Laxmi V. Baxi

Significance of prenatal diagnosis of umbilical cord cyst in a fetus with trisomy 18

An umbilical cord cyst was detected in a fetus who underwent ultrasonography at 38 weeks gestation for clinical suspicion of intrauterine growth retardation. Such an association should alert the clinician to the possibility of aneuploidy, thus guiding clinical management. This case represents the second report of a cystic umbilical lesion in a fetus with trisomy 18.

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 AIMSnInterleukin (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.nnnMETHODSnIn 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.nnnRESULTSnThere 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.nnnCONCLUSIONSnWe 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.

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‐18u2003±u2003IL‐12 on MNCs IFN‐γ protein production and ex vivo expansion and activation of CB with IL‐12u2003+u2003IL‐2u2003+u2003anti‐CD3u2003±u2003IL‐18. Basal and activated levels of IL‐18 were significantly higher in PB versus CB MNCs (Pu2003<u20030·05). IL‐18 mRNA was coincidental with protein levels and significantly lower in CB (Pu2003<u20030·05) and its half‐life significantly shorter in CB versus PB MNCs (Pu2003<u20030·05). IL‐18 synergistically with IL‐12 induced IFN‐γ production from PB greater than CB MNCs (Pu2003<u20030·05). NK cells expansion (Pu2003<u20030·001) and cytotoxicity (Pu2003<u20030·01) was significantly increased with IL‐12u2003+u2003IL‐2u2003+u2003anti‐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.

Fetal heart rate changes following maternal administration of a nasal decongestant

Repeated use of a long-acting sympathomimetic amine in the form of a nasal spray was associated with a nonreactive nonstress test and late decelerations in a patient at 41 weeks of gestation. Six hours after the last dose, these changes gradually disappeared.

Acute Alcohol Exposure Induces Apoptosis and Increases Histone H3K9/18 Acetylation in the Mid-Gestation Mouse Lung

Objective: Alcohol consumption causes cellular injury and excessive cell death. Recent studies indicate that ethanol can induce epigenetic alterations, particularly acetylation and methylation of histones and hypomethylation and hypermethylation of DNA. In the current study, we tested the hypothesis that acute exposure of pregnant mice to alcohol during mid-gestation can induce apoptosis and increase histone H3K9/18 acetylation in the fetal lung. The increased expression of histone H3K9/18 acetylation could alter the expression of genes that induce apoptosis. Study Design: C57BL/6J mice at day 13.5 of gestation were injected intraperitoneally with 2 doses of 25% ethanol (experimental) or Ringer solution (control) at 4-hour intervals. The fetuses were retrieved at 1, 3, 12, and 24 hours after alcohol exposure. The lungs were processed for detection of apoptosis by the terminal deoxynucleotidyl transferase biotin— deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) assay and for levels of acetylated histone H3K9/18 by immunohistochemistry. Results: In the control lungs, apoptosis was observed in 0.22% and 0.25% of the mesenchymal and epithelial cells, respectively. In contrast, at 24 hours after alcohol injection at E13.5, 3.4% of the mesenchymal and 4.0% of the epithelial cells in the lung were undergoing apoptosis (TUNEL-positive; P < .005). The number of positively stained cells and levels of acetylated histone H3K9/18 staining significantly increased 1 hour after alcohol injection (P < .05) and returned to basal levels after 12 hours. Conclusions: Acute alcohol exposure of pregnant mice at mid-gestation results in increased apoptosis in the fetal lung, and elevated levels of acetylated histone H3K9/18 precede the observation of apoptosis.

Single Fetal Demise in a Twin Gestation: Umbilical Vein Thrombosis

Background: Single fetal demise in a twin pregnancy is a rare event, the common causes being twin-twin transfusion syndrome, chromosomal or congenital anomalies and abnormalities of the umbilical cord and placenta. Umbilical vein thrombosis is a very rare cause of single fetal demise in twins. Case: Three days after a reassuring biophysical profile, a 40-year-old primigravida with twin pregnancy presented at 38 weeks’ gestation in early labor when demise of 1 of the twins was recognized. She underwent a cesarean section for arrest of labor, delivering twin A, a stillborn female weighing 2,360 g and twin B, a liveborn male weighing 2,200 g. Umbilical vein thrombus was noted in twin A. Conclusion: Umbilical vein thrombosis is a rare and sudden cause of fetal demise.

