Structural studies of ß-turn-containing peptide catalysts for atroposelective quinazolinone bromination.

We describe herein a crystallographic and NMR study of the secondary structural attributes of a ß-turn-containing tetra-peptide, Boc-Dmaa-D-Pro-Acpc-Leu-NMe2, which was recently reported as a highly effective catalyst in the atroposelective bromination of 3-arylquinazolin-4(3H)-ones. Inquiries pertaining to the functional consequences of residue substitutions led to the discovery of a more selective catalyst, Boc-Dmaa-D-Pro-Acpc-Leu-OMe, the structure of which was also explored. This new lead catalyst was found to exhibit a type I'ß-turn secondary structure both in the solid state and in solution, a structure that was shown to be an accessible conformation of the previously reported catalyst, as well.

In vivo determination of urinary stone composition using dual energy computerized tomography with advanced post-acquisition processing.

PURPOSE: We assessed whether dual energy computerized tomography with advanced post-image processing can accurately differentiate urinary calculi composition in vivo. MATERIALS AND METHODS: A total of 25 patients scheduled to undergo ureteroscopic/percutaneous nephrolithotomy were prospectively identified. Dual energy computerized tomography was performed using 64-slice multidetector computerized tomography. Novel post-processing (DECTSlope) used pixel by pixel analyses to generate data sets grayscale encoding ratios of relative differences in attenuation of low (DECT80 kVp) and high energy (DECT140 kVp) series. Surgical extraction and Fourier spectroscopy resulted in 82 calculi. Of these stones 51 showed minor admixtures (uric acid, ammonium urate, struvite, calcium oxalate monohydrate and brushite) and 31 were polycrystalline (mixtures of calcium oxalate monohydrate/dihydrate and calcium phosphate). Analyses identified stone clusters of equal composition and distinct attenuation descriptors on DECT140 kVp, DECT80 kVp and DECTSlope. Iterative cross-validation of the 3 dual energy computerized tomography data sets was used to identify characteristic attenuation limits for each stone type. RESULTS: Attenuatio profiles showed substantial overlap among various stones on DECT140 kVp (uric acid 427.3±168.1 HU, ammonium urate 429.9±99.7 HU, struvite 480.2±123.5 HU, calcium oxalate monohydrate 852.4±301.4 HU, brushite 863.7±180.1 HU and polycrystalline 858.1±210.5 HU) and on DECT80 kVp (uric acid 493.6±182.8 HU, ammonium urate 591.5±157.9 HU, struvite 712.4±173.9 HU, calcium oxalate monohydrate 1,240.5±494.7 HU, brushite 1,532.1±273.1 HU and polycrystalline 1,358.7±316.8 HU). Statistically spectral separation was not sufficient to characterize stones unambiguously based on DECT140 kVp/DECT80 kVp attenuation. Analysis of attenuation showed sufficient spectral separation on DECTSlope (uric acid 14.9±10.9 U, ammonium urate 56.1±1.8 U, struvite 42.7±1.4 U, calcium oxalate monohydrate 62.8±1.8 U and brushite 113.2±5.3 U). Polycrystalline stones (51.8±3.7 U) overlapped with struvite and ammonium urate stones. This overlap was resolved as all struvite/ammonium urate stones measured 900 HU or less and all polycrystalline stones measured more than 900 HU on DECT80 kVp. CONCLUSIONS: Dual energy computerized tomography with novel post-processing allows accurate discrimination among main subtypes of urinary calculi in vivo and, thus, may have implications in determining the optimum clinical treatment of urinary calculi from a noninvasive, preoperative radiological assessment.

Percutaneous biopsy of periarterial soft tissue cuffs in the diagnosis of pancreatic carcinoma.

