Development of the salmon louse Lepeophtheirus salmonis and its effects on juvenile sockeye salmon Oncorhynchus nerka.

Responses of sockeye salmon Oncorhynchus nerka during infection with Lepeophtheirus salmonis were assessed in controlled laboratory trials. Juvenile salmon were exposed to 100 copepodids fish-1 (Trials 1 and 2) or 300 copepodids fish-1 (Trial 3) at mean weights of approximately 40, 80 and 135 g, respectively. Infections occurred on all salmon in all trials, and mean abundances (infection densities) ranged between 3.3 and 19.4 lice fish-1 (0.08 and 0.44 lice g-1 fish) in Trial 1, between 7.2 and 18.3 (0.09 and 0.22) in Trial 2 and between 19.5 and 60.7 (0.15 and 0.46) in Trial 3. A cumulative mortality of 24.4% occurred in Trial 3. At attachment sites on gills, we observed hyperplasia of basal epithelial cells and fusion of secondary lamellae occasionally associated with a cellular infiltrate. At attachment sites on fins, partial to complete skin erosion occurred, with limited evidence of hyperplasia or inflammation. Scale loss and abrasions coincided with pre-adult lice around 20 d post infection (dpi). Plasma osmolality was significantly elevated in exposed fish in Trials 1 (21 dpi), 2 (15 and 36 dpi) and 3 (20 dpi), whereas haematocrit was significantly depressed in exposed fish in Trials 1 (21 and 28 dpi) and 3 (20 dpi). Plasma cortisol was significantly elevated in exposed fish at 20 dpi (Trial 3). Physiological changes and mortality were related to the intensity of infection and became most prominent with pre-adult stages, suggesting patterns of infection and response in sockeye salmon similar to those reported for Atlantic and Chinook salmon.

Induction of indoleamine 2,3-dioxygenase in vivo by IFN-con1.

Indoleamine 2,3-dioxygenase (IDO) activity as determined by increases in serum kynurenine was measured in a group of hepatitis C patients treated with consensus interferon (IFN-con1). Kynurenine levels increased significantly within 2 days of initiation of treatment but returned to normal values by week 4 after treatment. Although IDO is normally induced by IFN-gamma, no such IFN was detected by ELISA or biologic assays. Thus, consensus IFN induces low levels of IDO in vivo without an IFN-gamma intermediate.

Transcatheter radiofrequency ablation for congenital junctional ectopic tachycardia in infancy.

Congenital junctional ectopic tachycardia (JET) is a difficult to treat arrhythmia with a variably poor response to pharmacologic intervention. We report on the successful treatment of a 17-day-old infant with JET via transcatheter radiofrequency ablation of the arrhythmogenic focus resulting in resolution of the tachycardia and maintenance of normal atrioventricular nodal function. Transcatheter radiofrequency ablation techniques should be considered in infants with life-threatening arrhythmia recalcitrant to standard forms of drug therapy.

Lack of cystic fibrosis transmembrane regulator-type chloride current in pediatric human atrial myocytes.

Mature cardiomyocytes have been shown to possess a cyclic AMP-mediated chloride channel (I(Cl)) which is the product of the cystic fibrosis transmembrane regulator (CFTR) gene. Species variability has been demonstrated for other ion channels. This study was designed to evaluate human I(Cl) regulation using the whole-cell patch-clamp bioassay. Atrial tissue obtained from children undergoing congenital heart surgery was enzymatically dispersed into isolated myocytes. The patients ranged in age from 1 day to 11 years (mean 2 years). Isoproterenol was used to activate the cAMP second-messenger system in a potassium-free environment. Membrane calcium and sodium channels were pharmacologically blocked. Of 20 human atrial myocytes obtained from 13 pediatric patients, 80% had a small basal chloride current. The current could be inhibited by the anion transport blocker, 9-anthracene carboxylic acid. In 4 of 20 otherwise viable myocytes, no I(Cl) could be elicited, either at baseline or with beta-adrenergic stimulation. Of the 16 myocytes with a basal I(Cl), the current was unaffected by cAMP stimulation in 15 (94%) cells. There were no significant differences in age, gender or clinical status of patients whose cells conducted Cl- current compared with patients whose myocytes had no measurable I(Cl). Ten mature guinea pig ventricular myocytes were evaluated using the same whole-cell patch-clamp technique. Seven of 10 cells showed a reversible increase in I(Cl) with isoproterenol exposure. Despite presence of the CFTR gene in human cardiomyocytes, functional expression of the cAMP-activated I(Cl) does not appear evident in isolated pediatric atrial myocytes. Whether the pathophysiology of congenital heart disease may influence chloride current modulation via alterations in adrenergic tone, intracellular Ca2+ regulation, and cellular osmotic conditions remains to be established.

Evidence for presence of Ca2+ channel-gated Ca2+ stores in neonatal human atrial myocytes.

The characteristics of Ca2+ signaling in fura 2-loaded whole cell-clamped myocytes obtained from samples of human atrial appendages of 3-day to 4-yr-old patients were examined. In isolated myocytes, activation of Ca2+ current (ICa) (2.47 +/- 0.23 pA/pF) at 0 mV elicited sizable intracellular Ca2+ (Cai) transients (240 +/- 45 nM), which were caused by the release of Ca2+ from intracellular stores as they were suppressed in the presence of ryanodine or caffeine. The voltage dependence of both Cai transients and ICa were similar and bell shaped. The rate of release of Ca2+, normalized for the maximal Ca2+ release, increased with age, indicating increased efficiency of Ca2+ signaling in more mature myocytes. The results suggest that ICa-gated release of Ca2+ from the sarcoplasmic reticulum is the primary mechanism regulating the signaling of contraction in early postnatal as well as older human atrial myocytes.

Use of the rate-corrected JT interval for prediction of repolarization abnormalities in children.

A prolonged rate-corrected QT interval (QTc) may be associated with an increased risk of developing ventricular arrhythmias and sudden death, particularly in patients with the hereditary long QT syndrome (LQTS), myocardial ischemia, or antiarrhythmic medication toxicity. It is known that there are some patients with LQTS who sometimes have a borderline or normal QTc (< or = 0.45 second). Although the QTc has been the standard measurement of ventricular repolarization, it includes both depolarization and repolarization and may not always be a sensitive indicator of the type of repolarization abnormalities seen in LQTS. Intraventricular conduction abnormalities complicate evaluation of the QTc interval. The rate-corrected JT interval (JTc) is a more accurate measurement of ventricular repolarization, and therefore may be a more sensitive means of assessing abnormalities. The QTc on a resting electrocardiogram was determined in 40 patients with LQTS and in 31 patients with right bundle branch block after tetralogy of Fallot repair. These were compared with 1,000 age-matched control subjects. The right bundle branch block group had normal JT and JTc measurements, despite having prolonged QT and QTc intervals compared with controls. The JTc identified 85% of patients affected with LQTS compared with only 58% identified using only the QTc as a marker for the syndrome. The JTc is a more specific measurement of ventricular repolarization than the QTc by eliminating QRS duration variability. It appears to be a more sensitive predictor of repolarization abnormalities, and may be helpful in identifying patients with LQTS who have borderline or normal QTc measurements on resting electrocardiograms.