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Biomedical subjects

T S Rosen

Publications and source records attributed to T S Rosen.

At least 19 recordsLinked to original sources
PubMed1999

An ecological approach to development in children with prenatal drug exposure.

Knowledge about the effects of prenatal drug exposure on early development is reviewed within an ecological framework. The intersecting influences on maternal and child behavior in the early caregiving environment are considered, and similarities reported for drug-exposed children and other high-risk groups are noted. Data from a sample of 90 dyads are used to explore the impact of maternal stress, social support, and depression on children's behavior problems. Strategies for enhancing developmental outcomes in this population are discussed.

Child↗
PubMed1994

Prenatal cocaine exposure and the development of the human eye.

PURPOSE: The use of cocaine during pregnancy has been associated with congenital abnormalities of the developing eye. The authors report a prospective, controlled study of 40 cocaine-exposed and 40 nonexposed (control) preterm and full-term infants. METHODS: Detailed maternal and obstetric histories were obtained by chart review and interview. Infants with a positive urine toxicology screen for cocaine at birth or whose mothers tested positive for cocaine were recruited into the exposed group. Nonexposed infants were recruited at random from newborns admitted to the authors' nurseries. Mothers of these infants received routine prenatal care in the authors' clinics, and nonexposure was documented by maternal history and/or negative urine toxicologies that were available in 30% of these mother-infant pairs. General physical and ocular examinations, including measurement of axial length and intraocular pressure, were performed on all infants. RESULTS: Forty infants were recruited in each group, with gestational ages ranging from 25 to 42 weeks. Twenty-nine of the exposed infants and 26 of the control infants were full-term (gestational age, 37 weeks or older). A total of 160 eyes were examined. No differences were seen in the incidence of congenital anomalies, subconjunctival hemorrhages, retinal hemorrhages, or optic nerve abnormalities between the two groups. No differences in mean axial length (16.9 +/- 0.6 mm [exposed group] versus 17.1 +/- 0.7 mm [control group]) or intraocular pressure (15.4 +/- 3.8 mmHg [exposed group] versus 15.0 +/- 3.0 mmHg [control group]) were seen between full-term infants in both groups. Axial length correlated strongly with gestational age, birth weight, head circumference, and body length over the range of gestational ages evaluated in both groups. No effect of cocaine exposure on these correlations was demonstrated. The range of axial length was 12.1 to 18.0 mm in the exposed group and 12.4 to 18.6 mm in the control group. CONCLUSION: In this study group, no significant effect of prenatal cocaine exposure was seen on the infant eye. In both exposed and nonexposed groups, axial length measurements agreed closely with known statistical norms and correlated closely with other parameters of fetal growth.

Abnormalities, Drug-Induced↗
PubMed1993

Sympathetic innervation modulates ventricular impulse propagation and repolarisation in the immature rat heart.

OBJECTIVE: When cardiac sympathetic innervation in neonatal rats is retarded by antiserum to nerve growth factor, there is a corresponding increase in the QT interval on ECG. Since the propagation of the cardiac impulse and the repolarisation of cardiac cells both contribute to the QT interval, the aim of this study was to determine the role of sympathetic innervation in modulating ventricular impulse propagation and repolarisation. METHODS: Neonatal rats were treated for the first 10 days of life with nerve growth factor (NGF), its antiserum (As), or placebo. Standard microelectrode techniques were used to study the transmembrane action potential characteristics of subendocardial (ventricular septal) and subepicardial ventricular myocardium. Bipolar surface electrograms were used to record the velocity of impulse propagation and electron microscopy to examine the intercalated discs. RESULTS: In the subendocardium, the phase 0 upstroke velocity of the action potential (dV/dtmax) was lowest in the As treated rats. The latter group also showed the slowest conduction velocity. There were no differences in control action potential durations in the endocardium among the three groups, but in the epicardial tissues, action potential duration was longest in the As treated group. Thus the dispersion in action potential duration was smallest in the As treated animals. Electron microscopic studies of the intercalated discs of ventricular myocytes showed significant enhancement of nexal junction formation in NGF treated rats, whereas As treated animals showed a retarded pattern of both nexal and desmosomal junction formation. CONCLUSIONS: The differences in ultrastructure, conduction, and repolarisation seen in As and NGF treated animals may explain the prolonged QT interval seen in the As treated group.