Pancreatic cancer may present on computed tomography (CT) as an isolated cuff of tumor surrounding the superior mesenteric artery (SMA) or celiac trunk, without an identifiable pancreatic mass. We reviewed our experience with imaging-guided biopsy of the soft tissue cuff in this patient group. A retrospective review of our interventional database identified 163 patients referred for biopsy of suspected pancreatic carcinoma. Of these, eight patients underwent biopsy of an isolated cuff of soft tissue encasing the SMA (n = 6) or celiac trunk (n = 2). None of these eight patients had an identifiable pancreatic mass. The mean width of tissue cuff biopsied was 1.3 cm (range, 0.9-2.0 cm). Nine imaging-guided biopsies were performed in eight patients. Five biopsies were performed with color Doppler ultrasound and four with CT fluoroscopy. There was a median of two needle passes per procedure (range, 1-4). In six cases, a diagnosis of pancreatic adenocarcinoma was made at the first biopsy session. In one patient, ultrasound-guided biopsy was negative, but subsequent CT-guided biopsy was positive. In one additional patient with chronic pancreatitis, biopsy revealed benign fibrous tissue. There were no procedure-related complications. In patients with suspected pancreatic cancer (but without a focal parenchymal mass), imaging-guided biopsy of isolated periarterial tissue cuffs of tumor is accurate and safe.

Preoperative evaluation of potential renal donors using multidetector CT.

Preoperative knowledge of vascular anatomy and parenchymal disease is critical in patients undergoing laparoscopic donor nephrectomy. Multidetector computed tomography represents a substantial improvement in technology that lends itself to the comprehensive evaluation of renal donors. We describe and illustrate our computed tomographic technique in patients considering a donor nephrectomy.

Evaluation of the liver for metastatic disease.

Metastatic disease of the liver accounts for the vast majority of detected liver masses. In patients with suspected metastatic disease, cross-sectional imaging with ultrasound (US), computed tomography (CT), or magnetic resonance imaging (MRI) is critical. In the group of patients undergoing evaluation for hepatic surgery, it is even more important to optimize techniques to detect and localize metastatic disease. With improvements in technology and contrast agents, there are several approaches to imaging the liver for metastatic disease. The approach will vary by institution. This article will attempt to provide an overview of the general issues relevant to imaging metastatic disease, highlight the advantages and disadvantages of one modality compared to another, and illustrate the appearance of metastases using US, CT, and MRI.

Sonographically guided thrombin injection of iatrogenic femoral pseudoaneurysms: further experience of a single institution.

OBJECTIVE: In September 1998, we began to treat iatrogenic femoral pseudoaneurysms with direct thrombin injection under sonographic guidance. Our purpose was to determine the success and complication rate of this technique. SUBJECTS AND METHODS: We treated 114 consecutive patients who had iatrogenic femoral pseudoaneurysms using direct thrombin injection. A 22-gauge spinal needle was placed into the pseudoaneurysm lumen with sonographic guidance, and bovine or human thrombin (mean dose, 306 U; range, 50--1600 U) was injected under continuous color Doppler sonographic visualization. Distal pulses were monitored. Patient demographics, clinical variables, and pseudoaneurysm characteristics were collected. RESULTS: One hundred three (90%) of 114 patients had pseudoaneurysm thrombosis after the first procedure. Of the remaining 11 patients who required a second procedure 1 day later, thrombosis occurred in seven (64%) of 11. Thus, the overall success rate was 96% (110/114). Of the patients who required one injection, the mean thrombosis time was 12 sec (range, 3--90 sec). Three (3%) of 114 patients required conscious sedation. Of the patients with successful thrombosis, 24-hr follow-up sonograms showed no recurrent pseudoaneurysm. Four patients (4%) had potential complications: a "blue toe" 15 hr after the thrombin injection that resolved spontaneously, a groin abscess, leg ischemia that resolved spontaneously after 4 hr, and crampy buttock pain that resolved spontaneously. CONCLUSION: For the treatment of iatrogenic femoral pseudoaneurysms, thrombin injection under sonographic guidance is a quick and effective method of therapy. Failures and complications are infrequent. At our institution, sonographically guided thrombin injection has replaced compression repair.

CT fluoroscopy--guided interventional procedures: techniques and radiation dose to radiologists.

