Effect of leukocytapheresis therapy using a leukocyte removal filter in Crohn's disease

Eighteen patients with active Crohn's disease were treated with one leukocytapheresis session per week for a five-week intensive therapy, decreasing to one leukocytapheresis session per month for five sessions of initial maintenance therapy. Nutritional indices, inflammatory reactions, flow cytometry profiles, and cytokine production were also assessed before and after the intensive and initial maintenance therapy. Nine of the patients (50%) attained remission at the end of the intensive therapy. The nine non-remission patients had exhibited longer periods of suffering and more severely affected sites prior to the therapy. In 14 of 18 patients (77.8%), the nutritional indices, Internal Organization of Inflammatory Bowel Disease (IOIBD) score and Crohn's Disease Activity Index (CDAI) improved from the pretherapy levels, but only the remission group (50%) showed improvement in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). The remission group showed significantly higher pretherapy CD4+ CD45+ cell ratios and interleukin-2 (IL-2) production than the non-remission group, and significantly lower activated cells.     

Helicobacter pylori infection increases mucosal permeability of the stomach and intestine

It is important to study the effect of Helicobacter pylori infection on the permeability of the intestine. Permeability was evaluated by oral sucrose tolerance test using sucrose 25 g in 200 ml of water. Existence of H. pylori itself was associated with increased permeability of sucrose. Also, the permeability of sucrose increased as polymorphonuclear and lymphocyte infiltration increased. The increase of mucosal permeability suggests that antigens like protein penetrate into the body and result in systemic reactions. Thus, it is important to study the implication of increased permeability in relation not only to gastric diseases but also certain systemic diseases.     

Percutaneous transhepatic gallbladder stenting for recurrent acute acalculous cholecystitis after failed endoscopic attempt

Endoscopic gallbladder stenting is useful palliative therapy for acute cholecystitis in high‐risk patients. Although the success rate of endoscopic gallbladder stenting is 79%–100%, an alternative method has not been reported. We succeeded in employing a method for percutaneous gallbladder stenting (PTGS) and herein describe this new method. A patient with acute acalculous cholecystitis related to ischemic atherosclerotic vascular disease, cholangitis due to Lemmel syndrome, and severe congestive heart failure underwent PTGS through the cystic duct from the gallbladder to the duodenal papilla, because an endoscopic method failed in the treatment of Lemmel syndrome. Because we were unable to place endoscopic transpapillary gallbladder drainage, percutaneous transhepatic gallbladder drainage (PTGBD) was performed and both the cholecystitis and cholangitis ceased. PTGS was performed as an alternative to endoscopic gallbladder stenting. Access to the cystic duct and gallbladder was obtained by the PTGBD route, using a guidewire (0.035‐inch diameter) and seeking catheter (6.5 Fr) under fluoroscopic control. A 7‐Fr 12‐cm double‐pigtail biliary polyethylene stent was placed. The patient remained asymptomatic for 3 months after the PTGS until he died, of an acute recurrent myocardial infarction. This new PTGS placement is an alternative treatment for symptomatic gallbladder disease in patients with increased operative risk when the endoscopic method is unsuccessful.     

Early effects of lafutidine or rabeprazole on intragastric acidity: which drug is more suitable for on-demand use?

Background Medication for the relief of heartburn should have the rapid onset of action required for on-demand use. We studied the inhibition of gastric acid secretion by lafutidine and rabeprazole, given in single doses to fasting and postprandial subjects.Methods A total of 22 healthy male, Helicobacter pylori-negative volunteers participated in this randomized, two-way crossover study. They were randomly assigned to receive a single oral dose of 10mg lafutidine or 20mg rabeprazole after fasting overnight (12 subjects, fasting study) or after eating a test meal (noodles, 364kcal; protein, 10.1g; fat, 16g; carbohydrates, 44.9g; NaCl, 1.1g; 10 subjects, postprandial study). Intragastric pH was monitored continuously for 6h after treatment. The other drug was given after a washout period of at least 7 days, and intragastric pH was similarly monitored.Results In the fasting study, lafutidine sustained pH at >3 and >4 during the second, third, fourth, fifth, and sixth hours of the study for significantly longer than rabeprazole. During the first 6h after treatment, lafutidine sustained pH at more than 2, 3, 3.5, 4, 5, 6, and 7 longer than rabeprazole. In the postprandial study, lafutidine sustained pH >3 and >4 for longer periods than rabeprazole during the third, fourth, fifth, and sixth hours of the study. During the first 6h after treatment, lafutidine sustained pH at more than 2, 3, 3.5, 4, 5, 6, and 7 longer than rabeprazole.Conclusions Lafutidine 10mg produces a prompter rise in intragastric pH than rabeprazole 20mg in fasting and postprandial Helicobacter pylori-negative male subjects.     

