Fractional flow reserve (FFR): changing the practice of interventional cardiology.

Fractional flow reserve (FFR) has become an extremely valuable tool for assessing the hemodynamic significance of intermediate coronary lesions. This manuscript delineates the current guidelines regarding the use of FFR and discusses emerging indications for the use of this diagnostic tool and how they compare with and complement non-invasive or other invasive diagnostic modalities. The manuscript addresses some of the key unanswered questions related to FFR, the potential pitfalls of this tool and discusses future directions of use and research.

Dual antiplatelet therapy for primary and secondary prevention.

The concomitant use of aspirin and an ADP receptor (P2Y12) blocker, also known as dual antiplatelet therapy (DAPT), has been extensively investigated as a primary and secondary prevention strategy in an effort to reduce the risk of cardiovascular events. In this manuscript the authors review the current guideline recommendations for DAPT and discuss the scientific data that supports these recommendations. Reported are also the scientific knowledge gaps and how future studies are likely to delineate these issues. Incremental knowledge is not likely to be an alternative to individualized care provided by the astute clinician to his patient. In consideration for prescribing DAPT (drug, dosage and duration) the clinician will have to weigh the potential benefits (reduction in death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke) and risks (severe or life-threatening bleeding) for each and every patient.

Emerging oral anticoagulants for stroke prevention in patients with non-valvular atrial fibrillation.

In patients with atrial fibrillation (AF) warfarin has been the mainstay therapy for stroke prevention. In recent randomized clinical trials (RCTs) oral direct thrombin inhibitor (Dabigatran) and factor Xa inhibitors (Rivaroxaban and Apixaban) challenged the efficacy and safety benchmarks set by warfarin. These drugs boast a rapid onset of action, shorter half-life and fewer drug and dietary interactions. Moreover, these new anticoagulants do not require monitoring, titration or dose adjustments. These agents have already been approved for prevention of stroke or systemic embolism in patients with AF. Uncertainty regarding suitability, efficacy and safety in certain patient subsets and issues related to the ability effectively monitor the pharmacodynamic effects and reverse the therapeutic effects of these drugs should be addressed as we engage in a widespread use of these agents in various patient subsets.

Intrapartum translabial three-dimensional ultrasound visualization of levator trauma.

OBJECTIVES: The aim of this study was to visualize levator trauma by three-dimensional (3D) ultrasound performed during labor and soon after the crowning of the fetal head and to determine how often levator trauma occurs. METHODS: This was a prospective, observational study of 66 women enrolled during the first stage of labor. The women underwent intrapartum 3D transperineal ultrasound examination during the first and second stages of labor and within 12 h after delivery. Volume datasets were acquired and analyzed to determine the presence of levator trauma. RESULTS: Data from 10 of the 66 women were excluded from analysis-nine because they underwent Cesarean section in the first or second stage of labor and one because she underwent hysterectomy and no postpartum volumes were collected. Thus our study group comprised 56 women-35 nulliparous and 21 parous. A total of 504 volumes were collected in the 56 women (three volumes for each stage of labor). One hundred and twenty levator volumes were excluded from analysis, but volumes of acceptable quality were available for all three stages of labor in all women. Eleven (31.4%) of the 35 nulliparae had levator lesions detected postpartum and none of them had levator lesions before delivery. Five (23.8%) of the 21 parous women had a levator tear detected in their postpartum volumes. In two of these five women the levator tear was also present in both volumes taken during labor. CONCLUSIONS: Visualization of the levator ani during labor by 3D ultrasound examination is feasible. Comparison of volumes obtained during labor and within the first 2 h after delivery supports the theory that crowning of the head is the immediate cause of avulsion of the levator ani muscle.

The transvaginal probe as a uterine manipulator: a new technique to simplify transabdominal chorionic villus sampling in cases with difficult access to the trophoblast.

