Uneventful Term Pregnancy Research Articles

Serum mannose-binding lectin (MBL) concentrations are reduced in non-pregnant women with previous adverse pregnancy outcomes.

Mannose-binding lectin (MBL) is an important component of the innate immunity, and it is responsible not only for opsonization of micro-organisms, but also for efferocytosis. The aim of this study was to investigate whether MBL concentrations and lectin complement pathway activity are altered in non-pregnant women with previous adverse pregnancy outcomes. Patients were divided into four groups on the basis of their history of pregnancy complications, including control patients who had uncomplicated pregnancies and term deliveries (control, n=33), and three groups of patients with a history of pregnancy complications, including preterm labour (n=29), recurrent miscarriage (n=19) or unexplained intrauterine foetal death (IUFD; n=17). All women enrolled in the study had an interval of three to six months following their previous pregnancy, and they agreed to have a blood sample taken. We found significantly higher MBL concentrations and functional activity of the lectin complement pathway in healthy controls who had previous uneventful term pregnancies (1341ng/mL; activity 100% (IQR: 62%-100%)), compared to women with the history of IUFD (684ng/mL, P=.008; activity 8.5% (IQR: 0%-97.8%), P=.011), recurrent miscarriage (524ng/mL, P=.022; activity 44% (IQR: 4%-83%), P=.011) or preterm labour (799ng/mL, P=.022; activity 62.5% (IQR: 0%-83%), P=.003). Our results suggest that inadequate function of the complement lectin pathway is associated with a higher risk of preterm labour, recurrent miscarriage and unexplained intrauterine foetal death.

Enhanced Expression of TLR8 in Placental Tissue in Preeclampsia.

The expression of TLR8 in the placental tissue was studied in specimens from women of reproductive age with early- and late-onset preeclampsia (12 and 8 patients, respectively). The reference groups included 15 women: 10 with uneventful full-term pregnancy and 5 with preterm operative delivery on gestation weeks 28-33. The expression of TLR8 in placental structures was maximum in early-onset preeclampsia (p<0.01) characterized by the gravest clinical course, while the expression of TLR8 in late-onset preeclampsia was comparable with that in full-term pregnancy. This significant increase of TLR8 expression in placental tissue seemed to reflect activation of the key proinflammatory factors of congenital immunity and induction of the systemic inflammatory response. Manifest differences in the expression of TLR8 in late- and early-onset preeclampsia confirmed the hypothesis on different variants of this condition.

Laparoscopic Transabdominal Cerclage for Cervical Incompetence: A Feasible and Effective Treatment in 10 Steps

