Dissection of the aorta in Turner syndrome: two cases and review of 85 cases in the literature.

Girls and women with Turner syndrome are at risk for catastrophic aortic dissection and rupture, but the clinical profile for those at risk is not well described. In addition to reporting two new cases, we performed an electronic search to identify all reported cases of aortic dissection associated with Turner syndrome. Particular attention was paid to the reporting of systemic hypertension (HTN) and congenital heart disease (CHD) which are known risk factors for aortic disease in the general population. In total, 85 cases of aortic dissection in TS were reported between 1961 and 2006. Dissection occurred at a young age, 30.7 (range 4-64) years, which is significantly earlier than its occurrence in the general female population (68 years). Of the cases for which HTN and CHD were explicitly assessed, 15% had HTN alone, 30% had CHD alone and 34% had both. Importantly, in 11% of the cases, neither HTN nor CHD were identified, suggesting that TS alone is an independent risk factor for aortic dissection; however, the cases where no risk factors were identified were very poorly documented. Dissection in women with TS undergoing assisted reproductive techniques (ART) frequently resulted in death. The literature on aortic dissection in TS is sparse and most cases are poorly documented, making it difficult to establish firm guidelines regarding monitoring and treatment. A TS aortic dissection registry has been established to better determine the natural history and risk factors (http://www.tssus.org/readweb.asp?wid = 3092).

Natriuretic peptide signalling: molecular and cellular pathways to growth regulation.

The natriuretic peptides (NPs) constitute a family of polypeptide hormones that regulate mammalian blood volume and blood pressure. The ability of the NPs to modulate cardiac hypertrophy and cell proliferation as well is now beginning to be recognized. The NPs interact with three membrane-bound receptors, all of which contain a well-characterized extracellular ligand-binding domain. The R1 subclass of NP receptors (NPR-A and NPR-B) contains a C-terminal guanylyl cyclase domain and is responsible for most of the NPs downstream actions through their ability to generate cGMP. The R2 subclass lacks an obvious catalytic domain and functions primarily as a clearance receptor. This review focuses on the signal transduction pathways initiated by ligand binding and other factors that help to determine signalling specificities, including allosteric factors modulating cGMP generation, receptor desensitization, the activation and function of cGMP-dependent protein kinase (PKG), and identification of potential nuclear or cytoplasmic targets such as the mitogen-activated protein kinase signalling (MAPK) cascade. The inhibition of cardiac growth and hypertrophy may be an important but underappreciated action of the NP signalling system.

Recommendations for the diagnosis and management of Turner syndrome.

Comprehensive recommendations on the diagnosis of Turner syndrome (TS) and the care of affected individuals were published in 1994. In the light of recent advances in diagnosis and treatment of TS, an international multidisciplinary workshop was convened in March 2000, in Naples, Italy, in conjunction with the Fifth International Symposium on Turner Syndrome to update these recommendations. The present paper details the outcome from this workshop. The genetics and diagnosis of the syndrome are described, and practical treatment guidelines are presented.

Effect of intravenous propranolol or verapamil on infant orthodromic reciprocating tachycardia.

The effects of intravenous verapamil (0.15 mg/kg) and propranolol (0.2 mg/kg) with regard to atrioventricular (AV) conduction and tachycardia termination during paroxysmal atrial tachycardia were compared in 2 groups of infants (verapamil n = 14, propranolol n = 18, mean age 80 +/- 21 days, range 1 to 364). Using transesophageal recording techniques, tachycardia cycle length, AV intervals and ventriculoatrial intervals were measured before and after drug administration. Both intravenous propranolol and verapamil significantly prolonged tachycardia cycle length and AV interval (cycle length--propranolol 230 +/- 30 to 262 +/- 33 ms, p less than 0.05, verapamil 223 +/- 38 to 245 +/- 32 ms, p less than 0.05; AV interval--propranolol 98 +/- 26 to 126 +/- 38 ms, p less than 0.05, verapamil 96 +/- 19 to 109 +/- 24 ms, p less than 0.05). Neither drug prolonged the ventriculoatrial interval. Tachycardia terminated after intravenous verapamil in 11 of 14 infants (79% efficacy rate). Tachycardia terminated in 0 of 18 after intravenous propranolol (0% efficacy rate). In 8 infants an atrial deflection was recorded on the esophageal electrocardiogram at the time of tachycardia termination after intravenous verapamil, which suggested that tachycardia terminated by block occurring in the AV node. In 2 infants a ventricular deflection was recorded at the time of tachycardia termination after verapamil, which suggested that block occurred in the accessory connection. Both drugs prolonged tachycardia cycle length by prolonging AV conduction to a similar degree.(ABSTRACT TRUNCATED AT 250 WORDS)

Predicting hospital charge and length of stay for congenital heart disease surgery.

