Development of a Simple Model of Extrinsic Denervation of the Small Bowel in Mouse

Small bowel transplantation (SBT) is associated with poorly understood enteric dysfunction. The study of SBT in mice is hindered by the technical difficulty of orthotopic SBT in the mouse. Our aim was to develop an easy preparation of extrinsic denervation of the entire jejunoileum in mice as a model of orthotopic SBT. All neurolymphatic tissues accompanying the superior mesenteric artery (SMA) and vein (SMV) were ligated just distal to the middle colic vessels. The SMA and SMV were then stripped of investing adventitia, and the mesentery to jejunum and colon were transected radially. Jejunum and colon were not transected and reanastomosed. To confirm extrinsic denervation 1, 3, and 6 months later, segments of small bowel were stained for protein gene product 9.5 (PGP9.5) and tyrosine hydroxylase (TH). Tyrosine hydroxylase immunoreactive intensity was then quantified using a semiquantitative analysis. Immunohistochemical fluorescence showed persistence of PGP9.5 immunoreactivity confirming enteric nerves in jejunoileum; however, there was no TH immunoreactivity in jejunoileum in denervated mice despite the expected preservation of TH immunoreactivity in the still-innervated duodenum at 1 month. At 3 months, sparse immunoreactivity for TH was present, and by 6 months, reinnervation of TH-containing nerves appeared similar to controls. Quantification of intensity at each time-point further confirmed this trend. This technique in the mouse accomplishes a complete extrinsic denervation of jejunoileum early postoperatively (1 and 3 months); reinnervation occurs by 6 months. This is an easily learned murine model of orthotopic SBT. Presented at the American Gastroenterological Association during Digestive Disease Week in Los Angeles, CA, as a poster presentation on May 23 2006. Abstract published in GastroenterologyE 2006; 130:A604.     

Performance of Residents and Anesthesiologists in a Simulation-based Skill Assessment

Background: Anesthesiologists and anesthesia residents are expected to acquire and maintain skills to manage a wide range of acute intraoperative anesthetic events. The purpose of this study was to determine whether an inventory of simulated intraoperative scenarios provided a reliable and valid measure of anesthesia residents' and anesthesiologists' skill.

Methods: Twelve simulated acute intraoperative scenarios were designed to assess the performance of 64 residents and 35 anesthesiologists. The participants were divided into four groups based on their training and experience. There were 31 new CA-1, 12 advanced CA-1, and 22 CA-2/CA-3 residents as well as a group of 35 experienced anesthesiologists who participated in the assessment. Each participant managed a set of simulated events. The advanced CA-1 residents, CA-2/CA-3 residents, and 35 anesthesiologists managed 8 of 12 intraoperative simulation exercises. The 31 CA-1 residents each managed 3 intraoperative scenarios.

Results: The new CA-1 residents received lower scores on the simulated intraoperative events than the other groups of participants. The advanced CA-1 residents, CA-2/CA-3 residents, and anesthesiologists performed similarly on the overall assessment. There was a wide range of scores obtained by individuals in each group. A number of the exercises were difficult for the majority of participants to recognize and treat, but most events effectively discriminated among participants who achieved higher and lower overall scores.     

Calcaneal fractures

Fractures of the calcaneus generally occur in the event of high-energy trauma, resulting in complex, three-dimensionally oriented fracture patterns. Surgical management is generally indicated for displaced intra-articular fractures, which allows restoration of calcaneal height, width and overall morphology, in addition to the posterior facet articular surface where possible, and allows for a late in situ arthrodesis as a means of salvage in the event of posttraumatic arthritis. What follows is a brief discussion of our preferred methods in the diagnosis and management of calcaneal fractures.     

Fluoridated elastomers: effect on the microbiology of plaque.

