Peptidyl alpha-keto amides have been synthesized and tested as inhibitors of the cysteine protease calpain. A stereospecific synthesis was devised in which Cbz-dipeptidyl-alpha-hydroxy amides were oxidized with TEMPO/hypochlorite to the corresponding alpha-keto amides. This oxidation was accomplished in good yields and without epimerization of the chiral center adjacent to the ketone. The potent inhibition of porcine calpain I by the L,L diastereomers, combined with the poor inhibition by the L,D diastereomers, established the requirement for the all-L stereochemistry of the active inhibitor. The early lead inhibitors were very hydrophobic and, therefore, poorly soluble in aqueous solutions. Using the stereospecific route, new compounds were prepared with polar groups at the C- and N-termini. These modifications resulted in more soluble inhibitors that were still potent inhibitors of calpain. Studies of the stability of these alpha-keto amides showed that absolute stereochemistry can be maintained in acidic and unbuffered environments but general base-catalyzed epimerization of the chiral center adjacent to the ketone occurred rapidly. The alpha-hydroxy precursors were inactive as inhibitors of calpain, which supports the hypothesis that the alpha-keto compounds reversibly form an enzyme-bound tetrahedral species that results from the nucleophilic addition of the catalytic thiol of calpain to the electrophilic ketone of the inhibitor.

Accurate and rapid diagnostic imaging is essential for the appropriate management of acute gastrointestinal conditions. Computed tomography (CT) is the modality most often used in this setting because of its widespread availability and the relative speed, ease, and uniformity with which evaluations can be performed. CT allows the diagnosis of a wide spectrum of acute gastrointestinal diseases with the adjustment of only a few variables in the acquisition protocol. For example, the contrast material volume, injection rate, and delay before image acquisition can be manipulated to enhance vascular or organ-specific contrast for myriad gastrointestinal diagnoses. Magnetic resonance (MR) imaging has similarly robust potential, although its integration into the acute care setting requires greater technical and logistical effort. Improved MR imaging sequences, advances in coil technology, streamlined imaging protocols, and increased technical and professional familiarity with the modality make it an increasingly attractive option when there is concern about patient radiation exposure or allergy to iodinated contrast material. A variety of acute abdominal conditions, including pancreatic and biliary tract trauma, choledocholithiasis, gallbladder disease, acute pancreatitis, and appendicitis can be rapidly and accurately demonstrated with MR imaging. MR imaging also can play a vital role in the follow-up assessment of treatment response and in the diagnosis of indeterminate findings at CT or ultrasonography. Nevertheless, incompatibility of patient monitoring devices with the MR magnet, lack of MR imaging system availability, and the acuity of illness may limit the use of the modality.

As laparoscopic adjustable gastric banding is increasingly used, more patients will present to the emergency department with complications of the procedure, particularly complications from band slippage. Because the consequences of slippage may require acute surgical intervention, it is imperative that the radiologist is familiar with the surgical technique to correctly position the band and the appearances of a gastric band when correctly and incorrectly positioned. Identification of the O sign on radiography can potentially aid the radiologist, surgeon, or emergency department physician in the early detection of gastric band slippage and appropriate patient triage.

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Optimal CT pulmonary angiography (CTPA) is a prerequisite for accurate diagnosis and management of suspected venous thromboembolic disease (VTE) in the emergency department (ED). However, a certain proportion of CTPA studies are diagnostically limited or non-diagnostic due to various technical causes. In this study, we analyze the incidence and cause of suboptimal CTPA studies in the ED and assess the need for additional imaging. Reports of 1444 consecutive CTPAs performed in an ED on adult patients over a 25-month period beginning November 30, 2011, were reviewed. The observed suboptimal CTPA rate was 4.2 % (60/1444). The most common causes of limited or non-diagnostic CTPA in the ED were related to timing of contrast bolus or IV infiltration (26/60, 43.4 %), respiratory motion (16/60, 26.7 %), multifactorial causes (10/60, 16.7 %), and patient motion (8/60, 13.3 %). Of the 60 studies included, only 7 patients (11.7 %) underwent additional diagnostic imaging during the same hospital visit for VTE, while 3 patients (5.0 %) underwent additional imaging for suspected VTE over the next 2 months. A total of 2/60 (3.4 %) patients had documented acute PE on additional imaging performed either on the same hospital visit or within 2 months. Regardless of the factors contributing to suboptimal CTPA, only a very small proportion of patients receive additional imaging to evaluate for VTE, either on the same visit or during the next 2 months (16.7 %, 10/60 patients). A small number (3.4 %) of these patients have documented acute PE within 2 months when additional imaging tests were performed.