OBJECTIVES: To evaluate the efficacy of using the transvaginal probe to manipulate the uterus and change the position of the trophoblast, and to simplify access to the chorionic villus under difficult conditions. METHODS: One thousand five hundred and thirty-nine procedures were performed in our centre in 1524 pregnant women from September 2006 to September 2009. In 90 of these, a difficult access to the trophoblast was observed and uterine manipulation under continuous ultrasound guidance with a double needle technique, was applied to obtain the sample. Of these, 86 samples were taken from singleton pregnancies and 4 from two bichorionic twin pregnancies RESULTS: One thousand five hundred and thirty-nine transabdominal chorionic villus sampling (TA-CVS) procedures were conducted on 1524 pregnant women. As many as 1449 were performed without manipulation with the transvaginal probe and in 90 cases the manipulation was carried out. In 89 cases, access to the trophoblast was difficult and the uterus was manipulated, which enabled an adequate TA-CVS to be performed with a single aspiration. In one case, TA-CVS was not performed due to significant pelvic pain in a patient with a fixed, retroflexed uterus and a previous history of endometriosis. CONCLUSIONS: Uterine manipulation with the transvaginal probe may be a useful solution in cases where TA-CVS is limited by difficult access to the trophoblast.

Sonographic assessment of fetal spine and head position during the first and second stages of labor for the diagnosis of persistent occiput posterior position: a pilot study.

OBJECTIVES: The aim of this pilot study was to perform a preliminary investigation into the predictive values of the position of the fetal spine and of the occiput measured during the first and second stages of labor by intrapartum ultrasound for persistent occiput posterior (OP) position. METHODS: This was a prospective, cohort study, in which 100 women with singleton pregnancies were enrolled during the first or second stage of labor. The women underwent intrapartum transabdominal sonography and the positions of the fetal head and spine were recorded. The women were followed up until delivery and occiput position at birth was assessed. RESULTS: Eighty-four pregnancies were evaluated in the second stage of labor, with 74 of these also evaluated in the first stage. Fifty-one percent of fetuses were found to be in an OP position during the first stage of labor, but the majority of these rotated to an anterior position before delivery. There were six cases of OP at delivery, and all of these were among the 23 fetuses that were found to be in an OP position on ultrasound evaluation during the second stage of labor. All six were also found to have a posterior spine position during the second stage of labor, with this finding observed in only one fetus with occiput anterior position at delivery. CONCLUSIONS: The results of this study suggest that the position of the head and spine during the second stage of labor could be useful indicators for predicting the OP position at delivery. The results also suggest that the OP position at delivery results from a failure of rotation from the OP position, rather than a malrotation from the anterior position. Studies with larger sample sizes are needed to confirm these results.

Development of the Fetal Vermis: New Biometry Reference Data and Comparison of 3 Diagnostic Modalities-3D Ultrasound, 2D Ultrasound, and MR Imaging.

BACKGROUND AND PURPOSE: Normal biometry of the fetal posterior fossa rules out most major anomalies of the cerebellum and vermis. Our aim was to provide new reference data of the fetal vermis in 4 biometric parameters by using 3 imaging modalities, 2D ultrasound, 3D ultrasound, and MR imaging, and to assess the relation among these modalities. MATERIALS AND METHODS: A retrospective study was conducted between June 2011 and June 2013. Three different imaging modalities were used to measure vermis biometry: 2D ultrasound, 3D ultrasound, and MR imaging. The vermian parameters evaluated were the maximum superoinferior diameter, maximum anteroposterior diameter, the perimeter, and the surface area. Statistical analysis was performed to calculate centiles for gestational age and to assess the agreement among the 3 imaging modalities. RESULTS: The number of fetuses in the study group was 193, 172, and 151 for 2D ultrasound, 3D ultrasound, and MR imaging, respectively. The mean and median gestational ages were 29.1 weeks, 29.5 weeks (range, 21-35 weeks); 28.2 weeks, 29.05 weeks (range, 21-35 weeks); and 32.1 weeks, 32.6 weeks (range, 27-35 weeks) for 2D ultrasound, 3D ultrasound, and MR imaging, respectively. In all 3 modalities, the biometric measurements of the vermis have shown a linear growth with gestational age. For all 4 biometric parameters, the lowest results were those measured by MR imaging, while the highest results were measured by 3D ultrasound. The inter- and intraobserver agreement was excellent for all measures and all imaging modalities. Limits of agreement were considered acceptable for clinical purposes for all parameters, with excellent or substantial agreement defined by the intraclass correlation coefficient. CONCLUSIONS: Imaging technique-specific reference data should be used for the assessment of the fetal vermis in pregnancy.

