Characterisation of structurally modified analogues of glucagon as potential glucagon receptor antagonists.

Acute in vitro and in vivo biological activities of four novel structural analogues of glucagon were tested. desHis(1)Pro(4)-glucagon, desHis(1)Pro(4)Glu(9)-glucagon, desHis(1)Pro(4)Glu(9)Lys(12)FA-glucagon and desHis(1)Pro(4)Glu(9)Lys(30)FA-glucagon were stable to DPP-4 degradation and dose-dependently inhibited glucagon-mediated cAMP production (p<0.05 to p<0.001). None stimulated insulin secretion in vitro above basal levels, but all inhibited glucagon-induced insulin secretion (p<0.01 to p<0.001). In normal mice all analogues antagonised acute glucagon-mediated elevations of blood glucose (p<0.05 to p<0.001) and blocked corresponding insulinotropic responses. In high-fat fed mice, glucagon-induced increases in plasma insulin (p<0.05 to p<0.001) and glucagon-induced hyperglycaemia were blocked (p<0.05 to p<0.01) by three analogues. In obese diabetic (ob/ob) mice only desHis(1)Pro(4)Glu(9)-glucagon effectively (p<0.05 to p<0.01) inhibited both glucagon-mediated glycaemic and insulinotropic responses. desHis(1)Pro(4)-glucagon and desHis(1)Pro(4)Glu(9)-glucagon were biologically ineffective when administered 8h prior to glucagon, whereas desHis(1)Pro(4)Glu(9)Lys(12)FA-glucagon retained efficacy (p<0.01) for up to 24h. Such peptide-derived glucagon receptor antagonists have potential for type 2 diabetes therapy.

Dynamic functional and mechanical response of breast tissue to compression.

Physiological tissue dynamics following breast compression offer new contrast mechanisms for evaluating breast health and disease with near infrared spectroscopy. We monitored the total hemoglobin concentration and hemoglobin oxygen saturation in 28 healthy female volunteers subject to repeated fractional mammographic compression. The compression induces a reduction in blood flow, in turn causing a reduction in hemoglobin oxygen saturation. At the same time, a two phase tissue viscoelastic relaxation results in a reduction and redistribution of pressure within the tissue and correspondingly modulates the tissue total hemoglobin concentration and oxygen saturation. We observed a strong correlation between the relaxing pressure and changes in the total hemoglobin concentration bearing evidence of the involvement of different vascular compartments. Consequently, we have developed a model that enables us to disentangle these effects and obtain robust estimates of the tissue oxygen consumption and blood flow. We obtain estimates of 1.9+/-1.3 micromol/100 mL/min for OC and 2.8+/-1.7 mL/100 mL/min for blood flow, consistent with other published values.

Computerized mass detection for digital breast tomosynthesis directly from the projection images.

Digital breast tomosynthesis (DBT) has recently emerged as a new and promising three-dimensional modality in breast imaging. In DBT, the breast volume is reconstructed from 11 projection images, taken at source angles equally spaced over an arc of 50 degrees. Reconstruction algorithms for this modality are not fully optimized yet. Because computerized lesion detection in the reconstructed breast volume will be affected by the reconstruction technique, we are developing a novel mass detection algorithm that operates instead on the set of raw projection images. Mass detection is done in three stages. First, lesion candidates are obtained for each projection image separately, using a mass detection algorithm that was initially developed for screen-film mammography. Second, the locations of a lesion candidate are backprojected into the breast volume. In this feature volume, voxel intensities are a combined measure of detection frequency (e.g., the number of projections in which a given lesion candidate was detected), and a measure of the angular range over which a given lesion was detected. Third, features are extracted after reprojecting the three-dimensional (3-D) locations of lesion candidates into projection images. Features are combined using linear discriminant analysis. The database used to test the algorithm consisted of 21 mass cases (13 malignant, 8 benign) and 15 cases without mass lesions. Based on this database, the algorithm yielded a sensitivity of 90% at 1.5 false positives per breast volume. Algorithm performance is positively biased because this dataset was used for development, training, and testing, and because the number of algorithm parameters was approximately the same as the number.of patient cases. Our results indicate that computerized mass detection in the sequence of projection images for DBT may be effective despite the higher noise level in those images.

Computerized detection of mass lesions in digital breast tomosynthesis images using two- and three dimensional radial gradient index segmentation.

