Hyperreactio luteinalis in pregnancy and hyperandrogenism: a case report.

BACKGROUND: Hyperreactio luteinalis in pregnancy is associated with theca lutein cysts (TLCs) and androgenization. CASE: A 24-year-old, primigravid woman was referred at 35 weeks' gestation for bilateral enlarged cystic ovaries. She showed signs of androgenization. On ultrasonogram the ovaries bore a spoke-wheel appearance. A nonvirilized female infant was subsequently delivered by cesarean section because of obstruction of the birth canal by a large impacted ovarian cyst. There was an initial delay in lactogenesis; however, it was well-established after regression of the TLC, by postpartum week 6. Signs ofandrogenization resolved and testosterone levels returned to normal by 3 months postpartum. CONCLUSION: Hyperreactio luteinalis is associated with TLC and maternal androgenization in the antepartum period and persists into the postpartum period with subsequent resolution. Aromatization of testosterone in hyperreactio luteinalis prevents fetal virilization, unlike that seen with masculinizing ovarian tumors. There is some evidence of genetic predisposition and a possibility for recurrence in future pregnancies.

Complete hydatidiform mole and live fetus in a singleton pregnancy with confined placental mosaicism and fetomaternal hemorrhage: a case report.

BACKGROUND: Coexistence of complete mole and a live fetus is uncommon (1:22,000-100,000), more so with euploidy. CASE: We present a case of a molar pregnancy with a euploid fetus who had close fetal evaluation for second trimester bleeding. The patient presented at 29 weeks' pregnancy with decreased fetal movements, a result of fetomaternal hemorrhage. She underwent cesarean section and delivered a live infant. By close follow-up and a multidisciplinary approach, the appropriate diagnosis and a favorable outcome were achieved. Both mother and the child at 5 years of age are doing well. CONCLUSION: Detailed anatomic and molecular studies demonstrated a complete mole resulting from confined placental mosaicism, with molar tissue showing a single paternal allele at 8/8 informative loci, all shared with the fetus, thus this coexistent molar pregnancy was not that of a separate conceptus.

Interleukin (IL)-15 in combination with IL-2, fms-like tyrosine kinase-3 ligand and anti-CD3 significantly enhances umbilical cord blood natural killer (NK) cell and NK-cell subset expansion and NK function.

BACKGROUND AIMS: Interleukin (IL)-15 and fms-like tyrosine kinase-3 (FLT-3) are crucial factors for the development of human and murine natural killer (NK) cells. Previously, we have demonstrated significant ex vivo expansion and activation of unrelated cord blood (UCB) NK cells with an antibody/cytokine cocktail consisting of anti-CD3 + IL-2 + IL-12 + IL-7 and anti-CD3 + IL-2 + IL-12 + IL-18. METHODS: In the current experiments, we investigated the effects of short-term culture with anti-CD3 + IL-2 + FLT-3 + IL-15 on cord blood (CB) NK cell and NK-cell subset expansion and function. CB mononuclear cells were cultured for 48 h in AIM-V media or AIM-V + IL-2 (5 ng/mL) + anti-CD3 (50 ng/mL) + FLT-3 (50 ng/mL) ± escalating doses of IL-15 (1, 10 or 100 ng/mL). Flow cytometric analysis was performed using various fluorescent-conjugated monoclonal antibodies. In vitro cytotoxicity was determined with a standard europium assay against K562 and Daudi cells. RESULTS: There was a 4.8-fold significant increase in NK-cell population (CD3(-)/16(+)/56(+); P < 0.03), 21-fold significant increase in CD3(-)/56(+)/158a(+) (KIR2DL1/S1; P < 0.002), 46-fold significant increase in CD3(-)/56(+)/158b(+) (KIR2DL1/S2; P < 0.002) and 11.5-fold significant increase in CD3(-)/56(+)/NKB1(+) (KIR3DL1; P < 0.01). We also noted a significant increase in both NK and lymphokine-activated killer (LAK) cytotoxicity with IL-2 + anti-CD3 + FLT-3 + IL-15 (100 ng/mL) compared with IL-2 + anti-CD3 + FLT-3 and media alone against K562 (P < 0.01) and Daudi (P < 0.001), respectively. CONCLUSIONS: We have demonstrated a significant increase in UCB NK cells and NK cells expressing a variety of killer immunoglobulin-like receptor (KIR) receptors after short-term culture with anti-CD3, IL-2, FLT-3 and IL-15. Furthermore, there was a significant increase in in vitro NK/LAK cell cytotoxicity.