To demonstrate the surgical technique of laparoscopic cerclage (LAC) in nonpregnant women with a clinical diagnosis of cervical incompetence. In this video, the authors describe the complete procedure in 10 steps to standardize and facilitate the comprehension and performance of the procedure in a simple and safe way. Step-by-step video demonstration of the surgical technique. Private hospital in Curitiba, Paraná, Brazil. The patient was 32 years old (gravidity and parity, G3A3; late progressive miscarriage), had no comorbidities, and had a radiologic diagnosis of cervical incompetence. The main steps of LAC are described in detail. A complete laparoscopic approach was performed. Under general anesthesia, the patient was placed in the 0-degree supine decubitus position with arms alongside her body. The operative setup included a 15-mm Hg pneumoperitoneum created using the closed Veress technique and 4 trocars: a 10-mm trocar at the umbilicus for a 0-degree laparoscope; a 5-mm trocar in the right iliac fossa; a 5-mm trocar in the left iliac fossa; and a 5-mm trocar in the suprapubic area. After systematic exploration of the pelvic and abdominal cavities, the procedure began. Step 1 involved identification of anatomic key landmarks and exposure of the operation field. Step 2 involved opening of the anterior peritoneum. The anterior peritoneal reflection was opened over the peritoneum uterovesicalis and then extended laterally until the uterine artery could be clearly identified on both sides. Step 3 involved dissection of the avascular space on each side of the uterus. The vesical-cervical avascular space was created, and the bladder was pushed down, away from the isthmus area. Step 4 involved preparation for a perfect stitch placement. A 5-mm Mersilene suture (Ethicon, Somerville, NJ) with a straight needle was introduced by a suprapubic trocar into the abdominal cavity before a complete identification of uterine vessels at both the sides using atraumatic graspers. Step 5 involved identification of the perfect space in the posterior aspect for Mersilene suture placement. Step 6 was to make a perfect anterior stitch. For this, the needle was grasped at the proximal portion in a 90-degree angle. In posterior position and when helped by a cranial and posterior uterine mobilization, the needle passed through the right, broad ligament in the avascular space created on the anterior leaf and medially from the uterine artery until the tip of the needle was seen on the posterior face above the uterosacral ligament. All steps were possible by synchronic uterine mobilization. Step 7 was to make a perfect posterior stitch. The procedure was then repeated contralaterally following the same anatomic and technical precepts but from posteriorly to anteriorly. Step 8 involved correct positioning and orientation of the Mersilene suture far away from the ureter and medial to the uterine arteries 2 cm over the uterosacral ligaments. Step 9 involved fixation of the Mersilene suture with an adequate blocking sequence. Step 10 involved fixation of the Mersilene suture and reperitonealization. The tape was knotted with an adequate blocking intracorporeal suturing sequence at the cervicoisthmic junction, and a Monocryl 2-0 stitch (Ethicon, Somerville, NJ) was made to fix the knot and left it horizontally. Finally, the procedure was ended with anterior reperitonealization, covering all the plica uterovesicalis and mesh, leaving it completely extraperitoneal. The surgery ended without any intraoperative complications and within 30 minutes. Patient was discharged on the first day postoperatively and became pregnant 6 months after surgery, with a C-section delivery of a healthy term newborn at 39 weeks of gestational age. LAC in nonpregnant women with a diagnosis of cervical incompetence is safe and feasible in experienced hands, adding all the intrinsic advantages of minimally invasive surgery and providing better obstetric outcomes. In this patient, the procedure was performed without any intra- or postoperative complications, and the patient had an uneventful term pregnancy in the follow-up period. We must remember that adequate standardization of surgical procedures will help reduce the learning curve.

The Association between Abnormal Body Mass Index and First Trimester Spontaneous Abortion in Iraqi Women: Case Control Study

The lack of consensus regarding the effect of pre-pregnancy BMI on pregnancy outcome and in particular on the risk of early miscarriage, and the rarity of Iraqi literatures dealing with this subject, justified the planning and the conduction of this study on a sample of Iraqi pregnancy ladies that unfortunately developed spontaneous abortion in the Mid-Euphrates region of Iraq. Aim of the study: To evaluate the correlation between pre-pregnancy bMI and risk of spontaneous abortion. The study was conducted at the Department of Obstetrics and Gynecology in Al-Diwaniyah maternity and Child Hospital in AL-Diwaniyah Province, Mid-Euphrates region of Iraq. The study was started at January 2018 and ended at March 2019. bMI measurements of two groups of women, the first group included women with early spontaneous abortion and the second group included women with uneventful term or near term pregnancy, were obtained and contrasted. There was no significant difference in mean BMI between study and control groups, 24.60 ± 4.57 kg/m2 versus 23.55 ± 3.50 kg/m2, respectively (P = 0.195). However, the incidence rates of underweight and overweight were significantly higher in study than in control groups, 10% versus 1.7% and 40% versus 23.3%, respectively (P <0.05).

Mitochondrial Encephalopathy: First Portuguese Report of a VARS2 Causative Variant.

Combined oxidative phosphorylation deficiency 20 (COXPD20) is a mitochondrial respiratory chain complex (RC) disorder, caused by disease-causing variants in the VARS2 gene, which encodes a mitochondrial aminoacyl-tRNA synthetase. Here we describe a patient with fatal mitochondrial encephalopathy caused by a homozygous VARS2 gene missense variant. We report the case of a girl, the first child of non-consanguineous and healthy parents, born from an uneventful term pregnancy, who presented, in the neonatal period, major hypotonia and microcephaly. At 4 months of age she showed poor eye contact, nystagmus, global psychomotor development delay and failure to thrive, without dysmorphic features. Focal seizures started at 24 months which evolved to a severe epileptic encephalopathy and finally to super refractory status epilepticus, leading to her death at 28 months of age. Etiologic investigation encompassing metabolic and genetic causes failed to disclose a diagnosis. Post-mortem exome sequencing allowed the identification of a pathogenic variant in VARS2 gene in the homozygous state (c.1100C>T, p.Thr367Ile) in the patient, inherited from her heterozygous parents, leading to the diagnosis of COXPD2. To the best of our knowledge, this is the fifth case described in the literature of a child with disease-causing variant in VARS2. With this report we expand the knowledge about the phenotype associated with this very rare mitochondrial defect, further emphasizing the use of exome sequencing as a very powerful diagnostic tool.

