Clinical and cardiovascular magnetic resonance profile of cardiomyopathy patients from South Africa: Pilot of the IMHOTEP study.

BACKGROUND: Cardiomyopathy is an important cause of heart failure, however, there is notable lack of data on causes and manifestations of cardiomyopathy in Africa. AIMS: The African Cardiomyopathy and Myocarditis Registry Program (IMHOTEP) aims to address the knowledge gap on etiology, treatment, and outcomes of cardiomyopathy in sub-Saharan Africa. METHODS AND RESULTS: We conducted a single-center pilot study to delineate the clinical and cardiovascular magnetic resonance (CMR) phenotypes of cardiomyopathy in South African patients. Assessment of the first 99 adult incident cases [mean age 36.8 ± 12.5 years; females 53.5%] enrolled in IMHOTEP showed that dilated cardiomyopathy (n = 77) was commonest, followed by hypertrophic (n = 13), restrictive (n = 5) and arrhythmogenic (n = 4) cardiomyopathies. A broad range of etiologies were encountered with secondary causes identified in 42% of patients. Onset of symptoms in the peripartum period was observed in 47% of women, and peripartum cardiomyopathy was diagnosed in 32.1% of women recruited. In addition to electrocardiography and echocardiography, CMR was performed in 67 cases and contributed diagnostically in a third of cases. Acute inflammation was rarely observed [2%] on CMR, however, late gadolinium enhancement (LGE) was noted in 92% of cases. CONCLUSION: We report a diverse spectrum of causes of cardiomyopathy in the South African population, with secondary, potentially treatable, etiologies in a significant proportion of cases. CMR was useful in delineating specific phenotypes and etiologies, influencing clinical care. A higher-than-expected burden of LGE was observed in this young patient cohort - the implications of which are yet to be determined.

An evaluation of fetal heart rate characteristics associated with neonatal encephalopathy: a case-control study.

OBJECTIVE: We sought to identify fetal heart rate (FHR) characteristics that are associated with neonatal encephalopathy (NE). DESIGN: Retrospective case-control study. SETTING: A single medical centre in Shanghai, China, 2006-2015. SAMPLE: Women delivering a singleton, non-anomalous infant at ≥36 weeks' gestation diagnosed with NE (cases, n = 109) were compared with a group of women with unaffected infants (controls, n = 233). METHODS: Two physicians blinded to the outcome independently reviewed FHR tracings during the last 30 minutes of tracing prior to delivery. FHR characteristics were compared in the two groups and multivariable logistic regression was used to adjust for confounding. MAIN OUTCOME MEASURES: Adjusted odds ratio (aOR) and 95% confidence interval (CI) for the presence of specific FHR categories and characteristics. RESULTS: Category II FHR tracings were observed in 89% of women prior to delivery and were not independently associated with NE. Notably, a category III FHR was observed in 17.4% of women in the NE group compared with 0.9% of women in the control group (aOR 44.99, 95% CI 7.23-279.97). Bradycardia, minimal/absent variability, late decelerations and prolonged decelerations were independently associated with NE, whereas accelerations were protective. Similar findings were found when the cases were limited to NE with arterial cord pH <7.1 and in a subgroup analysis of women with category II tracings. CONCLUSIONS: Category III tracings, while infrequent, are not uncommon prior to delivery among fetuses who develop NE. In contrast, most FHR tracings are category II prior to delivery; however, individual FHR characteristics within this category are associated with NE. FUNDING: This research was supported by the Interdisciplinary Programme of Shanghai Jiao Tong University. TWEETABLE ABSTRACT: Category III tracings are not uncommon prior to delivery among fetuses who develop neonatal encephalopathy.

Prenatal vitamin C and E supplementation in smokers is associated with reduced placental abruption and preterm birth: a secondary analysis.