Overexpression of HOXB5, cyclin D1 and PCNA in congenital cystic adenomatoid malformation.

OBJECTIVE: We investigated the patterns of expression of HOXB5, cyclin D1 and proliferating cell nuclear antigen (PCNA) proteins in human congenital cystic adenomatoid malformation (CCAM) to establish the molecular basis of its etiology. METHODS: Immunohistochemistry was performed on frozen archival specimens of CCAM and normal lung tissue as controls using antibodies against HOXB5, cyclin D1 and PCNA proteins. RESULTS: Immunohistochemistry revealed a higher level of expression of HOXB5, cyclin D1 and PCNA predominantly in mesenchymal cells of the CCAM tissues as compared to normal adjacent control lung tissues. CONCLUSION: Elevated levels of immunohistochemical detection of HOXB5, cyclin D1 and PCNA were characteristic properties of lung tissue cells in CCAM. This elevated HOXB5 expression may correlate with the aberrant cellular differentiation observed in the CCAM disorder. Elevated expression of cyclin D1 and PCNA further suggests that increased cellular proliferation contributes to the overgrowth of lung tissue in CCAM.

Prenatal diagnosis of urinary ascites in a fetus with meningomyelocele.

Fetal or neonatal urinary ascites is a rare phenomenon, particularly when secondary to rupture of a neuropathic bladder in a fetus with meningomyelocele. To date, all similar cases have only been diagnosed in the neonatal period. We report a case of urinary ascites secondary to rupture of a neuropathic bladder, which was successfully diagnosed via fetal paracentesis at 37 weeks. The infant was delivered by elective cesarean section and managed immediately with therapeutic paracentesis and bladder catheterization. Voiding cystourethrogram on the fifth day of life showed the bladder had spontaneously healed. Early diagnosis and prompt intervention for bladder complications diagnosed in utero may prevent or minimize adverse consequences.

Recurrent cystic hygroma with hydrops.

OBJECTIVE: A patient whose 5 fetuses, including a set of twins, were affected by cystic hygroma (CH) and hydrops is presented. METHOD: A 39-year-old gravida 12 para 7, 2, 2, 8 was followed through her pregnancies. Both patient and her spouse are of Ashkenazi Jewish descent and are non-consanguineous. The spouse has Gaucher disease and is on replacement therapy. The patient is not a carrier of any known allele of Gaucher disease. In 2 pregnancies, an ultrasonogram done at 12 weeks revealed a septated CH in 3 fetuses. We have excluded Noonan syndrome, Fryns syndrome and Gunther's disease as the responsible causes for the recurrent CH and aneuploidy in at least 3 of these fetuses. RESULTS: The products of conception in 1 pregnancy showed low normal levels of glucocerebrosidase but no known Gaucher mutation. CONCLUSION: We present a patient with recurrent CH in 5 fetuses (4 pregnancies) of which 3 fetuses had a normal karyotype. This appears to be an autosomal recessive disorder.

Peritoneal inclusion cyst: effects on fertility and antepartum course.

BACKGROUND: Hormone changes are thought to influence the etiology and disease process of peritoneal inclusion cysts. The effects of fertility and pregnancy on preexisting cysts are unknown. CASE: A 29-year-old woman with recurrent peritoneal inclusion cyst and primary infertility conceived spontaneously after hysterosalpingogram. She presented in the first trimester with rapid, symptomatic enlargement of a 22-cm peritoneal inclusion cyst. Ultrasonogram-guided aspiration was performed. The remainder of her pregnancy and postpartum course were uncomplicated. CONCLUSION: The presence of a large peritoneal inclusion cyst does not preclude fertility. Pregnancy, a hyperestrogenic state, together with rising human chorionic gonadotropin is a risk for recurrence or enlargement of a preexisting peritoneal inclusion cyst. After conservative management with cystocentesis, there was no further enlargement as pregnancy progressed.

Effects of acute alcohol intoxication in the second trimester of pregnancy on development of the murine fetal lung.

