Mental health in international adoptees as teenagers and young adults. An epidemiological study.

Sweden has now around 38,000 individuals who have been adopted from other countries. Most often they are transracially adopted and have a different appearance from their new parents--"visible" adoptions. This study was made to explore the mental health of a teenager/young adult group that arrived with their families in the southernmost county of Sweden between 1970 and 1977. They were placed through the largest Swedish adoption agency at that time. One hundred and forty-seven families and their 211 adopted children, who were 13 years of age or older at the time of the investigation, were interviewed in their homes. CBCL, SCL-90, a self-esteem questionnaire, and two family relations inventories were also completed. Compared to nonadopted Swedish young persons of the same ages, who had been investigated with the same inventories in earlier epidemiological studies, the adoptees had as good mental health. The adoptees also reported good self-esteem. The pre-adoption conditions were more important than the age of arrival in itself for the risk of later maladaptation. Family relations, various aspects of identity, and peer relations explained much of the variance of mental health and self-esteem. Those who were most engaged in questions about their identity and felt mostly non-Swedish had more behaviour problems. The association, however, between the factor "Identity" and the mental health variables approached zero for the older subjects (18-27 years of age). The majority (about 90%) of the adoptees felt mostly Swedish. Seventy per cent didn't feel any connection to their country of origin.

Derivatives of (R)-2-amino-5-methoxytetralin: antagonists and inverse agonists at the dopamine D2A receptor.

A series of N-arylmethyl substituted (R)-5-methoxy-2-(propylamino)tetralins has been prepared and evaluated for affinity and efficacy at dopamine (DA) D2A receptors. The novel compounds appeared to be antagonists or inverse agonists. (R)-2-[(Benzyl)propylamino]-5-methoxytetralin (7) was characterized as a potent inverse agonists at DA D2A receptors in a [35S]GTPgammaS binding assay.

Prediction of sustained ventricular tachycardia inducible by programmed stimulation in patients with coronary artery disease. Utility of clinical variables.

BACKGROUND: Cardiologists often use clinical variables to determine the need for electrophysiological studies to stratify patients for risk of sudden death. It is not clear whether this is rational in patients with coronary artery disease, left ventricular dysfunction, and nonsustained ventricular tachycardia. METHODS AND RESULTS: We analyzed the first 1721 patients enrolled in the Multicenter UnSustained Tachycardia Trial to determine whether clinical variables could predict which patients would have inducible sustained monomorphic ventricular tachycardia. The rate of inducibility of sustained ventricular tachycardia was significantly higher in patients with a history of myocardial infarction and in men compared with women. There was a progressively increased rate of inducibility with increasing numbers of diseased coronary arteries. There was a significantly lower rate of inducibility in patients with prior coronary artery bypass surgery and in patients who also had noncoronary cardiac disease. The rate of inducibility was higher in patients of white race, patients with recent (

Interactions of ligands with active and inactive conformations of the dopamine D2 receptor.

The affinities of 19 pharmacologically diverse dopamine D2 receptor ligands were determined for the active and inactive conformations of cloned human dopamine D2 receptors expressed in Ltk cells. The agonist [3H]quinpirole was used to selectively label the guanine nucleotide-binding protein-coupled, active receptor conformation. The antagonist [3H]raclopride, in the presence of the non-hydrolysable GTP-analogue Gpp(NH)p and sodium ions and in the absence of magnesium ions, was used to label the free inactive receptor conformation. The intrinsic activities of the ligands were determined in a forskolin-stimulated cyclic AMP assay using the same cells. An excellent correlation was shown between the affinity ratios (KR/KRG) of the ligands for the two receptor conformations and their intrinsic activity (r=0.96). The ligands included eight structurally related and enantiopure 2-aminotetralin derivatives; the enantiomers of 5-hydroxy-2-(dipropylamino)tetralin, 5-methoxy-2-(dipropylamino)tetralin, 5-fluoro-2-(dipropylamino)tetralin and 2-(dipropylamino)tetralin. The (S)-enantiomers behaved as full agonists in the cyclic AMP assay and displayed a large KR/KRG ratio. The (R)-enantiomers were classified as partial agonists and had lower ratios. The structure-affinity relationships of these compounds at the active and the inactive receptor conformations were analysed separately, and used in conjunction with a homology based receptor model of the dopamine D2 receptor. This led to proposed binding modes for agonists, antagonists and partial agonists in the 2-aminotetralin series. The concepts used in this study should be of value in the design of ligands with predetermined affinity and intrinsic activity.