Action Potentials↗
PubMed1991

Beta adrenergic modulation of cardiac rhythm in a rat model of altered sympathetic neural development.

We previously have shown that treatment of neonatal rats (days 1-10) with Nerve Growth Factor (NGF) or its antibody (Ab) modifies alpha-adrenergic receptor-effector coupling, such that innervated hearts at day 10 show high levels of a 41 kDa GTP regulatory protein (G protein) that is a substrate for pertussis toxin and that links the alpha 1-receptor to the Na/K pump. This receptor-effector pathway results in alpha adrenergic-induced decreases in automaticity. In contrast, non-innervated hearts at day 10 show lower levels of the pertussis toxin sensitive G-protein and increases in automaticity induced by alpha-agonist. We now report the effects of administration of NGF, Ab or placebo on beta-adrenergic receptor-effector coupling in neonatal rats. Rats were administered NGF, Ab or placebo on days 1-10 of life. On day 10, the beta-receptor number and affinity and the stimulatory G-protein, Gs, were equivalent across groups. Moreover, the ventricular automatic response to beta-adrenergic receptor stimulation was equivalent across groups suggesting there was no change in receptor-effector coupling as a result of the difference in innervation. These results on beta-adrenergic receptor-effector coupling considered in light of our prior studies on alpha-adrenergic coupling suggest that the development of sympathetic innervation is more a determinant of alpha than beta adrenergic modulation of ventricular rhythm.

Adrenergic beta-Agonists↗
PubMed1990

Effects of prenatal methadone exposure on sex-dimorphic behavior in early school-age children.

Prenatal opiate exposure has been shown to alter the pattern of sex-dimorphic behavior in male and female rats. To conduct an exploratory study of opiate effects in humans, we compared the sex-dimorphic behavior of male and female offspring of women maintained on methadone during pregnancy to that of demographically matched control subjects. Standardized questionnaires completed by the primary caretakers served as assessment instruments. The six- to eight-year-old methadone-exposed boys showed more stereotypically feminine behavior than nonexposed male control subjects. There were no significant differences between methadone-exposed girls and their female control group. Based on these preliminary findings, we recommend that future follow-up studies of opiate-exposed children be broadened to include an assessment of their gender role behavior.

Child↗
PubMed1990

Mother-infant interaction in a multirisk population.

The relationship among maternal and observer ratings of infant temperament, observer ratings of maternal responsiveness, and maternal drug abuse habits, was studied in a population facing multiple risk factors. Intensity of maternal drug abuse was found to be negatively related to maternal ratings of infant temperament, and ratings of temperament were positively related to maternal responsiveness. Implications for research and practice are explored.

Alcoholism↗
PubMed1990

Resilient children: individual differences in developmental outcome of children born to drug abusers.

Since 1977, we have been following the neurobehavioral development of two groups of children: a group born to women on methadone maintenance and a drug-free comparison group. This study used the data on the children evaluated at 36 months of age to determine whether distinct patterns of developmental outcome can be identified, and which medical, familial, or environmental characteristics are associated with developmental differences. The children were clustered on four measures at 36 months: head circumference percentile, Merrill-Palmer Scale score, neurological evaluation, and referrals for developmental problems. Three distinct clusters emerged, with methadone children disproportionately frequent in Cluster 3, the group showing the poorest development. Comparisons of the clusters on a wide range of variables revealed consistent differences between Cluster 1 and Cluster 3 children in maternal responsiveness and incidence of neglect and family violence. These findings indicate that distinct developmental patterns do occur within this predominantly lower-class ghetto population; further, that children born to methadone-maintained women are more likely to show poor development. However, when the environment provides nurturance and stability, methadone children can show resilience and develop well.

