Vascular effects of sildenafil in hypertensive cardiac transplant recipients

BACKGROUND: Sildenafil is commonly used in the treatment of erectile dysfunction in hypertensive male cardiac transplant recipients (CTR); however, little is known about the vascular effects of sildenafil in these patients. METHODS: Central and peripheral arterial blood pressure (BP), heart rate, and brachial artery reactivity were determined in 15 hypertensive male CTR before and after oral sildenafil (50 mg) administration. RESULTS: Sildenafil improved brachial and aortic systolic BP, pulse pressure, aortic augmentation index, left ventricular tension time index, travel time of the reflected aortic pressure wave, and brachial artery reactivity (P <.01 for each comparison). No patient became hypotensive with sildenafil despite continuation of usual antihypertensive medications. CONCLUSIONS: Sildenafil (50 mg) is well tolerated in hypertensive CTR and improves BP, aortic augmentation index, and endothelial function. By decreasing the amplitude of the reflected pressure wave and delaying its return to the heart, sildenafil reduces left ventricular afterload and systolic stress.     

Role of glucose in chronic desensitization of isolated rat islets and mouse insulinoma (betaTC-3) cells to glucose-dependent insulinotropic polypeptide

It is well documented that the release of insulin from isolated perifused islets attenuates over time, despite a continued glucose stimulation. In the current study we have shown that potentiation of insulin release by the intestinal hormone glucose-dependent insulinotropic polypeptide (GIP) is also attenuated after its continuous application. In less than 20 h of maintained stimulus with either hyperglycaemia (11.0 mM glucose) or GIP (10 nM) under hyperglycaemic conditions, insulin release returned to basal values. This was not due to loss of islet viability or reduction in the releasable pool of insulin granules, as 1 mM isobutylmethylxanthine was able to stimulate equivalent insulin release under both conditions. Further examination of chronic GIP desensitization was examined in cultured mouse insulinoma (betaTC-3) cells. GIP-stimulated cAMP production was not greatly affected by the prevailing glucose conditions, suggesting that the glucose dependence of GIP-stimulated insulin release occurs distally to the increase in intracellular cAMP in betaTC-3 cells. The GIP-stimulated cAMP response curve after desensitization was of similar magnitude at all glucose concentrations, but GIP pretreatment did not affect forskolin-stimulated cAMP production. Desensitization of the cAMP response in betaTC-3 cells was shown not to involve induction of dipeptidyl peptidase IV or pertussis toxin-sensitive G-proteins, activation of protein kinase C or protein kinase A, or modulation of phosphodiesterase activity. Homologous desensitization of the insulin-potentiating activity of GIP was found to affect both GIP-stimulated and forskolin-stimulated insulin release, indicating desensitization of distal steps in the stimulus-exocytosis cascade.     

Pectin engineering: modification of potato pectin by in vivo expression of an endo-1,4-beta-D-galactanase

Potato tuber pectin is rich in galactan (oligomer of beta-1,4-linked galactosyl residues). We have expressed a fungal endo-galactanase cDNA in potato under control of the granule bound starch synthase promoter to obtain expression of the enzyme in tubers during growth. The transgenic plants displayed no altered phenotype compared with the wild type. Fungal endo-galactanase activity was quantified in the transgenic tubers, and its expression was verified by Western blot analysis. The effect of the endo-galactanase activity on potato tuber pectin was studied by Fourier transform infrared microspectroscopy, immuno-gold labeling, and sugar analysis. All analyses revealed alterations in pectin composition. Monosaccharide composition of total cell walls and isolated rhamnogalacturonan I fragments showed a reduction in galactosyl content to 30% in the transformants compared with the wild type. Increased solubility of pectin from transgenic cell walls by endo-polygalacturonase/pectin methylesterase digestion points to other changes in wall architecture.     

Patterns of expression of tumor markers on non-transformed human mammary epithelial cells cultured in vitro

We have examined the expression of 7 well defined tumor markers/tumor associated antigens (H type 2, X, Y, sialyl-Lea, CEA, MAM-6, and Tn) and a tumor associated antigen defined by a new own monoclonal antibody on non-transformed human epithelial cell lines derived from reduction mammoplasties by means of immunocytochemistry with monoclonal antibodies. Two cell types are discernible: slowly or non-proliferating, lumenal derived (I), and proliferating, stem cell-like, basal cell-derived cells (II). Five out of the 8 tumor markers were expressed on type I cells, and all 8 on type II cells. The number of positive cells varied considerably from a few to 100 per cent depending on the individual markers. The observed patterns proved to be characteristic and reproducible; they appear to reflect the developmental stage of the cells cultured in vitro rather than a direct influence of the culture conditions.     

