Evaluation of automated tool for two-dimensional fetal biometry.

OBJECTIVE: To evaluate whether an automated tool can recognize a structure of interest and measure fetal head circumference (HC), abdominal circumference (AC) and femur length (FL) on frozen two-dimensional ultrasound images. METHODS: Ultrasound examinations were performed in 100 singleton pregnancies between 20 and 40 weeks of gestation, ensuring an even distribution throughout gestational age. In each pregnancy, three standard biometric variables (HC, AC, FL) were measured each in three different images obtained for this purpose (i.e. nine independent image acquisitions). An algorithm (Philips Research) was used to detect the structure of interest and automatically place calipers for measurement. Caliper placement was assessed in two ways. First, subjective clinical assessment was performed to determine whether the caliper placement was correct, and caliper position was classified as 'acceptable for clinical use', 'minor adjustment required' or 'major adjustment required'. Second, the resulting automatic measurements were compared with manual measurements, taken in real time. Mean difference errors were calculated and expressed as percentages to correct for fetal growth with advancing gestation. RESULTS: After exclusion of one pregnancy due to missing images, a total of 891 images (297 for each biometric variable) from 99 pregnancies were analyzed. The algorithm failed to place calipers for the AC in nine images, whereas there were no failures in caliper placement for measurement of HC and FL. On subjective quality assessment of automatic caliper placement, in 475 (53.3%) images position of the calipers was judged to be clinically acceptable and did not require any adjustment, while in 317 (35.6%) and 90 images (10.1%) minor and major adjustments were required, respectively. The mean error between manual and automatic measurement of HC was -0.21 cm corresponding to a percentage error of -0.81% with 95% limits of agreement (LOA) between -3.73% and 2.12%. For AC and FL measurements, the mean error was, respectively, 0.72 cm (percentage error, 2.40%) with LOA between -9.48% and 14.27%, and 0.21 cm (percentage error, 3.76%) with LOA between -8.38% and 15.91%. CONCLUSIONS: The automated tool identified correctly the biometric variable of interest in 99% of frozen images. The resulting measurements had a high degree of accuracy and compared well with previously published manual-to-manual agreement. The measurements exhibited bias, with the automated tool underestimating biometry; this could be overcome by further improvements in the algorithm. Nevertheless, adjustable calipers for manual correction remains a requirement. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Estrogen receptor actions on vascular biology and inflammation: implications in vascular pathophysiology.

Whereas hormonal therapy (HT) may increase the risk of coronary heart disease (CHD) and stroke in menopausal women, epidemiological studies (protection in premenopausal women) suggest and experimental studies (prevention of fatty streak development in animals) demonstrate a major atheroprotective action of estradiol (E2). The understanding of the deleterious and beneficial effects of estrogens is thus required at both a cellular and molecular level. Both the endothelium and the immuno-inflammatory system play a key role in the development of fatty streak deposit as well as in the rupture of the atherosclerotic plaque. Whereas E2 favors an anti-inflammatory effect in vitro (cultured cells), it rather elicits a pro-inflammatory response in vivo at the level of several subpopulations of the immuno-inflammatory system, which could contribute to plaque destabilization. E2 promotes beneficial actions on the endothelium such as nitric oxide and prostacyclin production. E2 actions are essentially mediated by two molecular targets: estrogen receptor alpha (ER-alpha) and beta (ER-beta), but the former appears to mediate most of the actions of E2 on the endothelium and on the immune system. ER-alpha modulates target gene transcription through two activation functions (AF), AF-1 and AF-2, even though signalling via ER-alpha located at the plasma membrane (responsible for membrane-initiated steroid signalling (MISS)/(extra-genomic)) can also lead to an indirect effect on gene transcription. Recently, we demonstrated that ER-alpha AF-1 is not required for the vasculoprotective actions of E2, whereas it is necessary for the effects of E2 on its reproductive targets. These results suggest that selective estrogen receptor modulators stimulating ER-alpha with minimal activation of ER-alpha AF-1 could retain beneficial vascular actions, while minimizing the sexual effects.

Development of spray-dried acetaminophen microparticles using experimental designs.

Experimental factorial designs were built to investigate the effects of five parameters on production yields and moisture contents of spray-dried products. These factors concerned both the solution feed (drug concentration, colloidal silica concentration and polymer/drug ratio) and the spray dryer (inlet temperature and feed rate). Three formulations containing cellulose derivatives and acetaminophen were tested. The aim of the study was to optimize the operating conditions to maximize production yields while minimizing moisture contents. First screening experiments consisting of fractional factorial designs revealed the most significant factors to be inlet temperature, feed rate and their interaction for both formulations containing sodium carboxymethylcellulose and feed rate and colloidal silica concentration for the formulation containing microcrystalline cellulose. Then, the optimal operating conditions were estimated by response surface methodology. Central rotational composite designs showed quadratic models were adequate. New assays were carried out using these last conditions to evaluate both the repeatability and reproducibility of the spray-drying technique. Yields above 80% and moisture content of approximately 1% were reached. The characterization of microparticles revealed the poor flowability of the spray-dried products due to significant cohesiveness and very small size (less than 55 microm).

Vancomycin biodegradable poly(lactide-co-glycolide) microparticles for bone implantation. Influence of the formulation parameters on the size, morphology, drug loading and in vitro release.

