Nicotine induces a long QT phenotype in Kcnq1-deficient mouse hearts

We have previously shown that targeted disruption of the mouse Kcnq1 gene produces a long QT phenotype in vivo that requires extracardiac factors for manifestation (Casimiro et al., 2001). In the present study, we explore the hypothesis that autonomic neuroeffector transmission represents the "extra cardiac" stimulus that induces a long QT phenotype in mouse hearts lacking Kcnq1. Using the isolated perfused (Langendorff) mouse heart preparation, we challenged wild-type (Kcnq1+/+) and mutant (Kcnq1-/-) mouse hearts with nicotine, an autonomic stimulant. ECGs were recorded continuously, and QT intervals were compared at baseline and peak nicotine-induced heart rates. No significant differences in QT or any other ECG parameters were observed in Kcnq1+/+ versus Kcnq1-/- hearts at baseline. In the presence of nicotine, however, the JT, QT, and rate-corrected QT (QTc) intervals were significantly prolonged in Kcnq1-/- hearts relative to Kcnq1+/+ hearts (e.g., QTc = 92 +/- 11 ms versus 66 +/- 2 ms, respectively, p < 0.01). Similar findings were obtained when the hearts were challenged with either epinephrine or isoproterenol (0.1 microM each), thereby suggesting that sympathetic stimulation drives the long QT phenotype in Kcnq1-deficient hearts. This idea is supported by in vivo ECG data obtained from unrestrained conscious mice using radiotelemetry recording techniques. Again, no significant ECG differences were observed in Kcnq1-/- versus Kcnq1+/+ mice at baseline, but handling/injection stress led to significant QTc increases in Kcnq1-/- mice relative to wild-type controls (11 +/- 3 versus -1 +/- 1%, respectively, p < 0.05). These data suggest that sympathetic stimulation induces a long QT phenotype in Kcnq1-deficient mouse hearts.     

Maternal pulse oximetry perfusion index as a predictor of early adverse respiratory neonatal outcome after elective cesarean delivery.

OBJECTIVE: Evidence suggests increased morbidity, in particular early neonatal respiratory complications, in newborns from elective cesarean section compared with those from vaginal delivery. No reliable maternal predictors of adverse neonatal outcome at elective cesarean section are known. Here, we prospectively tested the hypothesis that a low maternal perfusion index at the baseline phase (i.e., preanesthesia) of the elective cesarean section is a predictor of early adverse neonatal respiratory outcome. DESIGN: Prospective cohort study. SETTING: Operating and delivery rooms of a public health hospital with a tertiary-level neonatal intensive care unit. PATIENTS: Forty-four healthy pregnant women with no known risk factors undergoing elective cesarean section at term gestation. INTERVENTIONS: Elective cesarean section was divided into nine phases. Analysis of pulse oximetry-derived signals (perfusion index, pulse rate, and oximetry) and systolic, diastolic, and differential blood pressure were recorded. Maternal arterial and venous newborn cord blood gas analyses and placental histology were evaluated. MEASUREMENTS AND MAIN RESULTS: Early respiratory complications (transient tachypnea of the newborn, n = 5; respiratory distress syndrome, n = 1) were observed in 13.6% (6 of 44) of the newborns. A maternal perfusion index < or = 1.9 (lower quartile) during the preanesthesia phase of the elective cesarean section was an independent predictor of early adverse neonatal respiratory outcome (odds ratio 68.0, 95% confidence interval 6.02-767.72; p < .0001). CONCLUSIONS: A decreased perfusion index value in the preanesthesia phase of elective cesarean section is a maternal predictor of increased neonatal morbidity and is significantly related to subclinical placental inflammatory disease. These observations suggest the feasibility of a noninvasive pulse oximeter prenatal screening of the high-risk fetus/newborn in elective cesarean section.     

Fetal growth after preterm premature rupture of membranes: is it related to amniotic fluid volume?

OBJECTIVE: Preterm premature rupture of membranes (PPROM) has been associated with an increased rate of fetal growth restriction (FGR). It is unknown whether impairment of fetal growth is mediated through external compression from decreased amniotic fluid volume or (an)other mechanism(s). METHODS: Over a three-year period all patients with singleton pregnancies experiencing PPROM at <37 weeks lasting greater than 10 days, and who underwent serial sonograms to assess fetal biometry after PPROM, were included in the study. Patients were excluded for congenital anomalies or other inherent risk factors for abnormal fetal growth. Fetal abdominal circumference (AC) percentiles were compared between the first sonographic exam after PPROM and the last exam before delivery. The median amniotic fluid index between PPROM and delivery was correlated with the change in AC percentiles while controlling for the duration of PPROM. Statistical analysis utilized one-way analysis of variance and correlation; a p value of <0.05 was considered significant. RESULTS: Twenty-two patients met our inclusion criteria with a mean duration (+/-SD) of PPROM of 58 days (+/-46). The median AFI during the PPROM period was not correlated with the change in AC percentiles after controlling for duration of PPROM (p = 0.49). CONCLUSIONS: The residual amniotic fluid volume after PPROM does not appear to correlate with fetal growth suggesting that the increased rate of FGR in PPROM is not secondary to oligohydramnios. We hypothesize that the intrauterine pathologic processes responsible for membrane rupture may also interfere with fetal growth.     