A multi-centre safety and efficacy trial of a preterm infant formula supplemented with long chain polyunsaturated fatty acids (LCP) (48 weeks PCA analysis)

LCP supplementation of premature infant formula has been shown to produce plasma and erythrocyte lipid profiles similar to human milk (HM)-fed preterm infants. Previous studies reported decreased growth with LCP supplemented formula. This prospective, double-blind, randomised, controlled, parallel trial compared safety, growth and phospholipid fatty acid (PFA) levels in preterm infants fed preterms formula with (L+) or without (Lo) LCP. The study consisted of Phase I: enrolment to 40 weeks (wk) postconceptual age (PCA); and Phase II: 40 to 48 wk PCA. Infants (birth weight 750-2000 g, 0-28 days of age) were fed L+ or L preterm formula, 24 Kcal/oz during Phase I, and 20 Kcal/oz during Phase II. A control group was exclusively HM-fed preterms who, if weaned at the end of Phase I, received L. HM and formula intake were unrestricted. Weight (wt), length (Lt), head circumference (OFC) and upper mid-arm circumference (MAC), and phospholipid profiles were measured at 40 and 48 wk PCA. Adverse events were monitored. 183/288 infants completed Phase II. There were no difference in growth rates between formula groups. At 48 wk PCA, mean PFA levels in infants fed L+ were similar to HM-fed and were significantly higher than the L fed group. Adverse events were similar between the 2 formula groups. The number of infants who were discontinued because of an adverse event was similar among all groups. In conclusion the LCP preterm infant formula is safe, support normal growth and maintains phospholipid profiles similar to HM-fed infants.(AU)

Neonatal morbidity after elective repeat cesarean section and trial of labor.

OBJECTIVE: To evaluate neonatal outcomes after an elective repeat cesarean section (ERCS) compared with a trial of labor (TOL). POPULATION AND METHOD: All mothers who underwent previous cesarean section and delivered singleton infants at term gestation were identified during a 1-year period. Neonatal outcomes were compared between infants delivered by ERCS (n = 497) and those delivered by TOL (n = 492), and between infants delivered by a successful (n = 336) and a failed (n = 156) TOL. A cohort of mothers and their term infants delivered by routine vaginal delivery were also identified. RESULTS: Infants delivered by ERCS had an increased rate of transient tachypnea compared with infants born by TOL (6% vs 3%). Compared with routine vaginal deliveries, the adjusted odds ratio of developing any respiratory problem after an ERCS was 2.3 (95% confidence interval [CI]: 1.4, 3.8), and for developing transient tachypnea was 2.6 (CI: 1.5, 4.5). In addition, two infants delivered by ERCS developed respiratory distress syndrome. Infants delivered after a TOL had increased rates of suspected and proven sepsis (5% vs 2% and 1% vs 0.1%, respectively). Compared with a successful TOL, the infants delivered by cesarean section after a failed TOL had more neonatal morbidity and had a longer hospital stay (4.8 +/- 2 vs 3.1 +/- 2 days). The odds ratio for developing any respiratory illness after a failed TOL was 2.1 (95% CI: 1.1, 4.1), for suspected sepsis was 4.8 (95% CI: 2.6, 9.0), and for proven sepsis was 19.3 (95% CI: 2.0, 187). Neonatal outcomes after a successful TOL were similar to routine vaginal births. CONCLUSION: Infants born by ERCS are at increased risk for developing respiratory problems compared with those born by TOL. However, TOL is associated with increased rates of suspected and proven sepsis. This appears to be limited to infants delivered by cesarean section after a failed TOL.

