The influence of variable-stiffness guide wires on basal biliary sphincter of Oddi pressure measured at endoscopic retrograde cholangiopancreatography.

BACKGROUND: Guide wires are commonly utilized to facilitate endoscopic procedures. However, their use may adversely influence the results of sphincter of Oddi manometry, thereby leading to erroneous diagnosis and therapy. The aim of this study was to evaluate the effect of guide wires on the basal pressure of the biliary sphincter of Oddi. METHODS: Forty-five consecutive patients with suspected sphincter of Oddi dysfunction were enrolled. Biliary sphincter of Oddi manometry was performed with and without a guide wire in the conventional retrograde fashion with a low-compliance infusion pump system, an aspirating catheter, and slow station pull-throughs. Three types of guide wires were studied: the Roadrunner (18 patients), the Glidewire (17 patients), and the standard Teflon guide wire (10 patients). The stiffness of the guide wires was tested and reported in Taber Stiffness Units (TSU; higher values represent greater stiffness). RESULTS: Biliary sphincter of Oddi manometry performed with a guide wire revealed higher basal pressure than the same measurement performed without a guide wire (52 +/- 33.4 mmHg vs. 34.4 +/- 20.5 mmHg; P = 0.001). Basal pressure changes induced by guide-wire use were highest in the Roadrunner group (32.9 +/- 33.9 mmHg), lowest in the standard Teflon group (11.6 +/- 8 mmHg; Roadrunner vs. standard Teflon: P = 0.02), and intermediate in the Glidewire group (17.1 +/- 22.1 mmHg). The use of a guide wire resulted in crossover from normal to abnormal basal pressure in 11 cases (Roadrunner, 7; Glidewire, 4) and from abnormal to normal in 2 (Roadrunner, 1; Glidewire, 1). Concordance between recordings obtained with and without guide wire was seen in 32 patients (71 %). Guide-wire stiffness was: Roadrunner: 0.74 TSU; Glidewire: 0.153 TSU; standard Teflon guide wire: 0.077 TSU. CONCLUSION: The use of guide wires frequently alters the basal biliary sphincter pressure, leading to incorrect diagnoses in approximately 40 % of cases. The basal pressure alterations depend on the stiffness of the guide wire used. Hence, the use of guide wires during sphincter of Oddi manometry is strongly discouraged.

Frequency of sphincter of Oddi dysfunction in patients with previously normal sphincter of Oddi manometry studies.

BACKGROUND AND STUDY AIMS: Sphincter of Oddi manometry (SOM), performed at endoscopic retrograde cholangiopancreatography (ERCP), is the gold standard for diagnosing sphincter of Oddi dysfunction (SOD). The question remains as to whether the short-term manometric recordings reflect the 24-hour pathophysiology of the sphincter. The aim of this study was to determine the frequency of SOD in persistently symptomatic patients with previously normal SOM studies. PATIENTS AND METHODS: All patients who underwent ERCP for suspected SOD over a 13-year period (1994 - 2007) were considered for inclusion in the study. Patients with an intact papilla and a previously normal SOM who had a repeat ERCP for persistent symptoms formed the study group. SOM was performed in conventional retrograde fashion. RESULTS: In all, 5352 patients without prior papillary intervention underwent SOM during the study period. A total of 1037 patients had normal SOM, and of these, 30 patients (27 female, mean age 40.1 years) underwent repeat ERCP for persistent symptoms. The median duration between the two ERCPs was 493.5 days (range 52-3538 days). In these 30 patients, SOD classification prior to the initial ERCP was: type I in one patient (not treated in 1994), type II in 17 patients, and type III in 12 patients. Of the 30 patients, 12 (40%) had normal SOM at repeat ERCP; SOD was diagnosed in 18/30 (60%) patients. CONCLUSIONS: A single SOM study may not represent the day-to-day physiology of the sphincter of Oddi; sphincter pathology may progress over time. One normal exam may not rule out SOD. A repeat ERCP with manometry may be warranted in a subset of patients with persistent debilitating symptoms and a high index of suspicion for SOD. Outcome data are needed to determine whether this approach justifies the potential risks of ERCP.

The GLFG repetitive region of the nucleoporin Nup116p interacts with Kap95p, an essential yeast nuclear import factor.