OBJECTIVE: We hypothesized that administration of alcohol during the second trimester of gestation at the pseudoglandular phase of lung development might lead to aberrant differentiation and growth, similar to that seen in congenital cystic adenomatoid malformation in human. We further hypothesized that these effects would be apparent morphologically and by altered Hoxb5 expression. STUDY DESIGN: C57BL/6J mice, exposed to ethanol at embryonic day (E) 11.5 to E13.5, which corresponds to the pseudoglandular stage of lung development, were examined at E18.5. The lungs were analyzed histologically by immunostaining. RESULTS: The average body and lung weight of alcohol-exposed (AE) fetuses were lower than those of control fetuses, the reduction in lung mass being more than the body weight. Histology showed that AE lungs were less developed and exhibited higher expression of Hoxb5 in AE lungs than controls. CONCLUSION: Alcohol exposure at E13.5 affected fetal lung development, with delayed differentiation and increased Hoxb5.

Rupture of the primigravid uterus: a review of the literature.

UNLABELLED: Uterine rupture is a catastrophic obstetric complication, associated with high rates of perinatal morbidity and mortality. The most common risk factor is previous uterine surgery, and most cases of uterine rupture occur in women with a previous cesarean delivery. Traditionally, the primigravid uterus has been considered almost immune to spontaneous rupture. In fact, although spontaneous rupture of the primigravid uterus is indeed a very rare event, a number of such cases have been reported recently. Prompt recognition of uterine rupture and expeditious recourse to laparotomy are critical in influencing perinatal and maternal morbidity. Not all uterine ruptures present with the typical clinical picture of abdominal pain, hypovolemia, vaginal bleeding, and fetal compromise. Therefore, it is important to maintain a high index of suspicion for uterine rupture in women presenting with some, or all, of these features, regardless of parity. Here we provide a systematic review of cases of spontaneous uterine rupture in primigravid women reported in the literature to date. Clinical presentation, differential diagnosis, common etiological factors, complication rates, and appropriate management of this rare obstetric event are discussed. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to recall that uterine rupture in a primigravida is a rare event, without typical signs and symptoms, and explain that the morbidity and mortality of the mother and child is directly related to a high index of suspicion and prompt treatment by the clinician.

Lyme disease in pregnancy: case report and review of the literature.

UNLABELLED: Lyme disease is the most common vector-borne disease in the United States. A number of other spirochetal diseases, if contracted in pregnancy, have been shown to cause fetal harm and there is concern over a similar effect with gestational borreliosis. Previously published individual case reports have suggested a possible association between gestational borreliosis and adverse pregnancy outcome; however, no specific pattern of teratogenicity has been shown, and a causal relationship has never been proven. In addition, larger epidemiological and serological series have consistently failed to demonstrate an increased risk to pregnant women who develop Lyme disease if they receive appropriate antimicrobial therapy. We describe a favorable outcome in a 42-year-old woman who developed Lyme disease in the third trimester and was treated with a full course of oral amoxicillin. In addition, we offer a review of the relevant literature regarding Lyme disease and pregnancy. The appropriate investigation and management of a woman with gestational borreliosis are discussed. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to recall that Lyme disease is not an uncommon disease during pregnancy and can occur in states outside of the Northeast, explain that the diagnosis is made clinically and may be confirmed by laboratory tests, state that treatment is recommended during pregnancy, and summarize that there is no consistent data of adverse fetal effects even though the placenta is infected.

False-positive quadruple screen test for trisomy 18 in a patient with a fetus with Bloom's syndrome.

In the literature, conflicting reports on the significance of false-positive maternal serum multiple marker testing for trisomy 18 are encountered; however, the biology of this finding is discussed infrequently. We present such a case in association with Bloom's syndrome in the fetus. The fetus had intrauterine growth restriction, seen early in the second trimester, oligohydramnios, and was delivered at 34 weeks of gestation for impending fetal compromise. We propose that the adverse outcome of the pregnancy with false-positive serum analyte testing for trisomy 18 might result from a small-sized placenta and perhaps pathology at receptor level.

Genetically re-engineered K562 cells significantly expand and functionally activate cord blood natural killer cells: Potential for adoptive cellular immunotherapy.

