Treatment of attention-deficit-hyperactivity disorder.
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Adrenergic alpha-Agonists↗
Biomedical subjects
J Elia
Publications and source records attributed to J Elia.
Multicenter open-label sertraline study in adolescent outpatients with major depression.
OBJECTIVE: The aim of this multicenter outpatient study was to assess the therapeutic benefits, response patterns, and safety of sertraline in adolescent major depressive disorder (MDD). METHOD: Fifty-three adolescent outpatients with MDD were treated in an open-label, 10-week, acute-phase trial with sertraline and, if responders, for an additional 12-week continuation phase. Diagnostic and response assessments included the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS), 17-item K-SADS-derived depression severity score, Hamilton Depression Rating Scale, Beck Depression Inventory, and Clinical Global Impression Scale. RESULTS: By 2 weeks, when analyzed as continuous variables, all severity scores showed significant differences from baseline. This pattern persisted through 10 weeks, with a significantly greater response occurring when treatment was extended from 6 to 10 weeks. Both clinician- and patient-rated improvement was maintained during continuation treatment. Response rates varied considerably when depression rating scales were analyzed categorically. Sertraline was generally well tolerated and did not induce manic symptoms. CONCLUSIONS: In open treatment of adolescent MDD with sertraline, significant improvement occurred early on and was maintained for 22 weeks. Absolute response rates varied depending on the rating scales used, definition of response, and length of treatment. Maximal response rates were obtained by clinician-defined ratings after 10 weeks of treatment.
Adolescent↗
Pancreatitis associated with serotonin-dopamine antagonists.
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Adolescent↗
Controlled stimulant treatment of ADHD and comorbid Tourette's syndrome: effects of stimulant and dose.
OBJECTIVE: To determine the effects of methylphenidate (MPH) and dextroamphetamine (DEX) on tic severity in boys with attention-deficit/hyperactivity disorder (ADHD) comorbid with Tourette's syndrome. METHOD: A 9-week, placebo-controlled, double-blind crossover using a wide range of doses was completed by 20 subjects in three cohorts. RESULTS: Relatively high doses of MPH and DEX in the first cohort produced significant increases in tic severity which were sustained on higher doses of DEX but which attenuated on MPH. Overall, 14 of 20 subjects continued stimulant treatment for 1 to 3 years, generally in combination with other psychotropics. Stimulant-associated adverse effects, including tic exacerbations, were reversible in all cases. CONCLUSION: A substantial minority of comorbid subjects had consistent worsening of tics on stimulants, although the majority experienced improvement in ADHD symptoms with acceptable effects on tics. MPH was better tolerated than DEX.
Analysis of Variance↗
Cerebrospinal fluid homovanillic acid predicts behavioral response to stimulants in 45 boys with attention deficit/hyperactivity disorder.
Central dopaminergic activity has been assumed to play a role in the efficacy of stimulant drugs in attention deficit/hyperactivity disorder (ADHD), although supporting evidence has been scant. This study examined baseline cerebrospinal fluid (CSF) of boys with ADHD in relation to response to three different stimulant drugs. Forty five boys with DSM-III-R-diagnosed ADHD had a lumbar puncture before double-blind trials of methylphenidate, dextroamphetamine, and placebo. Sixteen also received pemoline as part of a subsequent open trial. Stepwise linear regressions determined significant predictors of drug response. Our prior report of a positive significant correlation between CSF homovanillic acid (HVA) and ratings of hyperactivity on placebo was replicated in a new sample of 20 boys. After baseline symptom severity, CSF HVA was the best predictor of stimulant drug response, with significant independent contribution to four of the ten measures of hyperactivity that changed significantly with medication. Higher HVA predicted better drug response, and lower HVA was associated with worsening on some measures. This supports the mediating role of central dopaminergic activity in stimulant drug efficacy in childhood hyperactivity.
Attention Deficit Disorder with Hyperactivity↗
Isolation of human uteroglobin from blood filtrate.
