Hematemesis, a Distended Abdomen, and Pulseless Electrical Activity – An Unusual Presentation of Boerhaave’s Syndrome

Case Presentation An 82-year-old male with a past medical history significant for coronary artery disease with three stents placed over the last 15 months, diastolic heart failure with preserved EF, atrial fibrillation on warfarin, colon cancer status-post sigmoid resection and prostate cancer status-post prostatectomy who presented with three episodes of melena, hematemesis, and weakness. The patient was in his usual state of health prior to these symptoms. He had no history of gastrointestinal (GI) bleeding or other GI pathology and was a non-drinker and non-smoker. He denied frequent use of non-steroidal anti-inflammatory medications

From the Editors

The editorial staff would like to acknowledge the support of Dr. Diemer and Dr. Kane in producing this year’s Jefferson Forum. We appreciate your guidance and thank you for all that you have done to help bring this issue to print. We would also like to thank our internal medicine resident colleagues for contributing interesting and unique case reports, review articles, original research, travel experiences, and poetry. This issue of the Jefferson Forum could not have been done without your hard work and enthusiasm

Quality Improvement of Diabetic Care at a Resident Clinic

Our objective was to develop a quality improvement project on diabetes mellitus at our internal medicine residency clinic. Residents developed projects aimed at improving an aspect of diabetic care. Continuity of care, achievement of clinical targets, no-show rates, patient knowledge of diabetes, and preventive care were evaluated. Our data was obtained with a questionnaire and a retrospective review of medical records. A different provider was scheduled about every 1.78 visit. The no-show rate was 25.4%. About half of patients identified goal hgbA1c and BPs, and 35% and 60% achieved their hgbA1c and SBP goals respectively. Nearly all of the charts planned for screening exams. We concluded that our clinic needs to improve diabetes education, reaching clinical targets, continuity of care and no-shows. Incorporating a QI project into the clinic with one disease such as diabetes is an efficient way to include practice based learning into an internal medicine residency’s curriculum

RosettaScripts: A Scripting Language Interface to the Rosetta Macromolecular Modeling Suite

Macromolecular modeling and design are increasingly useful in basic research, biotechnology, and teaching. However, the absence of a user-friendly modeling framework that provides access to a wide range of modeling capabilities is hampering the wider adoption of computational methods by non-experts. RosettaScripts is an XML-like language for specifying modeling tasks in the Rosetta framework. RosettaScripts provides access to protocol-level functionalities, such as rigid-body docking and sequence redesign, and allows fast testing and deployment of complex protocols without need for modifying or recompiling the underlying C++ code. We illustrate these capabilities with RosettaScripts protocols for the stabilization of proteins, the generation of computationally constrained libraries for experimental selection of higher-affinity binding proteins, loop remodeling, small-molecule ligand docking, design of ligand-binding proteins, and specificity redesign in DNA-binding proteins

Specialized Peptidoglycan Hydrolases Sculpt the Intra-bacterial Niche of Predatory Bdellovibrio and Increase Population Fitness

Bdellovibrio are predatory bacteria that have evolved to invade virtually all Gram-negative bacteria, including many prominent pathogens. Upon invasion, prey bacteria become rounded up into an osmotically stable niche for the Bdellovibrio, preventing further superinfection and allowing Bdellovibrio to replicate inside without competition, killing the prey bacterium and degrading its contents. Historically, prey rounding was hypothesized to be associated with peptidoglycan (PG) metabolism; we found two Bdellovibrio genes, bd0816 and bd3459, expressed at prey entry and encoding proteins with limited homologies to conventional dacB/PBP4 DD-endo/carboxypeptidases (responsible for peptidoglycan maintenance during growth and division). We tested possible links between Bd0816/3459 activity and predation. Bd3459, but not an active site serine mutant protein, bound β-lactam, exhibited DD-endo/carboxypeptidase activity against purified peptidoglycan and, importantly, rounded up E. coli cells upon periplasmic expression. A ΔBd0816 ΔBd3459 double mutant invaded prey more slowly than the wild type (with negligible prey cell rounding) and double invasions of single prey by more than one Bdellovibrio became more frequent. We solved the crystal structure of Bd3459 to 1.45 Å and this revealed predation-associated domain differences to conventional PBP4 housekeeping enzymes (loss of the regulatory domain III, alteration of domain II and a more exposed active site). The Bd3459 active site (and by similarity the Bd0816 active site) can thus accommodate and remodel the various bacterial PGs that Bdellovibrio may encounter across its diverse prey range, compared to the more closed active site that “regular” PBP4s have for self cell wall maintenance. Therefore, during evolution, Bdellovibrio peptidoglycan endopeptidases have adapted into secreted predation-specific proteins, preventing wasteful double invasion, and allowing activity upon the diverse prey peptidoglycan structures to sculpt the prey cell into a stable intracellular niche for replication