Modulation of procainamide's effect on conduction by cellular uncoupling in perfused rabbit hearts.

INTRODUCTION: How cell-to-cell electrical coupling influences an antiarrhythmic agent's effect on conduction is largely unknown. To investigate this, we evaluated the effects of procainamide on myocardial conduction at decreasing degrees of cell-to-cell electrical coupling induced by graded doses of heptanol. METHODS AND RESULTS: Electrograms were recorded from 50 ventricular epicardial sites in a 1 cm x 0.5 cm area during pacing to produce conduction longitudinal or transverse to myocardial fiber orientation in Langendorff-perfused rabbit hearts. The effects of procainamide (15 mg/L) on conduction velocity were determined in the presence of increasing doses of heptanol (0.2, 0.5, and 1.0 mM). In addition, using standard microelectrode techniques in isolated superfused rabbit myocardium, intracellular potentials were recorded in the presence of 15 mg/L procainamide and heptanol (1.0 mM). In the absence of heptanol, procainamide slowed conduction velocity. In the presence of increasing doses of heptanol, procainamide's contribution to the depressant effect on conduction velocity was attenuated and reversed at the highest dose. The latter effect was preferentially seen for conduction longitudinal to myocardial fiber orientation. Heptanol had no effect on action potential amplitude or maximum rate of depolarization in the presence of procainamide. CONCLUSIONS: Procainamide's effect on conduction velocity is influenced by the underlying degree of cell-to-cell electrical coupling. The present model should be useful in evaluating the relative ability of other pharmacologic agents to modulate conduction under conditions of changing cell coupling.

Novel (R)-2-amino-5-fluorotetralins: dopaminergic antagonists and inverse agonists.

A series of secondary and tertiary N-alkyl derivatives of (R)-2-amino-5-fluorotetralin have been prepared. The affinities of the compounds for [3H]raclopride-labeled cloned human dopamine (DA) D2 and D3 receptors as well as [3H]-8-OH-DPAT-labeled rat hippocampal 5-HT1A receptors were determined. In order to selectively determine affinities for the high-affinity agonist binding site at DA D2 receptors, the agonist [3H]quinpirole was used. The intrinsic activities of the compounds at DA D2 and D3 receptors were evaluated in a [35S]GTP gamma S binding assay. The novel compounds were characterized as dopaminergic antagonists or inverse agonists. The antagonist (R)-2-(butylpropylamino)-5-fluorotetralin (16) bound with high affinity (Ki = 4.4 nM) to the DA D3 receptor and was the most D3-selective compound (10-fold). (R)-2-[[4-(8-Aza-7, 9-dioxospiro[4.5]decan-8-yl)butyl]propylamino]-5-fluorote tralin (18) bound with very high affinity to both DA D3 and 5-HT1A receptors (Ki = 0.2 nM) and was also characterized as a dopaminergic antagonist. (R)-2-(Benzylpropylamino)-5-fluorotetralin (10) behaved as an inverse agonist at both DA D2 and D3 receptors. It decreased the basal [35S]GTP gamma S binding and potently inhibited the DA-stimulated [35S]GTP gamma S binding. It is apparent that the intrinsic activity of a 2-aminotetralin derivative may be modified by varying the N-alkyl substituents.

Derivatives of (R)- and (S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin: synthesis and interactions with 5-HT1A receptors.

