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.     

A prospective, randomized, double-blind, placebo-controlled parallel-group dual site trial to evaluate the effects of a Bacillus coagulans-based product on functional intestinal gas symptoms

Background  

This randomized double blind placebo controlled dual site clinical trial compared a probiotic dietary supplement to placebo regarding effects on gastrointestinal symptoms in adults with post-prandial intestinal gas-related symptoms (abdominal pain, distention, flatulence) but no gastrointestinal (GI) diagnoses to explain the symptoms.     

Vertebroplasty as treatment of aggressive and symptomatic vertebral hemangiomas: up to 4 years of follow-up

Introduction  This study aimed to illustrate the validity of the treatment with vertebroplasty (VP) in patients with aggressive or symptomatic vertebral hemangioma (VH) with or without epidural extension. Methods  From January 2003 to December 2007, 24 consecutive patients have been treated with VP, for a total of 36 vertebral bodies affected by VH: two cervical, ten dorsal, 24 lumbar. All the patients complained of a pain syndrome resistant to continuous medical medication; four of 24 patients also presented aggressive magnetic resonance features of the vertebral lesion and two patients showed also epidural extension. A unipedicular approach has been performed in 16 patients; a bipedicular approach has been performed in six, while for the cervical spine an anterior–lateral approach with manual dislocation of the carotid axis has always been performed. Bone biopsy was never done. All procedures have been carried out with local anesthesia, except for the treatment of the cervical hemangiomas which has always been performed under general anesthesia. Four vertebral bodies in the same session have been treated in one case. Results  Results have been evaluated with the visual analog scale and the Oswestry Disability Index methods. In all the patients, in the following 24–72 h, a successful outcome has been observed with a complete resolution of pain symptom. Extravertebral vascular or discal cement leakage has been observed in four patients, without any onset of clinical radicular syndrome due to epidural diffusion. Clinical and radiological follow-up until 4 years has been performed in 12 patients and it showed stability of the treatment and absence of pain. Conclusions  Percutaneous treatment with VP for aggressive and symptomatic vertebral hemangiomas even with epidural extension is a valuable, mini-invasive, and quick method that allows a complete and enduring resolution of the painful vertebral symptoms without findings of fracture of a vertebral body adjacent or distant to the one treated.     

An unusual association of contralateral congenital small kidney, reduced renal function and hyperparathyroidism in sponge kidney patients: on the track of the molecular basis.

Of unknown pathogenesis, sponge kidney (SK) is variably associated with nephrocalcinosis, stones, nephronic tubule dysfunctions and precalyceal duct cysts. Amongst 72 unrelated renal SK patients with renal stone disease, we detected one with unilateral bifid renal pelvis and six with unilateral small kidneys (longitudinal diameter difference >15%). Secondary causes of small kidney were excluded. Of the seven cases, four had reduced renal function (67 vs 7% in the entire cohort), and three developed hyperparathyroidism during follow-up (43 vs 4%). The pathogenesis of SK ought to explain why anatomical structures of different embryological origin are involved (the precalyceal and collecting ducts and the nephron) and why there is frequent association with hyperparathyroidism. In embryogenesis, the metanephric blastema synthesizes the chemotactic glial-derived neurotrophic factor (GDNF) to prompt the ureteric bud to branch off from Wolff's mesonephric duct, and to approach and invade the blastema. The bud's tip expresses the GDNF receptor (RET). RET-GDNF binding is crucial not only for the correct formation of ureters and collecting ducts (both of Wolffian origin), but also for nephrogenesis. We advance the hypothesis that SK results from a disruption in the ureteric bud-metanephric blastema interface, possibly due to one or more mutations or polymorphisms of RET or GDNF genes. This would explain: the concurrent alterations in precalyceal ducts and the functional defects in the nephron, the occasional association with size and the functional asymmetry between the two kidneys, some degree of renal dysplasia causing the reduction in the glomerular filtration rate and (given the role of RET in parathyroid cell proliferation) the association with hyperparathyroidism.