Volume overload hypertrophy of the newborn heart slows the maturation of enzymes involved in the regulation of fatty acid metabolism.

OBJECTIVES: The purpose of this study was to determine the effect of volume overload hypertrophy in the newborn heart on the cardiac enzymes controlling fatty acid metabolism. BACKGROUND: Shortly after birth, a rise in 5'-adenosine monophosphate-activated protein kinase (AMPK) activity results in the phosphorylation and inhibition of acetyl coenzyme A (CoA) carboxylase (ACC), and a decline in myocardial malonyl CoA levels with increased fatty acid oxidation rates. Whether the early onset of hypertrophy in the newborn heart alters this maturational increase in fatty acid oxidation is unknown. METHODS: Newborn piglets underwent endovascular stenting of the ductus arteriosus on day 1 of life with a 4.5-mm diameter stent, resulting in a left to right shunt, and left ventricular (LV) volume loading. Left ventricular and right ventricular samples from fetal, newborn, three-week control and three-week stented animals were compared. RESULTS: Stenting resulted in echocardiographic evidence of volume overload and myocardial hypertrophy. In control animals, left ventricular ACC activity declined from 274 +/- 30 pmol/mg/min on day 1 to 115 +/- 12 after three weeks (p < 0.05), but did not display this maturation drop in hypertrophied hearts, remaining elevated (270 +/- 50 pmol/mg/min, p < 0.05). At three weeks, malonyl CoA levels remained 2.8-fold higher in hypertrophied hearts than in control hearts. In control hearts, LV AMPK activity increased 178% between day 1 and three weeks, whereas in hypertrophied hearts AMPK activity at three weeks was only 71% of control values, due to a significant decrease in expression of the catalytic subunit of AMPK. CONCLUSIONS: Early onset LV volume overload with hypertrophy results in a delay in the normal maturation of fatty acid oxidation in the newborn heart.

Human breast cancer susceptibility to paclitaxel therapy is independent of Bcl-2 expression.

In laboratory studies, ectopic overexpression of the antiapoptotic protein Bcl-2 has been shown to result in resistance to the cytotoxic effects of many chemotherapeutic drugs. Furthermore, posttranslational modification of moderately expressed endogenous Bcl-2 has been correlated with susceptibility to paclitaxel treatment in vitro. To determine whether tumor expression of Bcl-2 protein correlates with response and ultimate outcome in vivo, we quantified Bcl-2 expression by immunohistochemical analysis of archived biopsy specimens from metastatic breast cancer patients treated with single-agent paclitaxel. The statistical association between the degree of Bcl-2 expression, objective tumor response, and clinical outcome was then determined. In patients (n = 39) whose tumors had low (< or = 10% cells positive) Bcl-2 levels by immunohistochemical analysis, the overall response (complete response + partial response) rate was 21% versus an overall response rate of 22% in patients (n = 36) with high (>10% cells positive) Bcl-2 expression (P = 0.92). In patients with low Bcl-2 expression, the median time to progression was 126 days [95% confidence interval (CI), 63-160 days]. This was not significantly different than the 105 days for patients with high tumor Bcl-2 expression (95% CI, 84-214 days). The median survival time from initiation of paclitaxel therapy for patients with low Bcl-2 expression was 663 days (95% CI, 456-1119 days) and was not significantly different than the 450 days (95% CI, 239-1058 days) observed for patients with high Bcl-2 expression. In conclusion, we found that in metastatic breast cancer, there is no significant association between tumor Bcl-2 expression and response to paclitaxel, median time to progression, or survival, suggesting that the main mechanism of paclitaxelinduced cytotoxicity in breast tumors is independent of Bcl-2 expression.

Serial assessment of ductus arteriosus hemodynamics in hyaline membrane disease.