Second trimester levels of maternal serum total activin A and placental inhibin/activin alpha and betaA subunit messenger ribonucleic acids in Down syndrome pregnancy.

OBJECTIVES: Previous data have shown that inhibin A (alpha/betaA) is increased about twofold in maternal serum samples from Down syndrome pregnancy. Our objectives were to determine whether activin A (betaA/betaA) was similarly increased in maternal serum from pregnancies affected with fetal Down syndrome, and to investigate whether increased expression of each inhibin/activin subunit occurred in placental tissue from cases of fetal Down syndrome. DESIGN AND METHODS: Maternal serum total activin A levels were measured in 20 cases of fetal Down syndrome and 100 unaffected pregnancy samples. In addition, analysis of inhibin/activin alpha and betaA subunit mRNA levels was performed in placental tissue extracts from six cases of fetal Down syndrome and six tissues with a normal karyotype. RESULTS: The median total activin A level in the Down syndrome cases was 0.82 MoM (multiples of the median); values did not differ significantly (P = 0.36, Mann-Whitney U analysis) from those in unaffected pregnancies. The inhibin alpha subunit/GAPDH mRNA ratio, but not that of betaA subunit/GAPDH mRNA, was significantly greater (P < 0.01, ANOVA) in placental tissue from Down syndrome than in control placental tissue. CONCLUSIONS: Unlike inhibin A, activin A is not significantly increased in Down syndrome relative to unaffected pregnancy. Furthermore, increased amounts of maternal serum inhibin A in Down syndrome pregnancy probably result from increased placental expression of inhibin alpha, but not betaA, subunit.

An intrauterine progesterone contraceptive system (52 mg) used in pre- and peri-menopausal patients with endometrial hyperplasia.

An intrauterine progesterone contraceptive system (IPCS) (52 mg) was inserted in 25 women with cystic endometrial hyperplasia. Among these women, 11 complained of heavy climacteric symptoms and also received an oestrogen replacement therapy consisting of conjugated oestrogens (0.625 mg/day) administered cyclically for 3 out of 4 wk. Prior to the therapy and after 6 mth of treatment, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), oestrone (E1) and oestradiol (E2) plasma levels were measured and endometrial histology was evaluated. In the women receiving IPCS treatment alone, there were no significant changes in FSH, LH, PRL, E1 and E2 plasma levels. However, there were remarkable changes found in their endometrial histology. In the remaining women receiving both treatments there was a sharp decrease in FSH and LH plasma levels and an increase in E1 and E2 plasma levels, while the prolactin levels remained unchanged. With the exception of two of these women, the endometrial histology changed remarkably. The endometrial morphology of the two exceptions remained unchanged. All climacteric symptoms disappeared after the administration of both IPCS and the oestrogen replacement therapy. The remarkable changes which did occur in the endometrial histology resulted in a less active glandular epithelium and stromal decidual formation, thus proving a useful effect of treatment.

An investigation of psychopathology in nonreferred suicidal and nonsuicidal adolescents.

This investigation examined self-reported psychopathology in a school-based sample of 456 suicidal and nonsuicidal adolescents. The sample consisted of four groups: three at-risk for suicidal behavior based on current suicidal ideation as assessed by the Suicidal Ideation Questionnaire (SIQ; Reynolds, 1988), past suicide attempts, or both; and one nonsuicidal comparison group. Psychopathology was examined using ten scales from the Adolescent Psychopathology Scale (APS; Reynolds, 1998a) including: Major Depression, Conduct Disorder, Substance Abuse, Schizophrenia, Adjustment Disorder, Anorexia Nervosa, Borderline Personality Disorder, Obsessive-Compulsive Personality Disorder, Schizotypal Personality Disorder, and Avoidant Personality Disorder. Analyses were conducted separately for males and females using a MANOVA design that examined psychopathology severity among the four groups. Adolescents who engaged in past or current suicidal behavior had higher psychopathology severity scores compared to their nonsuicidal peers. Males with current suicidal thoughts who had attempted suicide had the highest levels of psychopathology severity compared to males in the other three groups. Females with a past suicide attempt or current suicidal ideation had higher psychopathology severity scores compared to nonsuicidal females. Results show greater psychopathology in school-based adolescents who have engaged in past and/or current suicidal behavior. The need for clinicians and mental health professionals working with at-risk youth to focus on concurrent psychopathology along with suicidal behavior is discussed.

