Cytotoxic activity of Crotalus molossus molossus snake venom-loaded in chitosan nanoparticles against T-47D breast carcinoma cells.

Nanomedicine has led to the development of new biocompatible and biodegradable materials able to improve the pharmaceutical effect of bioactive components, broadening the options of treatment for several diseases, including cancer. Additionally, some snake venom toxins have been reported to present cytotoxic activity in different tumor cell lines, making them an auspicious option to be used as cancer drugs. The present study aims to evaluate the cytotoxic activity of the northern black-tailed rattlesnake (Crotalus molossus molossus) venom-loaded chitosan nanoparticles (Cs-Venom NPs) against the T-47D breast carcinoma cell line. To do so, we first identified the significant proteins composing the venom; afterward, hemocompatibility and cytotoxic activity against tumoral cells were evaluated. The venom was then loaded into chitosan nanoparticles through the ionotropic gelation process, obtaining particles of 415.9±21.67 nm and ζ-potential of +28.3±1.17 mV. The Cs-Venom complex delivered the venom into the breast carcinoma cells, inhibiting their viability and inducing morphological changes in the T-47D cells. These features indicate that these nanoparticles are suitable for the potential use of C. m. molossus venom toxins entrapped within polymer nanoparticles for the future development and research of cancer drugs.

Clinical and Economic Evaluation after Adopting Contingent Cell-Free DNA Screening for Fetal Trisomies in South Spain.

INTRODUCTION: Contingent cell-free (cf) DNA screening on the basis of the first-trimester combined test (FCT) results has emerged as a cost-effective strategy for screening of trisomy 21 (T21). OBJECTIVES: To assess performance, patients' uptake, and cost of contingent cfDNA screening and to compare them with those of the established FCT. METHODS: This is a prospective cohort study including all singleton pregnancies attending to their FCT for screening of T21 at 2 university hospitals in South Spain. When the FCT risk was ≥1:50, there were major fetal malformations, or the nuchal translucency was ≥3.5 mm, women were recommended invasive testing (IT); if the risk was between 1:50 and 1:270, women were recommended cfDNA testing; and for risks bellow 1:270, no further testing was recommended. Detection rate (DR), false-positive rate (FPR), patients' uptake, and associated costs were evaluated. RESULTS: We analyzed 10,541 women, including 46 T21 cases. DR of our contingent strategy was 89.1% (41/46) at 1.4% (146/10,541) FPR. Uptake of cfDNA testing was 91.2% (340/373), and overall IT rate was 2.0%. The total cost of our strategy was €1,462,895.7, similar to €1,446,525.7 had cfDNA testing not been available. CONCLUSIONS: Contingent cfDNA screening shows high DR, low IT rate, and high uptake at a similar cost than traditional screening.

Association between sexual dysfunction and avulsion of the levator ani muscle after instrumental vaginal delivery.

INTRODUCTION: The effects of levator ani muscle (LAM) avulsion after instrumental delivery on the sexual function of patients are currently unknown. Therefore, the objective of our study was to use a validated questionnaire, namely, the Female Sexual Function Index (FSFI), to compare the sexual function in patients with and without LAM avulsion after instrumental vaginal delivery. MATERIAL AND METHODS: This was a prospective observational study of 112 primiparous women after instrumental (vacuum or forceps) vaginal delivery. The obstetric and general characteristics of the population were studied. At 6 months postpartum, the contraceptive method used and the occurrence of LAM avulsion (using four-dimensional transperineal ultrasound) were determined, and the FSFI was administered. RESULTS: A total of 100 patients (62 without avulsion and 38 with avulsion) completed the study. Thirty-eight (38%) were diagnosed with avulsion (42.1% after Kielland forceps delivery, 57.9% after Malmström vacuum delivery; P = .837). Women with LAM avulsion had significantly lower scores for desire (2.9 ± 1.2 vs 3.4 ± 1.1; P = .049), arousal (2.8 ± 1.7 vs 3.6 ± 1.4; P = .014), lubrication (2.3 ± 1.4 vs 3.0 ± 1.2; P = .011), orgasm (2.6 ± 1.6 vs 3.3 ± 1.2; P = .006) and satisfaction (3.1 ± 1.8 vs 3.9 ± 1.5; P = .051) than did women without LAM avulsion. The overall FSFI score was lower in patients with avulsion (16.7 ± 8.9 vs 20.7 ± 6.9, P = .033). These results were obtained after controlling for confounders (delivery mode, induced labor, birthweight, perineal tears, avulsion degree, contraceptive method and group assignment for the parent study) in the multivariate analysis (F = 4.974, P = .001). CONCLUSIONS: Patients with LAM avulsion present a higher degree of sexual dysfunction compared wiith patients without avulsion at 6 months after instrumental vaginal delivery.