Nup116p is a member of a family of five yeast nuclear pore complex (NPC) proteins that share an amino terminal region of repetitive tetrapeptide "GLFG" motifs. Previous experiments characterized the unique morphological perturbations that occur in a nup116 null mutant: temperature-sensitive formation of nuclear envelope seals over the cytoplasmic face of the NPC (Wente, S. R., and G. Blobel. 1993. J. Cell Biol. 123:275-284). Three approaches have been taken to dissect the structural basis for Nup116p's role in NPC function. First, deletion mutagenesis analysis of NUP116 revealed that the GLFG region was required for NPC function. This was not true for the other four yeast GLFG family members (Nup49p, Nup57p, Nup100p, and Nup145p). Moreover, deletion of either half of Nup116p's GLFG repeats or replacement of Nup116p's GLFG region with either Nup100p's GLFG region or Nsp1p's FXFG repetitive region abolishes the function of Nup116p. At a semipermissive growth temperature, the cells lacking Nup116p's GLFG region displayed a diminished capacity for nuclear import. Second, overexpression of Nup116p's GLFG region severely inhibited cell growth, rapidly blocked polyadenylated-RNA export, and fragmented the nucleolus. Although it inhibited nuclear export, the overexpressed GLFG region appeared predominantly localized in the cytoplasm and NPC/nuclear envelope structure was not perturbed in thin section electron micrographs. Finally, using biochemical and two-hybrid analysis, an interaction was characterized between Nup116p's GLFG region and Kap95p, an essential yeast homologue of the vertebrate nuclear import factor p97/Imp90/karopherin beta. These data show that Nup116p's GLFG region has an essential role in mediating nuclear transport.

GLE2, a Saccharomyces cerevisiae homologue of the Schizosaccharomyces pombe export factor RAE1, is required for nuclear pore complex structure and function.

To identify and characterize novel factors required for nuclear transport, a genetic screen was conducted in the yeast Saccharomyces cerevisiae. Mutations that were lethal in combination with a null allele of the gene encoding the nucleoporin Nup100p were isolated using a colony-sectoring assay. Three complementation groups of gle (for GLFG lethal) mutants were identified. In this report, the characterization of GLE2 is detailed. GLE2 encodes a 40.5-kDa polypeptide with striking similarity to that of Schizosaccharomyces pombe RAE1. In indirect immunofluorescence and nuclear pore complex fractionation experiments, Gle2p was associated with nuclear pore complexes. Mutated alleles of GLE2 displayed blockage of polyadenylated RNA export; however, nuclear protein import was not apparently diminished. Immunofluorescence and thin-section electron microscopic analysis revealed that the nuclear pore complex and nuclear envelope structure was grossly perturbed in gle2 mutants. Because the clusters of herniated pore complexes appeared subsequent to the export block, the structural perturbations were likely indirect consequences of the export phenotype. Interestingly, a two-hybrid interaction was detected between Gle2p and Srp1p, the nuclear localization signal receptor, as well as Rip1p, a nuclear export signal-interacting protein. We propose that Gle2p has a novel role in mediating nuclear transport.

Regulation of macrophage lysosomal secretion by adenosine, adenosine phosphate esters, and related structural analogues of adenosine.

Zymosan particle-stimulated beta-galactosidase secretion by mouse peritoneal macrophages was found to be inhibited by micromolar concentrations of adenosine, AMP, ADP, and ATP. Inhibition by all four agents was increased to approximately 80% by adding erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA; 10 microM) an adenosine deaminase inhibitor, to the incubation medium. The inhibition of lysosomal enzyme secretion by ATP, ADP, and AMP was reversed by adding alpha, beta -methylene ADP (100 microM), a 5'-nucleotidase inhibitor, to the incubation medium. Inhibition by adenosine, however, was unaffected by alpha, beta -methylene ADP indicating that the inhibition by AMP, ADP, and ATP only occurred after they had been converted to adenosine by cell surface phosphohydrolases, including 5'-nucleotidase. Theophylline, a competitive antagonist of the binding of adenosine to plasma membrane adenosine receptors, failed to reverse the inhibitory effect of adenosine indicating the probable site of adenosine action to be intracellular. Other purine nucleosides, e.g., guanosine, and several purine and ribosemodified structural analogues of adenosine also inhibited zymosan-stimulated beta-galactosidase secretion, while xanthosine and certain pyrimidine nucleosides, e.g., thymidine, were inactive in this respect.

