Cell-free fetal DNA and intact fetal cells in maternal blood circulation: implications for first and second trimester non-invasive prenatal diagnosis

Both intact fetal cells as well as cell-free fetal DNA are present in the maternal circulation and can be recovered for non-invasive prenatal genetic diagnosis. Although methods for enrichment and isolation of rare intact fetal cells have been challenging, diagnosis of fetal chromosomal aneuploidy including trisomy 21 in first- and second-trimester pregnancies has been achieved with a 50-75% detection rate. Similarly, cell-free fetal DNA can be reliably recovered from maternal plasma and assessed by quantitative PCR to detect fetal trisomy 21 and paternally derived single gene mutations. Real-time PCR assays are robust in detecting low-level fetal DNA concentrations, with sensitivity of approximately 95-100% and specificity near 100%. Comparing intact fetal cell versus cell-free fetal DNA methods for non-invasive prenatal screening for fetal chromosomal aneuploidy reveals that the latter is at least four times more sensitive. These preliminary results do not support a relationship between frequency of intact fetal cells and concentration of cell-free fetal DNA. The above results imply that the concentration of fetal DNA in maternal plasma may not be dependent on circulating intact fetal cells but rather be a product of growth and cellular turnover during embryonic or fetal development.     

Postpartum intrauterine device contraception: A review

AIM: To review the safety (infection, perforation) and efficacy (expulsion, continuation rates, pregnancy) of intrauterine device (IUD) insertion in the postpartum period. METHODS: MEDLINE, PubMed and Google Scholar were searched for randomized controlled trials and prospective cohort studies of IUD insertions at different times during the postpartum period. Time of insertion during the postpartum period was documented specifically, immediate post placenta period (within 10 min), early post placenta period (10 min to 72 h), and delayed/interval period (greater than 6 wk). Other study variables included mode of delivery, vaginal vs cesarean, manual vs use of ring forceps to insert the IUD. RESULTS: IUD insertion in the immediate postpartum (within 10 min of placental delivery), early postpartum (10 min up to 72 h) and Interval/Delayed (6 wk onward) were found to be safe and efficacious. Expulsion rates were found to be highest in the immediate postpartum groups ranging from 14% to 27%. Immediate post placental insertion found to have expulsion rates that ranged from 3.6% to 16.2%. Expulsion rate was significantly higher after insertion following vaginal vs cesarean delivery. The rates of infection, perforation and unplanned pregnancy following postpartum IUD insertion are low. Method of insertion such as with ring forceps, by hand, or another placement method unique to the type of IUD did not show any significant difference in expulsion rates. Uterine perforations are highest in the delayed/interval IUD insertion groups.Breastfeeding duration and infant development are not affected by delayed/interval insertion of the non-hormonal (copper) IUD or the Levonorgestrel IUD. Timing of the Levonorgestrel IUD insertion may affect breastfeeding. CONCLUSION: IUD insertion is safe and efficacious during the immediate postpartum, early postpartum and delayed postpartum periods. Expulsion rates are highest after vaginal delivery and when inserted during the immediate postpartum period. IUD associated infection rates were not increased by insertion during the postpartum period over interval insertion rates. There is no evidence that breastfeeding is negatively affected by postpartum insertion of copper or hormone-secreting IUD. Although perforation rates were higher when inserted after lactation was initiated. Randomized controlled trials are needed to further elucidate the consequence of lactation on postpartum insertion. Despite the concerns regarding expulsion, perforation and breastfeeding, current evidence indicates that a favorable risk benefit ratio in support of postpartum IUD insertion. This may be particularly relevant for women for whom barriers exist in achieving desired pregnancy spacing.     

