Structural insights into the ene-reductase synthesis of profens.

Reduction of double bonds of α,ß-unsaturated carboxylic acids and esters by ene-reductases remains challenging and it typically requires activation by a second electron-withdrawing moiety, such as a halide or second carboxylate group. We showed that profen precursors, 2-arylpropenoic acids and their esters, were efficiently reduced by Old Yellow Enzymes (OYEs). The XenA and GYE enzymes showed activity towards acids, while a wider range of enzymes were active towards the equivalent methyl esters. Comparative co-crystal structural analysis of profen-bound OYEs highlighted key interactions important in determining substrate binding in a catalytically active conformation. The general utility of ene reductases for the synthesis of (R)-profens was established and this work will now drive future mutagenesis studies to screen for the production of pharmaceutically-active (S)-profens.

Acute rejection following lung transplantation: limitations in accuracy of thin-section CT for diagnosis.

PURPOSE: To evaluate the sensitivity, specificity, predictive values, and accuracy of thin-section computed tomography (CT) for the diagnosis of acute rejection following lung transplantation and to determine whether any individual CT abnormalities are associated with histopathologically proved acute rejection. MATERIALS AND METHODS: Thin-section CT studies from 64 lung transplant recipients were retrospectively reviewed. CT studies were temporally correlated with various grades of biopsy-proved acute rejection (n = 34); 30 other CT studies were from a control group with no histopathologic evidence of acute rejection. Acute rejection was diagnosed as present or absent, and the diagnostic was calculated. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CT for the diagnosis of acute rejection were as follows: 35%, 73%, 60%, 50%, 53%, respectively. No individual CT finding was significantly associated with acute rejection. The sensitivity of CT for the detection of various grades of acute rejection was 17% for grade A1, 50% for grade A2, and 20% for grade A3. The combination of volume loss and septal thickening, with or without pleural effusion, was never seen in the absence of acute rejection. CONCLUSION: Thin-section CT has limited accuracy for the diagnosis of acute rejection following lung transplantation, and no individual CT finding is significantly associated with this diagnosis.

Comparison between MR imaging and 99mTc MIBI scintigraphy in the evaluation of recurrent of persistent hyperparathyroidism.

PURPOSE: To compare the sensitivity and positive predictive value of magnetic resonance (MR) imaging and technetium 99m 2-methoxyisobutyl-isonitrile (MIBI) scintigraphy for the detection of hyperfunctioning parathyroid tissue when used alone and in combination in a large patient population with recurrent or persistent hyperparathyroidism (HPT). MATERIALS AND METHODS: In 98 consecutive patients with biochemically proved recurrent or persistent HPT after surgery, MR imaging and 99mTc MIBI study findings were retrospectively reviewed and compared with surgical and histopathologic findings. The sensitivity and positive predictive value of MR imaging and 99mTc MIBI scintigraphy were compared with each other and in combination. RESULTS: In these patients, 130 abnormal parathyroid glands were identified at surgery. The sensitivity and positive predictive value of MR imaging were 82% (95% CI: 75%, 89%) and 89%, respectively; those for (99m)Tc MIBI scintigraphy were 85% (95% CI: 79%, 91%) and 89%. No significant difference was found between MR imaging and 99mTc MIBI scintigraphy for sensitivity (P =.7). The sensitivity and positive predictive value for the detection of abnormal parathyroid tissue on a per-gland basis increased to 94% (95% CI: 90%, 98%) and 98%, respectively, when only one of the two tests was required to be positive. CONCLUSION: MR imaging and 99mTc MIBI scintigraphy have similarly good sensitivity and positive predictive value for the detection of hyperfunctioning parathyroid tissue in patients after surgery. The combination of the two tests provided a substantial increase in sensitivity and positive predictive value.

Identification of pulmonary vein stenosis after radiofrequency ablation for atrial fibrillation using MRI.

Pulmonary vein stenosis is one of the frequent complications after radiofrequency ablation for atrial fibrillation. MRI plays an important role in depicting the pathoanatomic structure of the pulmonary veins, and measuring the blood flow velocity in the pulmonary veins before and after therapy, and is superior to transesophageal echocardiography for this purpose.

Early bronchiolitis obliterans following lung transplantation: accuracy of expiratory thin-section CT for diagnosis.

