Treatment with anti-factor VIIa in acute pancreatitis in rats: blocking both coagulation and inflammation?

OBJECTIVE: Acute pancreatitis starts as an autodigestive process restricted to the pancreas and progresses to a systemic inflammation via cytokine release into the blood stream. Several inhibitors of the coagulation cascade, including active-site-inactivated factor VIIa, have shown anti-inflammatory properties in other inflammatory models than acute pancreatitis. Free radical scavengers have proven useful in reducing the oxidative damage during hyperinflammatory conditions. The aim of this study was to investigate whether pretreatment with FVIIai would have any effect on the multiple organ dysfunction syndrome (MODS) in severe acute pancreatitis. MATERIAL AND METHODS: Experimental acute pancreatitis was induced by intraductal infusion of taurodeoxycholate in the pancreatic duct. The animals were pretreated with N-acetyl-cysteine and active-site-inactivated factor VIIa. Neutrophil infiltration in the lungs, ileum and colon was quantified by myeloperoxidase activity. Inflammatory markers, IL-6 and MIP-2, were measured using ELISA. RESULTS: Tissue infiltration of neutrophils in the lungs, ileum and colon significantly increased during acute pancreatitis as compared to sham operation. These levels were reduced by pretreatment with N-acetylcysteine and active-site-inactivated factor VIIa. Levels of interleukin-6 and macrophage inflammatory protein-2 increased significantly during acute pancreatitis. Pretreatment with NAC and FVIIai reduced these levels. CONCLUSIONS: Both N-acetylcysteine and active-site-inactivated factor VIIa showed powerful anti-inflammatory properties in experimental acute pancreatitis. As they exert their effects through different physiological mechanisms, they represent potential candidates for future multimodal treatment of acute pancreatitis.     

Delayed recovery of normal hematopoiesis in arsenic trioxide treatment of acute promyelocytic leukemia: a comparison to all-trans retinoic acid treatment

OBJECTIVE: To examine laboratory data including total blood cell count, leukocyte morphology and coagulation parameters during treatment for acute promyelocytic leukemia (APL) at a single institute, and compare the precise differences between all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3) treatment. PATIENTS AND METHODS: Sixteen patients with APL who were treated with ATRA or As2O3 alone and achieved complete remission (CR) were analyzed. ATRA 45 mg/m2/day was given orally until CR. As2O3 0.15 mg/kg/day was given intravenously until leukemic blasts and promyelocytes were eliminated from the bone marrow. RESULTS: All 7 patients in the ATRA-treated group were primary cases and all 9 patients in the As2O3-treated group were relapsed cases after the achievement of CR with the ATRA. There was no difference in the data before treatment between these two groups. The duration of leukocytopenia and neutropenia during As2O3 treatment was significantly longer than those of ATRA treatment. The nadir of leukocyte and neutrophil counts was observed later in the As2O3-treated group. Terminal neutrophil differentiation was observed more obviously in the ATRA-treated group. The red blood cell count and hemoglobin concentration decreased significantly at the end of As2O3 treatment and were lower than those of ATRA treatment. Platelets recovered earlier in the ATRA-treated group. Coagulation parameters were not significantly changed between the two groups. CONCLUSION: In comparison with ATRA treatment, the recovery of several components in the peripheral blood cells was delayed in As2O3 treatment. Therefore we should pay more and longer attention in As2O3 treatment.     

