Hysterosalpingo-contrast sonography of the uterus and fallopian tubes: results of a clinical trial of a new contrast medium in 120 patients

The feasibility, diagnostic efficacy, and patient tolerance of a new diagnostic modality, hysterosalpingo-contrast sonography (HyCoSy), were evaluated in a clinical study of 120 patients with suspected infertility. A new echogenic contrast medium for ultrasound was administered transcervically with conventional tools for hysterosalpingography or a balloon catheter. The flow of multiple fractions of the contrast medium through each fallopian tube was observed in real time in appropriate imaging planes by means of a transvaginal probe. All patent tubes were diagnosed correctly with HyCoSy, results comparing well with findings at hysterosalpingography or laparoscopy. With B-mode scanning only, sensitivity was 88% for the right tube and 90% for the left; specificity was 100% for each tube. The supplementary use of Doppler techniques (duplex, color Doppler) provided additional information in special cases of suspected tubal occlusion and led to an improvement in diagnostic accuracy. The contrast agent was well tolerated. HyCoSy demonstrates normal anatomy and tubal patency with high reliability and permits advance selection of patients in whom more invasive diagnostic procedures may be required.     

Stimulated acoustic emission to image a late liver and spleen-specific phase of Levovist in normal volunteers and patients with and without liver disease

Quantitative studies were performed to investigate liver- specific uptake of the microbubble Levovist®, using stimulated acoustic emission (SAE), which can detect microbubbles even when stationary or slow-moving. These comprised studies of biodistribution comparing the liver and kidney in five normal volunteers, reproducibility in 34 patients, comparison between cirrhotics and controls (n = 9 each) and maximal depth of effect at different frequencies (180 measurements in 31 patients). Stimulated acoustic emission lasted beyond 30 min, with strongly liver-specific properties in each volunteer and was highly reproducible. No difference in the amount of SAE in the superficial liver was seen between cirrhotic and normal livers, but attenuation was higher in cirrhotics. This demonstrates a frequency-dependent effect on liver SAE penetration. We conclude that the liver uptake of Levovist® lasts over 30 min, is reproducible, occurs even where diffuse liver disease is present and can be used to assess tissue attenuation in a novel fashion.     

Assessment of fetal and placental blood flow in primates using contrast enhanced ultrasonography.

Ultrasonographic contrast agents that stay within the vascular space and do not cross the placenta may permit differentiation between the maternal and fetal portions of the placenta and may be clinically useful for diagnosis of placental abnormalities. This study was performed to assess the effects of Levovist (Schering AG, Berlin) on the placental circulation and to determine whether hemodynamic effects on the fetus occur. Ten studies were performed in five pregnant macaques (median weight, 9.15 kg; range, 6.15 to 11 kg; median gestational age, 121 days; range, 34 days to term) under anesthesia. Gray scale, color, and duplex Doppler sonographic scans of the fetus and placenta were acquired using a 5 MHz curved array transducer. Fetal heart rate, resistive index, and systolic-diastolic ratios were measured in the fetal middle cerebral artery, aorta, umbilical artery, and uterine artery before and after administration of contrast agent. The following dose regimen was tested: 5 ml of physiologic saline solution followed by 0.1 ml/kg of 300 mg/ml Levovist (diagnostic dose), 0.5 ml/kg of 400 mg/ml Levovist (maximum dose), and 5 ml physiologic saline solution. The order of diagnostic dose and maximal dose was randomized among animals. Color enhancement of the basal portions of the placenta was documented after administration of contrast agent. Heart rate and middle cerebral artery systolic-diastolic ratio did not change between baseline and injections. A 7% decrease of the resistive index from baseline to maximum dose was measured in the uterine artery (not significant). A 7.7% decrease in the systolic-diastolic ratio from baseline to maximum dose was recorded in the umbilical artery. However, an identical change was measured after saline solution was injected. The resistive index in the aorta increased by 2.6% from baseline to maximum dose, a change that was not significant (P > 0.5). Ultrasonographic contrast enhancement of the maternal circulation in placenta is demonstrated to be without significant effects on the fetal circulation as measured in this limited population.     