A novel familial mutation in Alexander disease with marked variation in clinical severity

Objective: Alexander disease is a rare, often lethal disorder characterized by white-matter degeneration and cytoplasmic inclusions in astrocytes known as Rosenthal fibers, which are immunohistochemically positive to glial fibrillary acidic protein (GFAP). The disease typically results from dominant mutations in GFAP that arise de novo. However, series of familial cases with variable clinical manifestations have been described suggesting a potential recessive inheritance or germline mosaicism. We report a male infant with typical Alexander disease, inherited by his asymptomatic father with positive neuroimaging markers of the disease. Methods: Clinical histories were obtained and whole exome sequencing (WES) analyses in blood samples were performed through next generation sequencing. Results: We report a 6-month male, born of an uneventful term pregnancy, who presented with generalized hypotonia, chorioathetosis and drug-resistant seizures, without macrocephaly. Brain MRI showed symmetrical abnormalities of the basal ganglia, subcortical white matter abnormalities, mainly of the frontal area with contrast enhancement along with high intensity periventricular rim on T1. WES analysis of the patient revealed a heterozygous missense mutation, c.1120G>A (p.Glu374Lys) in GFAP gene, resulting in the substitution of the aminoacid glutamic acid with lysine at the protein level. Although this genetic change is novel, it was considered as pathogenic from in silico analysis. We therefore proceeded to genetic analyses of the remaining members of the family that revealed the same mutation in the asymptomatic father. A subsequent brain MRI showed white matter abnormalities suggestive of adult-onset Alexander disease. Conclusion: We present a familial case of Alexander disease caused by a novel mutation on GFAP gene. There is a marked discrepancy on clinical presentation between the father and the affected child imposing that there is a striking variation on penetrance of the mutated gene of unknown etiology. We suggest genetic analysis on parents of patients with Alexander disease even if asymptomatic.

Outcomes of prosthetic valve replacement in women of child-bearing age.

The outcomes of pregnancy are more favorable for women with bioprostheses than for those with mechanical prostheses. However, bioprostheses are associated with a high reoperation rate in young women and it remains unclear whether these young women can give birth without any complications. We analyzed the outcomes of prosthetic valve replacement and investigated the effectiveness and problems associated with bioprostheses in women of child-bearing age in Japan. The subjects of this study were six consecutive young adult women aged under 40years, who underwent prosthetic valve replacement between January 2007 and April 2016. Bioprostheses were selected for four of these six women in consideration of their child-bearing age. Mechanical valves were selected for the other two women who underwent the Konno procedure and double valve replacement (AVR, MVR) in view of their high risk for reoperation. The cardiac operations, although without mortality or morbidity, were complex and some involved multi-time procedures. Three of the women with bioprostheses had uneventful term pregnancies. These young women with bioprostheses were able to give birth safely; however, as multiple operations are often required, and bioprostheses may not be ideal for young women. Prosthetic valve selection for young women of child-bearing age requires adequate pregnancy counseling and long-term planning.

Congenital Leukemia: A Case Report

Congenital Leukemia is rare malignancy presenting at birth or shortly thereafter with non-specific signs and symptoms. We present a 7 day old female weighing 2500g, with fever, lethargy, poor feeding and failure to thrive, following uneventful full term pregnancy. Peripheral smear examination and leukemic cells in bone marrow established the diagnosis.

Laparoscopic fertility-sparing surgery for early stage ovarian cancer: a single-centre case series and systematic literature review.