OBJECTIVES: To assess the efficacy of Doppler echocardiography (DE) in the quantification of patent ductus arteriosus (PDA) shunt volume and to correlate PDA shunt volume with clinical outcome in infants with hyaline membrane disease. METHODS: Ninety-eight DE studies were performed in 30 preterm ventilated infants with hyaline membrane disease within the first 24 hours of age and then at 48-hour intervals to a maximum of three studies while ventilated with a final study after extubation. Right and left ventricular outputs (QRV and QLV, respectively) and PDA flow were calculated using cross-sectional area and flow velocity integrals. Left atrial-to-aortic root diameter measurements were also taken. Clinical outcomes were correlated with the shunt fraction (QLV/QRV). RESULTS: QLV/QRV demonstrated a linear relationship with the left atrial-to-aortic root diameter ratio (n = 92; r = .79). In the absence of a PDA (n = 33 studies), QRV versus QLV demonstrated a linear relationship (r = .88). In the presence of a PDA (n = 64 studies) the mean QLV (334 +/- 133 ml/kg per minute) was significantly greater than the mean QRV (237 +/- 84 ml/kg per minute). There was a linear relationship between QLV-QRV (PDA shunt volume) and PDA flow (n = 60; r = .84). In studies with exclusive left-to-right shunting at the PDA (n = 48), the mean QLV-QRV (112 +/- 83 ml/kg per minute) was significantly higher than in those with bidirectional shunting (n = 16; mean QLV-QRV = 50 +/- 27 ml/kg per minute). Two infants with severe intraventricular hemorrhage (IVH grade 3) and two infants with periventricular leukomalacia (PVL) had significantly higher QLV/QRV (2.09 +/- 0.36 and 1.67 +/- 0.02 respectively) than those with no IVH (n = 6; QLV/QRV = 1.31 +/- 0.18) or those with IVH grades 1 and 2 (n = 8; QLV/QRV = 1.48 +/- 0.27). There was no difference in QLV/QRV in infants with or without bronchopulmonary dysplasia and retinopathy of prematurity. Necrotizing enterocolitis did not develop in any of the 30 infants. CONCLUSION: PDA shunt volume can be quantified by DE. Larger studies are needed to correlate clinical outcome with QLV/QRV.

A novel method to create atrial septal defect using a cutting balloon in piglets.

A new method of creating atrial septal defect, using a 3- or 4-blade cutting balloon catheter combined with conventional static balloon dilation, is discussed. Radially directed surgical cuts made in the atrial septum were enlarged by balloon angioplasty, producing defects measuring 3 to 8 mm, with a mean Qp/Qs of 1.96/L.

Right pulmonary artery obstruction after pulmonary artery banding.

Serial assessment of pulmonary artery flow by Doppler echocardiography was carried out in 15 infants after pulmonary artery banding. Three infants were identified as having branch pulmonary artery obstruction based on diastolic pulmonary artery flow. It is concluded that this flow profile may be specific for branch pulmonary artery obstruction after pulmonary artery banding.

Neonatal spinal cord syndrome associated with hypoplastic aortic arch and anemia.

Spinal cord syndrome is a rare postoperative complication in neonates. We describe a case occurring after surgical treatment of a hypoplastic aortic arch in the presence of anemia.

The echocardiographic assessment of the human fetal foramen ovale.

The foramen ovale size and interatrial flow patterns were studied by combined real-time and Doppler echocardiography in 100 normal human fetuses between 20 and 38 weeks gestation. The foramen ovale, atrioventricular, and semilunar valve diameters increased linearly with gestational age. The foramen flap motion and interatrial flow patterns showed biphasic flow patterns with interatrial flow reversal with atrial systole. Color flow mapping of the diameter of the interatrial flow profile showed good correlation with the foramen ovale size as measured by two-dimensional echocardiography. These data represent the first large study of the normal human foramen ovale correlated with gestational age, thus expanding the reference base for ultrasound assessment of fetal heart.

Prenatal detection of foramen ovale obstruction without hydrops fetalis.

A case of prenatal echocardiographic diagnosis of obstruction of the foramen ovale is described. Presentation was the ultrasound detection of unexplained marked right atrial and right ventricular dilation without fetal hydrops. It is speculated that fetal outcome depends on the severity and time of onset of foramen ovale obstruction in utero.