Three hundred twenty-two consecutive operations between December 1985 and December 1989 for 10 types of low-risk congenital cardiac malformations were reviewed to determine the hospital charge and postoperative length of stay. Multiple regression analysis of variance was used to predict the influence of the primary diagnosis and various preoperative parameters. The average hospital charge was $27,262 +/- $20,644 and the postoperative length of stay was 9.3 +/- 8.3 days. Age at operation alone did not influence the dependent variables. The diagnosis of atrial septal defect (p = 0.002) or coarctation of the aorta (p = 0.002) decreased the mean charge, whereas the 8 other primary diagnoses did not significantly influence the mean charge. Other preoperative factors found to be predictive of increased hospital charge were: the date of operation (p < 0.001), cyanosis (p = 0.008), previous thoracic surgery (p = 0.02), failure to thrive (p < 0.001), associated major extra cardiac anomalies (p < 0.001), oxygen requirement (p = 0.02), and distance > 100 miles from home to hospital (p = 0.05). A primary diagnosis of atrial septal defect decreased the mean postoperative length of stay by 3.1 days (p < 0.001). Other preoperative conditions increased the mean postoperative length of stay: major extracardiac malformation (p < 0.001), failure to thrive (p < 0.001), and oxygen requirement (p = 0.003). Charge and length of stay equations were generated which may assist in the prediction of resource utilization in this patient population.(ABSTRACT TRUNCATED AT 250 WORDS)

Giant blood cyst of the aortic valve.

Beyond infancy, blood cyst of the aortic valve is not known to occur. We describe a 16-year-old girl who had aortic valve stenosis and regurgitation and giant blood cyst of the aortic valve. Serial echocardiograms over a 12-year period demonstrated gradual enlargement of the cyst.

Dissection of the aorta in Turner syndrome: two cases and review of 85 cases in the literature.

Patients with Turner syndrome (TS) are at risk for aortic dissection, but the clinical profile for those at risk is not well described. In addition to reporting two new cases, we performed an electronic search to identify all reported cases of aortic dissection associated with TS. In total, 85 cases of aortic dissection in TS were reported between 1961 and 2006. Dissection occurred at a young age, 30.7 (range 4-64) years, which is significantly earlier than its occurrence in the general female population (68 years). Importantly, in 11% of the cases, neither hypertension nor congenital heart disease were identified, suggesting that TS alone is an independent risk factor for aortic dissection; however, the cases where no risk factors were identified were very poorly documented. A TS aortic dissection registry has been established to determine the natural history and risk factors better (http://www.turnersyndrome.org/).

Glucose oxidation by Gluconobacter oxydans: characterization in shaking-flasks, scale-up and optimization of the pH profile.

In this study, the advantage of a novel measuring device for the online determination of oxygen and carbon dioxide transfer rates in shaking-flasks is reported for glucose oxidation by Gluconobacter oxydans. In this fermentation process, this device was used for the characterization of the oxidation pattern of different strains. G. oxydans NCIMB 8084 forms 2,5-diketogluconate from d-glucose in a multi-stage process via three different membrane-bound dehydrogenases. This strain was chosen for a scale-up of the process from shaking-flasks to a 2-l stirred vessel. An enhancement of 2,5-diketogluconate production was realized by controlling the pH at different levels during the fermentation.

Effect of atrial natriuretic peptide on vascular permeation in the ovine fetus.

To study the effect of atrial natriuretic peptide (ANP) on vascular permeation of albumin in the fetus, ANP (167-600 ng/min) was infused into eight ovine fetuses and saline vehicle was infused into eight twin controls (gestational age 127 +/- 3 d) over a 50-min period. Using two different radiolabeled albumin markers, we determined the tissue to blood isotope ratio (TBIR), an index of albumin permeation, and the albumin clearance. Although ANP had no hemodynamic effect, a marked increase in the hematocrit was observed in ANP-infused fetuses compared with initial values (0.37 +/- 0.04 vs 0.42 +/- 0.04, p < 0.005) but was unchanged in the twin fetuses receiving saline vehicle (0.35 +/- 0.03 versus 0.35 +/- 0.02). TBIR and albumin permeation were increased in combined tissues of ANP-infused fetuses compared with saline controls (TBIR: 1.49 +/- 0.58 versus 1.29 +/- 0.3, p < 0.001; albumin clearance: 1091 +/- 1279 versus 827 +/- 1464 nL/g/min, p < 0.01). In individual tissues, TBIR was significantly increased in skin (2.88 +/- 0.67 versus 1.55 +/- 0.35, p < 0.02), muscle (1.6 +/- 0.27 versus 1.24 +/- 0.26, p < 0.02), adrenal (1.33 +/- 0.10 versus 1.13 +/- 0.15, p < 0.02), bone (1.67 +/- 0.45 versus 1.20 +/- 0.40, p < 0.02), kidney (1.52 +/- 0.25 versus 1.24 +/- 0.26, p < 0.03), and gut (1.69 +/- 0.20 versus 1.39 +/- 0.34, p < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of types of pulmonary stenosis with the state of the ventricular septum in complete transposition of the great arteries.