OBJECTIVE: Smoking and pre-eclampsia (PE) are associated with increases in preterm birth, placental abruption and low birthweight. We evaluated the relationship between prenatal vitamin C and E (C/E) supplementation and perinatal outcomes by maternal self-reported smoking status focusing on outcomes known to be impacted by maternal smoking. DESIGN/SETTING/POPULATION: A secondary analysis of a multi-centre trial of vitamin C/E supplementation starting at 9-16 weeks in low-risk nulliparous women with singleton gestations. METHODS: We examined the effect of vitamin C/E by smoking status at randomisation using the Breslow-Day test for interaction. MAIN OUTCOME MEASURES: The trial's primary outcomes were PE and a composite outcome of pregnancy-associated hypertension (PAH) with serious adverse outcomes. Perinatal outcomes included preterm birth and abruption. RESULTS: There were no differences in baseline characteristics within subgroups (smokers versus nonsmokers) by vitamin supplementation status. The effect of prenatal vitamin C/E on the risk of PE (P = 0.66) or PAH composite outcome (P = 0.86) did not differ by smoking status. Vitamin C/E was protective for placental abruption in smokers (relative risk [RR] 0.09; 95% CI 0.00-0.87], but not in nonsmokers (RR 0.92; 95% CI 0.52-1.62) (P = 0.01), and for preterm birth in smokers (RR 0.76; 95% CI 0.58-0.99) but not in nonsmokers (RR 1.03; 95% CI 0.90-1.17) (P = 0.046). CONCLUSION: In this cohort of women, smoking was not associated with a reduction in PE or the composite outcome of PAH. Vitamin C/E supplementation appears to be associated with a reduction in placental abruption and preterm birth among smokers.

Evaluation of in vivo T cell kinetics: use of heavy isotope labelling in type 1 diabetes.

CD4(+) memory cell development is dependent upon T cell receptor (TCR) signal strength, antigen dose and the cytokine milieu, all of which are altered in type 1 diabetes (T1D). We hypothesized that CD4(+) T cell turnover would be greater in type 1 diabetes subjects compared to controls. In vitro studies of T cell function are unable to evaluate dynamic aspects of immune cell homoeostasis. Therefore, we used deuterium oxide ((2) H(2)O) to assess in vivo turnover of CD4(+) T cell subsets in T1D (n = 10) and control subjects (n = 10). Serial samples of naive, memory and regulatory (T(reg)) CD4(+) T cell subsets were collected and enrichment of deoxyribose was determined by gas chromatography-mass spectrometry (GC-MS). Quantification of T cell turnover was performed using mathematical models to estimate fractional enrichment (f, n = 20), turnover rate (k, n = 20), proliferation (p, n = 10) and disappearance (d*, n = 10). Although turnover of T(regs) was greater than memory and naive cells in both controls and T1D subjects, no differences were seen between T1D and controls in T(reg) or naive kinetics. However, turnover of CD4(+) memory T cells was faster in those with T1D compared to control subjects. Measurement and modelling of incorporated deuterium is useful for evaluating the in vivo kinetics of immune cells in T1D and could be incorporated into studies of the natural history of disease or clinical trials designed to alter the disease course. The enhanced CD4(+) memory T cell turnover in T1D may be important in understanding the pathophysiology and potential treatments of autoimmune diabetes.

Placental dysferlin expression is reduced in severe preeclampsia.

Dysferlin (DYSF) and myoferlin (MYOF), members of the ferlin family of membrane proteins, are co-expressed in human placental syncytiotrophoblast (STB). Although the role of these ferlin proteins in the placenta has yet to be established, it has been suggested that DYSF and MYOF may contribute to the stability of the apical STB plasma membrane. The release of STB-derived cellular debris increases in the setting of preeclampsia (PE), suggesting relative destabilization of the hemochorial interface. To test whether PE was associated with alterations in placental expression of DYSF and/or MYOF, a cross-sectional study was performed using specimens of villous placenta collected form women with severe PE (n=10) and normotensive controls (n=10). DYSF and MYOF expression were examined using quantitative real-time RT-PCR, immunoblotting, and immunofluorescence labeling of tissue specimens. Placental DYSF expression was 57% lower at the mRNA level (p=0.03) and 38% lower at the protein level (p=0.026) in severe PE as compared to normotensive subjects. There were no differences in placental MYOF protein or mRNA expression between these groups. No appreciable changes in the distribution of DYSF or MYOF within placental villi was observed in PE relative to control specimens. We conclude that DYSF expression is reduced in severe PE relative to gestational age-matched controls. As DYSF has a role in membrane repair, these data suggest a role for DYSF in the stability of the apical STB plasma membrane and may account, at least in part, for the increased shedding of microparticles from this membrane in PE.