砷剂和维甲酸对急性早幼粒细胞白血病凝血异常作用的临床研究

目的研究全反式维甲酸(ATRA)或三氧化二砷(As2O3)治疗急性早幼粒细胞白血病(APL)对患者凝血异常的作用,探讨APL患者出血形成机制.方法采用逆转录-聚合酶链反应(RT-PCR)检测APL细胞凝血酶调节蛋白(TM)和组织因子(TF)mRNA的转录;同时采用ELISA法测定患者治疗期间血浆的相关凝血参数及细胞促凝活性(PCA)的改变,临床监测APL患者出血症状变化.结果 APL患者在ATRA治疗期间血浆及APL细胞表面TM表达均显著上调,从治疗前血浆含量(5.07±0.53) μg/L,渐进上升到治疗后第5天(21.86±5.32) μg/L,达完全缓解(CR)后接近正常水平;而TM抗原由治疗前的(14.31±1.60)ng /107到治疗后20天上升至(21.61±6.82)ng /107细胞;血浆P选择素、可溶性纤维蛋白单体复合物和D-二聚体(D-D),在As2O3或ATRA治疗APL患者期间,均较治疗前显著下降(P值均<0.01);同时发现APL细胞TFmRNA异常表达增高,用ATRA或As2O3治疗APL患者期间均具有下调TF mRNA和蛋白表达的作用,在ATRA或As2O3治疗期间,TF抗原由治疗前的(14.81±6.23)ng/L,均呈显著下降,治疗20天后均未能检测到TF的表达 (P＜0.01),APL细胞的PCA亦呈显著下调,同时伴随临床出血症状明显改善.结论 As2O3或ATRA均可显著下调TF mRNA及其表达,减低PCA从而迅速纠正APL患者严重的出血症状.     

Oxidative stress in blood of patients with alcohol-related pancreatitis

To determine the possible role of oxidative stress in alcoholic pancreatitis, the authors measured the ability of blood neutrophils of 22 patients with acute and 20 patients with chronic alcoholic pancreatitis to produce superoxide anion (O2-) and hydrogen peroxide (H2O2), spontaneously and after in vitro stimulation with phorbol ester and compared it with that of neutrophils isolated from the blood of 16 healthy controls. In addition, they measured serum activities of superoxide dismutase, catalase, and the serum concentration of glutathione peroxidase (GPx). Phorbol ester-induced O2- and H2O2 production in neutrophils of patients with acute and chronic pancreatitis was greater than in controls, but these differences, except of superoxide anion production by neutrophils of patients with chronic pancreatitis, were not statistically significant because of large individual differences. Spontaneous resting production of O2- and H2O2 by neutrophils of patients with chronic pancreatitis was significantly greater than in the controls. Superoxide dismutase and catalase activity was greater in sera of both groups of patients with acute and chronic alcoholic pancreatitis than in controls, but GPx concentration was significantly less in the sera of patients with chronic pancreatitis. Impaired GPx production and increased production of O2- and H2O2 by neutrophils may result in increased lipid peroxidation and could play a role in the pathogenesis of chronic alcoholic pancreatitis.     

Recurrent acute pancreatitis and its relative factors

AIM: To evaluate the causes and the relative factors of recurrent acute pancreatitis. METHODS: From 1997 to 2000, acute pancreatitis relapsed in 77 of 245 acute pancreatitis patients. By reviewing the clinical treatment results and the follow-up data, we analyzed the recurrent factors of acute pancreatitis using univariate analysis and multivariate analysis. RESULTS: Of the 245 acute pancreatitis patients, 77 were patients with recurrent acute pancreatitis. Of them, 56 patients relapsed two times, 19 relapsed three times, each patient relapsed three and four times. Forty-seven patients relapsed in hospital and the other 30 patients relapsed after discharge. Eighteen patients relapsed in 1 year, eight relapsed in 1-3 years, and four relapsed after 3 years. There were 48 cases of biliary pancreatitis, 3 of alcohol pancreatitis, 5 of hyperlipidemia pancreatitis, 21 of idiopathic pancreatitis. Univariate analysis showed that the patients with local complications of pancreas, obstructive jaundice and hepatic function injury were easy to recur during the treatment period of acute pancreatitis (P= 0.022<0.05, P= 0.012<0.05 and P= 0.002<0.05, respectively). Multivariate analysis showed that there was no single factor related to recurrence. Of the 47 patients who had recurrence in hospital, 16 had recurrence in a fast period, 31 after refeeding. CONCLUSION: Acute pancreatitis is easy to recur even during treatment. The factors such as changes of pancreas structure and uncontrolled systemic inflammatory reaction are responsible for the recurrence of acute pancreatitis. Early refeeding increases the recurrence of acute pancreatitis. Defining the etiology is essential for reducing the recurrence of acute pancreatitis.     