The pulmonary valve and left ventricular outflow tract of 214 hearts with d-transposition of the great arteries (d-TGA) were visually inspected (126 of 214 with intact ventricular septum and 88 of 214 with ventricular septal defect [VSD]). Pulmonary stenosis (PS), either valvular, subvalvular, or in combination, was present in 26 cases and was found to be more common in the presence of a VSD (20.5%) than intact ventricular septum (6.3%). PS occurred more commonly in the presence of a supracristal VSD than an infracristal VSD (70%, 7 of 10 vs 15%, 10 of 66). Further, infracristal or supracristal VSDs were associated with different types of pulmonary obstruction. In seven of ten cases with infracristal VSD and PS, the stenosis was caused by an anomaly of an atrioventricular valve. In six of seven cases with supracristal VSD and PS, the latter was caused by membranous encirclement of the left ventricular outflow tract.

Newborn cardiorenal dynamics: a state of atrial natriuretic peptide unresponsiveness.

The newborn has an attenuated response to saline fluid challenge. We studied the response of endogenous atrial natriuretic peptides (ANF) to 10% body weight graded isotonic saline volume expansion (VE) in 14 anesthetized neonatal lambs which were either 1 day old or 7 days old. Plasma ANF values were unchanged at 3.3% and 10% VE compared with control values (56 +/- 28 vs. 66 +/- 17 and 66 +/- 37 pg/ml, not significant) in the 1-day-old lambs, whereas values increased significantly at both 3.3% and 10% VE (47 +/- 40 vs. 99 +/- 57 and 96 +/- 73, P = 0.022 and P = 0.018, respectively) in the 7-day-old lambs. No relationship existed between right atrial (RAP) or pulmonary capillary wedge pressures (PCWP) and plasma ANF in the 1-day-old lambs; however, a significant correlation existed (RAP, P = 0.015; PCWP, P = 0.022) in the 7-day-old lambs. In general, renal function was improved in the 7-day-old lambs compared with the 1-day-old lambs, but only changes in fractional sodium excretion were significantly different (P = 0.017). We speculate that ANF unresponsiveness in the 1-day-old lamb is related to physiological transitions during the birth process and that the maturation of the renal response to VE may require maturation of the atrial mechanism which permits ANF secretion.

Role of endogenous atrial natriuretic peptide in chronic anemia in the ovine fetus: effects of a non-peptide antagonist for atrial natriuretic peptide receptor.