Child, Preschool↗
PubMed1990

Sympathetic neural modulation of cardiac impulse initiation and repolarization in the newborn rat.

We injected neonatal rats with nerve growth factor, the antiserum to nerve growth factor, or placebo for the first 10 days of life. Our goal was to determine the relation between sympathetic innervation of the developing heart, the electrocardiographic expression of cardiac rhythm, and the response of the heart to alpha-adrenergic stimulation with phenylephrine. We were especially interested in the latter area because of the prior demonstration in isolated cell systems of sympathetic neural modulation of a 41-kDa GTP regulatory protein and alpha-adrenergic responsiveness. Ten- to 11-day-old rats treated with nerve growth factor had more complete sympathetic innervation, faster heart rates, and higher levels of the 41-kDa protein than the placebo group. Electrophysiological studies were performed on isolated ventricular septa superfused with Tyrode's solution at 37.0 degrees-37.5 degrees C. The electrophysiological response of septa to 10(-9) and 10(-8) M phenylephrine from the 10-11-day-old nerve growth factor group was comparable with that of 3-week-old control animals. In contrast, 10-11-day-old antiserum-treated rats had an abnormal innervation pattern, lower levels of the 41-kDa protein, and a more immature electrophysiological response to alpha-adrenergic stimulation than the placebo group. In addition, antiserum-treated rats had an abnormally prolonged electrocardiographic QT interval. Our results demonstrate for the first time in intact animals a direct link between sympathetic innervation and alpha-adrenergic receptor-effector coupling as well as the dependence on innervation of the modulation of impulse initiation by alpha-agonists. This sequence of developmental events may be important not only in the regulation of normal cardiac rhythm but also in the expression of certain pathological entities such as the congenital long QT syndrome and the sudden infant death syndrome.

Animals↗
PubMed1988

A canine model of torsades de pointes.

Although quinidine has been reported to induce QT interval prolongation and torsades de pointes clinically, the only experimental model currently available for quinidine-induced torsades de pointes requires the concurrent use of ischemia, reperfusion and cardiac pacing of the isolated, perfused heart. Our purpose in this study was to determine the circumstances under which quinidine might elicit torsades de pointes consistently in the intact dog. We found that maintenance of therapeutic plasma quinidine concentrations, alone, did not induce the arrhythmia. Rather, arrhythmia induction required the additional application of aconitine, which induces early afterdepolarizations and triggered activity. When aconitine was applied to two epicardial sites in dogs having quinidine-induced QT interval prolongation greater than 10%, torsades de pointes occurred in 80% of instances. When QT prolongation was less than 10%, aconitine-induced torsades de pointes was seen in only 21% of animals. Our results suggest that in a previously healthy heart quinidine-induced QT prolongation is, itself, insufficient to induce torsades de pointes consistently, and two independent sites of ectopic activity are needed as well. The ectopic foci appear to modulate one another's impulse initiation or activation sequence, thereby giving rise to the classical "twisting of the points" associated with the arrhythmia.

Aconitine↗
PubMed1988

The response to overdrive pacing of triggered atrial and ventricular arrhythmias in the canine heart.

Although triggered activity has been identified in isolated atrial tissue with the use of cellular electrophysiologic techniques, there has been no identification of triggered atrial arrhythmias in situ. Moreover, it is unclear whether triggered rhythms of different causes and sites of origin in the heart exhibit uniform responses to pacing that might aid in their identification. We therefore studied arrhythmias induced by overdrive pacing in three canine preparations, and based the analysis of our results on guidelines derived from microelectrode studies. We studied ventricular tachycardias induced by ouabain or by anterior wall myocardial infarction and atrial (coronary sinus) arrhythmias induced by the infusion of epinephrine into the great cardiac vein. In the ouabain and postinfarction preparations, right ventricular epicardial pacing induced ventricular premature beats or tachycardias whose recovery intervals after cessation of pacing shortened and showed overdrive acceleration as pacing rate increased. The first postpacing beat displayed progressive fusion with the paced beats but transient entrainment could not be induced. In the coronary sinus, the recovery intervals of impulses induced by epinephrine and pacing decreased as the drive rate increased, and inducibility of the paced rhythms increased at faster drive rates. Thus, the recovery intervals of triggered activity induced in the coronary sinus are phenomenologically similar to those of infarct- and digitalis-induced triggered rhythms. This is the first demonstration of consistent behavior in response to pacing of diverse types of triggered activity. Considered in light of the failure to induce transient entrainment, the results emphasize the potential utility of pacing in clinical identification of triggered rhythms and their differentiation from reentry.