The purpose of this study was to assess the possibility of isolating biologically active peptides from human blood using large volumes of blood filtrate, which are available from patients undergoing extracorporeal ultrafiltration because of renal insufficiency. This filtrate was submitted to six chromatographic separation steps, yielding one purified peptide which was completely analysed in its primary structure. It was found to be strikingly similar to proteins, described initially as rabbit uteroglobin (or blastokinin) and, more recently, from human bronchial lavage as the '10 kDa Clare cell protein', as well as from human urine as 'protein-1'. The natural molecule contains two chains of identical amino acid sequences of 70 residues which are arranged as an antiparallel dimer due to the disulphide bonds between two cysteines at positions 3 and 69. Mass analysis of the molecular forms yielded molecular weights from 15827 Da (non-oxidized form) to 15859 Da (bi-oxidized form). We conclude that this peptide isolated from the filtrate represents the human uteroglobin, and we demonstrate for the first time that this peptide may be involved as a humoral factor in reproductive or other physiological functions.
Amino Acid Sequence↗
Formal clinical evaluation of the CADD-Micro system for circadian delivery of FUDR in patients with metastatic renal cell cancer.
The CADD-Micro System (Sims Deltec, St. Paul, MN) was formally evaluated in patients with metastatic renal cell cancer, participating in a phase-III study comparing a 2-week circadian versus flat infusion of FUDR. Ten patients participated, 2 receiving five cycles of FUDR by a flat infusion, and 8 receiving 12 cycles of FUDR by circadian infusion. A total of 235 treatment days were evaluated. All patients had a Port-A-Cath in place for venous access. The patients completed a structured evaluation survey for each week of treatment regarding their interaction with the pump and an overall evaluation of the system and the patient information guide at the end of each 2-week course. Nurses from our home infusion program completed a separate evaluation. Overall patient and clinician perception of this pump was excellent. The main drawback had to do with the design of the battery compartment cover and the handling of the drug reservoir. The small size of the drug reservoir (10 mL) limits the usability of this pump to low-volume tasks.
Antimetabolites, Antineoplastic↗
Effect of dextroamphetamine and methylphenidate on calcium and magnesium concentration in hyperactive boys.
Levels of calcium in plasma, red blood cells, and mononuclear blood cells, levels of calcium in plasma, and the plasma calcium-to-magnesium ratio were measured at baseline and after 3 weeks of each drug phase of a double-blind, placebo-controlled study of methylphenidate and dextroamphetamine in hyperactive boys. Levels of magnesium in plasma were significantly higher after 3 weeks of dextroamphetamine treatment, and the calcium-to-magnesium ratio was significantly lower after 3 weeks of either drug compared with the baseline or placebo condition. There was no change in magnesium levels in red blood cells or mononuclear blood cells. These measures were obtained 30 minutes before the morning dose and at 9 a.m., 9:30 a.m., 10:30 a.m., 11:00 a.m., and noon on the last day of each 3-week phase. Analysis of variance revealed a drug effect on plasma magnesium and on the calcium-to-magnesium ratio but no drug x time interaction. Although these changes were not correlated with the time course of acute symptomatic response to stimulant therapy, the decrease in the ratio may be relevant to side effects and treatment resistance associated with stimulant use.
Attention Deficit Disorder with Hyperactivity↗
Cerebrospinal fluid monoamine metabolites in boys with attention-deficit hyperactivity disorder.
Cerebrospinal fluid (CSF), plasma, and urinary monoamine metabolites were determined for 29 boys, aged 6-12, with attention-deficit hyperactivity disorder (ADHD). Levels of CSF 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), the metabolites of serotonin, dopamine, and norepinephrine, respectively, correlated significantly with behavioral measures of aggression and impulsivity/hyperactivity. However, these correlations were in the unexpected direction; for example, CSF 5-HIAA correlated positively with the Brown-Goodwin Lifetime History of Aggression Scale. HVA in CSF was positively correlated with several measures of hyperactivity. The replicability of these findings, as well as possible socioenvironmental effects, and the predictive value of CSF monoamines in prepubertal hyperactivity are the subjects of ongoing study.