Decorin from different bovine tissues: study of glycosaminoglycan chain by PAGEFS

The sulphation pattern of glycosaminoglycan (GAG) plays a critical role in biological functions of proteoglycans. In this study, we showed that decorins from different bovine tissues present specific sulphation pattern coupled with peculiar biological activity. In order to elucidate chemical structure of decorin glycosaminoglycan chains, we improved an electrophoretic method to analyse fluorescent disaccharides from dermatan/chondroitin sulphate GAG chains. The disaccharide separation is based on minigels, and this technique was able to define the polysaccharide chain composition in terms of sulphated and not sulphated disaccharides. This approach allowed not only the measurement of few picomoles of material, but it also permits a rapid qualitative analysis of the GAG chains. Data obtained by PAGEFS indicate that the sulphation pattern of GAG is tissue specific and this finding may explain the different binding properties to von Willebrand factor of decorins.     

Metabolic transitions at menopause: In post-menopausal women the increase in serum uric acid correlates with abdominal adiposity as assessed by DXA

Objectives

The present study aimed to investigate any associations between parameters of body fat mass distribution and levels of serum uric acid (sUA), a well-documented cardiovascular risk factor, among non-obese women ranging from pre- to post-menopausal status.

Methods

In this cross-sectional population-based study we assessed body fat distribution by dual-energy-X-ray absorptiometry (DXA), and sUA levels in 101 pre- and 134 post-menopausal non-obese apparently healthy women.

Results

Multivariate stepwise regression analysis revealed that sUA was independently associated to the indicators of overall fatness, i.e. body mass index (β = 0.339, p < 0.001) and DXA-assessed total and percentage body fat (β = 0.366, p < 0.001 and β = 0.412, p < 0.001, respectively), only among post-menopausal women. Within this sample subset, trunk (i.e. central) fat mass emerged as a strong predictor of sUA (β = 0.408, p < 0.001), after taking the potential confounders (including body mass index) into account.

Conclusion

Central fat accumulation was found to be independently associated with higher sUA levels among non-obese women in post- but not among those in pre-menopause.     

Predictors of perinatal survival in a cohort of pregnancies with severe oligohydramnios due to premature rupture of membranes at <26 weeks managed with serial amnioinfusions

OBJECTIVE: To evaluate whether successful amnioinfusion is an independent predictor of perinatal survival in a cohort of cases with extreme and persistent oligohydramnios due to preterm premature rupture of membranes (pPROM) who reached viability and were managed with serial amnioinfusions. STUDY DESIGN: We included all consecutive singleton pregnancies with pPROM at <26 weeks and oligohydramnios lasting >4 days between 1/1991 and 12/2001 and who consented to undergo amnioinfusion (n=77). Women received serial transabdominal amnioinfusions in an attempt to maintain a pocket of fluid >2 cm. The procedure was deemed successful if the median deepest pocket of fluid during the latency period was >2 cm. Excluded were miscarriages (n=10), fetal deaths before viability (24 weeks) (n=15), and cases that did not develop oligohydramnios (n=17). Prenatal predictors of outcome were compared between cases who survived the perinatal period and those who did not using Wilcoxon rank-sum test, Fisher's exact test and stepwise logistic regression analysis, with a two-tailed P<0.05 considered significant. RESULTS: Of the 35 patients fulfilling the study criteria, 20 (57%) survived the perinatal period. Perinatal survivors had similar gestational age at pPROM (P=0.68) and at first amnioinfusion (P=0.53) as those who died in the perinatal period, but longer latency (P=0.013). Consequently, median gestational age at delivery [29.2 (25.4-35.3) weeks versus 26.1 (24.0-34.0) weeks, P<0.001] and median birth weight [1220 (650-2240) g versus 863 (520-2200) g, P=0.001] were significantly greater among survivors than among those who died. Significant predictors of survival at univariate analysis were entered into a stepwise logistic regression analysis in the chronological order in which they normally occur. The analysis demonstrated that successful amnioinfusion (OR=6.9, 95% CI 1.2-40.4) and administration of steroids (OR=14.6, 95% CI 1.5-144.1) were independent and significant predictors of perinatal survival. CONCLUSION: In a cohort of women with pPROM at <26 weeks and severe oligohydramnios managed with serial amnioinfusions, successful procedures and prenatal administration of corticosteroids are the only independent predictors of perinatal survival.