Polymerase chain reaction approaches to Culicoides (Diptera: Ceratopogonidae) identification.

Molecular genetic approaches such as polymerase chain amplification (PCR) of target genomic sequences are finding wide application in systematic and taxonomic studies of arthropods. PCR-based techniques that preclude the need for target DNA sequence information of the species of interest facilitate molecular taxonomic studies. Two such techniques, tDNA-PCR (DNA encoding tRNAs is the analyte) and RAPD-PCR (randomly amplified polymorphic DNA) were investigated for their ability to differentiate certain North American Culicoides spp. larvae and adults.

Successful treatment of supraventricular tachycardia-induced cardiomyopathy with amiodarone: case report and review of literature.

Permanent junctional reciprocating tachycardia (PJRT) is a rare cause of supraventricular tachycardia in the pediatric population and is resistant to most pharmacological therapy. A case of supraventricular tachycardia that, on the basis of postnatal electrocardiographic and Holter monitor evidence, was diagnosed as PJRT and presented in utero as an atypical tachycardia with severe tachycardia-induced cardiomyopathy confirmed postnatally is presented. It is the only case of which the authors are aware that was controlled in the neonatal period by amiodarone and that resulted in complete resolution of systolic dysfunction. The literature discussing how tachycardia may induce cardiomyopathy and the use of amiodarone in treatment both pre- and postnatally are reviewed.

Idiopathic dilation of the right atrium: case report and survey of the literature.

Idiopathic dilation of the right atrium (IDRA) is a rare cardiac anomaly of unknown etiology. Whether it is an acquired or congenital lesion is controversial. A case of IDRA detected in utero and confirmed postnatally is reported. The postnatal course was complicated by the development of atrial flutter successfully treated with sotalol. A review of the literature concerning IDRA is presented.

Use of transesophageal echocardiography in radiofrequency catheter ablation in children and adolescents.

OBJECTIVE: To assess the utility of transesophageal echocardiography (TEE) in radiofrequency (RF) catheter ablation of left-sided atrioventricular bypass tracts. PATIENTS: RF catheter ablation was assisted with TEE in 13 children and adolescents aged 9.9 to 16.3 years (mean 13.3). Results were compared with 21 procedures done in 19 patients (age 8.8 to 18 years, mean 14.5) without TEE assistance. MAIN RESULTS: RF ablation success rate was similar in both groups (90% to 92%). Successful RF ablation required 6 +/- 8 RF pulses in the TEE group and 10 +/- 7 RF pulses in the non-TEE group (nonsignificant). Fluoroscopy time was 36 +/- 17 mins and 54 +/- 28 mins, respectively (P = 0.03). Characteristic tenting of the fossa ovalis by a transseptal needle was easily visualized with TEE. TEE allowed for precise positioning of the ablation electrode on the mitral valve ring. At the successful site, the ventriculoatrial (VA) time was 42 +/- 10 ms in the TEE group and 52 +/- 16 ms in the non-TEE group (P = 0.05). The atrioventricular (A:V) ratio was 1.1 +/- 1.1 and 1.2 +/- 0.7, respectively (nonsignificant) with a large scatter of individual values. Electrogram amplitudes and VA conduction times that are desirable for RF ablation were also recorded on the mitral valve leaflets and over the coronary sinus. TEE visualized thrombus formation in the right atrium (three patients) and in the left atrium (two patients). CONCLUSIONS: TEE should be strongly considered as supplemental imaging for RF ablation of left-sided bypass tracts performed under general anesthesia in children and adolescents. TEE renders transseptal puncture safe. TEE may decrease fluoroscopic exposure. TEE confirmation of the ablation catheter tip in the angle between the coronary sinus and the mitral valve ring may allow limitation of unnecessary RF lesions and injury to the mitral valve. The demonstration of early intracardiac thrombus formation argues for prompt and full heparinization after transseptal puncture.

Intractable diarrhea in a newborn infant: microvillous inclusion disease.