PURPOSE: To determine the radiation dose to radiologists who perform computed tomographic (CT) fluoroscopic interventional procedures by using a quick-check method and a low-milliampere technique. MATERIALS AND METHODS: Two hundred twenty CT fluoroscopy--guided interventional procedures were performed in 189 patients. Procedures included 57 spinal injections, 17 spinal biopsies, 24 chest biopsies, 20 abdominal aspirations, 44 abdominal biopsies, and 58 abdominal drainages. Procedure details were prospectively recorded and included site, depth, target diameter, milliampere value, kilovolt peak, fluoroscopic time, and CT technique (continuous CT fluoroscopy, quick-check method, or a combination of these techniques). An individual collar and finger radiation detector were worn by each radiologist during each procedure to determine the dose per procedure. RESULTS: The quick-check technique was performed in 191 (87%) of 220 procedures. Four procedures were performed with continuous CT fluoroscopy, and a combination technique was used for 25 (11%) procedures. The overall mean CT fluoroscopic time was 17.9 seconds (range, 1.2--101.5 seconds). The mean milliampere value was 13.2 mA (range, 10--50 mA). The overall mean radiologist radiation dose per procedure was 2.5 mrem (0.025 mSv) (whole body). Individual procedure doses ranged from 0.66 to 4.75 mrem (0.007--0.048 mSv). The finger radiation dose was negligible. CONCLUSION: By using a low-milliampere technique and the quick-check method, CT fluoroscopic time and radiation exposure can be minimized.

An electronic device for needle placement during sonographically guided percutaneous intervention.

An electronic device for guiding needle placement during sonographically directed percutaneous intervention was tested in a phantom and then in patients. In the phantom, targeting accuracy was similar for use of the needle guide alone, the needle guide with the device, and freehand techniques with the device, but all were superior to the freehand technique alone (P <.001). In 34 (79%) of 43 patients, the device worked well.

Breath-hold three-dimensional CT of the liver with multi-detector row helical CT.

PURPOSE: To compare image quality on transverse source images and coronal and sagittal reformations to determine the feasibility of using single-breath-hold three-dimensional liver computed tomography (CT) with multi-detector row helical CT in patients suspected of having hepatic metastases. MATERIALS AND METHODS: Fifty-three patients underwent the protocol. Coronal and sagittal reformations were constructed. Images were reviewed for duration of scan acquisition and length and adequacy of z-axis coverage. Reformations were scored for visualization of portal and hepatic vein branches, liver edge sharpness, cardiac pulsation and respiratory motion artifacts, noise due to mottle, and overall impression. RESULTS: Mean z-axis coverage was 207 mm +/- 33 (SD) (range, 145-280 mm), with a mean acquisition time of 10.96 seconds +/- 1.78 (range, 7.73-14.93 seconds). In 44 (83%) patients, the entire liver was imaged on a single helical scan. Artifact from cardiac motion was not identified on the transverse source images in any patient but was identified on coronal images in eight (15%) and on sagittal images in seven (13%). Similarly, noise due to mottle was not identified on the transverse source images but was identified on coronal images in seven (13%) patients and on sagittal images in six (11%). CONCLUSION: It is feasible to perform single-breath-hold three-dimensional liver CT with multi-detector row helical CT technology. Reformations provide a unique perspective with which to view the liver and may improve diagnostic capacity.

Quantitative and qualitative evaluation of volume of low osmolality contrast medium needed for routine helical abdominal CT.

OBJECTIVE: The purpose of our study was to determine the minimum optimal dose of IV contrast medium for helical CT that can preserve image quality while reducing cost. SUBJECTS AND METHODS: Four hundred sixty-three patients from six centers were enrolled in a prospective trial in which patients were randomized into one of four weight-based dose categories of iopromide, 300 mg I/mL: 1.25, 1.50, 1.75, and 2.0 mL/kg. Six of 463 patients were excluded from analysis. A radiologist at each center who was unaware of the volume of contrast medium administered determined whether the scans were acceptable. The responses were analyzed by dose, in aggregate, and by weight. Enhancement values (in Hounsfield units) in regions of interest in the liver, pancreas, aorta, and kidneys were obtained at a single time during the scan. The participating radiologist was unaware of these values. Finally, three additional nonparticipating site observers assessed the images for acceptability, diagnostic quality, and overall level of confidence. A cost model comparing incurred charges in using 150 or 100 mL, or 1.5 mL/kg, of low osmolality contrast medium was developed from experience in an additional 303 patients. RESULTS: We found no clinically significant difference in acceptability of scans at doses greater than 1.5 mL/kg. However, significant variability occurred among the centers. The use of 1.5 mL/kg led to a savings of $9927.16 for 303 patients when compared with the use of 150 mL at list price. The cost is the same for 1.5 mL/kg or use of 100 mL of contrast medium. CONCLUSION: A weight-based dose at 1.5 mL/kg of low osmolality contrast medium can provide acceptable scans in most patients, with a significant cost savings.