Initial results for a computerized mass lesion detection scheme for digital breast tomosynthesis (DBT) images are presented. The algorithm uses a radial gradient index feature for the initial lesion detection and for segmentation of lesion candidates. A set of features is extracted for each segmented partition. Performance of two- and three dimensional features was compared. For gradient features, the additional dimension provided no improvement in classification performance. For shape features, classification using 3D features was improved compared to the 2D equivalent features. The preliminary overall performance was 76% sensitivity at 11 false positives per exam, estimated based on DBT image data of 21 masses. A larger database will allow for further development and improvement in our computer aided detection scheme.

Transvaginal interventional procedures: aspiration, biopsy, and catheter drainage.

Transvaginal ultrasonographically (US) guided procedures are simple and safe and often represent the only means of access to pelvic disease. Aspiration of cystic pelvic masses and core biopsy of solid pelvic masses can be easily performed by using the transvaginal route, an endoluminal US transducer, and a needle guide. Because of concerns about false-negative diagnosis and potential tumor seeding with biopsy of primary ovarian cystic lesions, the indications for transvaginal aspiration and biopsy of ovarian and adnexal lesions are predominantly therapeutic. Similarly, using an endoluminal probe with modification of the guide, one can also perform safe and effective trocar catheter drainage of pelvic abscesses via the transvaginal route. The transvaginal route is ideally suited to pelvic abscess drainage because of the proximity of the vaginal fornices to most pelvic fluid collections. The transvaginal route has the disadvantage of being semisterile; because of the risk of superinfecting previously noninfected pelvic pathologic conditions, the transvaginal approach should be used only for solid lesions or cystic lesions that can be completely aspirated. Familiarity with the transvaginal route of access is crucial for adequate treatment of many gynecologic and nongynecologic pelvic pathologic conditions.

Endovascular stent-graft in abdominal aortic aneurysms: the relationship between patent vessels that arise from the aneurysmal sac and early endoleak.

PURPOSE: To determine the association of patent sac branch vessels (lumbar and inferior mesenteric arteries [IMAs]) with early endoleak rate after stent-graft repair of abdominal aortic aneurysm (AAA). MATERIALS AND METHODS: Pre- and postoperative computed tomographic (CT) angiograms in 158 patients who underwent stent-graft AAA repair were retrospectively reviewed to determine the preoperative patency of IMAs and other sac branch vessels (feeders) and presence or absence of immediate postoperative endoleak. Relationships of early endoleak rate with total branch vessel, IMA, and lumbar artery patency and graft type were evaluated. RESULTS: There was a significant association between patency of sac feeders and rate of early endoleak, especially type 2. As total patent feeders increased from zero to three to four to six, total endoleak rate increased from 6% (one of 17) to 35% (30 of 86); type 2 endoleak rate, from 0% to 25%. IMA patency was significantly associated with total early endoleak rate. Increasing lumbar artery patency also was associated with significantly higher total and type 2 endoleak rates: With zero to three lumbar arteries, the total endoleak rate was 17% and type 2 endoleak rate was 13%, as compared with 60% and 50%, respectively, with more than six patent lumbar arteries. CONCLUSION: Sac branch vessel patency is associated with significantly higher early total and type 2 endoleak rates after stent-graft repair of AAAs; thus, patent sac branches play an important role in the pathogenesis of endoleaks.

An improved cosmid vector for the cloning of equine herpesvirus DNA.

We have modified the commercial cosmid vector, triple helix vector (THV), such that I-Sce-I restriction endonuclease sites flank the cloning site. I-Sce-I is a rare-cutting endonuclease which recognizes an 18-bp sequence. It does not restrict the genome of either of the equine herpesvirus 1 or 4 (EHV-1 and EHV-4) strains we have cosmid cloned. Thus, cosmid-cloned EHV fragments can be excised intact from the vector by I-Sce-I digestion, facilitating production of large overlapping EHV fragments for use in transfections to produce recombinant virus.

Chlamydial infections in women.

The impractical isolation procedures available to the general provider of women's health services make diagnosis difficult and often one of exclusion. Looking at the presence of antichlamydial antibodies in cervical secretions may be a more practical detector of infection. More research needs to be carried on in the area of isolation techniques. More importantly, nurse clinicians/practitioners need to be aware of the necessity of treating NGU contacts. As with many conditions, the asymptomatic carrier is the most important link in the control of the disease. Awareness of the potential of these infections will help in their control.