Phenotypic and functional properties of murine {gamma}{delta} T cell clones derived from malaria immunized, {alpha}{beta} T cell-deficient mice

Six murine T cell clones expressing TCR were generated frommalaria immunized, ß T celldeficient mice. Phenotypiccharacterization of these clones has revealed that, in contrastto conventional ß T cells, there is a considerabledegree of heterogeneity among these clones with regard to theirsurface markers and their lymphokine profile. One clone wasfound to display significant anti-parasite activity in vivoupon adoptive transfer. We attempted to determine whether theprotective clone differs in one or more key characteristicsfrom the non-protective clones. Although no obvious patternpeculiar to the protective clone was observed, it appears thatmore than one parameter may, in combination, define a distinctprotective phenotype, and thus explain the functional differencebetween the protective and non-protective clones.     

Effect of <Emphasis Type="Italic">Myracrodruon urundeuva</Emphasis> leaf lectin on survival and digestive enzymes of <Emphasis Type="Italic">Aedes aegypti</Emphasis> larvae

Aedes aegypti transmits the viruses that cause yellow and dengue fevers. Vector control is essential, since a vaccine for dengue has not as yet been made available. This work reports on the larvicidal activity of Myracrodruon urundeuva leaf lectin (MuLL) against A. aegypti fourth-stage larvae (L₄). Also, the resistance of MuLL to digestion by L₄ gut proteases and the effects of MuLL on protease, trypsin-like and α-amylase activities from L₄ gut were evaluated to determine if lectin remains active in A. aegypti gut and if insect enzyme activities can be modulated by MuLL. MuLL promoted mortality of L₄ with LC₅₀ of 0.202 mg/ml. Haemagglutinating activity of MuLL was detected even after incubation for 96 h with L₄ gut preparation containing protease activity. MuLL affected the activity of gut enzymes, inhibiting protease and trypsin activities and stimulating α-amylase activity. The results suggest that MuLL may become a new biodegradable larvicidal agent for dengue control. Larvicidal activity of MuLL may be linked to its resistance to proteolysis by larval enzymes and interference in the activity of digestive larval enzymes.     

Pregnancy rates and birth outcomes among women on efavirenz-containing highly active antiretroviral therapy in Botswana

BACKGROUND: Millions of HIV-infected women in developing countries are in need of safe and highly effective antiretroviral therapy. Pregnancy rates are usually high in developing countries, and efavirenz (EFV) use in women of childbearing age is of concern because of its potential teratogenicity. METHODS: As part of a prospective study comparing 6 initial highly active antiretroviral therapy (HAART) regimens, 3 of which contained EFV, pregnancy and birth outcomes were evaluated among female participants enrolled in a randomized clinical trial in Botswana. Before enrollment, all female participants indicated a willingness to avoid pregnancy for the 3-year duration of the study. Monthly urine pregnancy testing and regular contraceptive education and counseling were given to all women on study. RESULTS: Four hundred fifty-one (69.4%) of 650 enrolled study participants were female and experienced 71 pregnancies, for a rate of 7.9 per 100 person-years during the study. The mean time from HAART initiation to time of first pregnancy was 385 days. The median birth weight of babies was 2950 g (interquartile range: 2700-3250 g); the gender of babies (24 female and 15 male) and occurrence of early pregnancy loss (42%) and stillbirths (3%) did not differ between EFV- and non-EFV-exposed pregnancies (P=0.7). First-trimester EFV exposure occurred in 38 (53.5%) of the 71 pregnancies; 22 (57.9%) of these 38 pregnancies resulted in live births. One infant (4.5%) of the 22 EFV-exposed live births had a congenital abnormality with right limb shortening that was assessed to be unrelated to EFV exposure. CONCLUSIONS: The restoration of health and longevity in many HAART-treated women is often accompanied by childbearing, as evidenced by the large fraction of women in our cohort who became pregnant despite their initial statements of intent to avoid pregnancy. Of 22 first-trimester EFV-exposed live births, 1 neonate was found to have a major congenital abnormality; however, this defect was unrelated to EFV exposure. The small sample size is insufficient to estimate accurately the underlying risk of congenital malformation after exposure to EFV in early pregnancy, underscoring the importance of reporting to the existing international Antiretroviral Pregnancy Registry. In addition to accessing safe and effective HAART regimens, HIV-infected women require access to comprehensive family planning services, including contraception and procreation counseling.     

