Tentorial Venous Anatomy: Variation in the Healthy Population.

BACKGROUND AND PURPOSE: A new transtentorial venous system consisting of medial, intermediate, and lateral tentorial veins, connecting infra- and supratentorial compartments, was recently shown in 2 cadaver dissections and 2 patient scans. We sought to characterize the venous patterns within the tentorium and their relation to measures of skull development in a cohort of healthy adults. MATERIALS AND METHODS: We retrospectively reviewed tentorial venous anatomy of the head using CTA/CTV performed for routine care or research purposes in 238 patients. Included studies had adequate contrast opacification of venous structures and a section thickness of ≤2 mm; we excluded cases with space-occupying lesions and vascular pathologies. Tentorial angle, dural sinus configurations, and measures of skull base development were assessed as predictors of tentorial venous anatomy variation via Cramér V association, the binary encoded Pearson correlation, and nearest-point algorithm with the Euclidean distance metric for clustering. RESULTS: Tentorial vein development was related to the ringed configuration of the tentorial sinuses (P < .005). There were 3 configurations. Groups 1A and 1B (n = 50/238) had ringed configuration, while group 2 did not (n = 188/238). Group 1A (n = 38/50) had a medialized ringed configuration, and group 1B had a lateralized ringed configuration (n = 12/50). Measurements of skull base development were predictive of these groups. The ringed configuration of group 1 was related to the presence of a split confluens, which correlated with a decreased internal auditory canal-petroclival fissure angle. Configuration 1A was related to the degree of petrous apex pneumatization (P value = .010). CONCLUSIONS: Variations in the transtentorial venous system directly correlate with cranial development.

Protein phosphatase 1 regulatory subunit 1A in ewing sarcoma tumorigenesis and metastasis.

Protein phosphatase inhibitors are often considered as tumor promoters. Protein phosphatase 1 regulatory subunit 1A (PPP1R1A) is a potent protein phosphatase 1 (PP1) inhibitor; however, its role in tumor development is largely undefined. Here we characterize, for the first time, the functions of PPP1R1A in Ewing sarcoma (ES) pathogenesis. We found that PPP1R1A is one of the top ranked target genes of EWS/FLI, the master regulator of ES, and is upregulated by EWS/FLI via a GGAA microsatellite enhancer element. Depletion of PPP1R1A resulted in a significant decrease in oncogenic transformation and cell migration in vitro as well as xenograft tumor growth and metastasis in an orthotopic mouse model. RNA-sequencing and functional annotation analyses revealed that PPP1R1A regulates genes associated with various cellular functions including cell junction, adhesion and neurogenesis. Interestingly, we found a significant overlap of PPP1R1A-regulated gene set with that of ZEB2 and EWS, which regulates metastasis and neuronal differentiation in ES, respectively. Further studies for characterization of the molecular mechanisms revealed that activation of PPP1R1A by PKA phosphorylation at Thr35, and subsequent PP1 binding and inhibition, was required for PPP1R1A-mediated tumorigenesis and metastasis, likely by increasing the phosphorylation levels of various PP1 substrates. Furthermore, we found that a PKA inhibitor impaired ES cell proliferation, tumor growth and metastasis, which was rescued by the constitutively active PPP1R1A. Together, these results offered new insights into the role and mechanism of PPP1R1A in tumor development and identified an important kinase and phosphatase pathway, PKA/PPP1R1A/PP1, in ES pathogenesis. Our findings strongly suggest a potential therapeutic value of inhibition of the PKA/PPP1R1A/PP1 pathway in the treatment of primary and metastatic ES.

Incidence trends of keratinocytic skin cancers and melanoma in Israel 2006-11.