Phosphoinositide 3-kinase/Akt inhibition increases arsenic trioxide-induced apoptosis of acute promyelocytic and T-cell leukaemias

Recent studies suggest that the prosurvival signal transduction pathway involving phosphoinositide 3-kinase (PI3K)/Akt can confer an aggressive, apoptosis-resistant phenotype to acute leukaemia cells. We have investigated the effect of modulating this signalling pathway on the sensitivity of leukaemic cell lines (NB-4, CEM, Jurkat, MOLT-4) and acute promyelocytic primary blasts to apoptosis induced by 1 micromol/l As2O3. Whereas parental NB-4 cells did not display any phosphorylated (active) Akt, CEM, Jurkat and MOLT-4 cells exhibited high levels of Akt activation. Consistently, treatment of NB-4 cells with pharmacological inhibitors of the PI3K/Akt pathway (LY294002, wortmannin) did not increase sensitivity of these cells to arsenic trioxide (As2O3), whereas siRNA knock-down of Akt enhanced As2O3-induced apoptosis of CEM, Jurkat and MOLT-4 cells. Overexpression of a constitutively active Akt cDNA rendered NB-4 cells less susceptible to As2O3. Upon prolonged exposure to As2O3, we isolated a NB-4 cell clone that was resistant to As2O3 and displayed high levels of active Akt. LY294002 treatment of acute promyelocytic primary blasts with elevated Akt phosphorylation levels resulted in an increased sensitivity to As2O3. These results may provide a rationale for the development of combined or sequential treatment with PI3K/Akt inhibitors to improve the efficacy of As2O3 on acute leukaemias and also to overcome As2O3 resistance.     

The role of nitric oxide in caerulein-induced acute pancreatitis and the recovery process after inflammatory damage.

OBJECTIVES: Nitric oxide (NO) is involved in the control of pancreatic blood flow and secretion, and its role in the maintenance of pancreatic tissue has been suggested. The aim of our study was to evaluate the influence of NO on pancreatic trophic parameters during acute pancreatitis induction and the pancreas recovery process. DESIGN/METHODS: Acute pancreatitis was induced in rats by a supramaximal dose of caerulein. During acute pancreatitis induction, rats were treated with L-arginine (a substrate for NO synthesis), glyceryl trinitrate (NTG, NO donor), glycine, N(G)-nitro-L-arginine (L-NNA, NO synthase inhibitor), L-arginine + L-NNA, or saline. Pancreatic weight, total contents of RNA, DNA, protein, amylase and chymotrypsin as well as pancreas histology and the number of proliferating acinar cells were evaluated after pancreatitis induction in all groups and additionally after 7 and 14 days of recovery in untreated acute pancreatitis rats or those injected with L-NNA and/or L-arginine. RESULTS: Pancreas destruction after acute pancreatitis was evidenced by similar decreases of all parameters in untreated acute pancreatitis rats or those treated with L-NNA or glycine when compared to control healthy animals. The recovery process after acute pancreatitis was not affected by L-NNA injections; however, the increased cell proliferation occurred later than in untreated rats. NTG and especially L-arginine treatment resulted in significant attenuation of pancreas damage (partially prevented by L-NNA treatment) as evidenced by biochemical data with a slight improvement in morphology. Treatment with L-arginine alone or in combination with L-NNA resulted in augmented cell proliferation after acute pancreatitis induction followed by earlier recovery in comparison to untreated acute pancreatitis rats or the L-NNA-injected group. CONCLUSION: The present study suggests the involvement of NO in mild acute pancreatitis and in the recovery process after inflammatory damage.     