Prevalence of levator hiatal overdistension after vacuum and forceps deliveries.

INTRODUCTION: Levator ani avulsion rates after assisted vaginal delivery have been reported in the literature. However, there are no definitive data regarding the association between overdistention and assisted vaginal delivery. Therefore, our aim is to report overdistention rates after assisted vaginal delivery with a postpartum ultrasound examination. MATERIALS AND METHODS: This multicenter study involved a retrospective analysis of data from primiparous women (n = 602) who had previously been recruited at three tertiary hospitals between January 2015 and January 2017. Overdistention was assessed at 6 months postpartum using three-/four-dimensional transperineal ultrasound. Patients with levator ani muscle avulsion were excluded. Overdistention was defined as a levator hiatal area ≥ 25 cm2 on Valsalva. RESULTS: Of the 602 primiparous patients, 250 patients who satisfied the inclusion criteria (139 patients who underwent forceps delivery and 111 patients who underwent vacuum delivery) were evaluated. Overdistention occurred in 20% (50 of 250) of these patients. Overdistention was observed for 1% (1/111) of vacuum deliveries and 35.3% (49 of 139) of forceps deliveries. We found an increased risk of overdistention following forceps delivery compared to vacuum delivery, with a crude odds ratio (OR) of 59.9 (95% confidence interval [CI]: 8.1, 442.2) and an adjusted OR (adjusted for maternal age, second-stage duration, and head circumference) of 17.6 (95% CI: 2.3, 136.7). CONCLUSIONS: Postpartum overdistention occurred for 20% of assisted vaginal deliveries, with an increased risk of overdistention following forceps delivery compared to vacuum delivery.

Early fetal morphological evaluation (11-13 + 6 weeks) accomplished exclusively by transabdominal imaging and following routine midtrimester fetal ultrasound scan recommendations. Since when can it be performed?

Objectives: To establish the best timing for the realization of first-trimester-morphologic-evaluation, following routine midtrimester fetal-ultrasound-scan-recommendations (RFUSR), by performing exclusive transabdominal exploration, and to determine the sensitivity of the mentioned scan for diagnosis of major structural abnormalities.Method: Prospective observational study with 512 pregnant women with singleton gestations (438 low-risk, 74 high-risk) was conducted. Early fetal morphological evaluation (EFME) is performed in line with RFUSR (18-22 weeks) (ISUOG 2010) and a check-list structured evaluation was followed, between 11-13 + 6 weeks. Its performance is assessed in the correct identification of normal fetal anatomy, and its effectiveness in the detection of structural defectsResults: Five hundred and four pregnant women were evaluated, of which, 58.3% EFME are considered complete fetal anatomical surveys. Complete fetal anatomical surveys scans rise from 23.1% at 11-11 + 6 weeks to 63.8% at 13 + 3-13 weeks, with a clear turning point at 12 + 6-13 + 3 weeks (63.8%) (p < .05). From 12 + 6-13 + 3 weeks only renal (26.3%) and cardiac assessments (31.6%) present an inconclusive evaluation greater than 20%. Body mass index (23.9 versus 29.8) and estimated fetal weight (63 versus 86.7 g) influence EMFE's ability of identifying fetal structures (p < .05). EMFE presents sensitivity for the identification of structural malformations of 83.3% (20/24).Conclusions: From 12 + 6 weeks of gestation onwards, a complete fetal morphological evaluation can be performed in 63.8% of cases following the routine midtrimester fetal ultrasound scan recommendations (ISUOG's 20 weeks scan).

