Ann C. Celi

Thrombus formation: direct real-time observation and digital analysis of thrombus assembly in a living mouse by confocal and widefield intravital microscopy.

Summary.  We have developed novel instrumentation using confocal and widefield microscopy to image and analyze thrombus formation in real time in the microcirculation of a living mouse. This system provides high‐speed, near‐simultaneous acquisition of images of multiple fluorescent probes and a brightfield channel, and supports laser‐induced injury through the microscope optics. Although this imaging facility requires interface of multiple hardware components, the primary challenge in vascular imaging is careful experimental design and interpretation. This system has been used to localize tissue factor during thrombus formation, to observe defects in thrombus assembly in genetically altered mice, to study the kinetics of platelet activation and P‐selectin expression following vascular injury, to analyze leukocyte rolling on arterial thrombi, to generate three‐dimensional models of thrombi, and to analyze the effect of antithrombotic agents in vivo.

Acute Histologic Chorioamnionitis at Term: Nearly Always Noninfectious

Background The link between histologic acute chorioamnionitis and infection is well established in preterm deliveries, but less well-studied in term pregnancies, where infection is much less common. Methodology/Principal Findings We conducted a secondary analysis among 195 low-risk women with term pregnancies enrolled in a randomized trial. Histologic and microbiologic evaluation of placentas included anaerobic and aerobic cultures (including mycoplasma/ureaplasma species) as well as PCR. Infection was defined as ≥1,000 cfu of a single known pathogen or a ≥2 log difference in counts for a known pathogen versus other organisms in a mixed culture. Placental membranes were scored and categorized as: no chorioamnionitis, Grade 1 (subchorionitis and patchy acute chorioamnionitis), or Grade 2 (severe, confluent chorioamnionitis). Grade 1 or grade 2 histologic chorioamnionitis was present in 34% of placentas (67/195), but infection was present in only 4% (8/195). Histologic chorioamnionitis was strongly associated with intrapartum fever >38°C [69% (25/36) fever, 26% (42/159) afebrile, P<.0001]. Fever occurred in 18% (n = 36) of women. Most febrile women [92% (33/36)] had received epidural for pain relief, though the association with fever was present with and without epidural. The association remained significant in a logistic regression controlling for potential confounders (OR = 5.8, 95% CI = 2.2,15.0). Histologic chorioamnionitis was also associated with elevated serum levels of interleukin-8 (median = 1.3 pg/mL no histologic chorioamnionitis, 1.5 pg/mL Grade 1, 2.1 pg/mL Grade 2, P = 0.05) and interleukin-6 (median levels = 2.2 pg/mL no chorioamnionitis, 5.3 pg/mL Grade 1, 24.5 pg/mL Grade 2, P = 0.02) at admission for delivery as well as higher admission WBC counts (mean = 12,000cells/mm3 no chorioamnionitis, 13,400cells/mm3 Grade 1, 15,700cells/mm3 Grade 2, P = 0.0005). Conclusion/Significance Our results suggest histologic chorioamnionitis at term most often results from a noninfectious inflammatory process. It was strongly associated with fever, most of which was related to epidural used for pain relief. A more ‘activated’ maternal immune system at admission was also associated with histologic chorioamnionitis.

Association of epidural-related fever and noninfectious inflammation in term labor.

OBJECTIVE: To investigate the role of infection and noninfectious inflammation in epidural analgesia-related fever. METHODS: This was an observational analysis of placental cultures and serum admission and postpartum cytokine levels obtained from 200 women at low risk recruited during the prenatal period. RESULTS: Women receiving labor epidural analgesia had fever develop more frequently (22.7% compared with 6% no epidural; P=.009) but were not more likely to have placental infection (4.7% epidural, 4.0% no epidural; P>.99). Infection was similar regardless of maternal fever (5.4% febrile, 4.3% afebrile; P=.7). Median admission interleukin (IL)-6 levels did not differ according to later epidural (3.2 pg/mL compared with 1.6 pg/mL no epidural; P=.2), but admission IL-6 levels greater than 11 pg/mL were associated with an increase in fever among epidural users (36.4% compared with 15.7% for 11 pg/mL or less; P=.008). At delivery, both febrile and afebrile women receiving epidural had higher IL-6 levels than women not receiving analgesia. CONCLUSION: Epidural-related fever is rarely attributable to infection but is associated with an inflammatory state. LEVEL OF EVIDENCE: II

Myocardial Tissue Characterization by Autocorrelation of Two-dimensional Ultrasonic Backscatter

To evaluate a novel method for determining the spatial distribution of echocardiographic information based on the two-dimensional autocorrelation function, echocardiographic images were obtained from specific regions of interest from 10 healthy volunteers, seven patients with genetically defined hypertrophic cardiomyopathy, and nine patients with pressure-overload hypertrophy. The wavelength of distinct peaks from the two-dimensional autocorrelation of the images was compared between groups of patients and demonstrated a significant decrease in the mean length scale associated with distinct secondary correlation peaks in patients with hypertrophic cardiomyopathy or pressure-overload hypertrophy compared with healthy volunteers (p = 0.0009). With a discriminating wavelength of 3.3 mm, the sensitivity of this technique for detecting abnormal myocardium was 84% with a specificity of 89%. This study suggests that ultrasonic tissue characterization based on the two-dimensional autocorrelation function may have potential for distinguishing normal from abnormal myocardium and provides a rationale for textural approaches to ultrasonic tissue characterization.

Does the Addition of a Specialized Postpartum Clinic Improve the Care of Women With Preeclampsia

INTRODUCTION: Women with antepartum preeclampsia are at higher risk of developing cardiovascular disease. We sought to assess if the introduction of a specialized postpartum clinic decreases the rate of readmission and triage visits and increases the rate of primary care provider follow-up for women who had antepartum preeclampsia. METHODS: This is a retrospective comparative cohort study of women who had antepartum preeclampsia: 69 women who delivered in 2008 were compared with 69 women who followed in a specialized postpartum clinic from October 2011 to March 2013. &khgr;2 testing was used to compare the rate of readmission, triage visits, and primary care provider follow-up. RESULTS: There was no difference in the baseline characteristics between the two groups. There was a higher combined rate of readmission and triage visits after the introduction of the clinic, 8.7% compared with 21.7% (P<.039). A total of 85.7% of the readmissions and 62.5% of the triage visits occurred before the specialized postpartum clinic appointments. Furthermore, 66.7% of the readmissions and triage visits occurred within 10 days from delivery. There was a trend toward better primary care provider follow-up, 37.7% compared with 46.4% (P<.302). CONCLUSIONS: Our study shows that after the introduction of a specialized postpartum clinic, the rate of readmission and triage visits increased. This likely reflects a growing awareness surrounding preeclampsia and its associated long-term cardiovascular risks. Our study supports that earlier access to postpartum care, within 10 days, may reduce the rate of hospitalization and provide better access to clinical care. A trend toward increased primary care provider follow-up requires further investigation.