BackgroundThere is as yet limited evidence about fertility-sparing surgery for early ovarian cancer (EOC) carried out laparoscopically. We sought to analyze recurrence patterns and fertility outcome in a cohort of ovarian cancer patients who underwent fertility-saving laparoscopic surgical staging.MethodsWe conducted a retrospective analysis of prospectively collected data on all patients undergoing fertility-sparing laparoscopic staging procedures for presumed EOC at a single gynecologic oncology service. Oncologic safety and reproductive outcome were the main outcome measures. The pertinent literature is reviewed.ResultsThe study cohort consisted of 12 women. Cases included 5 invasive epithelial tumors and 7 nonepithelial tumors. The disease was reclassified to a higher stage in one woman. After a median follow up period of 38 months (range: 14–108), the overall survival was 100% and recurrence-free survival 90.9%. Five (100%) of patients who attempted pregnancy conceived spontaneously. Three of them had uneventful term pregnancy delivering healthy babies. The literature search yielded 62 cases of laparoscopic fertility conserving surgery for ovarian cancer. There were 4 (6.2%) recurrences. Cumulative pregnancy and live birth rate were not estimable as earlier publications lack essential data.ConclusionsLaparoscopic staging may represent a viable option for premenopausal women seeking fertility preservation in the setting of early ovarian cancer. More research is needed to determine whether laparoscopy may offer reproductive benefits to this particular population.

A novel mutation in a mother and a son with Aarskog-Scott syndrome

Aarskog-Scott syndrome, also termed as faciogenital dysplasia, is an X-linked disorder consisting of short stature, craniofacial dysmorphism, shawl scrotum, cryptorchidism, and interdigital webbing. Cardiac and central nervous system abnormalities and behavioral disorders can also be detected. The gene responsible for the syndrome is called FGD1, located at Xp11.21. A 7-year-old boy was admitted to our hospital due to short stature. He was born to non-consanguineous parents after an uneventful term pregnancy. Orchiopexy for bilateral cryptorchidism was performed when he was 2 years old. At physical examination, his height was under 3 percentile, and he had broad nasal bridge, hypertelorism, wide philtrum, brachydactyly, and interdigital webbing. Cranial magnetic resonance imaging and echocardiography revealed normal findings. An eye examination showed amblyopia and astigmatism. The mother had short stature and interdigital webbing as well. Mutational analyses revealed a novel mutation (c.308-2G), hemizygous in the boy and heterozygous in the mother. Aarskog syndrome (faciogenital dysplasia) should be kept in mind in children with short stature and interdigital webbing.

The Impact of Perceived Maternal Stress and Other Psychosocial Risk Factors on Pregnancy Complications

Abstract Objective The aim of this study was to ascertain the contribution of perceived maternal stress and other components of a psychosocial profile to the occurrence of complications of pregnancy. Methods We conducted a prospective cohort study of pregnant women in a tertiary perinatal centre in Eastern Townships, Quebec. Psychosocial profile was assessed between 10 and 20 weeks' gestation and 25 and 30 weeks' gestation using six validated self-administered questionnaires. After delivery, data related to maternal, perinatal, and neonatal outcomes were collected. Descriptive, bivariate, and ANOVA repeated measures were performed. Results Among 303 consenting women, 81 (26.7%) had at least one pregnancy complication. Biomedical risk factors were evenly distributed in both groups (with or without complications). Women with complications had higher mean perceived stress at 10 to 20 weeks than those with uneventful term pregnancies (32.6 ± 11.7 vs. 29.3 ± 10.3; P P P Conclusion Maternally perceived stress before 20 weeks' gestation is associated with complications of pregnancy and especially with preterm birth.

Autophagy in term normal human placentas

Autophagy is an inducible catabolic process that responds to environment and is essential for cell survival during stress, starvation and hypoxia. Its function in the human placenta it is not yet understood. We collected 14 placentas: 7 at vaginal delivery and 7 at elective caesarean section after uneventful term pregnancies. The presence of autophagy was assessed in different placental areas by immunoblotting, immunohistochemistry and electron microscopy. We found that autophagy is significantly higher in placentas obtained from cesarean section than in those from vaginal delivery. Moreover there is a significant inverse relationship between autophagy and umbilical arterial glucose concentration.