Are there differences in the damage to the pelvic floor between malmstrom's and kiwi omnicup vacuums? A multicenter study.

OBJECTIVES: The objective of this study is to investigate a multicenter study to establish if differences exist in the levator ani muscle avulsion (LAM) rates between deliveries performed with Malmstrom's vacuum and the Kiwi vacuum. STUDY DESIGN: A prospective, multicenter observational study with 199 primiparous subjects was performed. All patients had undergone vaginal delivery by vacuum (Malmstrom's or Kiwi). Avulsion was defined as an abnormal insertion of LAM in the lower pubic branch in the multiplanar mode, as identified in the three central sections by transperineal 3/4D echography 6 months after delivery. The area of ​​the levator hiatus was measured in the plane of minimum dimensions at rest, during the Valsalva maneuver and during contraction. RESULTS: LAM avulsion occurred in 33.1% of cases in which Malmstrom's vacuum was used and in 29.4% of cases in which the Kiwi vacuum was used (the difference was not statistically significant), which resulted in a crude odds ratio (OR) of 0.977 (0.426, 2.241; P = .957) and an adjusted OR of 2.90 (0.691; 12.20; P = .146). Women in the Malmstrom's vacuum group had a larger LHA at rest 14.77 vs 12.64 cm2 ; P = .001) and at maximum contraction (13.41 vs 10.83 cm2 ; P < 0.001) in comparison with the Kiwi group, although the difference did not reach statistical significance under Valsalva maneuver (18.71 vs 17.21 cm2 ; P = .051).Differences between both groups were detected in the measurements of the hiatus area levator at rest (14.77 vs 12.64 cm2 ), during the Valsalva maneuver (18.71 vs 17.21 cm2 ) and during maximum contraction (13.41 vs 10.83 cm2 ). CONCLUSIONS: In the present study, Malmstrom's vacuum was not associated with a higher risk of LAM in comparison with Kiwi's Omnicup.

A comparable rate of levator ani muscle injury in operative vaginal delivery (forceps and vacuum) according to the characteristics of the instrumentation.

INTRODUCTION: Forceps delivery is associated with a high rate of levator ani muscle (LAM) trauma (avulsion) at 35%-65% whereas data on avulsion rates after vacuum delivery vary greatly. Nevertheless, a common characteristic of all previous studies carried out to evaluate the association between instrumental deliveries (forceps and vacuum) and LAM avulsion, is the fact that characteristics of the instrumentation have not been described or evaluated. The objective of this study is to compare the rate of LAM avulsion between forceps and vacuum deliveries according to the characteristics of the instrumentation. MATERIAL AND METHODS: Prospective, observational study, including 263 nulliparous women, who underwent an instrumental delivery with either Malmström vacuum or Kielland forceps. The characteristics of the instrumentation, position (anterior position and other position) and height of the fetal head at the moment of instrumentation (low instrumentation [vertex at +2 station] and mid-instrumentation [head is involved but leading part above +2 station]) were assessed. Evaluation of LAM avulsion was performed at 6 months postpartum by three-/four-dimensional transperineal ultrasound. Using the multi-view mode, a complete avulsion was diagnosed when the abnormal muscle insertion was identified in all three central slices, that is, in the plane of minimal hiatal dimensions and the 2.5-mm and 5.0-mm slices cranial to this one. To detect a 30% or 15% difference in the LAM injury rate, with 80% power and 5% α-error, we needed, respectively 42 and 99 women per study group. RESULTS: In all, 263 nulliparous individuals have been evaluated (162 vacuum deliveries, 101 forceps deliveries). Instrumentation in an occipito-anterior position was more frequent in vacuum deliveries (75.3% vs 56.4%, P = .002), whereas other positions were more frequent in the forceps deliveries group (24.7% vs 43.6%). No statistically significant differences were noted regarding the height of the fetal head at the moment of instrumentation. No statistically significant differences were found in the presence of LAM avulsion (41.4% vs 38.6%) between vacuum and forceps deliveries. The univariate analysis of the crude odds ratio was 1.17, 95% CI 0.67-1.98, P = .70 for the avulsion of the LAM and the multivariate of the adjusted OR 0.90, 95% CI; 0.53-1.55, P = .71. CONCLUSIONS: We consider that, in our population, LAM avulsion rate should not be a factor taken into account when choosing the type of instrumentation (Malmström vacuum or Kielland forceps) in an operative delivery.