Disseminated intravascular coagulation following selective termination in a twin pregnancy. A case report.

OBJECTIVE: Coagulation abnormalities after single fetal demise are well described, but similar cases had not been previously reported following therapeutic selective termination. CASE: A 23-year-old G(3) P(2001) with a monochorionic-diamnionic twin pregnancy underwent selective termination at 20 4/7 weeks for severe twin-twin transfusion syndrome. Her fibrinogen thereafter decreased and she developed disseminated intravascular coagulopathy with pathological bleeding during a cesarean section. The maternal coagulopathy resolved postpartum. CONCLUSION: Coagulation disorders can follow selective termination. Recommendations to serially follow coagulation parameters after these procedures, however, cannot be based upon a single case.

The effects of repeat doses of antenatal corticosteroids on maternal adrenal function.

OBJECTIVE: The purpose of this study was to determine whether repeated doses of maternal corticosteroids suppress the maternal hypothalamic-pituitary-adrenal axis. STUDY DESIGN: The low-dose corticotropin stimulation test (1.0 microg intravenously) was administered a median of 3 days after the last betamethasone dose to 18 pregnant women who had received at least 2 weekly courses of antenatal betamethasone and to 6 control subjects matched for gestational age who had not received antenatal corticosteroids. RESULTS: The mean basal cortisol level was significantly depressed among women who had received betamethasone with respect to control subjects (1.9 +/- 1.5 vs 26.5 +/- 6.2 microg/dL; P <.001). The maternal cortisol level after corticotropin stimulation was significantly lower in all women who had received betamethasone (P <. 001). The mean time to attainment of peak cortisol level was significantly longer among women who had received betamethasone than among control subjects (37 +/- 6.8 vs 27.4 +/- 1.6 minutes; P <.001). CONCLUSIONS: Repeated courses of betamethasone lead to barely detectable maternal basal cortisol levels and secondary adrenal insufficiency.

Fetal scarless wound healing.

Advances in fetal monitoring and open fetal surgery for life-threatening congenital diseases have provided us with the unique opportunity to examine fetal surgical wound healing. Fetal wounds heal rapidly and without scarring. The exact mechanisms of fetal scarless healing remain unknown. This article illustrates the most current understanding of the fetal wound healing process by examining the intrinsic properties of fetal skin, fetal fibroblasts, wound matrix, fetal environment, and various cytokines. In fetal wound, transforming growth factor-beta and hyaluronic acid-rich wound matrix play pivoting roles in scarless repair. Different experimental strategies to manipulate the healing of adult wounds will be presented. These therapeutic measures are based on the scarless fetal wound repair model. We will also briefly comment on the current status of fetal surgery.

Spurious diagnosis of a cervical mass due to a laryngeal mask airway.

The laryngeal mask airway (LMA) has become a popular alternative to endotracheal intubation. We report a case in which appropriate LMA placement resulted in an unrecognized neck mass and subsequent erroneous diagnosis of cervical lymphadenopathy. Otolaryngologists should be aware that the LMA may result in alterations of neck anatomy.

Prostaglandin E2 cervical ripening without subsequent induction of labor.