The Impact of Perceived Maternal Stress and Other Psychosocial Risk Factors on Pregnancy Complications

ObjectiveThe aim of this study was to ascertain the contribution of perceived maternal stress and other components of a psychosocial profile to the occurrence of complications of pregnancy. MethodsWe conducted a prospective cohort study of pregnant women in a tertiary perinatal centre in Eastern Townships, Quebec. Psychosocial profile was assessed between 10 and 20 weeks’ gestation and 25 and 30 weeks’ gestation using six validated self-administered questionnaires. After delivery, data related to maternal, perinatal, and neonatal outcomes were collected. Descriptive, bivariate, and ANOVA repeated measures were performed. ResultsAmong 303 consenting women, 81 (26.7%) had at least one pregnancy complication. Biomedical risk factors were evenly distributed in both groups (with or without complications). Women with complications had higher mean perceived stress at 10 to 20 weeks than those with uneventful term pregnancies (32.6 ± 11.7 vs. 29.3 ± 10.3; P < 0.05). Among those with complications, women with preterm birth perceived even more stress at 10 to 20 weeks (34.4 ± 11.5 vs. 29.3 ± 10.3; P < 0.05) than those with term pregnancies. Peer social support at 25 to 30 weeks, in women with a complication, was reported to be less than in women with an uneventful term pregnancy (51.0 ± 16.6 vs. 55.5 ± 13.8; P < 0.05). Other psychosocial dimensions were similar in both groups. ConclusionMaternally perceived stress before 20 weeks’ gestation is associated with complications of pregnancy and especially with preterm birth.

Clot lysis time and thrombin activatable fibrinolysis inhibitor in severe preeclampsia with or without associated antiphospholipid antibodies

We investigated clot lysis time, thrombin activatable fibrinolysis inhibitor antigen (TAFI) levels and TAFI gene polymorphisms in pregnant patients with severe preeclampsia, with or without associated antiphospholipid syndrome (APS). The study groups included 82 pregnant patients without antiphospholipid antibodies with severe preeclampsia (PE group) and 10 pregnant APS patients who developed severe preeclampsia (APS-PE group). Controls included 76 primary pregnant APS patients (APS group) and 89 healthy pregnant patients (NOR group) with uneventful term pregnancy and delivery. Patients in the APS-PE, APS and NOR groups were sampled during each trimester of pregnancy and at 4-6 months and 12 months after delivery. Patients in the PE group were sampled during the third trimester and after delivery. Significantly prolonged clot lysis time after delivery was found in the PE, APS-PE and APS groups compared to the NOR group. The PE and APS-PE groups had longer clot lysis time than the APS group. Levels of TAFI were found to be higher after delivery in patients of the PE and APS-PE groups compared to the APS and NOR groups. Allele distribution of the TAFI gene polymorphisms was similar among the four study groups. We conclude that increased TAFI antigen levels and impaired fibrinolysis are pathogenetic factors in preeclampsia, regardless of whether or not preeclampsia is associated with the presence of antiphospholipid antibodies.

When Family Drawings Reveal Vulnerabilities and Resilience

Sonia's mother was concerned about her 9-year old daughter's aggression, defiant behavior, and distractibility. When she was 4-years, she kicked her bother and he lost a tooth as a result of the trauma. At this time, her pediatrician was concerned about hyperactivity, impulsivity, and defiance of authority and recommended a psychological evaluation. Sonia's father refused an evaluation and responded by physically abusing his wife while demanding a transfer to a new physician. Sonia's mother left her husband at this time and moved away with Sonia. Spousal abuse occurred frequently before the separation, and Sonia may have been physically abused as well. Currently, Sonia is in third grade where she is underperforming in many areas. She enjoys drawing and reading, but struggles to sit quietly and stay on task. Her teacher reports frequent vocal and physical disruptions. Homework takes an inordinate amount of time to complete. She does not have a sustained friendship; her mother feels that this is because other kids do not like being bossed by Sonia. Her mother is concerned about Sonia's behavior especially the unremorseful disruptive behavior toward her younger brother and grandmother. Sonia was born after an uneventful full-term pregnancy without evidence of maternal smoking, drugs, alcohol, or medications. Motor and social developmental milestones were achieved at the appropriate time. Language milestones were achieved early; her mother recalls that Sonia learned to read at the age of 3 years. Sonia's medical history is significant for obesity, seasonal allergic rhinitis, and delayed sleep onset with prolonged awakenings associated with nightmares. Her mother reports that Sonia "worries about everything," including thoughts that her brother will turn into a monster. When an argument occurs at home, she "gets scared," bites her nails, and cries. Sonia currently lives with her mother, 2 younger brothers, step-father, and grandparents. Family history is significant for drug abuse by her father and mental illness in the father's family. While conducting an interview with her mother, Sonia was asked to draw a picture of her family. Instead, she illustrated a book detailing her past experience in words accompanying each drawing. She described how she watched her father physically abuse her mother and her persistent fear of danger when conflict occurred at home. Although spelling was poor, her vocabulary, sequencing, and illustrations demonstrated above age-level skills for written expression and drawing. Examples of the writing that accompanied the drawings include: "I hate when my parents fight. I get scared and feel sick to my tummy like I want to throw up. I just hate that feeling!" "My mom told me she had a 'boyfriend.' These words were the most horrible I ever heard. Soon a nightmare began. Nightmares make me very, very scared."