BACKGROUND: The incidence of melanoma and keratinocyte cancers (KCs) is rising worldwide. Squamous cell carcinomas (SCCs) and basal cell carcinoma (BCCs) are the most common of all cancers. OBJECTIVES: To determine trends in the incidence of melanoma, BCC and SCC among 1·7 million members of Maccabi Healthcare Services (MHS) from 2006 to 2011. METHODS: Data on patients newly diagnosed with melanoma, SCC and BCC were collected from the MHS Cancer Registry and based on histology reports from the centralized pathology laboratory. Age-specific and overall age-adjusted European standardized rates were computed. Trends were estimated by calculating average annual percentage change (AAPC). RESULTS: During the 6-year study period, 16,079 patients were diagnosed with at least one BCC, 4767 with SCC and 1264 with invasive melanoma. Age-standardized incidence rates were 188, 58 and 17 per 100,000 person years for BCC, SCC and melanoma, respectively. All lesions were more common among men and primarily affected the elderly. BCC rates were stable throughout the study period [AAPC -0·7%, 95% confidence interval (CI) -4·5 to 3·2], while the incidence of SCC increased significantly (AAPC 15·5%, 95% CI 2·6-30·0). In contrast, melanoma rates continuously decreased (AAPC -3·0%, 95%CI -4·5 to -0·1). CONCLUSIONS: The incidence of KC in Israel is high. The disparities in incidence trends between SCC, BCC and melanoma allude to their different aetiologies. These findings underscore the importance of continuous monitoring, education and prevention programmes in a growing high-risk population.

Ozonation as a clean technology for fresh produce industry and environment: sanitizer efficiency and wastewater quality.

AIMS: Inactivating microbial contaminants in fresh produce commonly uses chlorine washing. The effectiveness of ozone was explored as an alternative to chlorine in produce washing for ensuring microbial safety while maximizing water reusability. METHODS AND RESULTS: An ozone washing system was designed to permit continuous addition of contaminated produce and the reuse of washing water. The effectiveness of ozonation (<2 mg l(-1) ) was determined using Bacillus subtilis spores as a stricter measure of efficiency with processing time of 10 min. As a comparison, chlorine (c. 100 mg l(-1) ) was tested in parallel. Water quality characteristics, including chemical oxygen demand, total suspended solids, disinfectants concentration and microbial reduction were measured. Ozonation showed an average of 1·56 log reduction of B. subtilis spores on lettuce, while chlorination achieved a 1·30 log reduction. The effluents after ozonation demonstrated improved water quality, both in physicochemical quality and microbial quality compared to chlorination. CONCLUSION: Aqueous ozone treatment is effective against microbial contaminants on fresh produce and enables extended use of washing water. SIGNIFICANCE AND IMPACT OF THE STUDY: The results provide significant data about ozone disinfection efficacy and its impact on the water reusability, which can facilitate the ozone utilization in the fresh produce production as an environmental friendly alternative.

CCR5 is required for regulation of alloreactive T-cell responses to single class II MHC-mismatched murine cardiac grafts.

The effector CD4 T-cell response in wild-type C57BL/6 recipients of single class II MHC-disparate B6.H-2(bm12) cardiac allografts is restricted by CD4(+)CD25(+) regulatory T cells (Tregs) resulting in long-term allograft survival. To investigate the role chemokine receptors might play in Treg function, this study tested the requirement for CCR5 on Tregs to suppress the alloimmune response in C57BL/6 recipients of B6.H-2(bm12) cardiac allografts. In contrast to the long-term survival of B6.H-2(bm12) allografts in wild-type recipients (>100 days), the allografts were acutely rejected within 25 days in CCR5(-/-) recipients with intense infiltration of CD4 T cells. Numbers and duration of donor-reactive CD4 T cells producing IFN-gamma and IL-4 were markedly increased in spleens of B6.CCR5(-/-) versus wild-type recipients. Wild-type and B6.CCR5(-/-) mice had equivalent numbers of splenic FoxP3(+) Tregs before and following transplantation, and these Tregs were equivalently suppressive in vitro. However, diminished numbers of FoxP3(+) Tregs infiltrated B6.H-2(bm12) allografts in B6.CCR5(-/-) recipients. Adoptive transfer of wild-type, but not CCR5-deficient, CD4(+)CD25(+) Tregs to CCR5(-/-) recipients restored long-term survival of B6.H-2(bm12) cardiac grafts. Collectively, these results indicate that CCR5 expression is required for the regulatory functions of Tregs that restrict alloreactive CD4 T-cell responses to single class II MHC-mismatched cardiac allografts.