Bifunctional nickel-iminodiacetic acid-core-shell silica nanoparticles for the exclusion of high molecular weight proteins and purification of His-tagged recombinant proteins.

Herein, silica nanoparticles were synthesized and chemically modified with iminodiacetic acid (IDA) and Ni2+ ions surrounded by a bis-acrylamide polymeric shell to obtain a new core-shell immobilized metal affinity chromatography (IMAC) based material. These Ni2+-IDA-core-shell silica nanoparticles (Ni2+-IDA-CSS-NP) represent a new alternative for purification of His-tagged proteins and exclusion of high molecular weight (HMW) proteins at the same time. Nanoparticles presented a final size of 479.6 ± 6.9 nm determined by dynamic light scattering (DLS) and a surface charge of -37.2 ± 0.5 mV. Successful incorporation of the different compounds at every phase of synthesis was evidenced by ATR-FTIR analysis. Ni2+-IDA-CSS-NP were used for isolation of His-tagged spo0F (6His-spo0F) from E. coli lysate. Ni2+-IDA-CSS-NP presented a capacity of 4.16 ± 0.45 µg mg-1. Purification of 6His-spo0F with high selectivity and the effective exclusion of HMW proteins were evidenced by SDS-PAGE and validated through mass spectrometry analysis.

Specific capture of glycosylated graphene oxide by an asialoglycoprotein receptor: a strategic approach for liver-targeting.

In this work, we report the evaluation of lactosylated graphene oxide (GO-AL) as a potential drug carrier targeted at an asialoglycoprotein receptor (ASGPR) from hepatic cancer cells. Structural-modification, safety evaluation, and functional analysis of GO-AL were performed. The structure and morphology of the composite were analyzed by scanning electron microscopy (SEM) and atomic force microscopy (AFM), while Raman and FTIR spectroscopy were used to track the chemical modification. For the safe application of GO-AL, an evaluation of the cytotoxic effect, hemolytic properties, and specific interactions of the glycoconjugate were also studied. SEM and AFM analysis of the GO showed graphene sheets with a layer size of 2-3 nm, though a few of them reached 4 nm. The Raman spectra presented characteristic peaks of graphene oxide at 1608 cm-1 and 1350 cm-1, corresponding to G and D bands, respectively. Besides, Si-O peaks for the APTES conjugates of GO were identified by FTIR spectroscopy. No cytotoxic or hemolytic effects were observed for GO samples, thus proving their biocompatibility. The interaction of Ricinus communis lectin confirmed that GO-AL has a biorecognition capability and an exposed galactose structure. This biorecognition capability was accompanied by the determination of the specific absorption of lactosylated GO by HepG2 cells mediated through the asialoglycoprotein receptor. The successful conjugation, hemolytic safety, and specific recognition described here for lactosylated GO indicate its promise as an efficient drug-delivery vehicle to hepatic tissue.

Effect of gamma irradiation doses in the structural and functional properties of mice splenic cells.

PURPOSE: Ionizing radiation is nowadays effectively used in cancer treatments. However, the effect of irradiation in immune-system cells is poorly understood and remains controversial. The aim of this work was to determine the effect of γ-irradiation in the structural and functional properties of mice splenic cells. MATERIALS AND METHODS: Structural traits of irradiated splenic cells were evaluated by Atomic Force Microscopy and Raman spectroscopy. Functional properties were measured by gene and protein expression by RT-qPCR and ELISA, respectively. The induced cytotoxic effect was evaluated by MTT assay and the phagocytic capability by flow cytometry. RESULTS: Membrane roughness and molecular composition of splenic adherent cells are not changed by irradiation doses exposure. An increase in transcription of pro-inflammatory cytokines was observed. While protein expression decreased in IL-2 dose-dependent, relevant differences were identified in the anti-inflammatory marker IL-10 at 27 Gy. An increase of cytotoxicity in irradiated cells at 7 Gy and 27 Gy doses was observed, while phagocytosis was slight increased at 7 Gy dose but not statistically significant. CONCLUSIONS: We have demonstrated that γ-irradiation affects the splenic cells and changes the cytokines profile toward a pro-inflammatory phenotype and a tendency to increase the cytotoxicity was found, which implies a stimulation of immune response induced by γ-irradiation.