Acute pancreatitis attributed to the use of interferon alfa-2b

Two patients experienced episodes of acute pancreatitis shortly after starting treatment with interferon alfa-2b (IFN-alpha) for a chronic hepatitis C infection. The first patient was a 40-year-old man who developed acute pancreatitis after 15 weeks of treatment with 3 MU IFN-alpha subcutaneously (SC) 3 times weekly and 1200 mg ribavirin. After disappearance of symptoms and normalization of laboratory values, oral intake of solid foods and IFN-alpha therapy were restarted. Within hours, a relapse of acute pancreatitis occurred. A rechallenge with IFN-alpha 4 days later was followed by a prompt increase in serum lipase level, and IFN-alpha therapy was discontinued. The second patient was a 38-year-old man who developed acute pancreatitis 2 hours after SC administration of 5 MU IFN-alpha. Ultrasound endoscopy showed sludge in the gallbladder. The patient was rechallenged 5 weeks later with 3 MU IFN-alpha SC. Although serum amylase and lipase levels increased after readministration of IFN-alpha, treatment was continued. The patient was readmitted 2 weeks later with severe abdominal pain, and IFN-alpha administration was discontinued. Considering the temporal relationship between the start of IFN-alpha treatment and development of acute pancreatitis, the absence of other clear etiologic factors for acute pancreatitis, disappearance of symptoms after discontinuation of IFN-alpha, and positive reactions to rechallenge, IFN-alpha is the most probable cause for development of acute pancreatitis in these patients.     

The frequency of bile duct crystals in patients with presumed biliary pancreatitis.

BACKGROUND: Previous studies of biliary microlithiasis in acute pancreatitis of uncertain etiology were conducted a few weeks to months after the acute episode. Bile obtained during urgent ERCP (less than 24 hours after admission) was studied for the presence of microlithiasis during the acute phase of acute pancreatitis of suspected biliary origin. METHODS: Fifteen consecutive patients with acute pancreatitis of suspected biliary origin were recruited from a population of 309 patients with acute pancreatitis (5%) treated during the last 4 years. Patients with gallstones on US and/or ERCP and those in whom the etiology of acute pancreatitis was certain were excluded. RESULTS: Microlithiasis (mostly calcium bilirubinate granules) was found in 12 (80%) cases. Despite endoscopic sphincterotomy 3 patients died within 2 weeks because of multisystemic organ failure. Among the 12 remaining patients, 2 (16%) developed gallbladder stones and 1 underwent cholecystectomy for cholecystitis (8%) during follow-up. The average length of follow-up was 30 months. No episodes of acute pancreatitis were noted during follow-up. CONCLUSIONS: In the acute phase of acute pancreatitis of suspected biliary origin, biliary microlithiasis was found in most cases. Endoscopic sphincterotomy appears to protect patients from further episodes of acute pancreatitis.     

Mortality in acute pancreatitis in Turku University Central Hospital 1971-1995.

BACKGROUND/AIMS: The role of surgical procedures in the treatment of acute pancreatitis is still unclear. The aim of the present study was to analyze the mortality in acute pancreatitis in Turku University Central Hospital during the last quarter century with special reference to the prevailing surgical treatment trends. METHODOLOGY: A total of 3921 patients with acute pancreatitis were treated 1971-1995. We analyzed the mortality in acute pancreatitis and the number of patients treated in the intensive care unit as well as the number of various surgical procedures used in the treatment of acute pancreatitis in each year 1971-1995. RESULTS: The most conspicuous finding was that the mortality in acute pancreatitis has not decreased any more during the last 15 years. Neither pancreatic resections nor peritoneal lavages seem to decrease the mortality. CONCLUSIONS: We conclude that despite various surgical procedures used in the treatment of acute pancreatitis the mortality in acute pancreatitis has not decreased any more during the last 15 years. Because of the retrospective nature of the current study the present results do not justify drawing any strict conclusions concerning the treatment of acute pancreatitis. However, the present results support the view that conservative treatment in the intensive care unit is justified as an initial therapy even in the fulminant attacks of acute pancreatitis.     

A randomised, double blind, multicentre trial of octreotide in moderate to severe acute pancreatitis

BACKGROUND—The pharmacological inhibition of exocrine pancreatic secretion with the somatostatin analogue octreotide has been advocated as a specific treatment of acute pancreatitis.
AIM—To investigate the efficacy of octreotide in acute pancreatitis in a randomised, placebo controlled trial.
METHODS—302 patients from 32 hospitals, fulfilling the criteria for moderate to severe acute pancreatitis within 96 hours of the onset of symptoms, were randomly assigned to one of three treatment groups: group P (n=103) received placebo, while groups O1 (n=98) and O2 (n=101) received 100 and 200 µg of octreotide, respectively, by subcutaneous injection three times daily for seven days. The primary outcome variable was a score composed of mortality and 15 typical complications of acute pancreatitis.
RESULTS—The three groups were well matched with respect to pretreatment characteristics. An intent to treat analysis of all 302 patients revealed no significant differences among treatment groups with respect to mortality (P: 16%; O1: 15%; O2: 12%), the rate of newly developed complications, the duration of pain, surgical interventions, or the length of the hospital stay. A valid for efficacy analysis (251 patients) also revealed no significant differences.
CONCLUSIONS—This trial shows no benefit of octreotide in the treatment of acute pancreatitis.