The present study investigates vancomycin microencapsulation in biodegradable PLAGA microparticles. To optimize encapsulation efficiency by the double emulsion (w/o/w) solvent evaporation/extraction process, two parameters were studied: surfactant (Span 80) rate and external aqueous phase saturation. In vitro dissolution studies, laser granulometry and scanning electron microscopy were performed to characterize the microparticles. The best results were obtained by stabilizing the first emulsion with 0.5% Span 80 and saturating the external phase with sodium chloride. Such parameters allowed a 95% drug encapsulation efficiency. This process yielded round microparticles with a mean diameter of approximately 170 microm and presenting a smooth surface without any pores. Moreover, this formulation induces a sustained drug release at a constant rate over a period of 10 days. Such materials could be associated with biphasic calcium phosphate granules to form an antibiotic-loaded injectable bone substitute offering a long-term activity in situ.

Spray-dried microparticulate systems containing acetaminophen.

The present work investigates the preparation and the release of acetaminophen from spray-dried microparticles. Two cellulose derivatives were tested as sustaining agents: microcrystalline cellulose (MCC) and sodium carboxymethylcellulose (NaCMC). In-vitro dissolution studies were carried out in dissolution media of different pH. With MCC, the adsorption of acetaminophen on the surface or in the pores of the polymer does not allow a significant sustained release of the drug, which completely dissolves in 1 h. Conversely, the use of NaCMC retards the release of acetaminophen over a period of 6-8 h. The drug release depends on the plasticizer used and on the pH of the dissolution medium, and the mechanism consists essentially in the diffusion of the drug through the swollen polymeric matrix. The pH dependence observed can be correlated with a lower hydrophylicity of the polymer in acidic medium, which retards gel formation.

Effects of cellulose derivatives and additives in the spray-drying preparation of acetaminophen delivery systems.

Microcrystalline cellulose (MCC), sodium carboxymethylcellulose (NaCMC), hydroxypropylmethylcellulose (HPMC), hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), and ethylcellulose (EC) were used for the production of time-controlled acetaminophen delivery systems using a spray-drying technique. The influence of factors such as polymer concentration, inlet temperature, and drug/polymer ratio were investigated. The product yields were a function of the type and concentration of the polymer, with the highest values being reached from feeds containing 1% MCC and EC. Parameters of 1% polymer concentration and an inlet temperature of 140 degrees C gave rise to optimal processing conditions. Using these parameters, the influence of some adjuncts, such as polyethylene glycol 6000 (PEG 6000), dibutyl sebacate (DBS), polyvinylpyrrolidone (PVP), and carboxylic acids such as citric acid (CA), phthalic acid (PA), succinic acid (SA), tartaric acid (TA), and oxalic acid (OA), on the spray-drying process was evaluated. Of the additives tested, PVP (with MCC), DBS (with EC), and PEG 6000 (with NaCMC) induced yield decreases from 70% to 49%, 66% to 39%, and 37% to 17%, respectively. As for carboxylic acids (with NaCMC), similar or better performances of 43%, 45%, 47%, and 49% were obtained with SA, OA, PA, and TA, respectively. Dissolution studies in pH 1 dilute HCl and pH 6.8 phosphate buffer dissolution media showed that formulations consisting of 1% polymer with a drug/polymer ratio of 1/1 exhibited the slowest drug release, with the spheroids coated with NaCMC and HEC showing the longest T50% values (with 45 and 53 min at pH 1 and 49 and 55 min at pH 6.8, respectively). Slightly better sustained drug release in pH 6.8 dissolution medium was reached, showing the following trend: HEC > NaCMC > MCC > EC > HPMC. Concerning the additives, the trends in dissolution T50% of drug revealed TA > SA > CA > OA > PVP > PA > DBS in acidic pH 1 dissolution medium and PVP > OA > TA > SA > PA > CA > DBS in phosphate buffer at pH 6.8.

Three-dimensional imaging of solid breast tumors with ultrasound: preliminary data and analysis of its possible contribution to the understanding of the standard two-dimensional sonographic images.

Reconstructed three-dimensional sonographic images are presented from patients having different histological types of breast tumors. Scanning is manual and performed using two-dimensional annular array, sector transducers fitted on a mechanical arm, to provide spatial location. The three-dimensional data are displayed using two different modalities. Planar reformatted sections allow the visualization of planes reconstructed along any direction chosen by the operator. Of particular interest are the reconstructions obtained along equatorial planes of the tumors, i.e. planes parallel to the chest wall and, consequently, to the fibroglandular layer of the breast. Volume rendering is obtained using the shaded-surface visualization technique.Three-dimensional imaging provides new information and allows a better interpretation of the standard two-dimensional images. Planar reformatted sections confirm that ductal carcinomas present margin jagging on all views, including the equatorial section planes. Using the shaded-surface visualization technique, these tumors appear with a spiked outer surface. Thus, the most specific sonographic finding associated with ductal carcinomas may be that margin jagging extends over the entire periphery of the mass. On planar reformatted sections, benign tumors are surrounded by a continuous hyperechogenic rim, i.e. the rim is present irrespective of the section plane orientation. Medullary carcinomas are also surrounded by a hyperechogenic rim. However, a clearly distinctive feature of these lesions is found on planar reformatted sections: the rim is discontinuous on certain section planes. A mass can be considered benign only if its rim is continuous, i.e. if it is present all around the tumor.