No Long-term Difference Between Fixed and Mobile Medial Unicompartmental Arthroplasty

Background  

Early studies in the literature reported relatively high early minor reintervention rate for the mobile-bearing unilateral knee arthroplasty (UKA) compared with short- and midterm survivorship after fixed- or mobile-bearing UKA. However, whether the long-term function and survivorship are similar is unclear.     

Spiral imaging on a small-bore system at 4.7t

Spiral imaging has a number of advantages for ultrafast data acquisition. However, implementation on high-field small-bore systems requires carefully addressing the issues of in-homogeneity-induced blurring and gradient hardware constraints. In this paper, spiral imaging on a 40-cm-bore 4.7T CSI Omega System (Bruker Instruments) is discussed. A constant-voltage gradient waveform design algorithm is developed to reduce readout times as well as minimize waveform distortions due to gradient amplifier nonlinearities. Residual errors are then measured and taken into account in the image reconstruction procedure. Multiple spiral interleaves as well as a multifrequency reconstruction algorithm are used to decrease blurring of off-resonance spins. Both phantom and in vivo images demonstrate the performance of the resulting pulse sequences.     

Single breath-hold whole-heart MRA using variable-density spirals at 3T.

Multislice breath-held coronary imaging techniques conventionally lack the coverage of free-breathing 3D acquisitions but use a considerably shorter acquisition window during the cardiac cycle. This produces images with significantly less motion artifact but a lower signal-to-noise ratio (SNR). By using the extra SNR available at 3 T and undersampling k-space without introducing significant aliasing artifacts, we were able to acquire high-resolution fat-suppressed images of the whole heart in 17 heartbeats (a single breath-hold). The basic pulse sequence consists of a spectral-spatial excitation followed by a variable-density spiral readout. This is combined with real-time localization and a real-time prospective shim correction. Images are reconstructed with the use of gridding, and advanced techniques are used to reduce aliasing artifacts.     

Reducing flow artifacts in echo-planar imaging

Echo-planar imaging (EPI) is very susceptible to flow artifacts. Two ways to improve its flow properties are presented. First, “partial flyback” is proposed to reduce artifacts arising from flow in the readout direction. Near the center of k-space, only the even echoes of the EPI echo-train are used. Partial flyback is shown to improve the readout-flow properties at the expense of a slight worsening of the phase-encode flow and off-resonance properties. We recommend that the flyback region acquire 95% of the energy in k-space. Second, “inside-out” EPI is used to reduce artifacts arising from flow in the phase-encode direction. Data collection begins at the center of k-space, with separate interleaves to acquire the top and bottom halves of k-space. Partial flyback is combined with partial-Fourier EPI and inside-out EPI. Partial-flyback inside-out EPI has worse off-resonance properties than partial-flyback partial-Fourier EPI but demonstrates better flow properties and does not require partial k-space reconstruction.     

Differences in MEG/EEG epileptic spike yields explained by regional differences in signal-to-noise ratios.

Controversy remains regarding the preferred modality, magnetoencephalography (MEG) or EEG, for the presurgical evaluation of patients with epilepsy. In general, it appears that the spike yields for MEG and EEG are similar in patients with temporal lobe epilepsy, and that for neocortical epilepsy the MEG spike yields may be larger than for EEG. In general, MEG/EEG spike yields depend on factors such as (1) the number of sensors, (2) the source depth and orientation, (3) the background activity, and (4) the smearing of the potential fields due to variations in skull resistivity in EEG. Because the contribution of all these factors are of the same order of magnitude, the authors took them all into account to predict the signal-to-noise ratio (SNR) of hypothetical spikes in different brain areas. In this study, it was assumed that spike sensitivity (and therefore the spike yield) increases with SNR. The estimated SNR values at temporal areas were comparable for MEG and EEG, which is in agreement with clinical findings that spike yields in temporal lobe epilepsy are similar. Furthermore, the SNR of MEG was substantially higher in the frontal area, indicating that in frontal lobe epilepsy MEG may be highly relevant to prescreening of epilepsy patients. This model-based approach indicates that SNR mapping clarifies differences between MEG and EEG findings that are difficult to understand on the basis of patient studies only.     

A three-dimensional spin-echo or inversion pulse

In theory, multidimensional pulses can be designed to be selective in any number of dimensions. In practice, available gradient power has enforced a limit to two dimensions. We show here that three-dimensional π pulses are feasible on commercial imaging machines provided that the range of offresonance frequencies are limited.