Keywords: acute pancreatitis; somatostatin; octreotide; randomised controlled multicentre trial     

Acute pancreatitis complicating acute exacerbation of chronic hepatitis B infection carries a poor prognosis

The clinical outcome of acute pancreatitis complicating acute exacerbation of chronic hepatitis virus B (HBV) infection has never been studied. Ninety patients with acute pancreatitis were recruited. Five patients (5.6%) (Group 1) had acute pancreatitis superimposed on acute exacerbation of chronic HBV infection with no other causes of acute pancreatitis being identified. The clinical outcome of these five patients was compared to the 85 non-HBV infected patients (Group 2) with acute pancreatitis. A third group (Group 3) of patients ( n =406) with acute exacerbation of chronic HBV infections without acute pancreatitis was also recruited for comparison. Group 1 had a significantly higher mortality rate (4 out of 5, 80%) compared to those of Group 2 (13 out of 85, 15.3%, P =0.0041) and Group 3 (9 out of 406, 2.2%, P  < 0.0001). In Group 1 patients, the acute pancreatitis occurred during the initial rise of HBV DNA with relatively low or normal level of alanine aminotransferase (ALT) in two patients, during the rise of ALT with declining level of HBV DNA in one patient, and during the cholestatic phase of the acute exacerbation in one patient. The acute pancreatitis was clinically silent and only diagnosed by computerized tomography in the remaining patient. Direct viral damage and/or immunological attack to the pancreatic tissue were probably the underlying pathogenesis of the acute pancreatitis in these patients.
In conclusion, acute pancreatitis complicating acute exacerbation of chronic HBV infection carried an extremely poor prognosis with high mortality.     

Influence of age on soluble E-cadherin serum levels prevents its utility as a disease marker in gastric cancer patients

Objective. Acute pancreatitis starts as an autodigestive process restricted to the pancreas and progresses to a systemic inflammation via cytokine release into the blood stream. Several inhibitors of the coagulation cascade, including active-site-inactivated factor VIIa, have shown anti-inflammatory properties in other inflammatory models than acute pancreatitis. Free radical scavengers have proven useful in reducing the oxidative damage during hyperinflammatory conditions. The aim of this study was to investigate whether pretreatment with FVIIai would have any effect on the multiple organ dysfunction syndrome (MODS) in severe acute pancreatitis. Material and methods. Experimental acute pancreatitis was induced by intraductal infusion of taurodeoxycholate in the pancreatic duct. The animals were pretreated with N-acetyl-cysteine and active-site-inactivated factor VIIa. Neutrophil infiltration in the lungs, ileum and colon was quantified by myeloperoxidase activity. Inflammatory markers, IL-6 and MIP-2, were measured using ELISA. Results. Tissue infiltration of neutrophils in the lungs, ileum and colon significantly increased during acute pancreatitis as compared to sham operation. These levels were reduced by pretreatment with N-acetylcysteine and active-site-inactivated factor VIIa. Levels of interleukin-6 and macrophage inflammatory protein-2 increased significantly during acute pancreatitis. Pretreatment with NAC and FVIIai reduced these levels. Conclusions. Both N-acetylcysteine and active-site-inactivated factor VIIa showed powerful anti-inflammatory properties in experimental acute pancreatitis. As they exert their effects through different physiological mechanisms, they represent potential candidates for future multimodal treatment of acute pancreatitis.     