The effect of customized insoles on the reduction of postwork discomfort.

This study examined the effect of customized insoles in relieving postwork discomfort in healthy individuals whose jobs require long periods of standing and walking. CompuSole insoles were worn by 122 New York City Police Department officers for up to 5 weeks for an average of 7 hours per day. The officers walked an average of 3 miles per day. Before the study, one-fifth of the police officers in this study experienced foot pain or discomfort at the end of their workday; 15% had calluses, corns, or athlete's foot; 18% had sought treatment for a foot problem in the past; and 20% had worn foot orthoses. There was a significant reduction in tiredness in the feet at the end of the day after wearing the insoles, but no improvement in back or leg discomfort. At the end of the workday, 68% had less foot discomfort and 60% were more comfortable at work when wearing the insoles.

Superselective microcoil embolization of colonic hemorrhage.

OBJECTIVE: We evaluated therapeutic microcoil embolization in a group of patients with severe colonic hemorrhage. MATERIALS AND METHODS: Twenty-seven patients with severe colonic bleeding due to diverticular disease (n = 19), angiodysplasia (n = 6), cecal ulcer (n = 1), or unknown cause (n = 1) underwent attempted microcoil embolization (n = 25). Microcatheters were used in all procedures, and embolization was performed at the level of the vasa recta or the marginal artery of Drummond. Branches of the superior mesenteric artery were embolized in 12 patients, branches of the inferior mesenteric artery were embolized in 12 patients, and branches of both the superior and inferior mesenteric arteries were embolized in one patient. RESULTS: Technical success was achieved in 93% (25/27) of the procedures. However, immediate hemostasis occurred in 96% (26/27) of patients because in one failed procedure, an occlusive dissection of the inferior mesenteric artery arrested bleeding. Three patients rebled within 24 hr. One patient was treated with endoscopic cauterization, and two patients underwent right hemicolectomy. One patient who underwent right hemicolectomy for rebleeding had ischemic changes found on pathologic analysis of the resected specimen, and a second patient who underwent embolization of branches of the superior and inferior mesenteric arteries developed bowel infarction requiring left hemicolectomy. Prolonged clinical success occurred in 81% (22/27) of patients. CONCLUSION: Therapeutic microcoil embolization for severe colonic hemorrhage is an effective and well-tolerated procedure.

Treatment of deep cerebral venous thrombosis by local infusion of tissue plasminogen activator.

BACKGROUND: Treatment of extensive intracranial venous sinus thrombosis with thrombolytic drugs is described, although the indications for and most efficacious technique for achieving thrombolysis remain uncertain. We report the successful lysis of superficial and deep venous system thrombosis by infusion of recombinant human tissue-type plasminogen activator (rt-PA) into the anterior superior sagittal sinus. CASE DESCRIPTION: A 34-year-old man presented with headaches followed by decreased level of consciousness and left hemiplegia. Angiography showed thrombosis of the superior sagittal and both transverse and straight sinuses with extension into the internal cerebral veins. The superior sagittal sinus was catheterized via a transfemoral route and rt-PA, 25 mg, was infused. There was no significant change in the thrombosis. The catheter was left in place and rt-PA was infused at 1 mg/minute for 19 hours. Repeat angiography showed resolution of the thrombosis. The patient was placed on heparin and then coumadin. He recovered completely. CONCLUSIONS: This report suggests that superselective infusion of thrombolytics into thrombosed intracranial venous sinuses can lyse intracranial venous sinus thrombosis. The thrombolytic agent must be infused for hours. The apparent successful lysis of clot in the deep venous system when infusion was into the superior sagittal sinus might be related to diffusion of rt-PA throughout the intracranial venous system or to improved venous outflow caused by lysis of clot in superficial dural sinuses.

Comparison of balloon- and mushroom-retained large-bore gastrostomy catheters.