Sensory processing in the Drosophila antennal lobe increases reliability and separability of ensemble odor representations

Here we describe several fundamental principles of olfactory processing in the Drosophila melanogaster antennal lobe (the analog of the vertebrate olfactory bulb), through the systematic analysis of input and output spike trains of seven identified glomeruli. Repeated presentations of the same odor elicit more reproducible responses in second-order projection neurons (PNs) than in their presynaptic olfactory receptor neurons (ORNs). PN responses rise and accommodate rapidly, emphasizing odor onset. Furthermore, weak ORN inputs are amplified in the PN layer but strong inputs are not. This nonlinear transformation broadens PN tuning and produces more uniform distances between odor representations in PN coding space. In addition, portions of the odor response profile of a PN are not systematically related to their direct ORN inputs, which probably indicates the presence of lateral connections between glomeruli. Finally, we show that a linear discriminator classifies odors more accurately using PN spike trains than using an equivalent number of ORN spike trains.     

Echo contrast agents improve flow display of color Doppler: in vitro studies

Flow detection by color Doppler is impaired by low velocity of flow and increasing attenuation and depth of ultrasound penetration. The effects of increased echogenicity on flow detection (Toshiba SSH 65A) were thus studied in a flow model, which yielded similar strengths of Doppler signals as seen in the clinical routine, by adding microbubble solutions to the blood analog fluid (45% aqueous glycerin) and comparing signal strength (score 0-5) prior to and after contrast. The flow within the plexiglass tube with less than 3 degrees angle of coincidence for Doppler interrogation was laminar with a parabolic velocity profile at physiological velocities and pressures. In comparison with various contrast agents at a flow velocity of 18 cm/sec and 19 dB attenuation, flow was not detectable in control color Doppler, after 4 mL of the blood analog fluid, and after 4 mL of an agitated saline solution 9 mg/mL, but visible after 4 mL of Echovist, a polysaccharide solution with reproducible bubble size and concentration and after 4 mL of an agitated polygelatin solution. Increasing concentration of Echovist (50-400 mg/mL) improved flow detection. Echovist 200 mg/mL enhanced the score by 1.1 + -0.6 for velocities 5-20 cm/sec (P less than 0.01), by 1.6 + -0.8 for 40-100 cm/sec (P less than 0.001), and by 1.1 + -0.6 for velocities greater than 150 cm/sec (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Modification of C-type inactivatingShaker potassium channels by chloramine-T

Shaker potassium channels undergo a slow C-type inactivation which can be hastened dramatically by single-point mutations in or near the pore region. We found that the oxidizing agent chloramine-T (Chl-T) causes an irreversible loss of current for those mutants which show C-type inactivation. For several mutants at position T449, which show a wide spectrum of inactivation time constants, the time constant of current rundown induced by Chl-T correlated with the speed of inactivation. Rundown was accelerated when the channels were in the inactivated state but rundown also occurred when channels were not opened or inactivated. Apparently, only those channels which can undergo C-type inactivation are accessible to Chl-T In order to gain information about the target amino-acid residue for the action of Chl-T and the structural rearrangements occurring during C-type inactivation, several mutant channel proteins were compared with respect to their response to Chl-T Since Chl-T can oxidize cysteine and methionine residues, we mutated the possible targets in and close to the pore region, namely C462 to A, and M440 and M448 to I. While the residues M440 and C462 were not important for channel rundown, mutation of M448 to I made the channels more resistant to Chl-T by about one order of magnitude. While inactivation was accelerated upon application of Chl-T in most mutants, mutation of M448 to I abolished this effect on the time course of inactivation, indicating that M448 is one of the target residues for Chl-T.