Intra and interobserver variability of intrapartum transperineal ultrasound measurements with contraction and pushing.

The aim of this study was to evaluate the inter- and intraobserver correlation of the different intrapartum-transperineal-ultrasound-parameters(ITU) (angle of progression (AoP), progression-distance (PD), head-direction (HD), midline-angle (MLA) and head-perineum distance (HPD)) with contraction and pushing. We evaluated 28 nulliparous women at full dilatation under epidural analgesia. We performed a transperineal ultrasound evaluating AoP and PD in the longitudinal plane, and MLA and HPD in the transverse plane. Interclass correlation coefficients (ICC) with 95% CIs and Bland-Altman analysis were used to assess intra- and interobserver measurement's repeatability. The ICC of the ITU for the same observer was adequate for all the parameters (p < .005) AoP 0.98 (95%CI, 0.96-0.99), PD 0.98 (95%CI, 0.97-0.99), MLA 0.99 (95%CI, 0.97-0.99), HPD 0.96 (95%CI, 0.88-0.99). The ICC of the ITU for interobserver was: AoP 0.93 (95%CI, 0.79-0.98), PD 0.92 (95%CI, 0.76-0.97), MLA 0.77 (95%CI, 0.42-0.92), HPD 0.47 (95%CI, -0.12-0.8). The HD had an interobserver correlation of 0.53 (95%CI, 0.1-0.9) (Kappa C). The mean difference of the AoP was 2.42°, of the PD 1 mm and 0.28° MLA (Bland-Altman test). ITU has an adequate intra- and interobserver correlation for its use with contraction and pushing under epidural analgesia. Impact statement What is already known on this subject: The intrapartum transperineal ultrasound parameters can be used with contraction and pushing under epidural analgesia. What the results of this study add to what we know: ITU may be used to evaluate the difficulty of instrumental delivery/to evaluate the difficulty of instrumentation in vaginal operative deliveries and this study concludes that ITU is reproducible during uterine contraction with pushing. What the implications are of these findings for clinical practice and/or further research: Therefore, ITU could be used without difficulty with an adequate intra- and interobserver correlation for the prediction of instrumentation difficulty in operative vaginal deliveries.

Molecular recognition of glyconanoparticles by RCA and E. coli K88 - designing transports for targeted therapy.

The targeted drug delivery has been studied as one of the main methods in medicine to ensure successful treatments of diseases. Pharmaceutical sciences are using micro or nano carriers to obtain a controlled delivery of drugs, able to selectively interact with pathogens, cells or tissues. In this work, we modified bovine serum albumin (BSA) with lactose, obtaining a neoglycan (BSA-Lac). Subsequently, we synthesized glyconanoparticles (NPBSA-Lac) with the premise that it would be recognized by microbial galactose specific lectins. NPBSA-Lac were tested for bio-recognition with adhesins of E. coli K88 and Ricinus communis agglutinin I (RCA). Glycation of BSA with lactose was analyzed by electrophoresis, infrared spectroscopy and fluorescence. Approximately 41 lactoses per BSA molecule were estimated. Nanoparticles were obtained using water in oil emulsion method and spheroid morphology with a range size of 300-500 nm was observed. Specific recognition of NPBSA-Lac by RCA and E. coli K88 was displayed by aggregation of nanoparticles analyzed by dynamic light scattering and atomic force microscopy. The results indicate that the lactosylated nanovectors could be targeted at the E. coli K88 adhesin and potentially could be used as a transporter for an antibacterial drug.

Intrapartum transperineal ultrasound used to predict cases of complicated operative (vacuum and forceps) deliveries in nulliparous women.