Who Rules the Roost?

Adam's mother was concerned about her 3-year-old son's hyperactivity, violence, and activity level. Adam and his mom had recently moved into a shelter for pregnant women. The rest of the residents are primarily in their early 20s, whereas Adam's mom is 42. She had found about 3 months ago that she was pregnant. This was her fourth pregnancy, second with this father, and he had recently left her when she refused an abortion. Her other children are 22 and 24 and live out of state. She has a history of opioid addiction. She had been on methadone during Adam's gestation and had recently started on buprenorphine to treat her addiction during this pregnancy as well. Adam is here today for his 3-year-old checkup and you had not seen him for a year. Mom states that he has been healthy but has become progressively active over the last year. He is very angry about his dad leaving, and according to Adam's mother "blames her" for sending him away. They are living in 1 room at the shelter, and mom is finding it increasingly difficult to keep him busy all day. When she goes out looking for a job, he is very challenging at the shelter, and she constantly receives complaints that he is "too loud" in the common rooms. She feels like she is at the end of her rope with him, he is constantly climbing, bolting from her, and taking risks.When you examine Adam, you find a robust, healthy young boy. His eye contact is good, and he is socially related but does actively explore your office. When he begins taking the instruments off your wall, his mother sits passively watching him. When he begins playing with the faucet, she half heartedly tells him to "stop" but he looks at her and continues splashing. He then begins flicking the light switch on and off in the room with no response from mom. When you ask about discipline, mom states "nothing works." When you ask about supports, she states "I have nobody except Adam and the new baby now."Adam was born after an uneventful full-term pregnancy with his mother on 100 mg methadone daily. She denies cigarette smoking, drugs, alcohol, or other medications. Urine testing throughout was positive only for opioids. Motor milestones were achieved at the appropriate time. Language milestones at the 2-year-old visit consisted of 10 single words. Now, he has a 50 single-word vocabulary but no 2-word combinations. He primarily takes whatever he wants and has a tantrum if mom cannot figure out what he desires. Adam's medical history is unremarkable. Family history is significant for drug abuse by her father and mother; mental illness in the father's family consisting of bipolar disorder in several uncles. Where do you go from here?

ORIGINAL ARTICLE: Thrombin Activatable Fibrinolysis Inhibitor and Clot Lysis Time in Pregnant Patients with Antiphospholipid Syndrome: Relationship with Pregnancy Outcome and Thrombosis

Antiphospholipid syndrome (APS) pregnancies are associated with thrombotic obstetric complications, despite treatment. This study evaluated Thrombin Activatable Fibrinolysis Inhibitor (TAFI) levels, TAFI gene polymorphisms and Clot Lysis Time (CLT) in pregnant patients with APS in relation to pregnancy outcome and thrombosis. Group 1 consisted of 67 pregnant patients with APS. Group 2 included 66 pregnant patients with uneventful term pregnancies and delivery. Patients were sampled during each trimester and at baseline. TAFI antigen and CLT and two polymorphisms of the TAFI gene, Ala147Thr and +1542C/G, were determined. Significantly prolonged CLT was found at baseline in Group 1. Allele distribution of the TAFI gene polymorphisms was similar in both groups. Basal TAFI and CLT in patients with APS having an adverse or a good obstetrical outcome were similar. Comparison of TAFI and CLT baseline levels in patients with APS with or without previous thrombosis showed no statistical differences. Patients with APS have impairment in fibrinolysis evidenced by prolonged CLT at baseline. TAFI and CLT do not seem to be useful as markers of obstetric outcome or risk of thrombosis in patients with APS.