The objective of this study was to investigate the effect of fluoridated elastomeric ligatures on the microbiology of local dental plaque in vivo. This randomized, prospective, longitudinal, clinical trial had a split-mouth crossover design. The subjects were 30 patients at the beginning of their treatment with fixed orthodontic appliances in the orthodontic departments of the Liverpool and the Sheffield dental hospitals in the United Kingdom. The study consisted of 2 experimental periods of 6 weeks with a washout period between. Fluoridated elastomers were randomly allocated at the first visit to be placed around brackets on tooth numbers 12, 11, 33 or 22, 21, 43. Nonfluoridated elastomers were placed on the contralateral teeth. Standard nonantibacterial fluoridated toothpaste and mouthwash were supplied. After 6 weeks (visit 2), the elastomers were removed, placed in transport media, and plated on agar within 2 hours. Nonfluoridated elastomers were placed on all brackets for 1 visit to allow for a washout period. At visit 3, fluoridated elastomers were placed on the teeth contralateral to those that received them at visit 1. At visit 4, the procedures at visit 2 were repeated. Samples were collected on visits 2 and 4. A logistic regression was performed, with the presence or absence of streptococcal or anaerobic growth as the dependent variable. A mixed-effects analysis of variance was carried out with the percentage of streptococcal or anaerobic bacterial count as the dependent variable. The only significant independent variables were the subject variable (P =<.001) for the percentage of streptococcal and anaerobic bacterial count and the visit variable for the percentage of streptococcal count (P =<.001). The use of fluoridated or nonfluoridated elastomers was not significant for percentage of either streptococcal (P =.288) or anaerobic count (P =.230). Fluoridated elastomers are not effective at reducing local streptococcal or anaerobic bacterial growth after a clinically relevant time in the mouth.     

Thrombotic Micro‐Angiopathy with Sirolimus‐Based Immunosuppression: Potentiation of Calcineurin‐Inhibitor‐Induced Endothelial Damage?

Thrombotic microangiopathy is a rare but important finding in the context of organ transplantation. Acute renal insufficiency in the setting of hemolysis and thrombocytopenia, a triad that constitutes 'hemolytic uremic syndrome', can be associated with, or triggered by, conditions such as verocytotoxin-producing Escherichia coli, viral infections, malignant hypertension, scleroderma, allograft rejection, lupus erythematosus, pregnancy, and medications including mitomycin C, calcineurin inhibitors, and oral contraceptives. After renal transplantation, it can occur, as either a de novo episode, or recurrent disease. Calcineurin inhibitors have long been associated with post-transplantation thrombotic microangiopathy. Sirolimus has been used as a primary immunosuppressant in patients transplanted with a history of earlier hemolytic-uremic syndrome, and also as rescue therapy in patients with calcineurin-inhibitor-associated thrombotic microangiopathy. We describe four cases where there was significant thrombotic microangiopathy in the context of contemporaneous or contiguous calcineurin inhibitor and sirolimus usage. As the intrarenal cyclosporin concentration is thought to be significantly elevated when cyclosporin and sirolimus are used together, this may explain these findings, and mandates caution in their co-administration.     

Camp Okizu: Preliminary Investigation of a Psychological Intervention for Siblings of Pediatric Cancer Patients

This research was conducted at a summer camp for siblings of children with cancer. The camp is designed to address emotional problems, provide peer interaction and validation, and bolster siblings' self-esteem. Standardized measures assessing posttraumatic stress, anxiety, quality of life, and self-esteem were administered to 77 siblings (ages 6-17) prior to attending camp and again 3 months after camp. From pre- to post-camp, the siblings reported statistically significant decreases in symptoms of posttraumatic stress and anxiety, and statistically significant improvements in quality of life and self-esteem. These preliminary findings are encouraging and suggest the value of camp as a psychological intervention and provide a model for other pediatric cancer facilities designing intervention programs for siblings.     

