Utility of endoscopic ultrasonography in endoscopic drainage of pancreatic pseudocysts in selected patients

OBJECTIVES: To determine the effect of endoscopic ultrasonography (EUS) on endoscopic drainage of pancreatic pseudocysts and to determine patency with fistula dilation and placement of multiple stents. PATIENTS AND METHODS: Between September 1995 and January 1999, 19 patients underwent endoscopic drainage of pancreatic pseudocysts, 17 of whom were assessed by EUS before drainage. Radial EUS scanning was used to detect an optimal site of apposition of pseudocyst and gut wall, free of intervening vessels. A fistula was created with a fistulatome, followed by balloon dilation of the fistula tract. Patency was maintained with multiple double pigtail stents. The primary goal of this retrospective study was to determine whether EUS affected the practice of endoscopic drainage of pancreatic pseudocysts. RESULTS: In 3 patients, drainage was not attempted based on EUS findings. In the other 13 patients (14 pseudocysts), creation of a fistula was successful on 13 occasions, and no immediate complications occurred. However, 1 patient subsequently developed sepsis that required surgery. All other patients were treated with balloon dilation, multiple stents, and antibiotics, with no septic complications. Of 14 pseudocysts (in 13 patients), 13 (93%) resolved. CONCLUSIONS: Results of EUS may alter management of patients considered for endoscopic drainage of pancreatic pseudocysts. Endoscopic ultrasonography was useful for selecting an optimal and safe drainage site. The combination of balloon dilation, multiple stents, and antibiotics appears to resolve pancreatic pseudocysts without septic complications.     

Design and preliminary evaluation of an expert system for platelet request evaluation

In spite of growing awareness of the potential risks associated with transfusion, the number of platelet units transfused in the United States continues to increase each year. There is a growing interest in ensuring that all transfusions are administered for appropriate reasons. Prospective review of requests for transfusions has been used to accomplish this goal. Although successful in reducing the number of inappropriate transfusions, this review method requires great time commitments by blood bank personnel and physicians. A knowledge-based system (ESPRE) that aids hospital blood bank personnel in the review of requests for platelet transfusions has been developed. The system automatically obtains most of the required patient data via a direct link to the hospital's main laboratory computers. The system generates a printed report that includes a list of patient-specific data, a list of the conditions for which a transfusion would be appropriate for the particular patient (given the clinical condition), and the conclusions drawn by the system. During a preliminary clinical evaluation of ESPRE, 73 randomly selected platelet transfusion requests were evaluated for approval by laboratory personnel and ESPRE. Overall, ESPRE would have approved 71 of the requests and laboratory staff would have approved 72. Forty-four percent of the requests would have been approved for the same reasons given by the staff. There were only three disagreements on final approval between ESPRE and blood bank personnel. This computerized expert system is a promising approach to the prospective review of all platelet transfusions.     

Listeria monocytogenes exploits cystic fibrosis transmembrane conductance regulator (CFTR) to escape the phagosome

Virulence of the intracellular pathogen Listeria monocytogenes (Listeria) requires escape from the phagosome into the host cytosol, where the bacteria replicate. Phagosomal escape is a multistep process characterized by perforation, which is dependent on the pore-forming toxin listeriolysin O (LLO), followed by rupture. The contribution of host factors to Listeria phagosomal escape is incompletely defined. Here we show that the cystic fibrosis transmembrane conductance regulator (CFTR) facilitates Listeria cytosolic entry. CFTR inhibition or mutation suppressed Listeria vacuolar escape in culture, and inhibition of CFTR in wild-type mice before oral inoculation of Listeria markedly decreased systemic infection. We provide evidence that high chloride concentrations may facilitate Listeria vacuolar escape by enhancing LLO oligomerization and lytic activity. We propose that CFTR transiently increases phagosomal chloride concentration after infection, potentiating LLO pore formation and vacuole lysis. Our studies suggest that Listeria exploits mechanisms of cellular ion homeostasis to escape the phagosome and emphasize host ion-channel function as a key parameter of bacterial virulence.     