INTRODUCTION: The objective of this study was to investigate the predictive value of intrapartum transperineal ultrasound in the identification of complicated operative (vacuum or forceps) deliveries in nulliparous women. MATERIAL AND METHODS: Prospective observational study of nulliparous women with an indication for operative delivery who underwent intrapartum transperineal ultrasound before fetal extraction. Managing obstetricians were blinded to the ultrasound data. Intrapartum transperineal ultrasound was performed immediately before blade application, both at rest and concurrently with contractions and active pushing. Operative delivery was classified as complicated when one or more of the following situations occurred: three or more tractions; a third-/fourth-degree perineal tear; significant bleeding during the episiotomy repair; major tear or significant traumatic neonatal lesion. RESULTS: A total of 143 nulliparous women were included in the study (82 vacuum-assisted deliveries and 61 forceps-assisted deliveries), with 20 fetuses in occiput posterior position. Forty-seven operative deliveries were classified as complicated deliveries (28 vacuum-assisted deliveries, 19 forceps-assisted deliveries). No differences in obstetric, intrapartum or neonatal characteristics were observed between the study groups, with the following exceptions: birthweight (3229 ± 482 uncomplicated deliveries vs. 3623 ± 406 complicated deliveries; p < 0.003) and number of vacuum tractions (1.4 uncomplicated deliveries, 4.5 complicated deliveries; p < 0.0005). The strongest predictors of a complicated delivery, using the area under the receiver-operating characteristics curve (AUC), were the angle of progression with active pushing (AoP2) (AUC 86.9%) and the progression distance with active pushing (PD2) (AUC 74.5%). The optimal cut-off value for predicting a difficult operative delivery was an AoP2 of 153.5° (sensitivity 95.2%; false-positive rate 5.9%) or PD2 of 58.5 mm (sensitivity 95.2%; false-positive rate 7.1%). CONCLUSIONS: The sonographic parameters AoP2 and PD2 can be used to predict cases of complicated operative deliveries in nulliparous women.

Intrapartum transperineal ultrasound as a predictor of instrumentation difficulty with vacuum-assisted delivery in primiparous women.

OBJECTIVES: To assess the capability of different intrapartum transperineal ultrasound parameters to predict the difficulty of vacuum extraction. This is a prospective observational study performed between 04/2012 and 03/2013 on 72 primiparous-women, ≥37-weeks with singleton pregnancies at full dilatation that underwent transperineal ultrasound before vacuum placement for foetal extraction. Working in a transperineal longitudinal plane we evaluated: progression-angle, progression-distance and head direction; in a transverse plane: midline-angle and head-perineum distance. The vacuum extractions were classified as easy-group (EG) (≤3 vacuum pulls), difficult/impossible-group (DG)(≥4 pulls). Occiput-posterior presentations were not assessed. RESULTS: Fifty-two (52) patients were studied (26 patients per study group). No differences were observed in obstetric, neonatal or intrapartum characteristics between the study groups, with the following exceptions: new-born (NB) weight (3147 g versus 3540 g) and the number of vacuum pulls (1.4 EG versus 4.3 DG; p < 0.0005). The progression angle was 133.1° (123°-143°) in EG and 109.2° (97.2°-121.2°) in DG (p < 0.0005); up direction of foetal head was 88% versus 34.5% (p < 0.0005); progression distance was 37 mm (26.6-47.4) versus 29.9 mm (8.8-51; p = 0.003); midline angle was 35° (15.4°-54.6°) versus 59.7° (34.5°-84.9°; p = 0.0005); head-perineum distance was 41.9 mm (35.2-48.6) versus 48.9 mm (40.5-57.3; p = 0.017). The area under the Receiver Operating Characteristic (ROC) curve for the progression angle was 0.9 (95%CI, 0.82-0.99), and the midline angle was 0.8 (95%CI, 0.67-0.92). CONCLUSION: If previous to the placement of the vacuum cup the progression angle is ≤120°, the foetal head direction is horizontal or down, and the midline angle is ≥35°, there is an 85% chance that the delivery will require more than 4 vacuum pulls.

Analysis of middle cerebral artery peak systolic velocity in monochorionic twin pregnancies as a method for identifying spontaneous twin anaemia-polycythaemia sequence.