A Feasibility Study of Smoking Cessation Utilizing an Exercise Intervention among Black Women: ‘Quit and Fit’

BackgroundWomen who engage in higher levels of exercise while trying to quit smoking have been shown to be less likely to relapse and to sustain their smoking abstinence longer. This study sought to examine the benefits of exercise for improving smoking cessation among Black women.MethodsWe evaluated the feasibility of a 12-week smoking and exercise intervention, Quit and Fit, tailored for Black women. All participants (intervention and control) received 12 weeks of smoking cessation counseling via telephone and 9 weeks of nicotine lozenges. Participants who were randomly assigned to the intervention condition were also assigned to a 12-week exercise group.ResultsThirty-eight women were enrolled and 27 completed a 12-week follow-up assessment. Women from the intervention group were more likely to complete the 12-week follow-up assessment compared to participants in the control group (80% vs. 61%). Overall, 7 of the 38 participants (18%) were abstinent at 12 weeks (biochemically verified by expired carbon monoxide). Among the 25 women who completed the 12-week follow-up, abstinence was reported in 33% of the intervention group and 20% of the control group. Using an intent-to-treat approach, 25% of women in the intervention group were abstinent at 12 weeks (n = 5), compared to 11.1% for the control group (n = 2). These differences were not statistically significant.ConclusionsThe overall retention rate was 71% (27/38) at 12 weeks with higher among the intervention group (16/20; 80%) compared to the control group (11/18; 61%). The study demonstrates that it is feasible to retain African-American women in a short-term study of smoking cessation and exercise.     

Clinically significant symptom change in children with attention‐deficit/hyperactivity disorder: does it correspond with reliable improvement in functioning?

This study examined the relation between clinically significant (CS) change in symptoms of attention‐deficit/hyperactivity disorder (ADHD) and of oppositional defiant disorder (ODD), and reliable change in multiple domains of functioning in children who participated in the Multimodal Treatment Study of Children with ADHD. Children with CS change in symptoms were significantly more likely than children without CS change to have reliable change across five domains of functioning. Interestingly, however, depending on the measure of functioning, 14 to 52% of children who did not achieve CS change in symptoms showed reliable improvement in functional domains. The results have implications for the definition and measurement of CS change in child treatment‐outcome studies. © 2008 Wiley Periodicals, Inc. J Clin Psychol 65:1–18, 2009.     

Increased plasma nitric oxide, L-arginine, and arginase-1 in cirrhotic patients with progressive renal dysfunction

Background and Aims:  Increased levels of nitric oxide (NO) are hypothesized to contribute to renal dysfunction in patients with decompensated cirrhosis. In this study, we examined whether splanchnic and/or peripheral NO levels and L-arginine (L-Arg) correlate with progressive renal dysfunction in cirrhotics.
Methods:  Serum NO metabolites (NOx) and L-Arg were measured in: controls ( n  = 10); organ donors ( n  = 12); compensated cirrhotics ( n  = 17), cirrhotics with ascites ( n  = 25), refractory ascites ( n  = 11) or hepatorenal syndrome type II (HRS) ( n  = 11) and chronic renal failure patients ( n  = 18).
Results:  Plasma NOx and L-Arg levels rose progressively with worsening renal function in decompensated cirrhotics. Both NOx and L-Arg levels were highest in patients with HRS ( P  < 0.001 and P  < 0.025, respectively). While there were no differences in NOx levels related to the site of sampling, L-Arg levels were lowest in hepatic venous blood. There were significant relationships of NOx and L-Arg with Model for End-Stage Liver Disease score and Child–Pugh scores ( P  < 0.04 and P  < 0.01, respectively). Multivariate analysis showed a significant relationship between NOx, L-Arg and HRS.
Conclusion:  Worsening renal function in decompensated cirrhosis is accompanied by progressive elevation in plasma NOx and L-Arg. These findings support the hypothesis that NO-mediated vasodilation is probably linked with the mechanism of progressive renal failure in decompensated cirrhotics.