[The problem approach in the teaching-learning process of communication]. / A problematização no processo ensino-aprendizagem da comunicação.

This article reports on an experience in the teaching of communication theory to nurse technician students in Curitiba, based on the use of problem solving skills. The results ratified Stefanelli's proposition concerning the teaching-learning process of the contents about human and therapeutic communication. Therapeutic communication strategies facilitate students' understanding, as well as the use of therapeutic communication in their relationship with patients. Learning was effective because teacher and students shared a common goal: the quality of nursing care.

[20 years of nursing courses at the Federal University of Parana and the careers of its graduates]. / Os vinte anos do curso de enfermagem na universidade federal do paraná e a trajetória de seus egressos.

This is a retrospective research with nurses graduated from the Federal University of Paraná (UFPR). A brief review of records such as meetings minutes, reports, and interviews documented the facts that built nursing from 1974 to 1994 at UFPR. The program graduated 467 nurses, to whom a questionnaire, containing open and closed questions, was sent. The sample was constituted of 62 graduates who answered the questionnaire. Qualitative and quantitative outcomes are presented in tables, providing support to curriculum changes and offering an alert to the need of conceptual clarification regarding teaching, practice and nursing research.

Quantitation of fetal DNA in maternal serum during the first trimester of pregnancy by the use of a DAZ repetitive probe.

Cell-free fetal DNA in maternal plasma or serum is at present widely investigated as a source of fetal genetic material, both in studies of pregnancy-related disorders and in planning strategies for non-invasive prenatal diagnosis. Despite the number of trials already performed on the quantitation of fetal DNA, data about the amount of DNA at the beginning of pregnancy, in particular in the first trimester, remain limited. A new probe mapping on the deleted in azoospermia (DAZ) repetitive region of the Yq chromosome was designed for an early assessment of fetal DNA concentration in maternal serum. Among 57 pregnant women prospectively studied in their first trimester, fetal DNA was detected already by the 5th gestational week, with the analysis becoming reliable by the 8th week of gestation when a 100% accuracy in fetal sex determination was achieved. Moreover, in the three cases of pregnancy ending in fetal loss, the amount of fetal DNA apparently decreased before the abortion was diagnosed, whereas it consistently showed an increasing trend in normal pregnancies. Real-time PCR with the use of DAZ multilocus probe can efficiently quantitate free fetal DNA in the maternal serum at the beginning of pregnancy.

Prolactin and certain obstetric stress conditions.

Prolactin levels were evaluated during certain stress conditions, obstetric or gynecologic surgical interventions, labor, and birth. In 68 patients undergoing voluntary abortion, prolactin levels were measured to study the effect of anesthetics and of dilatation and curettage on hormonal secretion. Prolactin levels were evaluated in five patients undergoing elective cesarean section and in five post-menopausal patients undergoing total abdominal hysterectomy with bilateral oophorectomy. Moreover, prolactin concentration in serial samples of blood was estimated in 32 normal patients with spontaneous vaginal delivery at term and in 16 newborns at term after 30-60 and 120 min following birth. Prolactin responsiveness to TRH was evaluated in 12 newborns at the 4th day of life. Plasma prolactin levels rose in all the stress conditions investigated except in labor, during which hormone levels showed a decrease starting 2 h before delivery and reaching the lowest value 1 h prior. From this moment on there was a remarkable rise in prolactin concentration, with a peak 1 h after delivery. The decrease in prolactin levels during labor could possibly be due to an increase in dopaminergic activity. Moreover, the finding of no variation of prolactin levels during induced abortion in a group of patients pretreated with methysergide supports the view that the serotoninergic system also affects prolactin release.