A regular Doppler control evaluation of middle cerebral artery peak systolic velocity is needed in order to identify twin anaemia polycythaemia sequence in monochorionic twin pregnancies. Here, we present a clinical case of spontaneous TAPS, and we review the diagnostic criteria and management strategies for this syndrome.

Stepwise sequential screening for Down's syndrome (combined test associated with modified genetic sonography) in pregnant women with low risk for chromosomal disorders.

OBJECTIVE: To assess the sensitivity (Sen) and false positive ratio (FPR) of stepwise sequential screening [1st step: combined test (CT), 2nd step: modified genetic sonography (major malformation and nuchal fold, MGS)] as a screening method for Down's syndrome (DS) in the general population of pregnant women. METHODS: Prospective study. During a 5-year study period (July 2005 to June 2010), 17,911 pregnant women were screened for DS using a stepwise sequential screening method (CT+MGS). We evaluated the Sen and FPR (95% CI) of the two chromosomal disorder screening methods for DS: CT and CT+MGS. RESULTS: Seventeen thousand nine hundred and eleven cases were analysed, including 67 with chromosome abnormalities and 45 with DS. The Sen of CT for DS was 80% (95% CI; 68.3-91.7) (36/45) with a FPR of 4.2% (95% CI; 3.9-4.5) (752/17, 866). The Sen of CT+MSG for DS was 93.3 (95% CI; 85.9-99) (42/45) with a FPR of 4.8% (95% CI; 4.5-5.1) (860/17, 866). CONCLUSIONS: MGS coupled with CT increases the Sen of DS diagnosis by 13.3% (95% CI; 2.7-25.9), with an increase in FPR of 0.6% (95% CI; 0.5-0.7).

Role of fetal echocardiography in stepwise sequential screening for chromosomal disorders (combined test associated with modified genetic sonography).

OBJECTIVES: To evaluate the contribution made by fetal echocardiography in identifying Down's syndrome (DS) and other chromosomal disorders in a stepwise sequential screening method (first step: combined test (CT), second step: modified genetic sonography (MGS) (major malformation and nuchal fold)), for DS in the general population of pregnant women. METHODS: Prospective study. During a 5-year study period (July 2005-June 2010) 17,911 pregnant women underwent CTs with MGS (with fetal cardiac morphological evaluation performed by obstetricians in a tertiary hospital) as a screening method for DS. We evaluated the sensitivity and false positive rate (FPR) (95% confidence interval (CI)) of three screening methods for DS and all chromosomal disorders: CT, CT + MGS, and CT + fetal echocardiography. RESULTS: A total of 17,911 cases were analyzed with 67 chromosome disorders and 45 DS cases being found. For DS, the CT sensitivity was 80% (95% CI; 68.3-91.7) (36/45) and 79.1% (95% CI; 69.4-88.8) (53/67) for all chromosome disorders, with a FPR of 4.2% (95% CI; 3.9-4.5) (752/17,866) and 4.1% (95% CI; 3.8-4.4) (735/17,844), respectively. For CT + MSG and CT + fetal echocardiography, the sensitivity for DS was 93.3% (95% CI; 85.9-0.99) (42/45) and 95.5% (95% CI; 90.5-0.99) (64/67) for all chromosome disorders. The FPR for CT + MSG was 4.8% (95% CI; 4.5-5.1) (860/17,866) and 4.6% (95% CI; 4.3-4.9) (836/17,844), respectively. The FPR of CT + fetal echocardiography was 4.4% (95% CI; 4.1-4.7) (792/17,866) for DS screening and 4.3% (95% CI; 4-4.6) (770/17,844) for chromosome abnormality screening. CONCLUSIONS: Fetal echocardiography is highly capable of identifying DS and other chromosomal disorders as a part of genetic sonography in stepwise sequential screening.

First trimester contingent test as a screening method for Down's syndrome. A prospective study in the general population.

