The role of cholecystectomy in reducing recurrent gallstone pancreatitis

BACKGROUND AND STUDY AIM: Endoscopic sphincterotomy (ES) or cholecystectomy can prevent recurrent acute pancreatitis (RAP) in patients with gallstone-related pancreatitis. However, it is unknown whether cholecystectomy after ES offers additional benefit in preventing RAP in these patients. This is a retrospective study to assess whether cholecystectomy can decrease the incidence of RAP in patients with gallstone-related pancreatitis. PATIENTS AND METHODS: Records from 139 patients with gallstone-related pancreatitis were analyzed. Of these, 58 patients had gallbladder stones with concomitant common bile duct (CBD) stones and 81 patients had gallbladder stones without CBD stones. Of the 58 patients who had both gallbladder and CBD stones, 37 (63.8 %) did not undergo cholecystectomy after ES (group 1) and 21 patients (36.2 %) did undergo cholecystectomy after ES (group 2). Of the 81 patients who had gallbladder stones but who did not have CBD stones, 54 (66.7 %) did not undergo cholecystectomy (group 3) and 27 (33.3 %) did undergo cholecystectomy (group 4). RESULTS: At the time of analysis, three patients (8.1 %) in group 1 and three patients (14.3 %) in group 2 developed RAP. There was no significant difference in the estimated probability of occurrence of RAP over time between group 1 and group 2 ( P = 0.41). However, there was a significantly higher probability of patients developing RAP over time in group 3 compared with group 4 (6/54 vs. 0/27 respectively, P = 0.04). CONCLUSION: In patients with gallbladder stones without CBD stones, cholecystectomy can decrease the incidence of RAP. In patients with both gallbladder and CBD stones, however, the risk of RAP was not further reduced by cholecystectomy after ES and complete removal of CBD stones.     

Glioma apoptosis induced by macrophages involves both death receptor-dependent and independent pathways

Apoptosis of glioma may represent a promising intervention for tumor treatment. Macrophages are able to induce apoptosis in a number of tumor cells, including glioma. It is known that apoptosis of cells is executed on either a death receptor-dependent or independent pathway. Whether and how apoptosis of glioma cells induced by activated macrophages is involved in these two pathways simultaneously are not known. Using in vitro and in vivo experimental models, we investigated Bcl-2 system and Fas/FasL channel, representing the death receptor-dependent and independent pathways, respectively, in glioma cells treated with the supernatant from the activated macrophages, which was rich in tumor necrosis factor-alpha and interferon-gamma. We found that levels of Fas and FasL were up-regulated both in vitro and in vivo, accompanying an increase in the expression of caspase-8. The number of apoptotic cells was also increased significantly, although the percentage of death cells exceeded the number of tumor cells positive for Fas or FasL. It was also evident that the expression of Bax was increased, whereas the level of Bcl-2 was decreased, in glioma cells treated with the supernatant from the activated macrophages. The alteration of molecules related to both death pathways led to apoptosis of glioma and the inhibition of xenograft glioma growth in mice. Apoptosis of glioma induced by the activated macrophage is executed by way of both death receptor-dependent and independent pathways, and such an apoptosis-induced approach can effectively inhibit the growth of glioma in vivo.     

Assessment of education and computerized decision support interventions for improving transfusion practice

BACKGROUND: Overuse of blood products is common, but prior efforts to improve transfusion decisions have met with limited success. STUDY DESIGN AND METHODS: This study examines transfusion practices before and after a conventional educational intervention followed by a randomized controlled trial of a decision support (DS) intervention with computerized physician order entry (CPOE) for red blood cell, platelet, and fresh-frozen plasma orders. The study was conducted in an academic medical center between April 2003 and June 2004. Orders originating from units not using CPOE with DS (e.g., the emergency department) were excluded. Junior housestaff were randomly assigned into a control group and an intervention group who received DS for transfusion orders. Transfusion orders were initially classified according to guideline rules as DS-agree or DS-disagree. Chart reviews assessed inappropriateness for all DS-disagree orders and a sample of DS-agree orders. The total of inappropriate transfusion orders included chart review confirmed DS-disagree orders and DS-agree orders reclassified as inappropriate. RESULTS: The percentages of inappropriate nonemergent transfusion orders during the baseline phase for the entire staff and randomly assigned junior housestaff were 72.6 percent (2154/2967) and 71.9 percent (1259/1752) and improved after conventional education to 63.8 percent (1699/2663; p < 0.0001) and 63.3 percent (1263/1996; p < 0.0001), respectively. The percentage of inappropriate orders in the DS intervention group continued to improve (59.6%, 804/1350; p < 0.0001). Physicians accepted 14 percent (133/939) of new DS-recommended orders, especially recommendations to increase transfusion doses (73%). CONCLUSIONS: Education and computerized DS both decreased the percentage of inappropriate transfusions, although the residual amount of inappropriate transfusions remained high.     