Complications of percutaneous endoscopic gastrostomy in head and neck cancer patients.

Percutaneous endoscopic gastrostomy (PEG) has been shown to benefit patients with resectable carcinoma of the head and neck. In order to determine whether patients with existing tumor or postresection anatomic changes of the upper respiratory tract can undergo this procedure with an acceptably low complication rate, 349 patients with attempted PEG were studied. The PEG procedure was successful in 114 of 122 carcinoma patients, as compared to 220 of 227 patients in a control group (patients with neurologic disease). Intraoperative complications preventing PEG placement included pharyngeal or esophageal obstruction, inadequate transillumination of the abdominal wall, and respiratory distress and occurred in 7% of carcinoma patients and 3% of controls. The incidence of airway obstruction during endoscopy was equal between groups (1%). Postoperative complications related to the gastrostomy tube were more frequent in the non-head and neck cancer group (14% versus 5%). Younger age, fewer concomitant medical problems, and better nutritional status may account for this difference. These findings suggest that preoperative, postoperative, and unresectable head and neck cancer patients are appropriate candidates for PEG, and postgastrostomy performance appears superior to that in other patient populations.

Comparison of rigid and flexible esophagoscopy in the diagnosis of esophageal disease: diagnostic accuracy, complications, and cost.

Rigid esophagoscopy has been used by otolaryngologists for evaluation of the esophagus for over 100 years. Few studies have examined the diagnostic accuracy of rigid esophagoscopy in patients with carcinoma of the head and neck. The goal of our study was to compare the diagnostic accuracy, complication rate, and costs of rigid esophagoscopy and flexible fiber-optic endoscopy in the evaluation of the esophagus in patients with head and neck carcinoma. We retrospectively reviewed the records of 195 patients with head and neck carcinoma who underwent both rigid esophagoscopy and flexible fiber-optic endoscopy within a 6-month period. We discovered 10 cases with discordant findings, of which 5 (50%) were esophageal carcinoma. The estimated cost was less for flexible endoscopy. No complications were reported in either procedure. Our study suggests that flexible fiber-optic endoscopy should replace rigid esophagoscopy in the evaluation of the esophagus in patients with head and neck carcinoma.

Gallstones: choosing the right therapy despite vague clinical clues.

Therapeutic decisions are quite clear-cut for asymptomatic gallstone disease and acute cholecystitis. However, the appropriate therapeutic course for older patients with chronic cholecystitis may be less obvious. Watchful waiting may be reasonable for patients with mild and infrequent symptoms. For healthy patients, cholecystectomy is recommended if symptoms are becoming more frequent and severe. Laparoscopy may reduce the complication rate and be safely performed even in those with underlying medical illness. Oral dissolution therapy can be attempted for qualifying symptomatic patients who are at poor surgical risk or who refuse surgery. Shock wave lithotripsy and contact dissolution therapy show some promise but are currently experimental.

Spatial and temporal operation of the Scotia Sea ecosystem: a review of large-scale links in a krill centred food web.

The Scotia Sea ecosystem is a major component of the circumpolar Southern Ocean system, where productivity and predator demand for prey are high. The eastward-flowing Antarctic Circumpolar Current (ACC) and waters from the Weddell-Scotia Confluence dominate the physics of the Scotia Sea, leading to a strong advective flow, intense eddy activity and mixing. There is also strong seasonality, manifest by the changing irradiance and sea ice cover, which leads to shorter summers in the south. Summer phytoplankton blooms, which at times can cover an area of more than 0.5 million km2, probably result from the mixing of micronutrients into surface waters through the flow of the ACC over the Scotia Arc. This production is consumed by a range of species including Antarctic krill, which are the major prey item of large seabird and marine mammal populations. The flow of the ACC is steered north by the Scotia Arc, pushing polar water to lower latitudes, carrying with it krill during spring and summer, which subsidize food webs around South Georgia and the northern Scotia Arc. There is also marked interannual variability in winter sea ice distribution and sea surface temperatures that is linked to southern hemisphere-scale climate processes such as the El Niño-Southern Oscillation. This variation affects regional primary and secondary production and influences biogeochemical cycles. It also affects krill population dynamics and dispersal, which in turn impacts higher trophic level predator foraging, breeding performance and population dynamics. The ecosystem has also been highly perturbed as a result of harvesting over the last two centuries and significant ecological changes have also occurred in response to rapid regional warming during the second half of the twentieth century. This combination of historical perturbation and rapid regional change highlights that the Scotia Sea ecosystem is likely to show significant change over the next two to three decades, which may result in major ecological shifts.