OBJECTIVE: We conducted a retrospective study to evaluate two different types of percutaneous fluoroscopic gastrostomy procedures and catheters. MATERIALS AND METHODS: Between July 8, 1999, and August 4, 2000, 80 percutaneous gastrostomy catheters were placed in 80 patients in 80 attempts. Twenty-five 16-, 18-, or 20-French balloon-retained catheters and 55 20-French mushroom-retained catheters were inserted. Typically, the type of catheters placed was based on operator preference. However, balloon-retained tubes were preferred for use in patients with obstructive head and neck or esophageal malignancies, and mushroom-retained catheters were preferred for use in demented or combative patients. Follow-up was conducted through chart reviews and telephone interviews. The technical success, procedural complications, and catheter complications were recorded. Chi-square statistical analysis was performed. RESULTS: Technical success was 100% (80/80 patients), and no procedural complications occurred. In patients who received balloon-retained catheters, the major complication rate was 0%, the minor complication rate was 8% (2/25 patients), and the tube complication rate was 68% (17/25 patients). The following complications occurred: catheter dislodgment (n = 17), superficial cellulitis (n = 1), and bleeding gastric ulcer (n = 1). In patients who received mushroom-retained catheters, the major complication rate was 0%, the minor complication rate was 3.6% (2/55 patients), and the tube complication rate was 3.6% (2/55 patients). The following complications occurred: superficial cellulitis (n = 2), tube occlusion (n = 1), and peristomal tube leakage (n = 1). No significant differences in major or minor complications were found between the gastrostomy procedures. Balloon-retained catheters had a significantly higher rate of tube complications (p < 0.001). CONCLUSION: Compared with balloon-retained catheters, mushroom-retained gastrostomy catheters are significantly more durable, more secure, and less prone to tube dysfunction. Mushroom-retained catheters should be the preferred type of gastrostomy catheter to place in patients whenever possible.

Metallic stents deployed in synthetic arteriovenous hemodialysis grafts.

OBJECTIVE: The purpose of our study was to review the success of metallic stent treatment of intragraft stenoses in patients with synthetic arteriovenous hemodialysis grafts. MATERIALS AND METHODS: Between May 1993 and May 1997, 19 metallic stents were placed in 11 patients (seven women, four men; age range, 41-83 years) to treat elastic intragraft stenoses or graft dissections. Before stent placement, all patients had experienced multiple episodes of graft thrombosis, had very limited vascular access for hemodialysis, and were considered poor surgical candidates. RESULTS: The technical success rate was 100%, and there were no procedural complications. Using life-table analysis, we found primary patency to be 36% at 6 months after stent placement, 12% at 12 months, and 12% at 18 months. Secondary patency was 91% at 6 months after stent placement, 71% at 12 months, and 47% at 18 months. The mean and median patencies per intervention were 4.2 and 3.6 months, respectively. Mean and median secondary graft patencies were both 14 months (range, 3 days-32 months). Puncture through the stents occurred during dialysis, causing stent distortion and fracture. Eight stents had a linear fracture suggesting compression contributed to the stent distortion. No clinically evident complications related to stent placement occurred. CONCLUSION: Metallic stent deployment can salvage access in synthetic arteriovenous grafts by alleviating intragraft stenoses. Patency of intragraft stents is similar to venous stents used to treat other hemodialysis-related stenoses; however, fracture of Wall-stents occurs with prolonged graft use, especially in areas of needle punctures.

Sonographic needle guidance in cholangiography in children.