PIP: Prolactin levels were evaluated during certain stress conditions, obstetric or gynecologic surgical interventions, labor, and birth. In 68 patients undergoing voluntary abortion, prolactin levels were measured to study the effect of anesthetics and of dilatation and curettage on hormonal secretion. Prolactin levels were evaluated in 5 patients undergoing elective cesarean section and in 5 postmenopausal patients undergoing total abdominal hysterectomy with bilateral oophorectomy. Moreover, prolactin concentration in serial samples of blood was estimated in 32 normal patients with spontaneous vaginal delivery at term and in 16 newborns at term after 30-60 and 120 minutes following birth. Prolactin responsiveness to TRH was evaluated in 12 newborns at the 4th day of life. Plasma prolactin levels rose in all the stress conditions investigated except in labor, during which hormone levels showed a decrease starting 2 hours before delivery and reaching the lowest value 1 hour prior. From this point on, there was a remarkable rise in plasma concentrations, with a peak 1 hour after delivery. The decrease in prolactin levels during labor could possibly be due to an increase in dopaminergic activity. Moreover, the finding of no variation of prolactin levels during induced abortion in a group of patients pretreated with methysergide supports the view that the serotoninergic system also affects prolactin release.

First-trimester fetal sex prediction by deoxyribonucleic acid analysis of maternal peripheral blood.

OBJECTIVES: We investigated whether the number of weeks of gestation influences the accuracy of first-trimester fetal sex prediction by analysis of deoxyribonucleic acid extracted from whole maternal blood. A comparison was also made to determine whether a difference exists between this approach and the deoxyribonucleic acid analysis of transcervical cells performed on the same group of subjects. STUDY DESIGN: Deoxyribonucleic acid was isolated from 50 maternal blood samples taken between gestational weeks 7 and 11. The sex of the fetus was assessed by nested polymerase chain reaction specific for the amelogenin gene. A receiver-operating characteristic curve analysis was used to correlate the accuracy of fetal gender prediction with the gestational age and also to compare the goodness of the 2 methods under investigation. RESULTS: Analysis of the receiver-operating characteristic curve provided a cutoff value of 9 weeks 4 days of gestation for both tests, indicating that a higher degree of accuracy in the sex assignment was obtained in those samples taken before or at this time. However, this difference was statistically significant only for analysis of deoxyribonucleic acid from maternal blood. The comparison between tests of deoxyribonucleic acid from maternal blood and from transcervical cells showed that the first approach is better, although a statistically significant difference was not found. CONCLUSION: Analysis of maternal blood deoxyribonucleic acid is a better approach than analysis of trans-cervical cell deoxyribonucleic acid in fetal sex prediction. The highest degree of accuracy is obtained when blood is drawn before 10 weeks of gestation. This can be important when sampling of chorionic villi should be avoided because of the risk of an X-linked disease when the fetal sex is female.

Analysis of fetal sex in TCC sample DNA: a contribution to the validation of this approach.

We compared two methods of collection of transcervical cell samples, mucus aspiration and cytobrush, with respect to the efficiency in determining fetal sex and we correlated the results with the week of gestation (7-11 weeks) to evaluate if the age of gestation influenced the success of the analysis. DNA extracted from TCC samples recovered by mucus aspiration (n = 27) and cytobrush (n = 36) were analysed by nested PCR to predict fetal sex. The statistical indices of sensitivity, specificity, positive predictive value and negative predictive value were determined, and compared with those of other studies previously performed. No statistically significant difference was found between the two methods of TCC sampling concerning the success of fetal sex prediction which was high for both methods (78 per cent and 89 per cent) and no correlation with the week of gestation was found. Transcervical cell sampling represents an encouraging prospect for first-trimester prenatal diagnosis even when the least invasive techniques are used.

Effects of L-arginine on utero-placental circulation in growth-retarded fetuses.