Recurrence rate of anastomotic biliary strictures in patients who have had previous successful endoscopic therapy for anastomotic narrowing after orthotopic liver transplantation.

BACKGROUND AND STUDY AIMS: The development of anastomotic strictures is one of the most common complications of orthotopic liver transplantation (OLT) with choledochocholedochostomy anastomosis. Endoscopic therapy with balloon dilation and/or stent placement is an effective therapy. The aim of this study was to assess the recurrence rate of anastomotic strictures and the features that predict recurrence after previously successful endoscopic therapy. PATIENTS AND METHODS: We searched the endoscopic retrograde cholangiopancreatography (ERCP) database for all patients who had had an OLT who were undergoing ERCP. The study cohort consisted of post-OLT patients who had a recurrence of anastomotic stricture after initial resolution following a course of endoscopic therapy. RESULTS: A total of 916 OLT operations were performed during the study period from June 1994 to November 2004. Out of this group, 143 patients (15.6 %) were diagnosed with anastomotic stricture and underwent a total of 423 ERCPs for endoscopic treatment. Twelve patients who are still undergoing endoscopic therapy were excluded from the analysis. The technical success rate was 96.6 %, and the endoscopic therapy was successful in 82 % of patients; 18 % had a recurrence of cholestasis and ERCP revealed a recurrence of the anastomotic stricture that required intervention. The mean time of follow-up after stent removal was 28 months (range 1 - 114 months). The study did not reveal any clinical or endoscopic parameters that could predict recurrence, though the presence of a biliary leak at initial ERCP and a longer time to initial presentation were factors that showed a trend toward an increased likelihood of recurrence. CONCLUSIONS: Biliary strictures remain a common complication after OLT, and in nearly one in five patients these strictures recur after initially successful endoscopic therapy. There were no clinical or endoscopic parameters identified in this study that predicted recurrence. Further study is needed to determine what type of endoscopic therapy would minimize the risk of stricture recurrence.

Therapeutic biliary endoscopy.

Some steps of progress have been seen in the area of biliary therapeutic endoscopy, in the understanding and management of primary sclerosing cholangitis, problems relating to liver transplantation, malignant biliary strictures, and complications after endoscopic retrograde cholangiopancreatography, as well as sphincter of Oddi dysfunction. These topics are reviewed here.

Computer programs in gastrointestinal endoscopy: issues, problems, and solutions.

For 10 years, a computerized gastrointestinal endoscopy database was promoted as necessary and desirable. At least 2 endoscopy societies, the American Society for Gastrointestinal Endoscopy (ASGE) and the World Society for Gastrointestinal Endoscopy (OMED), devoted considerable effort to develop appropriate terminology and structure. Numerous vendors and individuals developed software conforming, to various degrees, with the ASGE and OMED recommendations, and hundreds of institutions in the United States and an equal number worldwide have computerized their endoscopy paperwork. Dozens of articles and several large multicenter research efforts signal the usefulness of the database concept. Although desired, and apparently needed, endoscopy databases have not, however, caught the attention of a majority of physicians who could benefit from them--probably because of perceived difficulty with user interface. Whereas the keyboard has succeeded in virtually every other discipline, it is an enigma why there is so much anathema to this ubiquitous device among the majority of the medical community. Attempts at alternate input modalities, such as voice, resulted in several commercially available report-writers; however, the original database concept is insignificant in these current products. The international experience with this subject is reviewed with an optimistic prediction that a satisfactory doctor-computer interface will be developed, perhaps with totally new technology, and that continued interest, use, and development of an endoscopy database is justified.

Home infusion service delivery system model: a conceptual framework for family-centered care in pediatric home care delivery.

The Home Infusion Service Delivery System model is presented as a conceptual framework for the delivery of pediatric home care. This bicycle-shaped model provides important insights into the interrelationships of available resources for parents seeking home health care for their child. The model is based on nine key elements of family-centered care. Discussions of the model identify the roles and relationships among the family system, four interdependent service delivery systems, the physician, and a total quality management program that coordinates the health care delivery for the child. Examples focus on the delivery of pediatric home infusion therapy. By supporting the family as the primary care giver, this model provides a better fit between consumer need and service delivery.