Myocardial perfusion SPECT reconstruction: Receiver operating characteristic comparison of CAD detection accuracy of filtered backprojection reconstruction with all of the clinical imaging information available to readers and solely stress slices iteratively reconstructed with combined compensation

BACKGROUND: Past receiver operating characteristic (ROC) studies have demonstrated that single photon emission computed tomography (SPECT) perfusion imaging by use of iterative reconstruction with combined compensation for attenuation, scatter, and detector response leads to higher area under the ROC curve (A(z)) values for detection of coronary artery disease (CAD) in comparison to the use of filtered backprojection (FBP) with no compensations. A new ROC study was conducted to investigate whether this improvement still holds for iterative reconstruction when observers have available all of the imaging information normally presented to clinical interpreters when reading FBP SPECT perfusion slices. METHODS AND RESULTS: A total of 87 patient studies including 50 patients referred for angiography and 37 patients with a lower than 5% likelihood for CAD were included in the ROC study. The images from the two methods were read by 4 cardiology fellows and 3 attending nuclear cardiologists. Presented for the FBP readings were the short-axis, horizontal long-axis, and vertical long-axis slices for both the stress and rest images; cine images of both the stress and rest projection data; cine images of selected cardiac-gated slices; the CEQUAL-generated stress and rest polar maps; and an indication of patient gender. This was compared with reading solely the iterative reconstructed stress slices with combined compensation for attenuation, scatter, and resolution. With A(z) as the criterion, a 2-way analysis of variance showed a significant improvement in detection accuracy for CAD for the 7 observers (P = .018) for iterative reconstruction with combined compensation (A(z) of 0.895 +/- 0.016) over FBP even with the additional imaging information provided to the observers when scoring the FBP slices (A(z) of 0.869 +/- 0.030). When the groups of 3 attending physicians or 4 cardiology fellows were compared separately, the iterative technique was not statistically significantly better; however, the A(z) for each of the 7 observers individually was larger for iterative reconstruction than for FBP. Compared with results from our previous studies, the additional imaging information did increase the diagnostic accuracy of FBP for CAD but not enough to undo the statistically significantly higher diagnostic accuracy of iterative reconstruction with combined compensation. CONCLUSIONS: We have determined through an ROC investigation that included two classes of observers (experienced attending physicians and cardiology fellows in training) that iterative reconstruction with combined compensation provides statistically significantly better detection accuracy (larger A(z)) for CAD than FBP reconstructions even when the FBP studies were read with all of the extra clinical nuclear imaging information normally available.     

Ventilation imaging of the lung: Comparison of hyperpolarized helium-3 MR imaging with Xe-133 scintigraphy

RATIONALE AND OBJECTIVES: To compare hyperpolarized helium-3 (HHe) magnetic resonance imaging (MRI) of the lung with standard Xe-133 lung ventilation scintigraphy. MATERIALS AND METHODS: We performed a retrospective review of 15 subjects who underwent HHe MRI and Xe-133 lung ventilation imaging. Coronal MRI sections were acquired after a single inhalation of HHe gas, and standard posterior planar lung ventilation scintigraphy was performed during continuous breathing of Xe-133 gas. The first breath scintigram of each patient was compared with a composite MR image composed of the sum of the individual MR images and with the individual helium-3 MR images. Ventilation defects on the two imaging modalities were compared for size, conspicuity, and concordance in presence and location. Assessment was done separately for each of four lung quadrants. RESULTS: Comparing the composite HHe MR images with Xe-133 scintigraphy, ventilation defect size, conspicuity and concordance were the same in 67% (40/60), 63% (38/60), and 62% (37/60) quadrants, respectively. Comparing the individual HHe MR image sections with the Xe-133 ventilation scan, there was concordance between the ventilation defects in 27% (16/60) of quadrants. More defects were identified on the individual HHe MR images in 62% (37/60) of quadrants. CONCLUSION: There was good agreement between composite HHe MR image and first breath Xe-133 scintigraphic images, supporting the widely held assumption that HHe MRI likely depicts first breath lung ventilation.