BACKGROUND: To evaluate the effects of L-arginine (ARG) infusion, the nitric oxide as substrate, on the utero-placental circulation at third trimester. METHODS: Three groups of nine pregnant women each were infused i.v. with 30 g ARG, for 30 minutes. One group served as control, and the two remnants were composed by patients with intrauterine growth retardation with (IUGR-B) or without (IUGR-A) increased resistances in the utero-placental circulation. Changes of blood flow velocity waveforms of both uterine arteries and umbilical artery were recorded for 60 minutes. Blood pressure, serum nitrites/nitrates and growth hormone levels were also measured. RESULTS: No hemodynamic changes in utero-umbilical circulation were observed during infusion in any of the three groups. Considering the uterine arteries separately as placental and non-placental sided we found a significant decrease of non-placental side resistances in IUGR-B women. Indeed, the pulsatility index was lowered by 14%, in respect of baseline value. Serum nitrites/nitrates as well as serum growth hormone levels were significantly increased by ARG, in every woman, irrespective of the presence of fetal growth retardation. Blood pressure remained unaffected during infusion in every woman. CONCLUSIONS: These findings suggest that L-arginine infusion affects utero-placental circulation in patients with IUGR associated with increased uterine resistances. Such an action is specific and appears possibly to be mediated by a release of nitric oxide.

Non-invasive first trimester fetal gender assignment in pregnancies at risk for X-linked recessive diseases.

OBJECTIVES: Prenatal diagnosis in families affected by X-linked recessive disorders should ideally be limited to the subjects at increased risk, i.e. male fetuses, in order to avoid the risk of fetal loss due to the invasive procedure in healthy female fetuses. The aim of the study was to assess the fetal sex within the first trimester of gestation by two non-invasive approaches, using ultrasonography and a molecular analysis of fetal DNA extracted from whole maternal blood with specific markers, in order to avoid invasive sampling in female fetuses. METHODS: A total number of 18 fetuses at risk for an X-linked recessive disease were included in the present investigation. Maternal peripheral blood was analysed between 7 and 12 weeks of gestation by nested PCR for the detection of fetal DNA and the prediction of fetal gender. In addition, when the biparietal diameter (BPD) was between 21 and 23 mm, an ultrasonographic examination was carried out to assess the fetal gender. CVS was then performed in male fetuses only. RESULTS: Fetal gender was correctly assigned by ultrasonography between 21 and 23 mm of BPD in all the cases studied, whereas DNA extracted from whole maternal blood accurately predicted the gender in all the female cases (10), but failed in 4 out of 8 male fetuses, erroneously assigned as females. CONCLUSION: The present study shows that sonography is able to accurately predict the fetal gender within the first trimester of pregnancy, whereas the molecular analysis of DNA extracted from whole maternal blood is biased by false-Y-negative results in 50% of the cases.

Picosecond-resolution study of nonlinear scattering in carbon black suspensions in water and ethanol.

The physical origin of the nonlinear scattering of light induced by focusing of intense laser pulses onto carbon black suspensions (CBS's) is discussed through the interpretation of limitation, time-resolved pump-probe transmission, and angularly and time-resolved scattering experiments performed with picosecond resolution. Comparison of the experimental results performed on two different solutions of CBS's in water and in ethanol leads us to the conclusion that the scattering phenomenon begins most probably with growing microplasmas and that the influence of the solvent is significant only at longer times.

Early prenatal diagnosis of recurrent 46,XY partial gonadal dysgenesis.

OBJECTIVES: We present a case of early prenatal diagnosis of recurrent 46,XY partial gonadal dysgenesis, by combining early genetic and sonographic evaluations. METHODS: The conceptus of a mother with a first child affected by 46,XY gonadal dysgenesis was sonographically evaluated at 21- and 23-mm BPD (12(+2) and 12(+6) LMP-based age) and the female genitalia were observed. Karyotype analyses was performed on amniotic fluid and it revealed a 46,XY complement without mosaicism. SRY was amplified by PCR for molecular analyses. RESULTS: We observed a discordance between female phenotype detected at 21 and 23 mm of biparietal diameter (12(+2) and 12(+6) LMP-based age) and male karyotype. In the child and the fetus, seminiferous cords were not recognisable, whereas rare Leydig cells and no germ cells could be identified. Internal and external genitalia were sexually ambiguous in the child and feminized in the fetus. CONCLUSION: This is the first case of early prenatal diagnosis of recurrent 46,XY partial gonadal dysgenesis and it points to the importance of combining early analyses of genetic sex with sonography in the management of anomalies of sexual development, with particular regard to syndromes for which the risk of recurrence is little understood.