OBJECTIVES: To evaluate the possibility of implementing a contingent test as a screening method for Down's syndrome (DS) in the first trimester of pregnancy, and assess its sensitivity (Sen) and false positive rate (FPR). METHODS: Prospective study covering a 4-year study period (July 2006-June 2010). Pregnant women were offered a combined test (CT) as the first step of a contingent test. An intermediate risk group is identified in the CT (1/101 and 1/1000) and offered an ultrasound assessment of secondary s (nasal bone, ductus venosus, tricuspid regurgitation). RESULTS: CTs were performed on 10,452 pregnant women (24 cases of DS). In the intermediate risk group, which had 7 cases of DS, we performed secondary ultrasound marker assessment on 98.1% (1,017/1,036). The CT and the contingent test had a Sen of 83% (95% CI; 67.9-98) (20/24) and 70.8% (95% CI; 52.6-88.9) (17/24) with an FPR of 3% (95% CI; 2.7-3.3) (316/10,430) and 2% (95% CI; 1.7-2.3) (220/10,408), respectively. CONCLUSIONS: With the contingent test, we managed to reduce the FPR, but the Sen was too low for use as a screening method for DS.

Angiographic patency study of an albumin-free recombinant streptokinase formulation in acute myocardial infarction

PURPOSE: Fibrinolytic therapy restores coronary patency and reduces mortality in patients with acute myocardial infarction. Albumin is present in most of the streptokinase formulation as a stabilizer but it is not known whether it plays a role in the product's efficacy and safety profiles. The aim of this study was to assess 90 minutes-coronary patency of a new albumin-free recombinant streptokinase (rSK) formulation. METHODS . Patients with ischemic chest pain and ST-segment elevation, less than 12 hours after symptoms onset, without contraindications for fibrinolytic therapy, were included to receive 1.5 x 106 IU of rSK in a one-hour intravenous infusion. Angiography was performed 90 minutes after and coronary patency was classified according to the TIMI flow scales. RESULTS. The study enrolled 25 patients, 59.4 ± 9.2 years-old, 88 percent men and 92 percent white. The mean time interval between the symptoms onset and rSK infusion was 3.0 ± 2.0 hours. Patency rate (TIMI 2-3) of the infarct-related vessel was 72 percent (18/25). Partial or complete ST-segment resolution was achieved in 17 patients (68 percent). Hypotension and nauseas were the most frequent adverse events. Haemorrhage or in-hospital deaths were not reported. CONCLUSIONS. This study suggests that intravenous albumin-free rSK is a safe and appropriate therapy to get early (90-minute) coronary patency in patients with acute myocardial infarction(AU)

PROPÓSITO: Terapia fibrinolítica restablece la permeabilidad coronaria y reduce la mortalidad en pacientes con infarto agudo de miocardio. Albúmina está presente en la mayoría de la estreptoquinasa como la formulación de un estabilizador, pero no se sabe si juega un papel en la eficacia del producto y los perfiles de seguridad. El objetivo de este estudio fue evaluar 90 minutos permeabilidad coronaria de un nuevo albúmina libre de la estreptoquinasa recombinante (RSK) formulación. MÉTODOS. Los pacientes con dolor torácico y elevación del segmento ST, a menos de 12 horas después de los síntomas de inicio, sin contraindicaciones para la terapia fibrinolítica, se incluyeron para recibir 1,5 x 106 UI de RSK en una hora en perfusión intravenosa. Angiografía se realizó 90 minutos después de permeabilidad coronaria y se clasifican de acuerdo con el flujo TIMI escalas. RESULTADOS. El estudio reclutó 25 pacientes, 59,4 ± 9,2 años, 88 por ciento hombres y 92 por ciento blanco. La media de intervalo de tiempo entre la aparición de los síntomas y RSK perfusión fue de 3,0 ± 2,0 horas. Tasa de permeabilidad (TIMI 2-3) de los buques relacionados con el infarto fue del 72 por ciento (18/25). Parcial o completa del segmento ST resolución se logró en 17 pacientes (68 por ciento). Hipotensión y náuseas fueron los acontecimientos adversos más frecuentes. Hemorragia en el hospital o no se informaron muertes. CONCLUSIONES. Este estudio sugiere que la albúmina intravenosa sin RSK es un tratamiento seguro y apropiado para obtener temprano (90 minutos) permeabilidad coronaria en pacientes con infarto agudo de miocardio