Vaginitis emphysematosa: CT and review of the literature.

OBJECTIVE: This report describes the CT appearance of vaginitis emphysematosa. CONCLUSION: Vaginitis emphysematosa is characterized by gas-filled cysts in the vaginal wall, in a pattern similar to pneumatosis of the intestines or bladder. This bacterial vaginitis is benign and self-limited and does not signify the presence of tissue necrosis or life-threatening infection.

Neoadjuvant chemoradiation for localized adenocarcinoma of the pancreas.

BACKGROUND: The use of neoadjuvant (preoperative) chemoradiotherapy (CRT) for pancreatic cancer has been advocated for its potential ability to optimize patient selection for surgical resection and to downstage locally advanced tumors. This article reports our experience with neoadjuvant CRT for localized pancreatic cancer. METHODS: Since 1995, 111 patients with radiographically localized, pathologically confirmed pancreatic adenocarcinoma have received neoadjuvant external beam radiation therapy (EBRT; median, 4500 cGy) with 5-flourouracil-based chemotherapy. Tumors were defined as potentially resectable (PR, n = 53) in the absence of arterial involvement and venous occlusion and locally advanced (LA, n = 58) with arterial involvement or venous occlusion by CT. RESULTS: Five patients (4.5%) were not restaged due to death (n = 3) or intolerance of therapy (n = 2). Twenty-one patients (19%) manifested distant metastatic disease on restaging CT. Twenty-eight patients with initially PR tumors (53%) and 11 patients with initially LA tumors (19%) were resected after CRT. Histologic examination revealed significant fibrosis in all resected specimens and two complete responses. Surgical margins were negative in 72%, and lymph nodes were negative in 70% of resected patients. Median survival in resected patients has not been reached at a median follow-up of 16 months. CONCLUSIONS: Neoadjuvant CRT provided an opportunity for patients with occult metastatic disease to avoid the morbidity of resection and resulted in tumor downstaging in a minority of patients with LA tumors. Survival after neoadjuvant CRT and resection appears to be at least comparable to survival after resection and adjuvant (postoperative) CRT.

Staging of pancreatic cancer before and after neoadjuvant chemoradiation.

Neoadjuvant chemoradiation therapy is used at many institutions for treatment of localized adenocarcinoma of the pancreas. Accurate staging before neoadjuvant therapy identifies patients with distant metastatic disease, and restaging after neoadjuvant therapy selects patients for laparotomy and attempted resection. The aims of this study were to (1) determine the utility of staging laparoscopy in candidates for neoadjuvant therapy and (2) evaluate the accuracy of restaging CT following chemoradiation. Staging laparoscopy was performed in 98 patients with radiographically potentially resectable (no evidence of arterial abutment or venous occlusion) or locally advanced (arterial abutment or venous occlusion) adenocarcinoma of the pancreas. Unsuspected distant metastasis was identified in 8 (18%) of 45 patients with potentially resectable tumors and 13 (24%) of 55 patients with locally advanced tumors by CT. Neoadjuvant chemoradiation therapy and restaging CT were completed in a total of 103 patients. Thirty-three patients with potentially resectable tumors by restaging CT underwent surgical exploration and resections were performed in 27 (82%). Eleven (22%) of 49 patients with locally advanced tumors by restaging CT were resected, with negative margins in 55%; the tumors in these 11 patients had been considered locally advanced because of arterial involvement on restaging CT. Staging laparoscopy is useful for the exclusion of patients with unsuspected metastatic disease from aggressive neoadjuvant chemoradiation protocols. Following neoadjuvant chemoradiation, restaging CT guides the selection of patients for laparotomy but may overestimate unresectability to a greater extent than does prechemoradiation CT.