PURPOSE: To evaluate the accuracy of thin-section computed tomography (CT) with expiratory scans in diagnosing early bronchiolitis obliterans after lung transplantation. MATERIALS AND METHODS: Thin-section CT scans were reviewed by two observers blinded to the diagnoses in seven consecutive lung transplant recipients with histopathologically proved bronchiolitis obliterans (group A) and 21 with normal biopsy findings (group B). All patients had normal biopsy and stable pulmonary function test (PFT) results 2-36 weeks prior to CT. Patients with normal biopsy results were placed into subgroups based on abnormal (group B1) or stable (group B2) PFT results. Air-trapping extent on expiratory scans was scored on a 24-point scale. RESULTS: The mean air-trapping score in group A (6.6) was not significantly different from that in group B (4.5, P =. 17). The air-trapping score was significantly higher in groups A and B1 than in group B2 (6.2 and 2.6, respectively; P =.03). The frequency of an air-trapping score of 3 or more in groups A and B1 was significantly higher than that in group B2 (P =.03). By using a score of 3 or more to indicate air trapping, the sensitivity of expiratory CT was 74%, specificity was 67%, and accuracy was 71%. CONCLUSION: Thin-section CT, including expiratory scans, is of limited accuracy in diagnosing early bronchiolitis obliterans after lung transplantation.

Low-dose, dynamic, expiratory thin-section CT of the lungs using a spiral CT scanner.

Seventeen patients with lung transplants were evaluated with inspiratory, postexpiratory, and low-dose, dynamic expiratory thin-section computed tomography (CT). Region of interest measurements were performed on inspiration and expiration images with both techniques, and mean lung attenuation changes between inspiration and expiration images were calculated and compared. Dynamic expiratory thin-section CT resulted in a significantly greater increase in lung attenuation than postexpiratory thin-section CT. Dynamic expiratory thin-section CT may prove useful in the evaluation of patients with lung diseases characterized by air flow obstruction with little increase in patient radiation dose.

Incidental detection of thoracic sarcoidosis on whole-body 18fluorine-2- fluoro-2-deoxy-D-glucose positron emission tomography.

18 Fluorine-2- Fluoro-2-Deoxy-D-Glucose positron emission tomography (18FDG PET) allows imaging of sites with increased metabolic activity. Increased metabolic activity in mediastinal nodes in sarcoidosis has been described. We report the prospective diagnosis of thoracic sarcoidosis on 18FDG PET based on extensive, peripheral, upper lobe parenchymal, and mediastinal nodal tracer uptake.

Three-dimensional MR imaging of pulmonary vessels and parenchyma with NC100150 injection (Clariscan).

The influence of increasing doses of NC100150 Injection (Clariscantrade mark) and echo times on visualization of pulmonary vessels and parenchyma was evaluated. The effects of 0.5, 1, 2, 4, and 8 mg Fe/kg NC100150 Injection and echo times (TE) of 1.1, 1.8, 2. 2, and 4.3 msec were determined in six dogs using breath-hold three-dimensional (3D) spoiled gradient-echo magnetic resonance (MR) sequence. At 2 mg Fe/kg and TE of 1.1 msec, the signal-to-noise ratio of the central pulmonary arteries and parenchyma was significantly increased (5.3 +/- 2.2 to 50.3 +/- 2.4) and (2.2 +/- 0. 9 to 6.4 +/- 1.1), respectively. Using the TE of 1.1 msec, signal intensity in the main arteries continued to increase with increasing dose. Moreover, the enhancement of pulmonary parenchyma and microvasculature had a positive dose response. 3D MR imaging with ultrashort echo time and 2 mg Fe/kg NC100150 Injection produces angiograms with strong vascular contrast and allows qualitative assessment of pulmonary parenchyma and microvasculature.

MR imaging of the thoracic aorta.

MR imaging is an effective modality for noninvasive morphologic and functional assessment of the thoracic aorta. MR imaging provides several advantages for vascular imaging, including intrinsic contrast between the blood pool and vascular structures, multiplanar imaging capability, and the absence of ionizing radiation. By combining imaging and flow-sensitive techniques, MR imaging can be used to delineate morphology and to quantify bloodflow volume and velocity. In patients who need sequential examinations over time to monitor disease severity, a noninvasive technique such as MR imaging is desirable.

Multiple pulmonary nodules in AIDS: usefulness of CT in distinguishing among potential causes.

