Gallbladder ablation through radiologic intervention: an experimental alternative to cholecystectomy

Twenty pigs underwent (a) cystic duct occlusion by means of fluoroscopically guided transcatheter endoluminal bipolar radio-frequency (RF) electrocoagulation and (b) gallbladder sclerotherapy with one of two different regimens of ethanol and sodium tetradecyl-sulfate (STS). Serum ethanol levels and hepatic enzyme tests showed no acute toxicity. Postmortem histologic studies showed that the bile ducts beyond the occlusion site remained entirely unaffected in all animals. In three of four animals followed up for 2 weeks, the sclerosants induced necrosis of the gallbladder mucosa, but the adjacent liver, serosa, and blood vessels remained intact. In 13 of 16 animals followed up for 8 weeks, the gallbladder lumen was obliterated by fibrous scar tissue. In the animals treated with 95% ethanol and 3% STS, the gallbladder mucosa was necrotic in all areas after 2 weeks (two of two animals) and eradicated completely after 8 weeks (six of eight animals); the other regimen (70% ethanol plus 1% STS) was somewhat less effective. In this study, the combination of RF-mediated cystic duct occlusion and gallbladder sclerotherapy with ethanol and STS permitted gallbladder ablation in swine without toxic side effects.     

Comparison of a transfusion preparation of newly formed red cells and standard washed red cell transfusions in patients with homozygous beta- thalassemia

BACKGROUND: Previous studies of transfusions of newly formed red cells (neocytes) demonstrated modest extensions of transfusion interval in patients with homozygous beta-thalassemia. STUDY DESIGN AND METHODS: The clinical benefits of a new system of neocyte preparation (Neocel, Cutter Biological, Berkeley, CA), reported to combine ease of preparation with reduction in the transfusion requirements of thalassemia patients, were evaluated. Sixteen thalassemic patients who had undergone splenectomy received eight consecutive, standard, automated, washed red cell transfusions (standard transfusions), followed by eight transfusions with the neocyte preparation (neocyte transfusions). In each arm of the study, mean pretransfusion hemoglobin and mean red cell mass transfused were carefully controlled and were similar. RESULTS: A significant (p < 0.0001) extension of transfusion interval was observed in patients receiving neocyte transfusions (mean +/− SD; 38.7 +/− 34 days; range, 35.0-44.5), over that in those receiving standard transfusions (32.9 +/− 2.5 days; range, 29.6-38.5). The mean prolongation of transfusion interval by neocyte transfusion corresponded to a mean reduction of 25 mL in packed red cells transfused per kg of body weight per patient per year and a mean reduction in transfused iron of 15 percent per year per patient. During neocyte transfusions, blood preparation costs were considerably increased and donor exposure was significantly (p < 0.0005) higher than during the standard transfusion period. CONCLUSION: These data demonstrate that extension of the transfusion interval, and reduction in transfused iron, may be achieved in thalassemic patients by use of the Neocel system. These benefits are achieved, however, with substantial increases in donor exposure and in component preparation costs.     

Bcl-2–dependent oxidation of pyruvate dehydrogenase-E2, a primary biliary cirrhosis autoantigen, during apoptosis

The close association between autoantibodies against pyruvate dehydrogenase-E2 (PDC-E2), a ubiquitous mitochondrial protein, and primary biliary cirrhosis (PBC) is unexplained. Many autoantigens are selectively modified during apoptosis, which has focused attention on apoptotic cells as a potential source of "neo-antigens" responsible for activating autoreactive lymphocytes. Since increased apoptosis of bile duct epithelial cells (cholangiocytes) is evident in patients with PBC, we evaluated the effect of apoptosis on PDC-E2. Autoantibody recognition of PDC-E2 by immunofluorescence persisted in apoptotic cholangiocytes and appeared unchanged by immunoblot analysis. PDC-E2 was neither cleaved by caspases nor concentrated into surface blebs in apoptotic cells. In other cell types, autoantibody recognition of PDC-E2, as assessed by immunofluorescence, was abrogated after apoptosis, although expression levels of PDC-E2 appeared unchanged when examined by immunoblot analysis. Both overexpression of Bcl-2 and depletion of glutathione before inducing apoptosis prevented this loss of autoantibody recognition, suggesting that glutathiolation, rather than degradation or loss, of PDC-E2 was responsible for the loss of immunofluorescence signal. We postulate that apoptotic cholangiocytes, unlike other apoptotic cell types, are a potential source of immunogenic PDC-E2 in patients with PBC.     