Features and Choice of Treatment of Acute and Chronic Pancreatic Pseudocysts — with Special Reference to Invasive Intervention

Aims: It was the aim of this study to characterize the features of acute and chronic pancreatic pseudocysts (PPs) and to identify the factors predictive of the need for invasive treatment. Methods: Thirty-six patients with PPs treated at Nippon Medical School between January 1995 and December 2004 were studied retrospectively. The cases were divided into 4 groups based on 4 features: association with acute pancreatitis, association with chronic pancreatitis, spontaneous resolution, and persistent symptoms requiring therapeutic intervention. Group 1 included 9 patients with acute PPs which resolved spontaneously. Group 2 included 9 patients with acute PPs with persistent symptoms or associated complications requiring interventional treatment. Group 3 included 9 patients with chronic PPs which resolved spontaneously, and group 4 included 9 patients with chronic PPs with persistent symptoms or associated complications requiring interventional treatment. Results: Among the 36 patients, 13 were women and 23 were men. The etiologies were pancreatitis due to alcoholism in 18 cases (50.0%), biliary tract disease in 8 cases (22.2%) and other conditions in 10 cases (27.8%). The average duration of follow-up was 24.2 ± 18.5 months. The patients in group 1 were significantly older than those in group 2 (67.6 ± 16.1 vs. 40.6 ± 14.1 years; p = 0.011). The mean size of the PPs was significantly larger in groups 1 and 4 than in group 3 (p < 0.05) and significantly larger in group 2 than in group 4 (p < 0.05). There were no significant differences between groups 1 and 2 in the size of the PPs or in the Ranson score of previous pancreatitis. The increase in size of the PPs during follow-up in each of the spontaneously resolved groups (groups 1 and 3) differed significantly from that in each of the interventional treatment groups (groups 2 and 4; p < 0.05). The main cause of the acute pancreatitis in group 1 was biliary tract disease, while that in group 2 was alcoholism (significantly different, p < 0.05). The number of patients with symptoms related to pseudocysts at the time of diagnosis was significantly higher in group 1 than in group 3. Conclusions: Growth of the PPs during follow-up is the strongest predictor of the need for invasive treatment in both acute and chronic cases. Among acute PPs, the size of the pseudocyst is not in itself a predictor of invasive treatment. Invasive treatment may pose higher risks for pseudocysts with an etiology of alcoholic acute pancreatitis. However, the size of the pseudocyst may be a more important prognostic factor than an etiology of pancreatitis.     

Endoscopic sphincterotomy for acute relapsing pancreatitis associated with periampullary diverticula: a long-term follow-up

BACKGROUND AND STUDY AIMS: Periampullary diverticula (PAD) are extraluminal outpouchings of the duodenum arising within a radius of 2-3 cm from the ampulla of Vater. Data concerning the association of PAD with biliopancreatic disease are inconsistent, but an association between acute pancreatitis and PAD has been reported. The aim of this retrospective study was to evaluate the outcome of endoscopic sphincterotomy (ES) in a Greek cohort of patients with acute relapsing pancreatitis associated with PAD. PATIENTS AND METHODS: A total of 344 patients who had undergone ERCP between 1994 and 2005 for investigation of acute pancreatitis were retrospectively entered into a database. Of these patients, 11 (3.19% ; median age: 69 years; range: 58-78; 3 men, 8 women) were found to have acute relapsing pancreatitis associated with PAD. All patients underwent ES and were followed for new episodes of acute pancreatitis or other complications. RESULTS: No further episodes of acute pancreatitis occurred after ES, during a long-term follow-up (median: 4.3 years, range: 1.9-10.4). Two patients (18.2%) presented post-procedure mild pancreatitis and one patient (9.1%) post-ES stenosis with two small common bile duct stones and was treated with ES and extraction of stones. CONCLUSION: ES is the treatment of choice for patients with acute relapsing pancreatitis associated with PAD.     

急性胰腺炎患者T淋巴细胞亚群及补体的变化

目的研究急性胰腺炎患者发病及治愈后T细胞亚群及补体的变化。方法检测29例急性胰腺炎患者发病后和治愈后T淋巴细胞亚群及补体C3、C4,进行治疗前后比较并与对照组比较。结果急性胰腺炎发病后其T淋巴细胞亚群中CD^＋3、CD^＋4细胞和CD^＋4／CD^＋8比值均下降;血清补体C3、C4水平有不同程度的下降,以重症急性胰腺炎最明显;随着疾病的治愈,机体免疫功能逐步恢复,上述免疫学指标也大都能恢复到正常水平,但重症急性胰腺炎组C3、C4仍较正常低。结论急性胰腺炎患者存在不同程度的免疫功能损害,以重症急性胰腺炎明显。     