Restriction of uterine space reduces litter size in feral Ossabaw swine.

The influence of uterine crowding on litter size and the fetal capacity of the feral pig uterus were examined in a control (C) group and three groups of surgically altered feral (Ossabaw) gilts. The altered groups were unilaterally ovariectomized (UOX), unilaterally tubally ligated (UTL), or unilaterally hysterectomized-ovariectomized (UHOX). Litter sizes of C, UOX and UHOX at 30 days of gestation were similar and larger than the UTL group. At 45 days, litter size was reduced (P less than 0.06) in UHOX gilts. These results indicate that uterine capacity of feral swine is limiting after Day 30, and that the maximum litter size for the feral pig is 8 to 10.

Biochemical differences in the mechanism of macrophage lysosomal exocytosis initiated by zymosan particles and weak bases.

By utilizing compounds with different inhibitory properties, discrete biochemical differences were found in the mechanism of selective lysosomal enzyme secretion by macrophages in response to stimulation with zymosan particles and methylamine. Pretreatment of macrophages with trypsin markedly impaired the capacity of the cells to respond to stimulation with zymosan particles, but had no effect on methylamine-stimulated lysosomal enzyme secretion. Similarly, the addition of phenylmethanesulphonyl fluoride or EDTA to the incubation medium substantially inhibited zymosan-induced lysosomal enzyme secretion, whereas the methylamine-stimulated response was unaffected by these agents. The addition of 2-deoxyglucose to incubation media, however, strongly inhibited both zymosan- and methylamine-stimulated beta-galactosidase secretion. These findings are consistent with a mechanism for lysosomal enzyme secretion by macrophages, based on a receptor-dependent uptake of zymosan particles and a receptor-independent uptake of methylamine.

Defining the essential functional regions of the nucleoporin Nup145p.

Studies of the essential nucleoporin Nup145p have shown that its depletion is coincident with a block in RNA export and that deletion of its amino-terminal domain results in clustering of nuclear pore complexes. To further define the functional domains of Nup145p, we have characterized a panel of nup145 mutants. Deletions from both the amino terminus and the carboxy terminus resulted in temperature sensitive mutants that accumulated polyadenylated RNA in the nucleus at the non-permissive temperature. In addition, these mutants also displayed constitutive clustering of nuclear pore complexes in localized patches of the nuclear envelope. These results suggested that an internal region of Nup145p consisting of amino acids 593-893 is essential for function. Accordingly, when this region was deleted, growth was not supported at any temperature, whereas the region alone was able to complement a null mutation when expressed on a high copy plasmid. Previous studies have suggested that Nup145p is cleaved into two polypeptides of approximately 65 and 80 kDa. Interestingly, our experiments suggest that cleavage occurs in vivo. However, a small internal deletion of 17 amino acid residues that abolished cleavage had no effect on cell growth. Therefore, cleavage is not necessary for Nup145p function. When a sequence harboring the Nup145p cleavage site required for Nup145p cleavage was inserted in a chimeric protein, it was not sufficient for mediating cleavage. Cleavage likely requires a second region from amino acid residues 247-524 in addition to the cleavage site.

Assessment of technical competence during ERCP training.

BACKGROUND: Successful performance of diagnostic and therapeutic ERCP requires skillful manipulation of the duodenoscope and accessories. The evaluation process for assessing competency is still in evolution. Recommendations for the number of examinations has ranged from 35 to 200, made without the benefit of prospective data. METHODS: Pancreatic and common bile duct cannulation rates were prospectively recorded for 21 trainees and 9 proctors over 6 years in a large university-based training program. Trainee success rates were compared to those of the proctor and learning curves were constructed. RESULTS: Trainees performed 641 examinations over 6 years. Each did an average of 31 examinations (range, 10 to 96). For both pancreatic duct and common bile duct cannulation, there was a rapid linear rise of the success curve extending up to the fortieth procedure. Pancreatic duct cannulation rates exceeded those of the common bile duct. CONCLUSIONS: This is the first prospective evaluation of acquisition of skills in ERCP. Although the rapid rise of the learning curve ends at the fortieth examination, the 85% level of selective cannulation is not reached for the pancreas duct until the seventieth procedure and is not reached for the common bile duct even at 100 procedures. These data suggest a threshold of at least 100 procedures.