Natural killer (NK) cells play a significant role in reducing relapse in patients with hematological malignancies after allogeneic stem cell transplantation, but NK cell number and naturally occurring inhibitory signals limit their capability. Interleukin-15 (IL-15) and 4-1BBL are important modulators of NK expansion and functional activation. To overcome these limitations, cord blood mononuclear cells (CB MNCs) were ex vivo expanded for 7 days with genetically modified K562-mbIL15-41BBL (MODK562) or wild-type K562 (WTK562). NK cell expansion; expression of lysosome-associated membrane protein-1 (LAMP-1), granzyme B, and perforin; and in vitro and in vivo cytotoxicity against B-cell non-Hodgkin lymphoma (B-NHL) were evaluated. In vivo tumor growth in B-NHL-xenografted nonobese diabetic severe combined immune deficient (NOD-scid) gamma (NSG) mice was monitored by tumor volume, cell number, and survival. CB MNCs cultured with MODK562 compared with WTK562 demonstrated significantly increased NK expansion (thirty-fivefold, p < 0.05); LAMP-1 (p < 0.05), granzyme B, and perforin expression (p < 0.001); and in vitro cytotoxicity against B-NHL (p < 0.01). Xenografted mice treated with MODK562 CB experienced significantly decreased B-NHL tumor volume (p = 0.0086) and B-NHL cell numbers (p < 0.01) at 5 weeks and significantly increased survival (p < 0.001) at 10 weeks compared with WTK562. In summary, MODK562 significantly enhanced CB NK expansion and cytotoxicity, enhanced survival in a human Burkitt's lymphoma xenograft NSG model, and could be used in the future as adoptive cellular immunotherapy after umbilical CB transplantation. Future directions include expanding anti-CD20 chimeric receptor-modified CB NK cells to enhance B-NHL targeting in vitro and in vivo.

Pilot randomized controlled trial of interpersonal counseling for subsyndromal depression following miscarriage.

OBJECTIVE: Miscarriage, which occurs in 10% to 20% of clinically recognized pregnancies, is associated with an increased risk for subsyndromal depression. We examined whether Interpersonal Counseling (IPC) was superior to treatment as usual (TAU) in reducing subsyndromal depression among miscarrying women and, secondarily, superior to TAU in improving role functioning. METHOD: Nineteen of 20 eligible women participated in a randomized controlled trial of 1 to 6 weekly telephone sessions of IPC versus TAU, which consisted of whatever lay counseling or professional care women sought on their own initiative, from October 2001 to April 2002. The 2 trial arms were compared on mean within-subject change in Hamilton Rating Scale for Depression-17-item (HAM-D-17) scores and in role functioning scale scores (a 5-item modification of the 36-item Medical Outcomes Study questionnaire) from baseline to post-intervention. RESULTS: In the primary intent-to-treat analysis, the baseline mean HAM-D-17 scores were 18.0 (SD +/- 8.4) and 14.8 (SD +/- 6.6) in the IPC (N = 10) and TAU (N = 9) arms, respectively; post-intervention, the corresponding means were 11.6 (SD +/- 8.2) and 12.9 (SD +/- 8.3). The mean within-subject decline in HAM-D-17 scores was significantly greater in the IPC (6.4) than in the TAU (1.9) arm (difference in mean within-subject score decline, adjusted for design features, baseline HAM-D-17 scores and for baseline ethnic imbalance between study arms, 6.2 [95% CI = 0.4 to 12.0]). In a subordinate completers' analysis (N = 15), the corresponding mean decline and difference in adjusted mean decline were 8.0, 2.4, and 6.7 (95% CI = 0.4 to 13.1), respectively. Treatment was unrelated to improved role functioning. CONCLUSION: The efficacy of telephone-administered IPC for subsyndromal depression after miscarriage warrants testing in a full-scale randomized controlled trial.

Global prevalence of prothrombin gene mutation G20210A and implications in women's health: a systematic review.

Distribution of hereditary thrombophilic gene mutations differs globally. Prothrombin gene mutation G20210A is a common prothrombotic single-nucleotide polymorphism. In this systematic review, we provide a comprehensive report of the prevalence of prothrombin G20210A across the globe. Databases [Pubmed, Web of Science, Embase] were interrogated from their inception through December 2015 for articles reporting prothrombin G20210A prevalence rates and ethnicity. Prevalence rates were organized by continent and ethnoracial ancestry. A total of 113 articles were included with a total 61 876 participants tested for prothrombin G20210A. Reported prevalence rates varied from 0 to 15.9% among ethnic groups, with higher rates seen in the thromboembolism affected cohort compared with the unaffected cohort. Carrier rate distribution is supported by known historical migration patterns of global populations. This review of prothrombin G20210A prevalence may guide resourceful screening for identification of hereditary thrombophilia in female populations of interest with hypercoagulable states.