Gut Permeability in Patients with Acute Pancreatitis

Background: The bacterial contamination of pancreatic necrosis in acute pancreatitis is supposed to occur through translocation of intestinal bacteria. Increased gut permeability may be the initial phenomenon in this process. To test the hypothesis that gut permeability is increased in acute pancreatitis a clinical study was made where gut absorption and permeability were assessed with multi-sugar probes in patients with acute pancreatitis within 2 days after admission to hospital and again after recovery of disease. Methods and Results: Twenty-three patients with acute pancreatitis and 20 healthy controls were studied. According to Atlanta classification, 15 patients had mild and 8 patients severe pancreatitis. Gut absorption, assessed as the 5-h urine excretion of L-rhamnose, D-xylose and 3-O-methylglucose, was decreased in patients with acute pancreatitis and more pronounced in patients with severe pancreatitis (L-rhamnose and D-xylose: P &lt; 0.001; 3- O -methylglucose: P     

Arsenic trioxide and ascorbic acid: synergy with potential implications for the treatment of acute myeloid leukaemia?

Arsenic trioxide (As2O3) induces remission in a high proportion of patients with acute promyelocytic leukaemia (APL) via induction of apoptosis. Preliminary reports suggest that the apoptotic effect of As2O3 is not specific for APL but can also be observed in non-APL acute myeloid leukaemia (AML) cells, although these are less sensitive than APL cells. Ascorbic acid has recently been demonstrated to enhance the apoptotic effect of As2O3. We have therefore evaluated combined As2O3/ascorbic acid treatment in various clinical samples of AML. Our results indicate a significant synergistic effect of As2O3 and ascorbic acid, suggesting a possible future role of As2O3/ascorbic acid combination therapy in patients with AML.     

Acute Pancreatitis Secondary to Ciprofloxacin Therapy in Patients with Infectious Colitis

Background/Aims

Ciprofloxacin is considered to be a safe and effective treatment for acute infectious colitis. However, this drug may cause drug-induced pancreatitis, albeit rarely.

Methods

From March 2007 to February 2012, we studied 227 patients who were hospitalized for infectious colitis at St. Mary''s Hospital. All of the patients received ciprofloxacin therapy for the treatment of infectious colitis. We observed a few cases of rare adverse events, including ciprofloxacin-induced acute pancreatitis diagnosed based on the Naranjo algorithm.

Results

During ciprofloxacin therapy, seven of 227 patients (3.1%) developed rare pancreatitis as defined by the Naranjo algorithm; pancreatic enzyme activity was sporadically elevated with ciprofloxacin use. After ciprofloxacin administration, the average interval until the development of pancreatitis was 5.5 days (range, 4 to 7 days). On abdominal computed tomography, pancreatic swelling and homogenous enhancement was noted in three of seven patients. Complicating acute pancreatitis was gradually but completely resolved after cessation of ciprofloxacin administration. The mean recovery time was 11.3 days (range, 8 to 15 days).

Conclusions

We observed that ciprofloxacin-induced pancreatitis may occur with an incidence of approximately 3%. Ciprofloxacin-induced pancreatitis presents a short latency, suggesting an idiosyncratic hypersensitivity reaction. Practitioners should be aware that drug-induced pancreatitis can occur during ciprofloxacin therapy.     

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目的探讨系统性红斑狼疮(SLE)合并急性胰腺炎的临床特点、病因、发病机制和治疗方法。方法回顾性分析1983-01～2003-03北京协和医院住院治疗的SLE合并急性胰腺炎患者15例。结果急性轻型胰腺炎12例,重型胰腺炎3例。所有患者均给予中到大剂量糖皮质激素治疗,病情痊愈5例,好转5例,死亡5例。结论(1)急性胰腺炎是SLE病情活动的表现;(2)胰腺血管病变是导致胰腺炎的主要致病机制;(3)糖皮质激素可能不是导致胰腺炎的病因;(4)中到大剂量糖皮质激素治疗是安全有效的。