PURPOSE: To evaluate feasibility and benefits of sonographic guidance of percutaneous transhepatic cholangiography (PTC) in children with liver transplants. MATERIALS AND METHODS: The authors prospectively followed 24 PTC procedures in 19 pediatric patients (11 females, 8 males; age 3 months to 17 years) randomized to fluoroscopic or sonographic guidance. The number of needle passes, the contrast material dose, fluoroscopy time, and procedure time for each procedure were recorded. All patients were transplant recipients-six whole and 13 reduced-size grafts. Cases were randomly assigned to two groups: group I, fluoroscopically guided PTC (12 procedures); group II, sonographically guided PTC (12 procedures). RESULTS: The technical success rate was 92% (11 of 12) for each group. In group I, there were two procedure-related complications: postprocedural fever caused by biliary to portal vein fistula, and peritoneal bleeding requiring surgery. In group II, there were no procedure-related complications. A mean of 8.2 +/- 3.7 needle passes were required in group I compared to only 2.0 +/- 1.3 in group II (P < .0001). A mean contrast material dose of 19.5 mL +/- 13.4 was required in group I compared to only 2.5 mL +/- 1.9 in group II (P < .001). A mean procedure time of 15.7 minutes +/- 7.4 was required in group I compared to only 6.1 minutes +/- 4.5 in group II (P < .001). A mean fluoroscopy time of 10.4 minutes +/- 5.0 was required in group I compared to only 1.0 minutes +/- 0.7 in group II (P < .0001). CONCLUSION: In pediatric patients who have undergone liver transplantation, sonographic guidance significantly decreases the number of needle passes, contrast material dose, and fluoroscopy time required for PTC.

Radiologic placement of tunneled hemodialysis catheters in occluded neck, chest, or small thyrocervical collateral veins in central venous occlusion.

PURPOSE: To evaluate interventional radiologic placement of tunneled hemodialysis catheters in small thyrocervical collateral veins or in occluded veins in the neck or chest in patients with limited venous access. MATERIALS AND METHODS: A femoral venous approach was used to recanalize occluded veins or catheterize small collateral veins in 24 patients in whom all major central veins were occluded. A loop snare or catheter was used as a target for antegrade puncture. Metallic stents were deployed if necessary. Once antegrade access was secured, catheters were placed in a conventional fashion. RESULTS: Technical success was achieved in 22 (88%) of 25 procedures (one patient underwent two procedures). All catheters functioned immediately after placement. There were two procedural complications: a vasovagal episode requiring intravenously administered atropine sulfate and an episode of respiratory distress requiring intubation. There were no instances of pneumothorax, nerve injury, or bleeding complications. Catheter malfunction requiring exchange occurred at a rate of 0.67 per 100 catheter days. Infection requiring catheter removal occurred at a rate of 0.06 per 100 catheter days. Primary patency was 90% at 1 month, 71% at 6 months, and 25% at 12 months. Secondary patency was 100% at 6 months and 70% at 12 months. CONCLUSION: In patients undergoing hemodialysis in whom conventional venous access sites have been exhausted, interventional radiologic venous recanalization for the placement of permanent catheters is safe and effective. Catheters placed in recanalized veins or small collateral veins have shorter primary patency rates compared with those of conventionally placed catheters, but the former can be maintained for relatively long periods.

Percutaneous transhepatic cholangiography and biliary drainage in pediatric liver transplant patients.

OBJECTIVE: In children with liver transplants, percutaneous transhepatic cholangiography has a critical role in evaluation and treatment of biliary complications. The purpose of this study was to evaluate the technical success and complication rates of percutaneous transhepatic cholangiography and biliary drain placement in children who underwent liver transplantation. MATERIALS AND METHODS: Between January 1, 1995 and July 1, 1999, 120 pediatric percutaneous transhepatic cholangiography procedures were performed in 76 patients (34 boys, 42 girls; age range, 5 months to 18 years; mean age, 5.3 years). Patients had received left lateral segment, whole-liver, or split-liver transplant grafts. Retrospective review of all pertinent radiology studies and electronic chart review were performed. RESULTS: A diagnostic cholangiogram was obtained in 96% (115/120) of all procedures and drainage catheter placement was successful in 89% (88/99) of attempts. In patients with nondilated intrahepatic bile ducts, a diagnostic cholangiogram was obtained in 92% (46/50) of procedures, and drainage catheter placement was successful in 76% (19/25) of attempts. Minor complications occurred in 10.8% (13/120) of procedures and included transient hemobilia with mild drop in hematocrit level (n = 2), mild pancreatitis (n = 1), fever with bacteremia (n = 5), and fever with negative blood cultures (n = 5). Major complications occurred in 1.7% (2/120) of procedures and included sepsis (n = 1) and hemoperitoneum requiring immediate surgery (n = 1). CONCLUSION: Percutaneous transhepatic cholangiography and biliary drainage can be performed with high technical success and low complication rates in pediatric liver transplant patients, even in those with nondilated intrahepatic ducts.