OBJECTIVE: To determine whether outpatient administration of intracervical prostaglandin (PG) E2 gel decreases the interval to delivery and duration of labor. METHODS: A randomized, double-blind, placebo-controlled trial compared the intracervical placement of 0.5 mg PGE2 gel with placebo in 61 pregnant women at 38 weeks' or greater gestation with Bishop scores less than 9. Transvaginal cervical length, fetal fibronectin, and Bishop score were assessed before gel placement. Subjects were then allowed to go into spontaneous labor unless an indication for induction developed. RESULTS: Thirty women were assigned to PGE2 and 31 to placebo. There were no significant demographic differences between the groups and there were no differences in cervical length, fetal fibronectin status, or Bishop scores. Fifteen women in the PGE2 group and five in the placebo group went into labor and delivered within the first 2 days after gel placement (P = .007). The median interval to delivery was significantly shorter in the PGE2 group, at 2.5 days, compared with placebo, at 7 days (P = .02). Nulliparas in the PGE2 group had a median interval to delivery of 2 days, compared with 7 days for nulliparas receiving placebo (P = .03). Active phases of labor were significantly shorter in the PGE2 group and for women with a negative fetal fibronectin test who received PGE2. CONCLUSION: Outpatient administration of intracervical PGE2 gel shortened intervals to delivery and shortened labor.

Interleukin-1 alpha, epidermal growth factor, and transforming growth factor-beta exhibit differential kinetics on endothelin-1 synthesis in amnion cells.

OBJECTIVE: To investigate the effects of three cytokines, interleukin-1 alpha (IL-1 alpha), epidermal growth factor (EGF), and transforming growth factor-beta (TGF-beta), on the regulation of endothelin-1 (ET-1) mRNA and protein production in human amnion cells. METHODS: Human amnion cells were harvested from uncomplicated pregnancies undergoing elective cesarean delivery at term and grown in primary monolayer culture. Cells were treated with IL-1 alpha, EGF, and TGF-beta for dose-response and time course experiments. Northern analysis was used to determine ET-1 mRNA expression, and enzyme-linked immunosorbent assay was used for ET-1 peptide determination. RESULTS: Interleukin-1 alpha, EGF, and TGF-beta induced the expression of ET-1 mRNA and protein in a dose- and time-dependent fashion. The kinetics of ET-1 mRNA production did not differ markedly with respect to the inducing cytokine, but the kinetics of ET-1 protein production was quite different. Interleukin-1 alpha and EGF stimulated a rapid increase in ET-1 that peaked by 24 hours, and the levels declined to just above the detection limit by 72 hours. In contrast, TGF-beta-stimulated cells showed modest ET-1 production at early times (4-24 hours) and then gradually increased and peaked at 72 hours. CONCLUSIONS: Cytokines modulate the expression of ET-1 mRNA and its cognate protein in human amnion cells. The differential kinetics of ET-1 peptide expression in amnion cells suggests that ET metabolism as well as synthesis contribute to the net expression of endothelin in amnion.

The effect of the source of transfused blood on the rate of consumption of transfused red blood cells in pregnancies affected by red blood cell alloimmunization.

OBJECTIVE: Our purpose was to compare the rate of consumption of maternally donated red blood cells with the rate of red blood cells from volunteers in fetuses affected by red blood cell alloimmunization. STUDY DESIGN: The rate of hemoglobin decline was calculated in 293 fetal transfusions in 52 pregnancies, in 43 patients affected by red blood cell alloimmunization from 1987 to 1996. Fifty-eight transfusions were excluded from analysis. Hemoglobin decline was stratified by gestational age. The rates of consumption were compared with use of unpaired t tests. RESULTS: The rates of hemoglobin decline (in grams per deciliter per day) were 18 to 24 weeks, 0.47 volunteer and 0.38 maternal (p = 0.174); 25 to 28 weeks 0.41 volunteer, 0.34 maternal (p = 0.46); 29 to 32 weeks, 0.35 volunteer, 0.33 maternal; > or = 33 weeks, 0.37 volunteer, 0.25 maternal, p = 0.048). Hemoglobin decline was less for the maternal donation group than for the volunteer donation group throughout gestation, becoming significant only in fetuses at > or = 33 weeks. CONCLUSION: In the red blood cell-alloimmunized fetus, there is less consumption of maternal than of volunteer red blood cells. This difference reaches a statistical significance only in late gestation.

The seroprevalence of the rubeola antibody in a prenatal screening program.

