Biliary complications after liver transplantation: With special reference to the biliary cast syndrome and techniques of secondary duct repair

In 93 consecutive cases of orthotopic liver transplantation, there were 24 examples of biliary obstruction and eight of bile fistula formation. Six of the obstructed livers developed biliary cast formation so extensive that the smaller intrahepatic ducts became plugged to an extent that they could no longer have been treated by surgical means. In each of the six cases, the most important causative factor was neglected obstruction of the large bile ducts with the intrahepatic lesions apparently being late and secondary. Stone and/or cast formation also occurred in other obstructed livers in the presence of bile fistulas, but these deposits were limited to the large ducts where they could have been or were removed. Although homograft bile undoubtedly has increased lithogenicity at certain postoperative times, the data from the present study have shown that biliary sludge formation essentially is always associated with defective bile duct reconstruction, and the observations have underscored the urgency with which reoperation must be considered. Techniques of secondary intervention have been described, with emphasis on conversion of cholecystojejunostomy to choledochojejunostomy. This operation has permitted salvage of homografts in eight of nine trials and the survival of seven patients. © 1977

Infections Complicating Orthotopic Liver Transplantation: A Study Emphasizing Graft-Related Septicemia

In 93 recipients of 102 orthotopic liver homografts, the incidence of bacteremia or fungemia exceeded 70%. The graft itself was usually an entry site for systemic infection after both immunologic and nonimmunologic parenchymal injury, especially if there was defective biliary drainage. The role of the homograft itself as the special infectious risk factor has prompted increased use of defunctionalized jejunal Roux limbs to reduce graft contamination. It has also stimulated very aggressive postoperative diagnostic efforts to rule out remedial mechanical complications of the transplant. © 1976, American Medical Association. All rights reserved

Standardising neonatal and paediatric antibiotic clinical trial design and conduct: the PENTA-ID network view.

Antimicrobial development for children remains challenging due to multiple barriers to conducting randomised clinical trials (CTs). There is currently considerable heterogeneity in the design and conduct of paediatric antibiotic studies, hampering comparison and meta-analytic approaches. The board of the European networks for paediatric research at the European Medicines Agency (EMA), in collaboration with the Paediatric European Network for Treatments of AIDS-Infectious Diseases network (www.penta-id.org), recently developed a Working Group on paediatric antibiotic CT design, involving academic, regulatory and industry representatives. The evidence base for any specific criteria for the design and conduct of efficacy and safety antibiotic trials for children is very limited and will evolve over time as further studies are conducted. The suggestions being put forward here are based on the adult EMA guidance, adapted for neonates and children. In particular, this document provides suggested guidance on the general principles of harmonisation between regulatory and strategic trials, including (1) standardised key inclusion/exclusion criteria and widely applicable outcome measures for specific clinical infectious syndromes (CIS) to be used in CTs on efficacy of antibiotic in children; (2) key components of safety that should be reported in paediatric antibiotic CTs; (3) standardised sample sizes for safety studies. Summarising views from a range of key stakeholders, specific criteria for the design and conduct of efficacy and safety antibiotic trials in specific CIS for children have been suggested. The recommended criteria are intended to be applicable to both regulatory and clinical investigator-led strategic trials and could be the basis for harmonisation in the design and conduct of CTs on antibiotics in children. The next step is further discussion internationally with investigators, paediatric CTs networks and regulators

Potential of mean force and the charge reversal of rodlike polyions

A simple model is presented to calculate the potential of mean force between a polyion and a multivalent counterion inside a polyelectrolite solution. We find that under certain conditions the electrostatic interactions can lead to a strong attraction between the polyions and the multivalent counterions, favoring formation of overcharged polyion-counterion complexes. It is found that small concentrations of salt enhance the overcharging, while an excessive amount of salt hinders the charge reversal. The kinetic limitations to overcharging are also examined.Comment: To be published in the special issue of Molecular Physics in honor of Prof. Ben Wido

Loss of idealism or realistic optimism? A cross‐sectional analysis of dental hygiene students’ and registered dental hygienists’ professional identity perceptions