Animals↗
PubMed1987

Developmental changes in the effects of lidocaine and quinidine on the canine heart.

We studied the developmental changes that occur in the use-dependent effects of lidocaine and quinidine on the intact canine heart. At comparable intravenous dosages, adults showed higher total and free plasma lidocaine concentrations than young dogs, whereas for quinidine, the total and free levels were comparable. Lidocaine demonstrated a use-dependent depressant effect on intraventricular conduction in adults that was significantly greater than that in the young, and it significantly accelerated repolarization (QT interval) in the adult. In contrast, comparable effects of quinidine were seen on conduction in adult and young dogs, while repolarization was prolonged more in the young. These effects on conduction and repolarization in the adult and young hearts were explained by our earlier cellular electrophysiologic studies. Our findings indicate the following: (a) developmental changes in the cellular electrophysiologic effects of specific antiarrhythmic drugs are predictive of the effects in the in situ heart; (b) these effects are further modified by developmental differences in drug metabolism and protein binding; (c) developmental changes in the effects of one antiarrhythmic local anesthetic are not necessarily predictive of those for another; and (d) the effects of drugs on the adult heart may be, but are not necessarily, predictive of those in the young.

Aging↗
PubMed1985

Methadone-maintained mothers: 3-year follow-up of parental functioning.

A group of 57 methadone-maintained mothers and 31 matched drug-free controls were compared on their ability to provide adequate child care, capacity for satisfying interpersonal relationships, and motivation for self-improvement. Results indicate that, as a group, methadone mothers require more assistance in parenting, are more socially isolated, and are less likely to pursue vocational and educational activities. The interpersonal and environmental impact of poor parenting further compounds the effects of in utero exposure to methadone, placing these infants at high risk.

Child Development↗
PubMed1985

Gentamicin kinetics in the neonate.

Gentamicin serum levels were measured and elimination half-life was calculated in a group of neonates with postconceptual ages ranging between 25-42 weeks. Infants were receiving intravenous gentamicin (2.5 mg/Kg/dose) at various dosage intervals and t 1/2e was calculated using a one-compartment open model. Evidence of gentamicin accumulation was present in 82% of infants 34 weeks. T 1/2e was 8.8 +/- .7 hours in infants 30 weeks, 7.8 +/- 1.1 hour in infants between 30-34 weeks and 6.2 +/- .5 in infants greater than 34 weeks. The results of the study suggest that gentamicin elimination is related to postconceptual age and that infants treated with recommended dosage regimens may have possible gentamicin tissue accumulation and nephrotoxicity. Therefore, the dosage interval may have to be lengthened to 18 hours in infants less than 34 weeks with close gentamicin plasma level monitoring.

Bacterial Infections↗
PubMed1984

Gentamicin absorption during prophylactic use for necrotizing enterocolitis.

Gentamicin absorption was measured after oral administration in 18 neonates treated prophylactically in an attempt to decrease the incidence of necrotizing enterocolitis. Patients were given 10 mg/kg/day in four divided doses via nasogastric tube for a total of 10 days. Levels were assayed using the Emit system. Serum levels ranged between 0 and 2.2 micrograms/ml. Mean levels over 10 days were 0.42 +/- (SD) 0.47 micrograms/ml and did not vary significantly from day to day. From these data we conclude that enterally administered gentamicin is not absorbed to a degree that would result in toxic or even therapeutic serum concentrations.

Birth Weight↗