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Biomedical subjects

Lynn L Simpson

Publications and source records attributed to Lynn L Simpson.

14 recordsLinked to original sources

Higher rate of stillbirth at the extremes of reproductive age: a large nationwide sample of deliveries in the United States.

OBJECTIVE: The purpose of this study was to assess the effect of maternal age on the rate of stillbirth in a large, nationwide sample of deliveries in the United States. STUDY DESIGN: Data were derived from the Nationwide Inpatient Sample for the years 1995 through 2002. With the use of ICD-9 codes, the rate of stillbirth was determined as a function of maternal age. Multivariate regression analysis was used to assess the effect of maternal age on the odds of stillbirth, with adjustment for multiple known risk factors for stillbirth. RESULTS: There were 5,874,203 deliveries that were identified for analysis. The unadjusted rate of stillbirth was elevated for teenagers and for women aged > or =35 years. In the multivariate analysis, compared with women 20 to 34 years old, women who were < or =19 years old were more likely to have a pregnancy outcome of stillbirth (odds ratio, 1.11; 95% CI, 1.08-1.14), as were women who were 35 to 39 years old (odds ratio, 1.28; 95% CI, 1.24-1.32) and women who were > or =40 years old (odds ratio, 1.72; 95% CI, 1.63-1.81). CONCLUSION: The extremes of maternal age are associated with an increased risk for stillbirth, even after adjustment for a large number of known predisposing conditions.

Adolescent↗

Vaginal birth after cesarean delivery in twin gestations: a large, nationwide sample of deliveries.

OBJECTIVE: The purpose of this study was to assess the maternal morbidity associated with attempted vaginal birth after cesarean (VBAC) in twin gestations using a large, nationwide sample of deliveries. STUDY DESIGN: Data for this study were obtained from an administrative dataset, the Nationwide Inpatient Sample, a representative sample of discharges from non-Federal hospitals, for the years 1993 to 2002. Patients admitted nonemergently for the delivery of twin gestations who had a history of previous cesarean delivery were selected. Patients that either delivered vaginally or who had discharge codes that indicated labor before cesarean delivery were defined as the trial of labor group, while patients who had a cesarean delivery without discharge codes that indicated labor were defined as the elective cesarean group. Various complications of delivery were analyzed for each group. RESULTS: We identified 4705 women who underwent an elective cesarean delivery and 1850 women who underwent a trial of labor. For women who had a trial of labor, 836 (45.2%) delivered vaginally. The rate of uterine rupture was higher in the trial of labor group than in the elective cesarean group (0.9% vs 0.1%, P < .001), and the rate of wound complications was lower (0.6% vs 1.3%, P < .02). The rates of other complications including hysterectomy, transfusion, major postpartum infection, thromboembolism, uterine dehiscence, and pelvic hematoma were not significantly different between the 2 groups. CONCLUSION: Our study showed a significantly higher rate of uterine rupture in the trial of labor group that is similar to the rates reported for trial of labor after cesarean in singleton pregnancies.

Adult↗

Antenatal sonographic prediction of twin chorionicity.

OBJECTIVE: We sought to determine the accuracy of antenatal diagnosis of twin chorionicity at a single tertiary care center and assess the consequences of incorrect diagnoses. STUDY DESIGN: Twins with chorionicity diagnosed by ultrasound < or = 24 weeks' gestation were retrospectively reviewed. Chorionicity was assigned by sonographic findings including placental location(s), the lambda and T-signs, and/or fetal gender(s). Postnatal diagnosis was determined by placental histopathologic examination. Medical records of antenatal-postnatal discordant chorionicities were reviewed for adverse sequelae. RESULTS: Chorionicity was correctly assigned antenatally in 392/410 (95.6%) twins. The sensitivity, specificity, and positive and negative predictive values of monochorionicity assessed < or = 14 weeks were 89.8%, 99.5%, 97.8%, and 97.5%. Corresponding statistical values for the second trimester were 88.0%, 94.7%, 88.0%, and 94.7%. Two cases of inaccurate antenatal diagnoses affected patient counseling or were associated with adverse clinical outcomes. CONCLUSION: Antenatal assessment of chorionicity is accurate; however, incorrect diagnoses do occur and can affect reliable patient counseling and management.