Chronic fetal anemia causes polyhydramnios and fetal hydrops and is associated with increased fetal diuresis and natriuresis. To determine the role of atrial natriuretic peptide (ANP) in the renal adaptation to chronic fetal anemia we studied the effects of HS-142-1 (HS), a specific inhibitor of the guanylate cyclase-linked ANP receptor (ANP-GC), in two groups of chronically instrumented unanesthetized sheep fetuses. Seven fetuses were made anemic by serial isovolemic hemorrhage over 1 wk, and five fetuses served as nonanemic controls. Over the 7 d of hemorrhage ANP concentrations increased (45 +/- 7 to 234 +/- 15 fmol/mL). Hematocrit and arterial blood oxygen content were significantly lower in the anemic compared with the nonanemic fetuses (13.8 +/- 0.7 versus 34.6 +/- 2.3% and 0.7 +/- 0.1 versus 2.6 +/- 0.2 mmol/L). Before HS urine flow rate, urinary sodium excretion, fractional excretion of sodium, and renal blood flow were increased in the anemic fetuses, and the extracellular fluid volume (inulin space) was increased (674 +/- 94 versus 497 +/- 71 mL/kg). However, GFR was not different between the groups. HS caused a significant increase in the central venous pressure of the anemic fetuses (0.49 +/- 0.03 to 0.70 +/- 0.05 kPa). Urinary excretion of cGMP was considered to be a marker of endogenous ANP renal effect and was measured before and after a single bolus of HS (5.2 +/- 0.30 mg/kg). HS decreased urinary cGMP excretion to 50 and 37% of baseline levels in anemic and nonanemic fetuses, respectively. Urine flow decreased in both nonanemic and anemic fetuses (0.48 +/- 0.13 to 0.25 +/- 0.06 and 1.30 +/- 0.66 +/- 0.06 mL/min). Sodium excretion decreased in both groups after HS (19 +/- 5 to 9 +/- 2 and 83 +/- 16 to 39 +/- 5 mumol/min). GFR decreased after HS (3.0 +/- 0.8 to 2.4 +/- 0.5 and 3.6 +/- 0.3 to 2.6 +/- 0.2 mL/min. Fraction excretion of sodium also decreased in both groups after HS (4.6 +/- 2.7 to 2.7 +/- 0.5 and 16.1 +/- 2.4 to 11 +/- 1.6). Percent decreases in urine flow, sodium excretion, GFR, and fractional excretion of sodium observed in the anemic fetuses were not statistically different from the nonanemic fetuses. Urine flow and sodium excretion did not decrease to control levels after HS, suggesting that factors in addition to ANP contribute to the natriuresis seen with chronic anemia. After HS a transient increase in renal blood flow was observed in the nonanemic fetuses. An immediate and sustained further increase in renal blood flow was observed in the anemic fetuses (336 +/- 37 to 436 +/- 58 mL/min/100 g of kidney). Decreasing GFR and increasing renal blood flow suggests HS may alter the renal microcirculation by reversing ANP-induced constriction of the glomerular efferent arteriole. We conclude that sustained increases of the central venous pressure suggest that ANP inhibition results in decreased fluid movement into perivascular tissue. Endogenous ANP may help to maintain basal renal function in the normal fetal kidney and participates in the renal adaptation to chronic fetal anemia. ANP may promote urine flow and sodium excretion by its effects on both the renal microcirculation and the sodium reabsorptive capacity of the nephron.

Left ventricular outflow tract obstruction defined by active three-dimensional echocardiography using rotational transthoracic acquisition.

A rotational data acquisition system was used to create three-dimensional images from thoracic and subxiphoid echocardiographic windows in children with various types of subaortic stenosis. Thirteen patients, ranging in age from 2 days to 17 years, were examined. Subaortic obstruction was caused by a discrete fibrous ridge in six patients, hypertrophic cardiomyopathy in two patients, subaortic tunnel in two patients, and septal malalignment, restrictive VSD, and abnormal suture placement each in one patient. Unique views could be obtained equivalent to surgical or autopsy dissections, and allowed more complete understanding of morphology than conventional imaging techniques.

Extracellular signal-regulated protein kinase activation is required for the anti-hypertrophic effect of atrial natriuretic factor in neonatal rat ventricular myocytes.

Atrial natriuretic factor (ANF) inhibits proliferation in non-myocardial cells and is thought to be anti-hypertrophic in cardiomyocytes. We investigated the possibility that the anti-hypertrophic actions of ANF involved the mitogen-activated protein kinase signal transduction cascade. Cultured neonatal rat ventricular myocytes treated for 48 h with the alpha(1)-adrenergic agonist phenylephrine (PE) had an 80% increase in cross-sectional area (CSA). ANF alone had no effect but inhibited PE-induced increases in CSA by approximately 50%. The mitogen-activated protein kinase/ERK kinase (MEK) inhibitor PD098059 minimally inhibited PE-induced increases in CSA, but it completely abolished ANF-induced inhibition of PE-induced increases. ANF-induced extracellular signal-regulated protein kinase (ERK) nuclear translocation was also eliminated by PD098059. ANF treatment caused MEK phosphorylation and activation but failed to activate any of the Raf isoforms. ANF induced a rapid increase in ERK phosphorylation and in vitro kinase activity. PE also increased ERK activity, and the combined effect of ANF and PE appeared to be additive. ANF-induced ERK phosphorylation was eliminated by PD098059. ANF induced minimal phosphorylation of JNK or p38, indicating that its effect on ERK was specific. ANF-induced activation of ERK was mimicked by cGMP analogs, suggesting that ANF-induced ERK activation involves the guanylyl cyclase activity of the ANF receptor. These data suggest that there is an important linkage between cGMP signaling and the mitogen-activated protein kinase cascade and that selective ANF activation of ERK is required for the anti-hypertrophic action of ANF. Thus, ANF expression might function as the natural defense of the heart against maladaptive hypertrophy through its ability to activate ERK.