Quality of life,work productivity impairment and healthcare resources in inflammatory bowel diseases in Brazil

BACKGROUND Inflammatory bowel diseases(IBD) have been associated with a low quality of life(QoL) and a negative impact on work productivity compared to the general population.Information about disease control,patient-reported outcomes(PROs),treatment patterns and use of healthcare resources is relevant to optimizing IBD management.AIM To describe QoL and work productivity and activity impairment(WPAI),treatment patterns and use of healthcare resources among IBD patients in Brazil.METHODS A multicenter cross-sectional study included adult outpatients who were previously diagnosed with moderate to severe Crohn's disease(CD) or ulcerative colitis(UC).At enrolment,active CD and UC were defined as having a Harvey Bradshaw Index≥8 or a CD Activity Index≥220 or calprotectin 200 μg/g or previous colonoscopy results suggestive of inadequate control(per investigator criteria) and a 9-point partial Mayo score≥5,respectively.The PRO assessment included the QoL questionnaires SF-36 and EQ-5 D-5 L,the Inflammatory Bowel Disease Questionnaire(IBDQ),and the WPAI questionnaire.Information about healthcare resources and treatment during the previous 3 years was collected from medical records.Chi-square,Fisher's exact and Student's t-/Mann-Whitney U tests were used to compare PROs,treatment patterns and the use of healthcare resources by disease activity(a=0.05).RESULTS Of the 407 patients in this study(CD/UC:64.9%/35.1%,mean age 42.9/45.9 years,54.2%/56.6% female,38.3%/37.1% employed),44.7%/25.2% presented moderate-to-severe CD/UC activity,respectively,at baseline.Expressed in median values for CD/UC,respectively,the SF-36 physical component was 46.6/44.7 and the mental component was 45.2/44.2,the EQ-visual analog scale score was 80.0/70.0,and the IBDQ overall score was 164.0/165.0.Moderate to severe activity,female gender,being unemployed,a lower educational level and lower income were associated with lower QoL(P 0.05).Median work productivity impairment was 20% and 5% for CD and UC patients,respectively,and activity impairment was 30 %,the latter being higher among patients with moderate to severe disease activity compared to patients with mild or no disease activity(75.0% vs 10.0%,P 0.001).For CD/UC patients,respectively,25.4%/2.8% had at least one surgery,38.3%/19.6% were hospitalized,and 70.7%/77.6% changed IBD treatment at least once during the last 3 years.The most common treatments at baseline were biologics(75.3%)and immunosuppressants(70.9%) for CD patients and 5-AS A compounds(77.5%) for UC patients.CONCLUSION Moderate to severe IBD activity,especially among CD patients,is associated with a substantial impact on QoL,work productivity impairment and an increased number of IBD surgeries and hospitalizations in Brazil.     

Ectopic mineralization of connective tissue in Abcc6-/- mice: effects of dietary modifications and a phosphate binder--a preliminary study

Abstract:  Pseudoxanthoma elasticum (PXE), a heritable multisystem disorder, is caused by mutations in the ABCC6 gene. We have developed a murine model for PXE by targeted inactivation of the corresponding mouse gene. A feature of this mouse model is ectopic mineralization of connective tissue capsule surrounding the bulb of vibrissae. This study was designed to investigate the effect of dietary sevelamer hydrochloride (Renagel®), a phosphate binder, and specific mineral modifications on ectopic mineralization of connective tissue in Abcc6 ^–/– mice. Three groups were fed a specific diet: (i) a standard rodent diet, (ii) a standard rodent diet supplemented with sevelamer hydrochloride, and (iii) a custom experimental diet with specific mineral modifications (high phosphorus, low calcium and low magnesium). The degree of mineralization was determined in hematoxylin-eosin-stained sections using computerized morphometric analysis and by chemical assays to measure the calcium and phosphorus content of the vibrissae. The results indicated increased mineralization in the Abcc6 ^–/– mice fed a standard diet or a diet with mineral modifications as compared with control mice fed a standard diet. However, feeding Abcc6 ^–/– mice with diet supplemented with sevelamer hydrochloride did not improve mineralization, in comparison to mice fed with normal diet. Collectively, these results suggest that the mineralization process in PXE may be exacerbated by changes in mineral intake. The role of dietary minerals, and phosphorus in particular, as well as that of phosphate binders, in ectopic mineralization of PXE, merits further investigation.