Analogs of the 5-HT1A receptor antagonist (S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin [(S)-1,(S)-UH301] have been prepared. The C8-substituent has been varied, and in some derivatives one of the N-propyl groups has been exchanged for a 4-(8-aza-7,9-dioxospiro[4.5]decan-8-yl)-butyl group. The novel compounds have been evaluated for affinity to rat brain 5-HT1A receptors in competition experiments with [3H]-8-OH-DPAT. In addition, the efficacy of the compounds was assessed by their ability to inhibit the VIP-stimulated cAMP formation in GH4ZD10 cells expressing rat 5-HT1A receptors. Varying degrees of intrinsic activity was revealed among the compounds tested, i.e., the profiles ranged from full agonists to antagonists. All R-enantiomers are characterized as full agonists at 5-HT1A receptors, whereas partial agonists or antagonists were found among the corresponding S-enantiomers. Substitution of one of the N-propyl groups for a 4-(8-aza-7,9-dioxospiro[4.5]decan-8-yl)butyl group seems to increase efficacy as well as affinity for 5-HT1A receptors. A favorable interaction with an accessory binding site by the N-4-(8-aza-7,9-dioxospiro[4.5]decan-8-yl)butyl group may contribute to the increased affinity.

Effect of bundle branch block on local electrogram morphologic features: implications for arrhythmia diagnosis by stored electrogram analysis.

Analysis of stored local ventricular electrogram recordings is a useful diagnostic tool in the evaluation of patients with implantable cardioverter defibrillators. Visual analysis of local electrogram morphologic features has been demonstrated to be useful in distinguishing ventricular tachycardia from supraventricular rhythm. The effect of bundle branch block (BBB) aberration during supraventricular tachycardia on local electrogram morphologic features is not entirely clear. Erroneous diagnoses resulting from a change in electrogram morphologic features with BBB may occur. To determine whether the development of BBB can produce a change in local electrogram morphologic features and whether this change is dependent on the site of recording, we retrospectively reviewed local electrogram recordings from 23 patients who had intermittent BBB during electrophysiologic evaluation of documented or suspected supraventricular tachycardia. Local electrogram recordings from catheters placed in the right ventricular apex and coronary sinus during supraventricular tachycardia with BBB aberrancy were compared with recordings during narrow complex supraventricular tachycardia or normal sinus rhythm. Bipolar recordings were made with a 5 mm interelectrode distance with filter settings at 40 to 400 Hz. Three independent blinded observers defined the paired electrograms as the same or distinctly different. During right BBB a change in electrogram morphologic features was demonstrated in 11 (85%) of 13 recordings from the right ventricular apex and in only 1 (8%) of 12 recordings from the coronary sinus. In contrast, during left BBB a change in electrogram morphologic features was seen in 6 (100%) of 6 recordings from the coronary sinus and in only 1 (8%) of 13 recordings from the right ventricular apex. These results demonstrate that when the described recording techniques are used, a change in local ventricular electrogram morphologic features BBB is predominantly manifest in recording sites ipsilateral to the BBB, whereas recording sites contralateral to the BBB are relatively unaffected. This information may have implications regarding interpretation of stored electrograms when an attempt is made to establish a rhythm diagnosis leading to implantable cardioverter defibrillator therapy.

The 5-HT1A receptor antagonist (S)-UH-301 augments the increase in extracellular concentrations of 5-HT in the frontal cortex produced by both acute and chronic treatment with citalopram.

