Normal Range for Maternal Lactic Acid during Pregnancy and Labor: A Systematic Review and Meta-Analysis of Observational Studies.

OBJECTIVE: This article systematically reviews the literature to establish the normal range of lactic acid in healthy pregnant women. STUDY DESIGN: Ovid MEDLINE, Embase.com, and Clinicaltrials.gov were searched to identify studies that reported maternal lactic acid in healthy pregnant women. Pooled aggregate means and two standard deviations for each time period were computed using the inverse variance weighting technique. Analyses were performed separately for 1st, 2nd, and 3rd trimesters, scheduled cesarean delivery, early labor, active labor, 2nd stage of labor, and delivery. RESULTS: Overall, 22 studies met the inclusion criteria. There were 1,193 patients, and 2,008 observations identified. All time periods had maternal venous lactic acid aggregate means and two-standard-deviation ranges less than 4 mmol/L. Outside of labor, all ranges were less than 2 mmol/L. All labor periods had a range higher than 2 mmol/L. While the pooled ranges were less than 4 mmol/L, many individual studies reported ranges > 4 mmol/L during labor. CONCLUSION: This meta-analysis suggests that venous lactic acid levels can be used as a screening tool in pregnant women just as the test would be used in nonpregnant women, except that elevations may be seen during labor, especially later in labor when there is maximal skeletal muscle contraction.

Effect of Glucose on 3D Cardiac Microtissues Derived from Human Induced Pluripotent Stem Cells.

Maternal hyperglycemia is a risk factor for fetal cardiac anomalies. This study aimed to assess the effect of high glucose on human induced pluripotent stem cell-derived cardiomyocyte self-assembly into 3D microtissues and their calcium handling. Stem cells were differentiated to beating cardiomyocytes using established protocols. On the final day of the differentiation process, cells were treated with control media, 12 mM glucose, or 12 mM mannitol (an osmolality control). Once beating, the cardiac cells were dissociated with trypsin, collected, mixed with collagen, and plated into custom-made silicone micro molds in order to generate 3D cardiac microtissues. A time-lapse microscope took pictures every 4 h to quantify the kinetics of cellular self-assembly of 3D cardiac tissues. Fiber widths were recorded at 4-h intervals and plotted over time to assess cardiomyocyte 3D fiber self-assembly. Microtissue calcium flux was recorded with optical mapping by pacing microtissues at 0.5 and 1.0 Hz. Exposure to high glucose impaired the ability of cardiomyocytes to self-assemble into compact microtissues, but not their ability to spontaneously contract. Glucose-exposed cardiomyocytes took longer to self-assemble and finished as thicker fibers. When cardiac microtissues were paced at 0.5 and 1.0 Hz, those exposed to high glucose had altered calcium handling with shorter calcium transient durations, but larger amplitudes of the calcium transient when compared to controls. Additional studies are needed to elucidate a potential mechanism for these findings. This model provides a novel method to assess the effects of exposures on the cardiomyocytes' intrinsic abilities for organogenesis in 3D.

Pregnancy programming and preeclampsia: identifying a human endothelial model to study pregnancy-adapted endothelial function and endothelial adaptive failure in preeclamptic subjects.

We have previously reported that the increase in vasodilator production in an ovine model pregnancy is underpinned by an increase in connexin 43 (Cx43) gap junction function, so allowing more uterine artery endothelial cells to produce a more sustained Ca(2+) burst response to agonist stimulation. Since activation of endothelial nitric oxide synthase (eNOS) requires elevated [Ca(2+)]i, it follows that the direct result of enhanced bursting in turn is an increase in nitric oxide (NO) production per cell from more cells, and for a longer period of time. Preeclampsia (PE) is associated with endothelial vasodilatory dysfunction, and the endocrine profile of women with PE includes an increase in a number of factors found in wound sites. The common action of these growth factors and cytokines in wound sites is to mediate Cx43 dysfunction through kinase phosphorylation and closure. Translational studies are now needed to establish if inhibitory phosphorylation of Cx43 in human endothelium is the cause of endothelial dysfunction in PE subjects and if so, to identify the kinase pathways best targeted for therapy in PE subjects. Consistent with this we have already shown endothelial Ca(2+) and NO responses of human umbilical vein from normal subjects are similar to that of ovine pregnant uterine artery, and that those same responses in cords from PE subjects are blunted to levels more typical of nonpregnant uterine artery. In this review we summarize the further evidence that growth factors and cytokines may indeed mediate endothelial dysfunction in PE subjects through closure of Cx43 gap junctions. We also consider how we may clinically translate our studies to humans by using intact umbilical vein and isolated HUVEC in primary culture for an initial screen of drugs to prevent deleterious Cx43 phosphorylation, with the ultimate goal of reversing PE-related endothelial dysfunction.

Vulvar abscess: a retrospective review.

Vulvar abscesses can progress to cause significant illness requiring disfiguring surgical debridement, broad spectrum antibiotics, and require hospitalization. A retrospective review of de-identified charts of 13 patients admitted for inpatient care for vulvar abscesses from 2004-2009 at West Virginia University Hospitals was conducted. Risk factors for vulvar abscess in these patients included obesity and diabetes. Body mass index (BMI) is directly proportionate to the size of the abscess and increased risk of intensive care unit admission. Most patients did not seek medical care prior to hospital admission. Polymicrobial infections were common, and methicillin resistant Staphylococcus aureus was seen in two cases. The presence of multiple risk factors increased the length of hospitalization. Clinicians should be aware of these risk factors and initiate aggressive therapy for patients with elevated BMI or multiple risk factors.

Assay of the von Willebrand factor (VWF) propeptide to identify patients with type 1 von Willebrand disease with decreased VWF survival.

Type 1 von Willebrand disease (VWD) is characterized by a partial quantitative deficiency of von Willebrand factor (VWF). Few VWF gene mutations have been identified that cause dominant type 1 VWD. The decreased survival of VWF in plasma has recently been identified as a novel mechanism for type 1 VWD. We report 4 families with moderately severe type 1 VWD characterized by low plasma VWF:Ag and FVIII:C levels, proportionately low VWF:RCo, and dominant inheritance. A decreased survival of VWF in affected individuals was identified with VWF half-lives of 1 to 3 hours, whereas the half-life of VWF propeptide (VWFpp) was normal. DNA sequencing revealed a single (heterozygous) VWF mutation in affected individuals, S2179F in 2 families, and W1144G in 2 families, neither of which has been previously reported. We show that the ratio of steady-state plasma VWFpp to VWF:Ag can be used to identify patients with a shortened VWF half-life. An increased ratio distinguished affected from unaffected individuals in all families. A significantly increased VWFpp/VWF:Ag ratio together with reduced VWF:Ag may indicate the presence of a true genetic defect and decreased VWF survival phenotype. This phenotype may require an altered clinical therapeutic approach, and we propose to refer to this phenotype as type-1C VWD.