Chorion↗

Characterization of cord blood natural killer and lymphokine activated killer lymphocytes following ex vivo cellular engineering.

Cord blood (CB) natural killer (NK) and lymphokine-activated killer (LAK) cytotoxic cells are poorly characterized but might be used to treat minimal residual and/or recurrent malignant disease. Currently, there is no mechanism to use CB for adoptive cancer cellular immunotherapy after CB transplantation (CBT). Recognizing this as a deficiency, we hypothesized that CB aliquots could be engineered ex vivo for potential donor lymphocyte infusion after CBT. Cryopreserved CB aliquots were thawed, depleted of monocytes, and cultured in serum-free medium alone or serum-free medium with anti-CD3 and interleukins 2, 7, and 12 combined with antibody/cytokines for 48 hours. Immunophenotyping, cytotoxicity, and proliferation were evaluated. A significant expansion of CD3+ was seen, in addition to increases in lymphocyte subsets of CD8+, CD8+/CD25+, and CD3+/45RO+ versus medium alone. A significant enhancement of CD3 proliferation (P<.001), NK cytotoxicity, NK subset expansion, LAK cytotoxicity, and T-helper 1 subset expansion was also demonstrated. Significant enrichment was seen in NK CD16+/CD56+bright, CD16+/CD56+dim, CD56+bright and CD56+dim/KIR3DL1+, CD56+bright and CD56+dim/KIR2DL1+, CD56+bright and CD56+dim/KIR2DL2+ and CD94+/NKG2a+ subsets. These increases in CB NK subsets were in part secondary to augmentation of cell survival. Further, survival of NOD-SCID mice xenografted with human K562 cells and treated with CB cells expanded with antibody/cytokines was significantly higher than that in animals that received no treatment (phosphate buffered saline) and those that were treated with CB ex vivo expanded in medium alone (P<.005, respectively). These data suggest that cryopreserved CB cells could be ex vivo engineered for potential use as adoptive cancer cellular immunotherapy for donor lymphocyte infusion after CBT.

Animals↗

Increased induction of allogeneic-specific cord blood CD4+CD25+ regulatory T (Treg) cells: a comparative study of naïve and antigenic-specific cord blood Treg cells.

OBJECTIVE: The genetic and immunological mechanism(s) responsible for the significant decrease in the incidence of graft-vs-host disease (GVHD) following HLA-disparate unrelated cord blood transplantation remains largely unknown. In this study, we investigated if cord blood (CB) CD4(+)CD25(+) T cells play a significant role in reducing the immune responses of allo-reactive CD4(+)CD25(-) T lymphocytes. METHODS: We compared CB CD4(+)CD25(-) and CD4(+)CD25(+) T cells, either naïve or antigenic stimulated, to their counterparts in unmobilized adult peripheral blood (APB) with respect to genetic expression patterns, immunophenotype, suppressive activity, and mechanism(s) of suppression. RESULTS: Both naïve CB and APB CD4(+)CD25(+) T cells expressed similarly elevated mRNA levels of CTLA-4, GITR, Foxp3, CD25, and elevated protein levels of CTLA-4 (p < 0.001) and GITR (p < 0.001). However, only naïve APB but not CB CD4(+)CD25(+) T cells showed suppression of allogeneic responses. Stimulation of CD4(+)CD25(-) T cells by MUTZ-iDC (MUTZ-3-specific immature dendritic cells) elicited amplification of these genes and potent suppression (69% +/- 5% and 71% +/- 3% suppression, p < 0.001, CB and APB, respectively) on CD4(+)CD25(-) T cell proliferation induced by MUTZ-iDC but not by unrelated stimulators. Compared to that from unmobilized APB, a significantly higher percentage (2.7-fold +/- 0.5-fold; p < 0.002) of CD4(+)CD25(+)CTLA-4(+) T regulatory (Treg) cell subsets were induced from CB CD4(+)CD25(-) T cells following allogeneic stimulation. CONCLUSION: Our results suggest that CB CD4(+)CD25(+) Treg cells, which are induced at a higher rate by allogeneic stimulation when compared to unmobilized APB, can readily function as potent allogeneic immune suppressors and may in part contribute to the decrease in CB alloantigen recognition and activation of CB CD4(+)CD25(-) T cells.