In a recent study, utilizing single cell recording techniques, we have shown that administration of 5-HT1A receptor antagonists, e.g. (S)-UH-301, to rats concomitantly treated, acute or chronically, with the selective serotonin reuptake inhibitor (SSRI) citalopram significantly increases the activity of 5-hydroxytryptamine (5-HT) containing neurons in the dorsal raphe nucleus (DRN). Here we report correlative experiments using microdialysis in freely moving animals to measure extracellular levels of 5-HT and its metabolite 5-hydroxyindole acetic acid (5-HIAA) in the frontal cortex, a major projection area for DRN-5-HT neurons. Acute administration of (S)-UH-301 (2.5 mg/kg s.c.) or citalopram (2.0 mg/kg s.c.) increased 5-HT concentrations with a maximum of about 70% and 185%, respectively, above baseline. However, when (S)-UH-301 was administered 30 min before citalopram the maximal increase in 5-HT levels was approximately 400%. In rats chronically treated with citalopram (20 mg/kg/day i.p. for 14 days) basal 5-HT concentrations in the frontal cortex were significantly increased and 5-HIAA concentrations were decreased when measured 10-12 h, but not 18-20 h, after the last injection of citalopram, as compared to basal 5-HT and 5-HIAA concentrations in chronic saline-treated rats. When (S)-UH-301 (2.5 mg/kg s.c.) was administered 12 h, but not 20 h, after the last dose of citalopram it produced a significantly larger increase in extracellular concentrations of 5-HT than in control rats. However, in rats pretreated with a single, very high dose of citalopram, 20 mg/kg i.p., administration of (S)-UH-301 at 12 h after citalopram did not increase 5-HT levels. The augmentation by (S)-UH-301 of the increase in brain 5-HT output produced by acute administration of citalopram is probably due to antagonism of the citalopram induced feedback inhibition of 5-HT cells in the DRN, as previously suggested. However, the capacity of (S)-UH-301 to further increase the already elevated extracellular concentrations of 5-HT in brain in animals maintained on a chronic citalopram regimen, in which significant tolerance to the initial feedback inhibition of DRN-5-HT cells and developed, represents a novel finding. Generally, the reduced feedback inhibition of 5-HT neurons obtained with chronic citalopram treatment, and the associated elevation of brain 5-HT concentrations, may be related to functional desensitization of somatodendritic 5-HT1A autoreceptors in the DRN. This phenomenon may also largely explain the larger increase in 5-HT output produced by (S)-UH-301 in chronic citalopram treated animals as compared to its effect in control animals. Yet, a contributory factor may be a slight, remaining feedback inhibition of the 5-HT cells caused by residual citalopram at 12, but not 20 h after its last administration. Previous clinical studies suggest that addition of a 5-HT1A receptor antagonist to an SSRI in the treatment of depression may accelerate the onset of clinical effects. Moreover, in therapy-resistant cases maintained on SSRI treatment, addition of a 5-HT1A receptor antagonist may improve clinical efficacy. Since the therapeutic effect of SSRIs in depression has been found to be critically linked to the availability of 5-HT in brain, our experiments results support, in principle, both of the above clinically based notions.

Heterogeneity of retrograde fast-pathway conduction pattern in patients with atrioventricular nodal reentry tachycardia: observations by simultaneous multisite catheter mapping of Koch's triangle.

BACKGROUND: Selective ablation of either the fast of the slow pathway resulting in cure of AV nodal reentry tachycardia (AVNRT) has led to the concept that these pathways are discrete, anatomically defined structures. We hypothesized that if a discrete retrograde fast pathway exists, it should be possible to record a single focus of early atrial activation near the apex of Koch's triangle, with sequential spread of depolarization to the rest of the atria. METHODS AND RESULTS: We evaluated 46 patients (33 women, 13 men; mean age, 45 +/- 17 years) undergoing electrophysiology study and catheter ablation for typical AVNRT. Retrograde atrial activation during AVNRT (337 +/- 43 ms) and ventricular pacing at a similar cycle length (352 +/- 51 ms) was recorded in the region of Koch's triangle with a decapolar catheter in the His bundle position, a multipolar catheter in the coronary sinus, and a deflectable quadripolar catheter along the tricuspid annulus anterior to the coronary sinus ostium. Earliest atrial activation was recorded at the apex of the triangle of Koch in 38 patients during ventricular pacing and in 43 patients during AVNRT. A broad wave front of atrial activation was recorded in 17 patients during ventricular pacing and in 26 patients during AVNRT. During AVNRT, only 2 patients had a single early site with focal and sequential activation along the tendon of Todaro. There was concordance in the pattern of atrial activation between ventricular pacing and AVNRT in only 21 of 46 patients. CONCLUSIONS: Retrograde atrial activation over the fast pathway is heterogeneous within Koch's triangle and the coronary sinus, both for the entire population and for individual patients during different modes of activation. These data do not support the concept of an anatomically discrete retrograde fast pathway.