OBJECTIVE: To evaluate the seroprevalence of the rubeola (measles) antibody in several obstetric populations. METHODS: In this cross-sectional study, women presenting for prenatal care underwent measurement of antibodies to the rubeola virus. The study population presented for care at either an urban medical center (group I) or a suburban medical center (group II). These groups were divided further into those receiving care in a resident-supervised clinic (A) and those in a private-practice setting (B). RESULTS: A total of 768 women were tested. Seventy-five (9.8%) women had rubeola antibody titers less than or equal to 0.13 and were classified as seronegative. The lowest percentage of seronegative women (3.2%) was found at the urban resident-supervised clinic site. The highest percentage of seronegative women (20.5%) was found in the suburban resident-supervised clinic site. Women classified as seronegative were younger, with a mean age of 25.0 years. No significant difference was observed based on gravidity, parity, or care received in an urban versus suburban private-practice setting. CONCLUSION: We suggest that an appreciable number of women presenting for prenatal care may lack antibodies to the rubeola virus. In the interest of personal and public health, populations believed to be at risk may benefit from ongoing surveillance of immune status and appropriate vaccination. Additional study is necessary to define best those groups that would benefit from surveillance and vaccination.

A randomized trial of early discharge and nurse specialist transitional follow-up care of high-risk childbearing women.

In a randomized clinical trial, quality of health care as reflected in patient outcomes and cost of health care was compared between two groups of high-risk childbearing women: women diagnosed with diabetes or hypertension in pregnancy. The control group (N = 52) was discharged routinely from the hospital. The intervention group (N = 44) was discharged early using a model of clinical nurse specialist transitional follow-up care. During pregnancy, the intervention group had significantly fewer rehospitalizations than the control group. For infants of diabetic women enrolled in the study during their pregnancy, low birth weight (< or = 2,500 g) was three times more prevalent in the control group (29%) than in the intervention group (8.3%). The postpartum hospital charges for the intervention group were also significantly less than for the control group. The mean total hospital charges for the intervention group were 44% less than for the control group. The mean cost of the clinical specialist follow-up care was 2% of the total hospital charges for the control group. A net savings of $13,327 was realized for each mother-infant dyad discharged early from the hospital.

Tumour necrosis factor-alpha induces cyclo-oxygenase-2 gene expression in first trimester trophoblasts: suppression by glucocorticoids and NSAIDs.

Tumour necrosis factor-alpha (TNF-alpha) is a pleiotropic cytokine which stimulates the synthesis and release of prostaglandins (PGs) in several in vitro and in vivo models of preterm labour. While TNF-alpha simulated PG production has been described in decidual, amnion and myometrial cells, to date no studies have focused on the role of TNF-alpha in the stimulation of arachidonic acid metabolism in placental trophoblast cells. Cyclo-oxygenase-2 (COX-2) is the rate-limiting enzyme in PG biosynthesis and is expressed de novo during cellular activation by cytokines. To test whether TNF-alpha alters expression of COX-2, trophoblasts from first trimester chorionic vili were cultured as a continuous cell line and treated with TNF-alpha alone or with TNF-alpha and dexamethasone (Dex). Total RNA and protein were extracted from the trophoblasts and subjected to Northern and immunoblot analysis, respectively. Northern blots were hybridized with a 32P-labelled probe encoding the COX-2 cDNA and immunoblots were incubated with anti-COX-2 antibodies. There was a time- and dose-dependent increase in COX-2 mRNA and protein expression in cells stimulated with TNF-alpha. The effect of TNF-alpha on COX-2 mRNA and protein expression was inhibited by dexamethasone (Dex). To examine the production of PGE2 and PGF(2 alpha), specific RIAs were performed on culture media from similarly stimulated cells. PG accumulation after TNF-alpha stimulation occurred in a time- and dose-dependent fashion with a similar inhibition of PG accumulation after Dex exposure. To be certain that TNF-alpha stimulated PGE2 production was, indeed, a result of COX-2 induction, RIAs were carried out with the COX-2-selective inhibitor NS-398. Cells stimulated with the NS-398 after TNF-alpha exposure demonstrated suppression of TNF-alpha-stimulated PGE2 formation. The results suggest that TNF-alpha elicits part of its pathophysiologic effects in preterm labour via alterations in COX-2 gene expression within the placental microenvironment.