Radiologic gastrostomy placement: pigtail- versus mushroom-retained catheters.

OBJECTIVE: Two different types of percutaneous fluoroscopic gastrostomy procedures were prospectively evaluated. SUBJECTS AND METHODS: Between January 1, 1998, and August 10, 1999, 127 percutaneous gastrostomy catheters were placed in 128 patients in 128 attempts. Seventy-five 12- or 14-French pigtail-retained catheters and fifty-two 20-French mushroom-retained catheters were inserted. Catheters were generally placed on the basis of operator preference except pigtail-retained tubes were preferentially placed in patients with head and neck or esophageal malignancies and mushroom-retained catheters were preferentially placed in neurologically compromised or combative patients. The technical success, procedural complications, and catheter complications were recorded. Statistical analysis was performed. RESULTS: Ninety-nine percent (127/128) of the procedures were successful, and there were no procedural complications. One catheter was not placed because the colon intervened between the abdominal wall and stomach. In patients who received pigtail-retained catheters, the major complication rate was 3% (2/75), the minor complication rate was 8% (6/75), and the tube complication rate was 36% (27/75). The following complications were seen: tube occlusion (n = 12), inadvertent catheter removal (n = 8), peristomal tube leakage (n = 7), superficial cellulitis (n = 4), aspiration pneumonia (n = 2), and T-fastener cellulitis (n = 2). In patients who received mushroom-retained catheters, the major complication rate was 0%, the minor complication rate was 2% (1/52), and the tube complication rate was 2% (1/52). Complications were superficial cellulitis (n = 1) and partial catheter fracture (n = 1). There were no significant differences in major and minor complications between procedures. Pigtail-retained catheters had a significantly higher rate of tube complications (p < 0.001) CONCLUSION: Compared with pigtail-retained catheters, mushroom-retained gastrostomy catheters are more durable and secure and are less prone to tube dysfunction. These catheters should be preferentially placed when possible.

Identification of a sequence element from p53 that signals for Mdm2-targeted degradation.

The binding of Mdm2 to p53 is required for targeting p53 for degradation. p73, however, binds to Mdm2 but is refractory to Mdm2-mediated degradation, indicating that binding to Mdm2 is not sufficient for degradation. By utilizing the structural homology between p53 and p73, we generated p53-p73 chimeras to determine the sequence element unique to p53 essential for regulation of its stability. We found that replacing an element consisting of amino acids 92 to 112 of p53 with the corresponding region of p73 results in a protein that is not degradable by Mdm2. Removal of amino acids 92 to 112 of p53 by deletion also results in a non-Mdm2-degradable protein. Significantly, the finding that swapping this fragment converts p73 from refractory to sensitive to Mdm2-mediated degradation supports the conclusion that the amino acids 92 to 112 of p53 function as a degradation signal. We propose that the presence of an additional protein recognizes the degradation signal and coordinates with Mdm2 to target p53 for degradation. Our finding opens the possibility of searching for the additional protein, which most likely plays a critical role in the regulation of p53 stability and therefore function.

Percutaneous treatment of portal venous stenosis in children and adolescents with segmental hepatic transplants: long-term results.

PURPOSE: To evaluate the long-term effectiveness of the percutaneous treatment of portal venous stenoses in children and adolescents with reduced-size hepatic transplants. MATERIALS AND METHODS: During the past 5 years, percutaneous transhepatic balloon venoplasty was attempted in 25 children and adolescents with anastomotic portal venous stenoses that occurred after reduced-size hepatic transplantation. All procedures were performed with direct puncture of the intrahepatic portal vein and with subsequent balloon dilation. Intravascular stents were deployed in patients with suboptimal results after dilation or with recurrent stenoses. RESULTS: Percutaneous venoplasty was technically successful in 19 of 25 patients. In the remaining six patients, portal venous occlusion precluded access to the extrahepatic portal vein. Intravascular stents were deployed in 12 patients for "elastic" (n = 5) or recurrent (n = 7) stenoses. Seven patients who underwent successful venoplasty without stent placement have required no further intervention. All stents have remained patent without further intervention. Portal venous patency has been maintained for 5-61 months (mean time, 46 months) in all 19 patients. CONCLUSION: Percutaneous treatment of portal venous stenoses is effective and long lasting in children with reduced-size hepatic transplants. In patients with elastic or recurrent lesions, portal venous stents have excellent long-term primary patency despite continued patient growth. Successful, percutaneous transhepatic venoplasty eliminates the need for surgical revision, portacaval shunting, or repeat transplantation.