The 5-HT1A receptor antagonist (S)-UH-301 decreases dopamine release in the rat nucleus accumbens and striatum.

In this study we employed in vivo microdialysis to examine the effects of the selective 5-HT1A receptor antagonist (S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin [(S)-UH-301] on extracellular concentrations of dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens (NAC) and dorsal striatum of awake freely moving rats. Systemic administration of (S)-UH-301 (1.25, 2.5, 5.0 mg/kg s.c.) dose-dependently decreased extracellular concentrations of DA, DOPAC and HVA in the NAC. (S)-UH-301 (2.5 mg/kg s.c.) also decreased DA, but not DOPAC and HVA, concentrations in the striatum. Infusion of low concentrations (1, 10 microM) of (S)-UH-301 into either the NAC or the striatum did not affect DA levels, while only the highest concentration (1,000 microM) significantly decreased DA levels in both areas. Similarly, infusion of the selective 5-HT1A receptor agonist (R)-8-hydroxy-2-(di-n-propylamino)tetralin [(R)-8-OH-DPAT] only in high concentrations (100, 1,000 microM) decreased DA levels in both regions. These data suggest that (S)-UH-301 decreases DA release both in the NAC and the striatum probably indirectly via its purported DA-D2/D3 receptor agonistic properties. However, the observed inhibitory effect of (S)-UH-301 on DA release in the studied brain regions may also be explained, at least partly, by a serotonergic influence on the DA systems, acting at 5-HT1A receptor sites located elsewhere in the brain.

Synthesis and pharmacology of the enantiomers of UH301: opposing interactions with 5-HT1A receptors.

The (S)-enantiomer of 5-fluoro-8-hydroxy-2-(dipropylamino) tetralin [(S)-2a; (S)-UH301] was the first reported 5-HT1A receptor antagonist. We now give a full account on the synthetic effort leading to the preparation of the racemate and the enantiomers of 2a. The crystal and molecular structure of 2a. HBr has been determined by X-ray diffraction and the absolute configuration has been deduced using statistical tests of the crystallographic R values. The unit cell is tetragonal (P4(1)2(1)2) with a = b = 13.2235(2), c = 39.560(1) A and contains two crystallographically independent molecules in each asymmetric unit. The two solid state conformers differ in the conformation of the N-propyl groups. The pharmacological characterization of the enantiomers was done by use of in vivo biochemical and behavioural assays in rats. The (R)-enantiomer of 2a is a 5-HT1A receptor agonist of low potency while (S)-2a does not exhibit any agonist properties at 5-HT1A receptors. As a consequence of the opposing effects of the enantiomers, the racemate, rac-2a, does not produce any clear-cut effects in rats. The reduced efficacy of (S)-2a as compared to the well known 5-HT1A receptor agonist 8-hydroxy-2-(dipropylamino) tetralin (1;8-OH-DPAT) may be due to the fluoro-substituent induced negative potential of the aromatic ring.

Efficacy of antitachycardia pacing in patients presenting with cardiac arrest.