PURPOSE: To determine whether the computed tomographic (CT) appearances of multiple pulmonary nodules in patients with acquired immunodeficiency syndrome (AIDS) can help differentiate the potential infectious and neoplastic causes. MATERIALS AND METHODS: The thoracic CT scans obtained in 60 patients with AIDS and multiple pulmonary nodules were reviewed retrospectively by two thoracic radiologists who were blinded to clinical and pathologic data. The scans were evaluated for nodule size, distribution, and morphologic characteristics. CT findings were correlated with final diagnoses. RESULTS: Thirty-six (84%) of 43 patients with opportunistic infection had a predominance of nodules smaller than 1 cm in diameter, whereas 14 (82%) of 17 patients with a neoplasm had a predominance of nodules larger than 1 cm (P <.001). Of the 43 patients with opportunistic infection, 28 (65%) had a centrilobular distribution of nodules; only one (6%) of 17 patients with a neoplasm had this distribution (P <.001). Seven (88%) of eight patients with a peribronchovascular distribution had Kaposi sarcoma (P <.001). CONCLUSION: In patients with AIDS who have multiple pulmonary nodules at CT, nodule size and distribution are useful in the differentiation of potential causes. Nodules smaller than 1 cm, especially those with a centrilobular distribution, are typically infectious. Nodules larger than 1 cm are often neoplastic. A peribronchovascular distribution is suggestive of Kaposi sarcoma.

Imaging evaluation of suspected pulmonary embolism.

Venous thromboembolism (VTE) is a common disorder that is difficult to diagnose clinically but carries significant morbidity and mortality if untreated. Additionally, although demonstrated to be of benefit in cases of proven deep vein thrombosis (DVT) and pulmonary embolism (PE), anticoagulation therapy is not without risk. Because the clinical exam is known to be unreliable for the detection of both DVT and PE, many imaging modalities have been used in the diagnostic imaging algorithm for the detection of VTE, including chest radiography, ventilation/perfusion (V/Q) scintigraphy, pulmonary angiography, and recently, spiral computed tomography (CT) and magnetic resonance imaging (MRI). Chest radiographic findings in acute PE include focal oligemia, vascular enlargement, atelectasis, pleural effusions, and air space opacities representing pulmonary hemorrhage or infarction. The chest radiograph can occasionally be suggestive of PE but is more often nonspecifically abnormal. The main use of the chest radiograph in the evaluation of suspected PE is to exclude entities that may simulate PE and to assist in the interpretation of V/Q scintigraphy. Lower extremity venous compression ultrasonography (CU) is both sensitive and specific for the diagnosis of femoropopliteal DVT, and the value of negative CU results has been established in outcomes studies. However, the reliability of CU for the detection of isolated calf vein thrombosis is not well established, and the clinical significance of such thrombi is debatable. Additional methods such as color and spectral Doppler analysis are also useful in the diagnostic evaluation of DVT but are best considered as adjuncts to the conventional CU examination rather than as primary diagnostic modalities themselves. Compression ultrasonography and Doppler techniques are useful in the evaluation of suspected upper extremity DVT; spectral Doppler waveform analysis is particularly useful to assess for the patency of veins that cannot be directly visualized and compressed with conventional gray-scale sonography. V/Q scintigraphy has been the initial modality obtained in patients suspected of PE for a number of years. Although many studies have investigated the role of V/Q scintigraphy in the evaluation of VTE, the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study has provided the most useful information regarding the utility of V/Q scintigraphy in this setting. A high probability scan interpretation is sufficient justification to institute anticoagulation, and a normal perfusion scan effectively excludes the diagnosis of PE. A normal/near normal scan interpretation also carries a sufficiently low prevalence of angiographically proven PE to withhold anticoagulation. Although the prevalence of PE in the setting of low probability scan interpretations is low and several outcomes studies have demonstrated a benign course in untreated patients with low probability scan results, patients with inadequate cardiopulmonary reserve do not necessarily have good outcomes. Such patients deserve more aggressive evaluation. Patients with intermediate probability scan results have a 20% to 40% prevalence of angiographically proven PE and thus require further investigation. The radionuclide investigation of DVT includes such techniques as radionuclide venography and thrombus-avid scintigraphy. Although these methods have not been as thoroughly evaluated as CU, studies thus far have indicated encouraging results, and further investigations are warranted. Pulmonary angiography has been the gold standard for the diagnosis of PE for decades. Studies have indicated that angiography has probably been underutilized by referring physicians for the evaluation of suspected PE, likely because of the perception of significant morbidity and mortality associated with the procedure. (ABSTRACT TRUNCATED)

Aneurysm of saphenous vein coronary bypass graft: diagnosis by computed tomography.

A patient with a history of coronary artery bypass graft surgery underwent computed tomography scanning for evaluation of a lung mass. A heterogeneous mediastinal mass discovered incidentally on computed tomography scanning was shown to be a saphenous vein bypass graft aneurysm.