Collapsin Response Mediator Protein 4 Expression is Associated with Liver Metastasis and Poor Survival in Pancreatic Cancer

Background

Pancreatic cancer is an aggressive malignancy with one of the worst mortality rates of all cancers. Recently, collapsin response mediator proteins (CRMPs) were reported to be associated with proliferation, apoptosis, differentiation, and invasion in several cancers. However, CRMP expression and their role in pancreatic cancer have not been investigated. This study aimed to clarify the clinical significance of CRMPs in pancreatic cancer.

Methods

Expression of crmp genes in 11 pairs of pancreatic cancer and corresponding noncancerous pancreas tissues were examined by real-time RT-PCR. Knockdown of CRMP4 expression using siRNA was examined in pancreatic cancer cell lines to determine whether CRMP4 regulates cell proliferation and invasion in vitro. Furthermore, CRMP4 protein levels in primary tumors of pancreatic cancer (n = 53) were examined by immunohistochemistry and compared with the clinicopathological features of the tumors.

Results

Of all the CRMPs, only CRMP4 was differentially expressed in pancreatic cancer tissues (p = 0.008). CRMP4 knockdown using siRNA reduced cellular invasion, but did not affect proliferation. The expression of CRMP4 was detected immunohistochemically in 34 (64.2 %) of the 53 pancreatic cancer samples, and CRMP4 expression was correlated with severe venous invasion (p = 0.044), stage (p = 0.019), and liver metastasis (p = 0.021). Multivariate analyses suggested that venous invasion and CRMP4 overexpression were prognostic factors for survival.

Conclusions

Our results suggested that CRMP4 is significantly associated with poor prognosis by promoting liver metastasis and can serve as a novel therapeutic target for pancreatic cancer.

     

Paraoxonase-1 activity affects the clopidogrel response in CYP2C19 loss-of-function carriers

Background

The impact of paraoxonase-1 (PON1) activity on the response to clopidogrel may differ in patients treated with drug-eluting stents (DES) in association with CYP2C19 loss-of-function (LOF) polymorphisms.

Methods

This study included 112 Japanese patients receiving clopidogrel (75 mg/day) and aspirin (100 mg/day) who underwent optical coherence tomography (OCT) examination 9 months after DES implantation. The CYP2C19 genotype was analyzed and LOF carriers (*1/*2, *1/*3, *2/*2, *3/*3, *2/*3) were identified. At the 9-month follow-up, platelet reactivity was determined by measuring the P2Y12 reactivity unit (PRU) using a VerifyNow P2Y12 assay, PON1 activity was evaluated and intra-stent thrombus was evaluated by OCT.

Results

Of the 112 Japanese patients, 75 were LOF carriers (67.0%). The patients were divided into tertiles according to the PON1 activity (tertile 1; < 230 U/L, tertile 2; 230–283 U/L, tertile 3; > 283 U/L). In the VerifyNowP2Y12 analysis, tertile 1 had a higher PRU than tertiles 2 and 3 in LOF carriers, and there was no difference among tertiles in non-carriers. The highest incidence of intra-stent thrombus was observed in tertile 1 followed by tertiles 2 and 3 in LOF carriers, whereas there was no such difference in non-carriers. Multivariate analysis revealed that LOF carriers and PON1 activity tertile 1 were independent predictors of intra-stent thrombus in all patients. In LOF carriers, tertile 1 was the only independent predictor for intra-stent thrombus.

Conclusion

Low PON1 activity is associated with a low response to clopidogrel and a high frequency of intra-stent thrombus only in LOF carriers.