Antigen Presentation↗

Selective termination procedures in monochorionic pregnancies.

Monochorionic twins have placental anastomoses that to varying degrees create a common circulation. This presents unique challenges for the performance of selective fetal termination in cases of twin-twin transfusion syndrome, twin reversed arterial perfusion sequence, or discordant twin abnormalities. Multiple methods of interrupting the affected twin's circulation have been attempted with variable success. One of the most frequent complications of any approach is iatrogenic preterm premature rupture of membranes. Laser coagulation in the midtrimester appears to be safe and effective; however, it is only available at limited centers. Currently, bipolar coagulation is the method of choice in the second half of pregnancy. The recently reported technique of radiofrequency ablation appears to be successful with minimal complications. Exploration of further percutaneous and noninvasive techniques, as well as interventions to decrease the morbidity arising from preterm membrane rupture, may lead to increased survival of the remaining twin and reduced risk of maternal complications.

Female↗

Previous cesarean delivery: understanding and satisfaction with mode of delivery in a subsequent pregnancy in patients participating in a formal vaginal birth after cesarean counseling program.

The objective of this study was to determine patient satisfaction with delivery experience in a pregnancy subsequent to primary cesarean and to evaluate knowledge about a trial of labor after cesarean in patients enrolled in a formal vaginal birth after cesarean educational program. During a 12-month period, women with a history of cesarean delivery who were participating in a formal counseling program regarding the risks and benefits of vaginal birth after cesarean were surveyed in the antepartum and postpartum periods. Patient demographics, past birth experience, understanding of the risks and benefits of vaginal birth after cesarean, pregnancy outcomes, and ratings of satisfaction and recovery following the current delivery were collected. Patients were divided into four groups depending on their mode of delivery in the current pregnancy: group 1 succeeded at vaginal birth, group 2 underwent repeat cesarean in labor, group 3 delivered by cesarean before labor, and group 4 chose repeat cesarean. Ninety-five patients enrolled in the study. There were 26 patients in group 1, 18 patients in group 2, 16 patients in group 3, and 35 patients in group 4. The four groups had significant differences in patient satisfaction following the current delivery compared with the previous cesarean delivery ( p = 0.001). The patients who had a successful trial of labor exhibited the largest median change in score. The patients who delivered by cesarean during labor had the smallest median change in score. Nonetheless, 92% of these patients were pleased that they had attempted a vaginal birth. When questioned about the risks associated with a trial of labor after cesarean delivery, 92% of postpartum patients answered all questions correctly. Patients participating in a formal counseling program exhibit a high level of understanding about the risks and benefits of a trial of labor. Although the most satisfied patients were those who succeeded at vaginal birth, most women valued the opportunity to attempt a vaginal birth regardless of outcome.

Apgar Score↗

Immaturity of IL-18 gene expression and protein production in cord blood (CB) versus peripheral blood (PB) mononuclear cells and differential effects in natural killer (NK) cell development and function.

We have previously demonstrated dysregulation of IL-12 and IL-15 gene and protein expression between activated cord blood (CB) versus peripheral blood (PB) mononuclear cells (MNCs). In the present study, we compared IL-18 gene expression and protein production and IL-18 mRNA half-life in basal versus activated CB versus PB MNCs, the effects of IL-18 +/- IL-12 on MNCs IFN-gamma protein production and ex vivo expansion and activation of CB with IL-12 + IL-2 + anti-CD3 +/- IL-18. Basal and activated levels of IL-18 were significantly higher in PB versus CB MNCs (P < 0.05). IL-18 mRNA was coincidental with protein levels and significantly lower in CB (P < 0.05) and its half-life significantly shorter in CB versus PB MNCs (P < 0.05). IL-18 synergistically with IL-12 induced IFN-gamma production from PB greater than CB MNCs (P < 0.05). NK cells expansion (P < 0.001) and cytotoxicity (P < 0.01) was significantly increased with IL-12 + IL-2 + anti-CD3 and IL-18. In summary IL-18 gene expression and protein production are significantly decreased in activated CB versus PB MNCs, in part secondary to increased degradation of CB IL-18 mRNA. These results may have implications for the mechanism(s) in part responsible for the immaturity of CB T-cell immunity.