Percutaneous biliary drainage in patients with nondilated intrahepatic bile ducts.

OBJECTIVE: We evaluated the technical success and complications of percutaneous transhepatic biliary drainage in patients with nondilated intrahepatic bile ducts. MATERIALS AND METHODS: Between January 1, 1996, and August 31, 1998, 130 percutaneous transhepatic biliary drainage procedures were performed on patients with nondilated intrahepatic bile ducts. This group comprised primarily patients who had received liver transplants or who had sustained iatrogenic bile duct injuries. Access in all procedures was performed using a one-step system consisting of a 21-gauge needle and an .018-inch guidewire. The technical success and complications of the procedures were evaluated. RESULTS: Percutaneous biliary drainage was successful in 117 (90%) of 130 attempts. In four patients, two attempts were required to place a drainage catheter. The overall complication rate was 9%. There were seven (5%) minor complications and five major complications (4%). No procedure-related deaths occurred. CONCLUSION: Percutaneous biliary drainage can be performed with a high success rate in patients with nondilated intrahepatic ducts. The incidence and types of complications in this population were similar to those reported in patients with intrahepatic ductal dilatation.

Autoproteolysis in nucleoporin biogenesis.

We have molecularly characterized a proteolytic cleavage in conserved nuclear pore complex proteins. This cleavage, previously demonstrated to be essential for the biogenesis of two nuclear pore complex proteins in mammals (Nup98 and Nup96) and yeast (Nup145-N and Nup145-C), occurs between Phe and Ser residues within a highly conserved domain in a polyprotein precursor. Here, we show that a protease is not involved in the cleavage event. By using a combination of domain mapping and site-directed mutagenesis, we demonstrate that the human nuclear pore complex protein Nup98 specifically cleaves itself between F863 and S864. A region of Nup98, amino acids 715-920, is able to cleave, whereas a smaller region, amino acids 772-920, does not cleave. In addition, we have generated a Nup98 mutant that cleaves under defined conditions in vitro. Further, the two cleaved fragments of Nup98 form a complex, providing a possible mechanism whereby specific, yet low-affinity, binding between Nup98 and Nup96 is responsible for the nuclear targeting of Nup96. Although apparently unrelated evolutionarily, Nup98 has converged on an autoproteolytic biogenesis mechanism similar to that of hedgehog proteins, the inteins, and the N-terminal nucleophile proteins.

Exchange of poorly functioning tunneled permanent hemodialysis catheters.

OBJECTIVE: The usefulness of exchanging poorly functioning tunneled permanent hemodialysis catheters in patients with end-stage renal disease was evaluated. MATERIALS AND METHODS: We retrospectively reviewed case histories of 51 consecutive patients who underwent 88 catheter exchanges because of poor flow rates. All hemodialysis catheters were initially placed by the radiology service using image guidance. Catheter exchanges were performed through the existing subcutaneous tract over two stiff hydrophilic guidewires and without additional interventions such as fibrin sheath stripping or venoplasty. Life table analysis was performed to evaluate catheter patency rates after initial placement (primary patency) and after multiple exchanges (secondary patency). RESULTS: The technical success rate for hemodialysis catheter exchange was 100%. Primary catheter patency was 42% at 60 days and 16% at 120 days. Secondary patency was 92% at 60 days and 82% at 120 days. The cumulative infection rate was 1.1 per 1000 catheter days. No complications from the procedure occurred. CONCLUSION: Catheter exchange is an effective means of prolonging catheter patency in patients with end-stage renal disease and limited central venous access.