Nonenhanced helical CT and US in the emergency evaluation of patients with renal colic: prospective comparison.

PURPOSE: To compare nonenhanced helical computed tomography (CT) with ultrasonography (US) for the depiction of urolithiasis. MATERIALS AND METHODS: During 9 months, 45 patients (mean age, 44 years; mean weight, 92.5 kg) prospectively underwent both nonenhanced helical CT (5-mm collimation; pitch of 1.5) and US of the kidneys, ureters, and bladder. US evaluation included a careful search for ureteral calculi. Presence of calculi and obstruction and incidental diagnoses were recorded. Clinical, surgical, and/or imaging follow-up data were obtained in all patients. The McNemar test was used to compare groups. RESULTS: Diagnoses included 23 ureteral calculi and one each of renal cell carcinoma, appendicitis, ureteropelvic junction obstruction, renal subcapsular hematoma, cholelithiasis, medullary calcinosis, and myelolipoma. CT depicted 22 of 23 ureteral calculi (sensitivity, 96%). US depicted 14 of 23 ureteral calculi (sensitivity, 61%). Differences in sensitivity were statistically significant (P: =.02). Specificity for each technique was 100%. When modalities were compared for the detection of any clinically relevant abnormality (eg, unilateral hydronephrosis and/or urolithiasis in patients with an obstructing calculus), sensitivities of US and CT increased to 92% and 100%, respectively. One case of appendicitis was missed at US, whereas medullary calcinosis and myelolipoma were missed at CT. CONCLUSION: Nonenhanced CT has a higher sensitivity for the detection of ureteral calculi compared with US.

Detection of hepatic lesions in candidates for surgery: comparison of ferumoxides-enhanced MR imaging and dual-phase helical CT.

OBJECTIVE: The purpose of this study was to compare the use of phased array MR imaging of the liver at 1.5 T with and without ferumoxides with dual-phase helical CT for the detection of hepatic lesions in candidates for hepatic surgery. SUBJECTS AND METHODS: Patients with known or suspected hepatic lesions who were eligible for surgery underwent dual-phase helical CT at 20 and 70 sec after the start of contrast material injection and phased array MR imaging using fast spin-echo T2-weighted imaging and gradient-echo T1-weighted imaging before and after ferumoxides infusion of 0.56 mg of iron per kilogram of body weight. Three observers who were unaware of the surgical findings separately reviewed the CT scans and unenhanced and enhanced MR images of 24 patients who completed the protocol. The observers' findings were compared with results obtained at surgery using intraoperative sonography and having histopathologic confirmation. Statistical analysis was performed using a segment-by-segment analysis. RESULTS: Eighty-two lesions were found at surgery. The sensitivity of CT, unenhanced MR imaging, and enhanced MR imaging for blinded observers was 60.4%, 62.0%, and 68.2%, respectively. The specificity was 89.2%, 81.9%, and 81.6%, respectively. Five lesions in three patients were not detected preoperatively using any of the techniques. MR imaging found additional lesions not detected on CT in four patients; CT detected one additional lesion not seen on MR imaging. CONCLUSION: Ferumoxides-enhanced MR imaging of the liver shows a trend toward increased sensitivity compared with dual-phase helical CT. Specificity of helical CT was superior to that of enhanced MR imaging for most observers.

Value of prone positioning in the ultrasonographic diagnosis of gallstones: prospective study.

To determine prospectively the value of prone/postprone positioning in the sonographic detection of gallstones, 682 patients were scanned in the recumbent, erect, and prone or postprone positions. The gallbladder was evaluated for an intraluminal hyperechoic focus, shadowing, and gravitational dependence and was identified in 679 patients. Among these, 28% had cholelithiasis. In five cases, prone positioning alone revealed gallstones. In 11 of 140 cases, gravitational dependence was only seen with prone scanning. The gallbladder was seen more frequently when the patients were prone than erect. Prone or postprone scanning is a useful supplement to the gallbladder examination, allowing increased demonstration of gravitational dependence and increased stone detection.

Use of fibrin sealant as a hemostatic agent after liver biopsy in swine.