Apoptosis↗

Screening for congenital heart disease.

Congenital heart disease has the characteristics of a disease that is suited to screening, and the four-chamber view is an effective screening tool with a sensitivity of 40% to 50%. The use of multiple cardiac views can increase the pre-natal detection to 60% to 80%. Given that most infants with congenital heart disease are born to low-risk women, routine screening is warranted. Early pre-natal diagnosis provides an opportunity to exclude associated extracardiac and chromosomal abnormalities, discuss pregnancy options, adjust obstetric management, prepare parents for delivery of an affected baby, and plan delivery in a tertiary care center. Despite the widespread use of ultrasonography, only 15% to 30% of infants with congenital heart disease are identified prenatally. There is a need to do better.

Female↗

Fetal diaphragmatic hernia and upper limb anomalies suggest Brachmann-de Lange syndrome.

We describe two independent cases of Brachmann-de Lange syndrome (BDLS) in which second trimester fetal sonographic studies showed the presence of a diaphragmatic hernia and upper limb anomalies. In both cases the karyotypes were normal. Intrauterine growth restriction (IUGR) developed in the third trimester. Postnatal and postmortem physical examinations demonstrated typical physical findings associated with BDLS. The prenatal diagnosis of diaphragmatic hernia with associated anomalies should prompt consideration of an underlying genetic etiology.

Adult↗

Maternal medical disease: risk of antepartum fetal death.

Although certain maternal medical conditions increase the risk of antepartum fetal death, improvements in medical and obstetric care have decreased the likelihood of stillbirth. This article examines the current stillbirth rates reported in pregnancies complicated by common medical diseases. The reported stillbirth rates are expressed as the number of stillbirths occurring at > or = 20 weeks of gestation per 1,000 births in patients with the condition. Overall, about 10% of all fetal deaths are related to maternal medical illnesses such as hypertension, diabetes, obesity, systemic lupus erythematosus, chronic renal disease, thyroid disorders, and cholestasis of pregnancy. The early recognition of maternal medical diseases provides an opportunity for increased surveillance and interventions that may lead to more favorable pregnancy outcomes.

Cholestasis↗

Indications for fetal echocardiography from a tertiary-care obstetric sonography practice.

PURPOSE: The present study was conducted to evaluate the indications for fetal echocardiography in a tertiary-care obstetric sonography practice and to determine the incidences of confirmed congenital heart disease for each primary indication. METHODS: A retrospective analysis of all pregnant women referred to a pediatric cardiology unit for fetal echocardiography by the tertiary-care sonography unit over a 2-year period was performed. The primary indications for referral for fetal echocardiography were obtained from the sonographers' reports. Outcome data were extracted from the fetal echocardiograms, postnatal echocardiograms or pathology and autopsy reports, and patient medical records. RESULTS: Of 6,002 pregnant women who had undergone prenatal sonographic examination during the study period, 275 (4.6%) had been subsequently referred for fetal echocardiography. The most common primary indication for referral had been abnormal cardiac findings on the prenatal sonographic examination, which had been present in 64 (23.3%) of the 275 cases. In 44 (69%) of those 64 cases, congenital heart disease had been confirmed. Among the 211 patients who had had normal cardiac findings on prenatal sonography but had been referred for fetal echocardiography owing to other primary indications, congenital heart disease had been confirmed in only 7 cases (3.3%). CONCLUSIONS: An abnormal cardiac finding during prenatal sonographic examination is a common primary indication for fetal echocardiography and is more useful for identifying congenital heart disease than are other risk factors. Careful routine cardiac screening during routine prenatal sonographic examination may facilitate further investigation and treatment.

False Positive Reactions↗