The efficacy of antitachycardia pacing (ATP) incorporated into implantable cardioverter defibrillators (ICDs) was assessed in 29 consecutive survivors of cardiac arrest, not attributable to acute myocardial infarction, ischemia, or drug and electrolyte effects. The cohort included 25 men and 4 women with a mean age of 65 years and a mean left ventricular ejection fraction of 29%. Seventeen patients had coronary artery disease, 11 had nonischemic dilated cardiomyopathy, and 1 had long QT syndrome. Programmed stimulation yielded monomorphic ventricular tachycardia (VT) in 17 patients, polymorphic VT in 6, and no inducible VT in 6. During a mean follow-up of 22 months, a total of 91 episodes of monomorphic VT occurred, 73 of which were successfully pace terminated (83%). Monomorphic VT amenable to pace termination recurred only in the group that had this arrhythmia inducible. The recurrent arrhythmias in the 12 patients having either no inducible VT or polymorphic VT were all rapid VTs, having a cycle length < 220 ms; and therefore, not amenable to pace termination. These results suggest that ATP incorporated into ICDs is useful in survivors of cardiac arrest and may significantly reduce the number of shocks that these patients would otherwise receive. Programmed stimulation may also help to define those patients who would receive the maximum benefit from ATP.

5-HT1A receptor antagonists increase the activity of serotonergic cells in the dorsal raphe nucleus in rats treated acutely or chronically with citalopram.

In this study we have examined the acute effects of systemic administration of the selective serotonin reuptake inhibitor (SSRI), citalopram, in combination with either of the two selective 5-HT1A receptor antagonists, [(S)-5-fluoro-8-hydroxy-2-(dipropylamino)-tetralin [(S)-UH-301] or (+)-N-tertbutyl 3-(4-(2-methoxyphenyl)piperazin-1-yl)-2-phenyl-propionamide dihydrochloride [(+)-WAY100135], on the activity of single 5-HT neurons in the dorsal raphe nucleus (DRN) of anesthetized rats using extracellular recording techniques. Acute administration of citalopram (0.3 mg/kg i.v.) significantly decreased the firing rate of DRN-5-HT cells most likely as a result of indirect stimulation of inhibitory somatodendritic 5-HT1A autoreceptors located on 5-HT cells in the DRN. This effect of citalopram was completely reversed by (S)-UH-301 (0.5 mg/kg i.v.) and partly by (+)-WAY100135 (0.5 mg/kg i.v.). Furthermore, the inhibitory effect of citalopram on the activity of 5-HT neurons was significantly attenuated by pretreatment with (S)-UH-301 (0.25 mg/kg i.v.) or (+)-WAY100135 (0.25 mg/kg i.v.). We have also studied the effects of (S)-UH-301 (0.03-0.50 mg/kg i.v.) on the firing rate of single DRN-5-HT cells in rats chronically treated with citalopram (20 mg/kg/day i.p. x 14 days). Administration of (S)-UH-301 significantly and dose-dependently increased the activity of 5-HT cells in citalopram-treated rats, but did not affect these neurons in saline-treated (1 ml/kg/day i.p. x 14 days), control rats. Our results thus suggest that 5-HT1A receptor antagonists can augment both the acute and chronic effects of citalopram on central serotonergic neurotransmission.(ABSTRACT TRUNCATED AT 250 WORDS)

Life events and behavioural deviances in childhood: a longitudinal study of a normal population.

A semi-structured interview based upon Coddington's life event questionnaire was revised and modified to measure life changes in children of possible importance for the development of physical and mental illness. A normal population of 193 children was investigated in 1981-83 and followed up after six years. The life events during the intervening period are described and correlated to child behavioural symptom load and family function before and after. Both the life event load and the adjustment ability of the child make significant contributions to the prediction of child disturbance in the follow-up.

Twenty-month outcome in ventilator-dependent, very low birth weight infants born during the early years of dexamethasone therapy.