A newborn male presented with watery diarrhea, dehydration and metabolic acidosis. Severe secretory diarrhea of variable magnitude persisted when the patient was on parenteral nutrition with no oral intake. Initial light microscopic evaluation of a small intestinal mucosal biopsy showed partial villous atrophy and crypt hypoplasia. Ultrastructural studies of the villous enterocyte revealed internalized inclusions of microvilli, typical of microvillous inclusion disease. Presented are a case report and a discussion of the differential diagnosis of watery diarrhea in the neonate, as well as a short review of microvillous inclusion disease.

Membrane crosstalk in secretory epithelial cells mediated by intracellular chloride concentration.

Fluid secretion by epithelial cells is modulated by agents which activate Cl- channels in the apical membrane. To sustain secretion, Cl- influx across the basolateral membrane must also be accelerated. To examine cellular mechanisms which couple Cl- efflux across the apical membrane to Na(+)-coupled Cl- entry across the basolateral membrane, we employed optical imaging techniques utilizing single rat salivary acinar cells. Na+ influx was negligible in resting cells, but was rapidly increased by carbachol due to activation of a Na(+)-H+ exchanger, Na(+)-K(+)-2Cl- cotransporter and likely a non-selective cation channel. Receptor stimulation was not necessary since elevation of [Ca2+]i by thapsigargin activated the Na+ transporters at equivalent rates. Cell acidification, activation of protein kinase C, and cell shrinkage, other events associated with the rise of [Ca2+]i, had little effect on Na+ transport in resting cells. Nevertheless, stimulation of cells in a medium which prevented normal Ca(2+)-induced cell shrinkage prevented activation of all three pathways. The block of the activation was not overcome by osmotic shrinkage, but was relieved when intracellular Cl- concentration ([Cl-]i) was allowed to fall, including conditions in which [Cl-]i fell in the absence of cell shrinkage. Activation of a Na(+)-H+ exchanger, Na(+)-K(+)-2Cl- cotransporter, and non-selective cation channel therefore exhibit a requirement for agonist-induced fall in [Cl-]i. Low [Cl-]i may create a permissive environment for Ca(2+)-dependent activation of multiple Na+ transport pathways, providing for crosstalk which coordinates transport activities of apical and basolateral membranes in secretory epithelial cells.

Fiber characteristics of qiviut and guard hair from wild muskoxen (Ovibos moschatus).

In response to increasing commercial interest and the high market value of qiviut (the downy underwool of the muskox), we have employed standards and measurements used in the wool and cashmere industries to describe qiviut fiber characteristics. Fleece samples (qiviut with guard hair) were shaved from the midshoulder of 299 wild muskox hides of known sex and age (1, 2, 3, and 4+ yr) during the Banks Island, Canada, muskox harvest in November 1997. Samples were analyzed for fiber diameter distribution of raw fiber and qiviut, scoured and qiviut yields, and lengths of guard hair and qiviut fiber. We found a sex x age interaction for average fiber diameter (AFD) in raw fiber (P= 0.002) and qiviut (P < 0.001) only. Adult males had significantly coarser AFD than females (21.5 microm, males vs 20.1 microm, females and 18.2 microm, males vs 17.5 microm, females) for raw fiber and qiviut, respectively. Qiviut AFD from yearlings was 1.7 microm finer than the AFD of adult qiviut. Fiber diameter distribution (SD) decreased with age in the raw sample (P < 0.003) and qiviut (P < 0.001) and qiviut SD was greater (P < 0.001) in males than in females. Qiviut theoretical yield (% mass of fibers < or = 30 microm) increased (P < 0.001) with age, and females had higher theoretical yields than males (P < 0.001). Scoured yield did not vary between sexes in any age class and averaged 93.3%. Qiviut staple length did not differ with either age or sex. In summary, differences between the sexes were small up to the 3rd yr, and these differences were not likely to be of commercial importance. However, considering that AFD is a primary commercial criterion of value, AFD changes from 16.5 microm in yearlings to 18.2 microm in adults and from 17.5 microm in adult females to 18.2 microm in adult males would be expected to result in significant differences in commercial value.