Prevalence of fragile X syndrome in males and females in Indonesia

AIM: To investigate the prevalence of fragile X syndrome (FXS) in intellectually disabled male and female Indonesians. METHODS: This research is an extension of a previously reported study on the identification of chromosomal aberrations in a large cohort of 527 Indonesians with intellectual disability (ID). In this previous study, 87 patients had a chromosomal abnormality, five of whom expressed fragile sites on Xq27.3. Since FXS cannot always be identified by cytogenetic analysis, molecular testing of the fragile X mental retardation 1 CGG repeat was performed in 440 samples. The testing was also conducted in the five previously identified samples to confirm the abnormality. In total, a molecular study was conducted in 445 samples (162 females and 283 males). RESULTS: In the cohort of Indonesian ID population, the prevalence of FXS is 9/527 (1.7%). The prevalence in males and females is 1.5% (5/329) and 2% (4/198), respectively. Segregation analysis in the families and X-inactivation studies were performed. We performed the first comprehensive genetic survey of a representative sample of male and female ID individuals from institutions and special schools in Indonesia. Our findings show that a comprehensive study of FXS can be performed in a developing country like Indonesia where diagnostic facilities are limited. CONCLUSION: The prevalence of FXS is equal in females and males in our study, which suggests that the prevalence of FXS in females could be underestimated.     

Multi-unit ribozyme-mediated cleavage of bcr-abl mRNA in myeloid leukemias

Chronic myelogenous leukemia is characterized by the Philadelphia chromosome, which at the molecular level results from the fusion of the bcr gene on chromosome 22 and the abl gene on chromosome 9. The bcr-abl fusion gene encodes a novel tyrosine kinase with transforming activity. In this study, we have synthesized a multi-unti ribozyme that targets bcr-abl mRNA. In vitro ribozyme cleavage reactions show increased cleavage efficiency of this multi-unit ribozyme compared with single or double ribozymes. The multiunit ribozyme was then transfected into murine myeloblasts transformed with the bcr-abl gene (32D cells). Ribozyme transfection was accomplished either by liposomes or using follic acid-polylysine as a carrier. Multi-unit ribozyme transfection reduced the level of bcr-abl mRNA 3 logs when transfected via folate receptor-mediated uptake into transformed 32D cells. These results suggest that a multi-unit ribozyme could be an effective therapeutic agent for the treatment of Philadelphia chromosome-positive chronic myelogenous leukemia.     

Contrast medium-induced adverse reactions: economic outcome

Because the cost of managing an expected greater number of adverse reactions when high-osmolality contrast media (HOM) are used could offset the higher material cost of low-osmolality contrast media (LOM), a prospective study was done of 795 inpatients undergoing any of four procedures involving intravascular injection of HOM: cardiac catheterization, peripheral angiography, head computed tomography (CT), or body CT. The resources used in managing HOM-induced adverse reactions were measured, and the costs of these resources were estimated. Four hundred five patients (51%) had adverse reactions. Reactions were grouped into three classes according to their severity. Class 1 (mild) reactions occurred in 358 patients (45%), class 2 (moderate) reactions occurred in 44 patients (6%), and class 3 (severe) reactions occurred in three patients (0.4%). Ninety-nine patients (12%) consumed resources as a result of an adverse reaction. The average cost of these resources per patient undergoing examination was $1.07 to the radiology department, $5.83 to the hospital, and $12.93 to a charge-paying insurer. Mean (+/- standard deviation) cost to the hospital for managing class 1, class 2, and class 3 reactions were $2.52 +/- $5.33, $24 +/- $54, and $910 +/- $749, respectively. By comparison, the difference in material cost of HOM versus LOM ranged from $93 for body CT to $179 for cardiac catheterization. Even if LOM were to induce no adverse reactions, the increased material cost associated with universal substitution of LOM for HOM would be greater than the expected cost of managing adverse reactions when HOM are used.     

Atrial G protein-activated K+ channel: expression cloning and molecular properties.

Activity of several ion channels is controlled by heterotrimeric GTP-binding proteins (G proteins) via a membrane-delimited pathway that does not involve cytoplasmic intermediates. The best studied example is the K+ channel activated by muscarinic agonists in the atrium, which plays a crucial role in regulating the heartbeat. To enable studies of the molecular mechanisms of activation, this channel, denoted KGA, was cloned from a rat atrium cDNA library by functional coupling to coexpressed serotonin type 1A receptors in Xenopus oocytes. KGA displays regions of sequence homology to other inwardly rectifying channels as well as unique regions that may govern G-protein interaction. The expressed KGA channel is activated by serotonin 1A, muscarinic m2, and delta-opioid receptors via G proteins. KGA is activated by guanosine 5'-[gamma-thio]triphosphate in excised patches, confirming activation by a membrane-delimited pathway, and displays a conductance equal to that of the endogenous channel in atrial cells. The hypothesis that similar channels play a role in neuronal inhibition is supported by the cloning of a nearly identical channel (KGB1) from a rat brain cDNA library.