Pharmacokinetics of oral and intravenous ofloxacin in children with multidrug-resistant typhoid fever.

The pharmacokinetics of oral and intravenous ofloxacin (7.5 mg.kg of body weight-1 given over 30 min) were studied in an open crossover study of 17 Vietnamese children, aged between 5 and 14 years, with acute uncomplicated typhoid fever. Following oral administration, the median (95% confidence interval [CI]) time to peak concentration of ofloxacin in serum (Cmax) was 1.7 h (1.4 to 1.9 h) and the mean (95% CI) Cmax was 5.5 mg.liter-1 (4.7 to 6.3 mg.liter-1) compared with a Cmax of 8.7 mg.liter-1 (7.6 to 9.7 mg.liter-1) following the intravenous infusion. The median (95% CI) total apparent volume of distribution following the first intravenous dose, 1.35 liter.kg-1 (1.17 to 1.73 liter.kg-1), was significantly larger than that following the second dose, 0.99 liter.kg-1 (0.86 to 1.17 liter.kg-1; P < 0.0005), although the estimates for systemic clearance were similar: 0.255 liter.kg-1 h-1 (0.147 to 0.325 liter.kg-1 h-1) compared with 0.172 liter.kg-1 h-1 (0.127 to 0.292 liter.kg-1 h-1; P = 0.14). The mean residence times (95% CI) following intravenous and oral administration were similar: 5.24 h (4.84 to 6.58 h) and 6.24 h (5.32 to 7.85 h), respectively. The mean (95% CI) oral bioavailability was 91% (74 to 109%). The peak concentrations in serum were 10 to 100 times higher than the maximum MICs for ofloxacin against multidrug-resistant Salmonella typhi isolated in this area. Although the systemic clearance values were higher than those reported previously for adults, these data overall suggest that weight-or area-adjusted dose regimens for the treatment of typhoid in older children should be the same as those for adults.     

A microarray study to characterize the molecular mechanism of TIMP-3-mediated tumor rejection.

Glial cell invasion is a multistep cellular process that involves a complex system of tightly regulated proteases (matrix metalloproteinases; MMPs) and their endogenous inhibitors (tissue inhibitors of metalloproteinases; TIMPs) to mediate the degradation of the basement membrane and extracellular matrix. Tissue inhibitor of metalloproteinases-3 (TIMP-3) is a matrix-bound inhibitor of MMPs. In the present study, we have overexpressed the TIMP3 gene in human glioma cells with a herpes simplex virus type 1 amplicon-based vector. Oligonucleotide DNA arrays were employed to identify genes that were differentially modulated by the overexpression of TIMP-3. Consistent with the function of TIMP-3, genes associated with angiogenesis, growth factors, cytokines, death receptors, and substrates of the various MMPs were found to be up-regulated. Furthermore, caspases are important in the signaling pathway of cellular apoptosis, and the overexpression of TIMP-3 in glioma cells is tightly associated with the activation of caspases, including caspase-1, at both the mRNA level (P=0.0371) and the protein level. Moreover, the activation of an apoptotic pathway via the overexpression of TIMP-3 induced apoptosis of transduced human glioma cells in vitro and the growth inhibition of human glioma tumor xenografts in immunodeficient mice.     

Impact of a designated hepatology nurse on the clinical course and quality of life of patients treated with rebetron therapy for chronic hepatitis C.

A two- to three-fold increase in mortality from hepatitis C is predicted in the next 10-20 years as the largest cohort of patients age. More qualified providers are needed to care for this population. The objective of this study was to assess the impact of a hepatology nurse practitioner as compared to care by a physician on the quality of life and treatment outcomes of patients with chronic hepatitis C. Seventy-five patients with chronic hepatitis C were assigned to either a nurse practitioner or physician and asked to complete a SF-36 Health Survey quarterly to measure their perceived quality of life.Two-sided t-tests comparing the quality of life scores in the physician and nurse practitioner groups at weeks 1, 12, and 24 were calculated using SPSS version 12.0 (Chicago, IL). Although marginal differences between physicians and nurse practitioners were noted for physical function at week 1, bodily pain at week 12, and role physical at week 24 by the patients, no statistically significant differences were observed overall in the quality of life scores reported by the patients according to healthcare provider. The treatment outcome data for the nurse practitioner groups showed 12/25 (48%) of patients with genotype 1 achieved a sustained virologic response as did 13/22 (59%) of patients with genotype 2 or 3. In the physician groups, 11/27 (41%) of patients with genotype 1 achieved a sustained virologic response as did 14/23 (61%) of patients with genotype 2 or 3. These results suggest nurse practitioners can provide effective care to the chronic hepatitis C population.