Uncovering cryptic evolutionary diversity in extant and extinct populations of the southern Australian arid zone Western and Thick-billed Grasswrens (Passeriformes: Maluridae: Amytornis)

Published online: 08 June 2013The Western and Thick-billed Grasswrens (Aves: Passeriformes: Maluridae:Amytornis textilis and A. modestus, respectively) exemplify issues surrounding the evolution, biogeography and conservation of Australia's arid and semi-arid zone fauna. The two species together have historically occurred across much of southern Australia. They showed high intraspecific taxonomic diversity and short range endemism but suffered high rates of recent anthropogenic extinction. Of 11 named and one un-named subspecies, five are extinct and three are vulnerable or critically endangered. To clarify taxonomic issues, and to understand their pre-extinction phylogeography and identify extant populations and taxa of conservation value, we sequenced ~1000 bp of the mtDNA ND2 gene from all extant populations and all but one extinct population. We confirmed reciprocal monophyly of A. modestus and A. textilis and identified strong phylogeographic structure associated with morphological divergence within each species. Populations of A. t. myall at the western edge of their range in South Australia may preserve “ghost” lineages of extinct subspecies from Western Australia as a result of ancient gene flow. Our results support recent taxonomic revisions, and highlight the critical importance of including samples of extirpated populations and extinct species to fully understand and interpret extant diversity. Conservation and management plans should recognise and seek to preserve the unique evolutionary diversity present in surviving populations.Jeremy J. Austin, Leo Joseph, Lynn P. Pedler, Andrew B. Blac

Poem

She is a small lady, 85 years old

From the Editors

As the Jefferson Forum embarks on its 11th issue a number of additions have beeninstituted. First, we are proud to announce new faculty collaborators with Dr. StevenHerrine, Dr. Danielle Duffy, Dr. Daniel Frisch, Dr. Anjali Avadhani, Dr. JosephDesimone and Dr. Edward Ruby. Our faculty has helped us with creating a new section of outstanding articles thatwe introduce in this issue. The “Best Of” designation allows us to highlight articlesthat were chosen by peer and faculty review as the best example of academic worksubmitted in each field of medicine. We hope that this addition will inspire moreresidents and faculty to get involved with the journal

Postoperative Adjuvant Chemotherapy or BCG for Colon Cancer: Results from NSABP Protocol C-01.

Data are presented from 1,166 patients with Dukes B and C carcinoma of the colon who were entered into the National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol C-01 between November 1977 and February 1983. Patients were randomized to one of three therapeutic categories: 1) no further treatment following curative resection (394 patients); 2) postoperative chemotherapy consisting of 5-fluorouracil, semustine, and vincristine (379 patients); or 3) postoperative BCG (393 patients). The average time on study was 77.3 months. A comparison between patients receiving postoperative adjuvant chemotherapy and those treated with surgery alone indicated that there was an overall improvement in disease-free survival (P = .02) and survival (P = .05) in favor of the chemotherapy-treated group. At 5 years of follow-up, patients treated with surgery alone were at 1.29 times the risk of developing a treatment failure and at 1.31 times the likelihood of dying as were similar patients treated with combination adjuvant chemotherapy. Comparison of the BCG-treated group with the group treated with surgery alone indicated that there was no statistically significant difference in disease-free survival (P = .09). There was, however, a survival advantage in favor of the BCG-treated group (P = .03). At 5 years of follow-up, patients randomized to the surgery-alone arm were at 1.28 times the risk of dying as were similar patients treated with BCG. Further investigation disclosed that this survival advantage in favor of BCG was a result of a diminution in deaths that were non-cancer related. When analyses were conducted on which events not related to cancer recurrence were eliminated, the survival difference between the BCG and control groups became nonsignificant (P = .40); the cumulative odds at 5 years decreased from 1.28 to 1.10. The findings from this study are the first from a randomized prospective clinical trial to demonstrate that a significant disease-free survival and survival benefit can be achieved with postoperative adjuvant chemotherapy in patients with Dukes B and C carcinoma of the colon who have undergone curative resection