effectively reduce the systemic inflammatory response and pancreatic inflammation, and reduce mortality.
Objective To explore the effects of ulinastatin (UTI) on renal apoptosis and expression of bcl-2 in rats with severe acute pancreatitis (SAP). Methods Sixty rats weighing 250-300 g were randomized divided into 3 groups: pseudo-operation group (SO group, n=20), SAP group (n=20) and UTI treated group (UTI group, n=20). The model of SAP was established by retrograde injection of 5% sodium taurocholate solution into the biliopancreatic duct in the rats. Serum Cr and BUN were determined. The left kidneys were resected for light and electronic microscopic study. Renal cell apoptosis was determined by TUNEL. Expression of bcl-2 was detected by immunohistochemical staining of SABC. Results Serum Cr, BUN, renal cell apoptotic index and bcl-2 expression were markedly increased in SAP group compared with SO group （P＜0.05， P＜0.01）, Renal tissue injuries were aggravated in SAP group under light and electronic microscopic study as well. In UTI group, serum Cr, BUN and renal cell apoptotic index were decreased significantly while the expression of bcl-2 increased remarkably and renal tissue injuries relieved compared with SAP group （P＜0.05）. Positive correlations were found between the renal cell apoptotic index and BUN as well as Cr (r=0.807, P＜0.05; r=0.812, P＜0.05). Conclusion The protective effect of UTI on SAP renal injury is probably through increasing bcl-2 expression and decreasing apoptosis.
【Abstract】Objective To study the influence of early hemofiltration on plasma concentrations of proinflammatory cytokines TNF-α and IL-1β and their transcription levels in severe acute pancreatitis (SAP) pigs. Methods The model of SAP was induced by retrograde injection of artificial bile into pancreatic duct in pigs. Animals were divided randomly into two groups: SAP hemofiltration treatment group (HF group, n=8) and SAP no hemofiltration treatment group (NHF group, n=8). TNF-α and IL-1β plasma concentrations were measured by ELISA. Their transcription levels in the tissues of pancreas, liver and lung were assayed by semi-quantitative reverse transcription polymerase chain reaction. Results After hemofiltration treatment, the plasma concentrations of TNF-α and IL-1β increased gradually but were lower than those of NHF group at the same time spot 〔at 6 h after hemofiltration treatment, (618±276) pg/ml vs (1 375±334) pg/ml and (445±141) pg/ml vs (965±265) pg/ml, P＜0.01〕. At 6 h after hemofiltration treatment, the transcription levels of TNF-α and IL-1β in tissues of pancreas, liver and lung were lower than in NHF group (57.8±8.9 vs 85.7±17.4, 48.0±8.1 vs 78.1±10.2, 46.2±9.6 vs 82.4±10.5; 55.9±9.0 vs 82.2±15.7, 40.6±9.2 vs 60.0±10.6, 35.7±9.8 vs 58.1±9.3, P＜0.01). Conclusion Early hemofiltration can reduce TNF-α and IL-1β plasma concentrations and transcription levels in SAP pigs.
ObjectiveTo evaluate the effect of the early enteral nutrition（EEN） on the natural course in dogs with severe acute pancreatitis（SAP）.MethodsSAP model was induced by injecting 1 ml/kg of combined solution of 5% sodium taurocholate and 8 000-10 000 BAEE units trypsin/ml into pancrease via pancreatic duct.Fifteen dogs were divided into parenteral nutrition(PN) group and EEN group.Two groups were isonitrogenous and isocaloric.EEN was used at postoperative 24 h.Systemic plasma endotoxin level was quantified by the chromogenic limulus amebocyte lysate technique.Both portal and systemic blood sample were obtained before and 1，4，7 d following SAP, and cultured for aerobic as well as anaerobic bacterial.Serum glucose, calcium,amylase and lysosomal enzymes were determined.All dogs were injected with 1.85×106 Bq 125IBSA 4 h before sacrificed.The 125IBSA index of the pancreas/muscle and pancreas/blood was measured,and pancreas pathology was observed.Specimens of tissue from mesenteriolum and mesocolon lymph nodes,lung,pulmonary portal lymph nodes and pancreas were removed,weighed and homogenized in grinding tubes.Aliquots of the homogenata were cultured as blood mentioned above.The thickness of mucosa,the whole gut layer,the height of intestinal villi and their protein and DNA contents in the intestinal and transverse colon were determined.ResultsThe study showed that EEN significantly reduced the levels of systemic plasma endotoxin and the magnitude of bacterial translocation to the portal and systemic blood and distant organ,serum glucose in PN group was higher than that in EEN after SAP 4 d.There were no difference between two groups in the data of serum calcium,amylase and lysosomal enzymes,pathologic index and 125IBSA index of pancreas/muscle and pancreas/blood.EEN improved the gut barrier function by increasing the thickness of mucosa,the whole gut layer and the height of intestinal villi,increasing its protein and DNA contents in the bowel.ConclusionOur results suggest that EEN is safe and effective,and can decrease the rate of intestinal bacterial translocation.
【Abstract】Objective To investigate a more rational modality which is in the treatment of severe acute pancreatitis (SAP) and effective in preventing liver from damages due to SAP. Methods SAP model was established by retrograde injection of 5% sodium taurocholate (1.0 ml) in the subserosa of pancreas in rats (n=80) weighting 200-250 g.The rats were catheterized using PE-50 angiocatheter from femoral artery to celiac trunk. Then they were randomly divided into four groups. Twenty animals served as controls (A group) and received only fluid infusion. The 40 animals, B and C group (20 animals in each one group) received continuous regional arterial infusion (CRAI) of somatostatin （4 μɡ/kg） and the medicines improving microcirculatory (dextran-40 1.5 ml, dopamine hydrochloride 5 μg/kg, anisodaminum 1.5 ml/kg) respectively. The other 20 animals (D group) were treated by somatostatin combined with the medicine improving microcirculatory through CRAI simultaneously with the induction of pancreatitis. The AST, ALT, ALP and serum amylase were recorded, the liver and pancreas tissue were observed pathologicaly after 6 hours. Results There were a ignificant decrease in the serum amylase in B group (Plt;0.05) and D group (Plt;0.05). The AST, ALT, ALP was decreased in B and D group (Plt;0.05). The damage to liver and pancreas were reduced in D group. Conclusion CRAI is effective in preventing liver damages due to SAP and is an effective way in the treatment of SAP.