ObjectivesThe dental hygiene profession in the U.S. is in the process of establishing a direct access model of care and contributing to the creation of the profession of a dental therapist. The objectives were to analyse the professional role perceptions of dental hygiene students and registered dental hygienists in these times of change. Specifically, it was explored whether dental hygiene students’ current professional identities differ (i) from their expected future identities, and (ii) from dental hygienists’ current and (iii) past identities.MethodsSurvey data were collected from 215 dental hygiene students concerning their present and future role perceptions, and from 352 registered dental hygienists concerning their present and past professional identity perceptions.ResultsStudents’ future professional identity perceptions were even more positive than their very positive current perceptions of their professional role components. Students’ current perceptions of professional pride, professional ambition, work ethic and patient relations were more positive than dental hygienists’ current perceptions of these professional role components. A comparison of students’ current perceptions with dental hygienists’ current and retrospective descriptions showed that students were more positive than dental hygienists in each case.ConclusionsThe fact that dental hygienists had less positive role perceptions than dental hygiene students might lead to the conclusion that a loss of idealism occurs over the course of a professional lifespan. However, dental hygienists actually improved their role perceptions over time and students’ future descriptions were more positive than their current descriptions, supporting the interpretation that realistic optimism dominates professional role perceptions in these times of change.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141357/1/idh12287_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141357/2/idh12287.pd

A Protein‐Based Pentavalent Inhibitor of the Cholera Toxin B‐Subunit

Protein toxins produced by bacteria are the cause of many life-threatening diarrheal diseases. Many of these toxins, including cholera toxin (CT), enter the cell by first binding to glycolipids in the cell membrane. Inhibiting these multivalent protein/carbohydrate interactions would prevent the toxin from entering cells and causing diarrhea. Here we demonstrate that the site-specific modification of a protein scaffold, which is perfectly matched in both size and valency to the target toxin, provides a convenient route to an effective multivalent inhibitor. The resulting pentavalent neoglycoprotein displays an inhibition potency (IC50) of 104 pM for the CT B-subunit (CTB), which is the most potent pentavalent inhibitor for this target reported thus far. Complexation of the inhibitor and CTB resulted in a protein heterodimer. This inhibition strategy can potentially be applied to many multivalent receptors and also opens up new possibilities for protein assembly strategies

A head-to-head comparison of speckle tracking echocardiography and feature tracking cardiovascular magnetic resonance imaging in right ventricular deformation

Aims: Speckle tracking echocardiography (STE) and feature tracking cardiovascular magnetic resonance imaging (FT-CMR) are advanced imaging techniques which are both used for quantification of global and regional myocardial strain. Direct comparisons of STE and FT-CMR regarding right ventricular (RV) strain analysis are limited. We aimed to study clinical performance, correlation and agreement of RV strain by these techniques, using arrhythmogenic right ventricular cardiomyopathy (ARVC) as a model for RV disease. // Methods and results: We enrolled 110 subjects, including 34 patients with definite ARVC, 30 preclinical relatives of ARVC patients, and 46 healthy control subjects. Global and regional RV longitudinal peak strain (PS) were measured by STE and FT-CMR. Both modalities showed reduced strain values in ARVC patients compared to ARVC relatives (STE global PS: P < 0.001; FT-CMR global PS: P < 0.001) and reduced strain values in ARVC relatives compared to healthy control subjects (STE global PS: P = 0.042; FT-CMR global PS: P = 0.084). There was a moderate, albeit significant correlation between RV strain values obtained by STE and FT-CMR [global PS r = 0.578 (95% confidence interval 0.427–0.697), P < 0.001]. Agreement between the techniques was weak (limits of agreement for global PS: ±11.8%). Correlation and agreement both deteriorated when regional strain was studied. // Conclusion: RV STE and FT-CMR show a similar trend within the spectrum of ARVC and have significant correlation, but inter-modality agreement is weak. STE and FT-CMR may therefore both individually have added value for assessment of RV function, but RV PS values obtained by these techniques currently cannot be used interchangeably in clinical practice