When Family Drawings Reveal Vulnerabilities and Resilience

Sonia's mother was concerned about her 9-year old daughter's aggression, defiant behavior, and distractibility. When she was 4-years, she kicked her bother and he lost a tooth as a result of the trauma. At this time, her pediatrician was concerned about hyperactivity, impulsivity, and defiance of authority and recommended a psychological evaluation. Sonia's father refused an evaluation and responded by physically abusing his wife while demanding a transfer to a new physician. Sonia's mother left her husband at this time and moved away with Sonia. Spousal abuse occurred frequently before the separation, and Sonia may have been physically abused as well.Currently, Sonia is in third grade where she is underperforming in many areas. She enjoys drawing and reading, but struggles to sit quietly and stay on task. Her teacher reports frequent vocal and physical disruptions. Homework takes an inordinate amount of time to complete. She does not have a sustained friendship; her mother feels that this is because other kids do not like being bossed by Sonia. Her mother is concerned about Sonia's behavior especially the unremorseful disruptive behavior toward her younger brother and grandmother.Sonia was born after an uneventful full-term pregnancy without evidence of maternal smoking, drugs, alcohol, or medications. Motor and social developmental milestones were achieved at the appropriate time. Language milestones were achieved early; her mother recalls that Sonia learned to read at the age of 3 years.Sonia's medical history is significant for obesity, seasonal allergic rhinitis, and delayed sleep onset with prolonged awakenings associated with nightmares. Her mother reports that Sonia "worries about everything," including thoughts that her brother will turn into a monster. When an argument occurs at home, she "gets scared," bites her nails, and cries. Sonia currently lives with her mother, 2 younger brothers, step-father, and grandparents. Family history is significant for drug abuse by her father and mental illness in the father's family.While conducting an interview with her mother, Sonia was asked to draw a picture of her family. Instead, she illustrated a book detailing her past experience in words accompanying each drawing. She described how she watched her father physically abuse her mother and her persistent fear of danger when conflict occurred at home. Although spelling was poor, her vocabulary, sequencing, and illustrations demonstrated above age-level skills for written expression and drawing. Examples of the writing that accompanied the drawings include: "I hate when my parents fight. I get scared and feel sick to my tummy like I want to throw up. I just hate that feeling!" "My mom told me she had a 'boyfriend.' These words were the most horrible I ever heard. Soon a nightmare began. Nightmares make me very, very scared."

Contribution and limit of the model of perfused cotyledon to the study of placental transfer of drugs. Example of a protease inhibitor of HIV: Nelfinavir

Objectives The perfused cotyledon model is a very useful method to study placental transfer of drugs. Here we studied placental transfer of the human immunodeficiency virus protease inhibitor nelfinavir using the non-recirculating dual human placental perfusion with a main goal to determining the clearance index of nelfinavir as related to maternal concentrations, and analyze the conditions under which ex vivo and in vivo data can be correlated. Study design Thirteen human cotyledons, obtained after uneventful term pregnancies, were perfused in an open double circuit with nelfinavir (320–4436 μg/l) and a freely diffusing marker antipyrine 20 mg/l, in the presence of an albumin concentration of 2 g/l. Drug concentrations were determined by high-performance liquid chromatography. Results The mean clearance index of nelfinavir was very weak when maternal concentrations were under 500 μg/l (0.03 ± 0.05). For maternal concentrations above 1200 μg/l, the mean fetal transfer rate was 14 ± 3.4%, the mean clearance index was 0.39 ± 0.10 and the fetal concentrations were between 133 and 671 μg/l. There was a good correlation between maternal and fetal concentrations ( r = 0.86; p < 0.001). Conclusions Our study with nelfinavir has achieved a good correlation between ex vivo and in vivo data. Our results also indicate that studies must be conducted under well defined conditions to obtain accurate and comparable data, underlining the fact that the ex vivo perfused cotyledon remains difficult to standardize as a model system.

Postpartum thunderclap headache

Two days after giving birth to a healthy baby following an uneventful term pregnancy, a healthy 31-year-old woman experienced a severe, diffuse “thunderclap” headache and generalized seizures. She had not received spinal anesthesia during labour. Her blood pressure was 140/90 mm Hg. Results of