PURPOSE: To determine whether fibrin sealant injected into the tract created by liver biopsy can be used to decrease postprocedural bleeding. An innovative delivery system was used to deploy the fibrin sealant. MATERIALS AND METHODS: Fibrin sealant is a hemostatic agent consisting of a suspension of fibrinogen and thrombin. A delivery system was devised whereby fibrin sealant could be injected into the tract created by liver biopsy. Thirty swine were randomized into three groups: control (n = 10), heparin (n = 10), and warfarin (n = 10). Each swine underwent laparotomy and was randomized to undergo three to five open liver biopsies with either a 14-gauge cutting needle in conjunction with the fibrin sealant device or a standard 14-gauge cutting needle alone. Forty-seven biopsy procedures were performed with the device; 64 biopsy procedures were performed without the device. Immediate blood loss per biopsy (mL) was estimated based on the size of the blood stain on a sponge. Specimens were assessed for sample size. RESULTS: Immediate blood loss with and without the device, respectively, was: control, 0.1 mL, 5.4 mL; heparin, 0 mL, 7 mL; warfarin, 0.1 mL, 9.3 mL. These differences were significant (P < .01) for each group of swine. In 43 of 47 biopsies (91%), the device functioned without difficulty. There was no difference in sample size when the device was used. CONCLUSIONS: The fibrin sealant device is effective in reducing bleeding after open liver biopsy in anticoagulated and nonanticoagulated swine. The promising results suggest that a trial of percutaneous liver biopsy in swine should be considered.

Transjugular intrahepatic portosystemic shunts (TIPS): effects of respiratory state and patient position on the measurement of Doppler velocities.

OBJECTIVE: The purpose of this prospective study was to examine the effects of patient position and respiratory state on the measurements of Doppler velocities in transjugular intrahepatic portosystemic shunts. SUBJECTS AND METHODS: Thirty-eight transjugular intrahepatic portosystemic shunts in 34 consecutive patients were studied using Doppler sonography. Peak velocities were measured in the mid shunt with the patient in three positions (supine, sitting upright, and left lateral decubitus) and two respiratory states (deep inspiration and quiet respiration). A mixed linear regression model was used to assess statistically significant differences among the six velocity measurements. RESULTS: Peak velocities in the mid stent averaged 22 cm/sec greater in quiet respiration than in deep inspiration, which was a significant difference (p < 0.00001). Differences in velocities in the three patient positions were not significant (p = 0.53). Using 90-190 cm/sec as the normal range, the peak velocity shifted from normal to abnormal levels by changing respiratory state in 17 (45%) of 38 studies. Using 60 cm/sec as the lower normal limit, the peak velocity fell below the normal range with inspiration in 10 (26%) of 38 studies. In 12 (32%) of 38 studies, a decline in peak velocity exceeding 50 cm/sec could be induced by inspiration. CONCLUSION: Peak systolic velocity in transjugular intrahepatic portosystemic shunts is substantially altered by the respiratory state of the patient at the time of the measurement, but not by the patient position. Respiratory state must be taken into account in the interpretation of peak velocity for shunt stenosis.

Partial NMR assignments for uniformly (13C, 15N)-enriched BPTI in the solid state.

We demonstrate that high-resolution multidimensional solid state NMR methods can be used to correlate many backbone and side chain chemical shifts for hydrated micro-crystalline U-13C,15N Basic Pancreatic Trypsin Inhibitor (BPTI), using a field strength of 800 MHz for protons, magic angle sample spinning rates of 20 kHz and proton decoupling field strengths of 140 kHz. Results from two homonuclear transfer methods, radio frequency driven dipolar recoupling and spin diffusion, were compared. Typical 13C peak line widths are 0.5 ppm, resulting in Calpha-Cbeta and Calpha-CO regions that exhibit many resolved peaks. Two-dimensional carbon-carbon correlation spectra of BPTI have sufficient resolution to identify and correlate many of the spin systems associated with the amino acids. As a result, we have been able to assign a large number of the spin systems in this protein. The agreement between shifts measured in the solid state and those in solution is typically very good, although some shifts near the ion binding sites differ by at least 1.5 ppm. These studies were conducted with approximately 0.2 to 0.4 micromol of enriched material; the sensitivity of this method is apparently adequate for other biological systems as well.