Fetal Response Time to Transplacental Digoxin Therapy for Supraventricular Tachyarrhythmia: A Meta-Analysis

We performed a meta-analysis of all published cases of fetal supraventricular tachyarrhythmia (SVT) treated with maternally administered oral digoxin. The purpose of the study was to determine the expected therapeutic response time and thereby facilitate clinical management of fetal SVT. A statistically significant association was found between the duration of therapy and the probability of therapeutic success. Sixty percent of fetuses responded within 10 days of initiating oral digoxin and 80% within 17 days. We have constructed a graph of the expected fetal response rate over time. Our findings also suggest that cases that have been reported as treatment failures were in fact treated for a significantly shorter duration than fetuses in whom SVT was controlled. Ninety-two percent of failures were treated for 7 days or less. No other significant differences could be detected between the groups. Our findings elucidate the expected response rate of fetal SVT to oral digoxin therapy and suggest that many cas...

Porphyria cutanea tarda and pregnancy.

Porphyria cutanea tarda (PCT) is an inborn error of metabolism. It is one of a family of six genetically distinct porphyrias and is characterized by a disorder of heme synthesis, resulting in the excess accumulation and excretion of uroporphyrins and coproporphyrins. To the best of our knowledge this is the first report of a successful pregnancy in a patient undergoing active therapy for this biochemical and clinical abnormality.

Doppler Ultrasound Characteristics of Fetal Nasal Flow in Pregnancies Complicated by Diabetes Mellitus

The purpose of our study was to determine the Doppler ultrasound characteristics of fetal breathing-related nasal fluid flow velocity in pregnancies complicated by diabetes mellitus and to examine any changes in the timing parameters of fetal breath cycle relative to maternal blood glucose level. Fetal nasal fluid flow velocity was studied in 67 women at 30-41 weeks of gestation. In 37 cases, the pregnancy was uncomplicated; in 13 cases, the pregnancy was complicated by type I diabetes mellitus; and in 17 cases, the pregnancy was complicated by gestational diabetes. At the examination, subjects with diabetes mellitus were grouped by glucose control (normoglycemic and hyperglycemic) and by gestational age: 30-36 weeks and 37-41 weeks. Maternal hyperglycemia was defined as a plasma glucose value ranging from 140 to 205 mg per 100 ml. A continuous videotape record of the spectral Doppler imaging of fluid flow velocity in the nose was made during each study session. Based on a sample of 25 consecutive fetal breaths, the timing components of breath cycles were determined: time of inspiration (Ti), time of expiration (Te), breath-to-breath interval (Ttotal), and ratio of Ti and Te (Ti/Te). There was a statistically significant difference between the Ttotal (msec) at 30-36 weeks gestation in the cases of diabetes mellitus with maternal normoglycemia (1,050 +/- 68 SEM) and uncomplicated pregnancy with maternal normal carbohydrate intolerance (1,221 +/- 52). There was a similar difference in the values of Te (552 +/- 37 and 660 +/- 29, respectively) at 30-36 weeks. In cases of maternal hyperglycemia at 30-36 weeks gestation, the value of Te (689 +/- 84) was significantly higher than in cases of normoglycemia (552 +/- 37). At 37-41 weeks gestation, only the fetal Ti/Te ratio in normoglycemic diabetic patients was significantly lower than in an uncomplicated pregnancy. No differences were found in the other timing parameters at this gestational age group in cases of diabetes mellitus relative to maternal blood glucose level. No relationship was found between the value of maternal blood glucose and either fetal Ttotal (r2 = 0.003), or Ti/Te ratio (r2 = 0.0001) in cases of diabetes mellitus. Expiratory phase of fetal breath cycle even in well-controlled normoglycemic diabetic women, is significantly shorter than in uncomplicated pregnancies before 37 weeks of gestation. Maternal hyperglycemia in these cases prolonged the duration of expiratory phase of fetal breath cycle and significantly decreased the Ti/Te ratio more than 15% at 30-36 weeks of gestation. It is suggested that blood glucose level is involved in the regulation of fetal respiratory center in pregnancies complicated by diabetes mellitus.

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.