We sought to examine the effect of the introduction of dexamethasone therapy on health, growth, and neurodevelopmental outcome in very low birth weight (VLBW) infants at 20 months of age. We compared outcomes in all 86 VLBW infants (mean birth weight 871 gm, mean gestational age 26.4 weeks) who were ventilator dependent on day 21 of life during the 2 years preceding October 1988 (period 1), when dexamethasone therapy became accepted clinical practice in our unit, with outcomes in all 124 infants (mean birth weight 891 gm, mean gestational age 26.9 weeks) with similar ventilator status during the subsequent 2 years (period 2). In addition, we compared outcomes in infants who received dexamethasone during period 2 with those in a concurrent cohort of less ill infants who were not given dexamethasone. There were no significant differences between periods 1 and 2 in mortality rates after 21 days (17% vs 21%), need for home oxygen (23% vs 25%), oxygen dependence at 20 months of corrected age (11% vs 10%), rate of neurosensory impairment (24% vs 25%), and mean Bayley Mental scores (81.5 vs 77.2) or Psychomotor Development Index (81.6 vs 71.1). Infants who received dexamethasone during period 2 had significantly more severe lung disease and poorer respiratory, growth, and developmental outcomes. We conclude that VLBW infants with ventilator-dependent chronic lung disease have very poor outcomes, even when treated with dexamethasone. More information is needed from prospective, randomized trials before dexamethasone can be accepted as routine therapy for chronic lung disease.

Characterization of return cycle responses predictive of successful pacing-mediated termination of ventricular tachycardia.

OBJECTIVES: The purpose of this study was to characterize response patterns during overdrive pacing that predict successful termination of ventricular tachycardia. BACKGROUND: Overdrive pacing during ventricular tachycardia typically results in entrainment at slow pacing rates and in termination or acceleration at faster rates. The factors that determine the critical paced cycle length that results in tachycardia termination have not been extensively studied. METHODS: Ventricular tachycardias in 14 patients with coronary artery disease were studied with overdrive pacing at several cycle lengths. Return cycles were measured after each additional paced beat at each paced cycle length. The return cycle responses during pacing trials that resulted in tachycardia termination and those that resulted in entrainment were compared. RESULTS: Three return cycle responses were identified: flat, plateau and increasing. Twenty trials of overdrive pacing resulted in tachycardia termination; all were characterized by an increase in the return cycle with the delivery of each successive beat in the pacing drive until the tachycardia terminated (increasing response). Thirty-four pacing trials resulted in entrainment and not termination; these were characterized either by a constant return cycle (flat response) or an initial increase in return cycle followed by a longer, constant return cycle (plateau response) with the delivery of additional paced beats. The longest paced cycle length that resulted in tachycardia termination correlated with the relative refractory period of the circuit, defined as the tachycardia cycle length minus the fully excitable gap (r2 = 0.764, p = 0.0001). Tachycardia termination was not observed unless the paced cycle length was shorter than the relative refractory period of the circuit. CONCLUSIONS: The critical paced cycle length that causes termination of ventricular tachycardia depends on the relative refractory period of the circuit because this factor determines whether the nth + 1 beat of the pacing drive will encounter partially recovered tissue. These data provide insights into the mechanism of pacing-mediated tachycardia termination and entrainment and are applicable to the development of improved antitachycardia pacing algorithms.

Pneumopericardium in very low birth weight infants.

The objective of this study was to describe the incidence, neonatal correlates, and outcome of pneumopericardium (PPC) in very low birth weight (VLBW) < or = 1.5 kg infants. Forty-seven VLBW infants with a PPC, born during 1977 to 1989, were compared with a cohort of 1302 ventilated VLBW infants. PPC developed in 2% of 2389 VLBW infants and 3.5% of 1349 ventilated infants. The mean birth weight (1008 +/- 220 gm), and mean gestation (27 +/- 2 weeks) of the PPC cohort was similar to the control cohort. Thirty-two (68%) of the infants with PPC were male, compared with 691 (53%) of the ventilated infants (p < 0.05). Eight (17%) of the infants with PPC survived, compared with 780 (60%) of the control cohort (p < 0.00001). The oxygenation index significantly increased before PPC, and was significantly higher in nonsurvivors than survivors. Four (50%) of the PPC survivors had neurodevelopmental impairment at 20 months, compared with 35% of the control cohort. Pneumopericardium is a rare event with high morbidity and mortality. Clinicians should suspect this diagnosis in VLBW infants with a rising oxygenation index and subsequent acute deterioration.