Aggression↗
Thyroid function and attention-deficit hyperactivity disorder.
OBJECTIVE: To examine thyroid indices in a community referred sample of boys with attention-deficit hyperactivity disorder (ADHD) for evidence of generalized resistance to thyroid hormone (GRTH). METHOD: TSH, T3, and T4 values were gathered prospectively in 53 physician, school, and/or parent referred ADHD subjects, and in 41 age and gender-matched normal controls. RESULTS: None were in the range suggestive of global or pituitary thyroid hormone resistance. CONCLUSIONS: GRTH is rare, and thyroid function should not be measured routinely in nonfamilial ADHD.
Attention Deficit Disorder with Hyperactivity↗
Antidepressant treatments in children and adolescents. I. Affective disorders.
Part I of this review critically evaluates antidepressants' benefits for children and adolescents with affective disorders. The effectiveness of antidepressants is characterized with specific references regarding diagnostic methodology, measurement characteristics, response definitions, recovery rates, length of treatment, and plasma level monitoring. Antidepressants' efficacy for depressed youths is quite circumscribed, and their superiority to placebo remains unproved. Their intriguing lack of efficacy in affective disorders is discussed based on methodological issues and from a theoretical perspective. Clinical and research implications are presented.
Adolescent↗
Antidepressant treatments in children and adolescents: II. Anxiety, physical, and behavioral disorders.
Part II of this review critically evaluates antidepressants' (AD) efficacy in children and adolescents with anxiety, physical, and behavioral disorders as well as AD's side-effect spectrum. AD are administered increasingly to youths with specific anxiety syndromes phenomenologically paralleling those in adults which are responsive to AD (e.g., panic, obsessive-compulsive disorders). While several trials have not substantiated earlier theoretical considerations suggesting their usefulness in separation anxiety, their recent success in ameliorating obsessive-compulsive symptoms is encouraging. Systematic drug treatment studies however are limited because of the common overlap of anxiety syndromes with each other and other prominent psychiatric disturbances. More consistent benefits with AD are seen in the physical (e.g., enuresis, bulimia nervosa) and behavioral disorders (e.g., attention deficit-hyperactivity disorder). The wide-ranging benefits of AD in nonaffective disorders suggest AD are more appropriately viewed as broad spectrum pharmacotherapeutics.
Adolescent↗
Classroom academic performance: improvement with both methylphenidate and dextroamphetamine in ADHD boys.
Daily academic classroom performance was recorded in a day hospital school using a commonly employed reading and math series as part of an 11-week double-blind, placebo controlled, crossover comparison of dextroamphetamine (d-AMPH) and methylphenidate (MPH) in 33 hyperactive boys. Students attempted more math and reading tasks while on either active drug. The percent correct and the number of attempted problems of the reading series improved with both drugs while the percent correct for the math series occurred with d-AMPH only. No dose-response relationship was found for either stimulant. Moderate, transient adverse effects were common for both drugs.
Achievement↗
Drug treatment for hyperactive children. Therapeutic guidelines.
Attention deficit hyperactivity disorder (ADHD) is a common childhood behavioural disorder and medication is one of the principal treatments. Methylphenidate and dexamphetamine (dextroamphetamine) have a long record of use in children and well proven efficacy, and are the preferred drugs. Current clinical guidelines recommend a trial of methylphenidate and of dexamphetamine for each child meeting criteria for the disorder in order to maximise response rate and minimise adverse effects.
Antidepressive Agents, Tricyclic↗
Ly-1 B-lineage cells downregulate the number and proliferation of B-cell precursors.
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Animals↗
Biological correlates of impulsive disruptive behavior disorders: attention deficit hyperactivity disorder, conduct disorder, and borderline personality disorder.
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Adolescent↗
Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease.
Neurological dysfunction, seizures and brain atrophy occur in a broad spectrum of acute and chronic neurological diseases. In certain instances, over-stimulation of N-methyl-D-aspartate receptors has been implicated. Quinolinic acid (QUIN) is an endogenous N-methyl-D-aspartate receptor agonist synthesized from L-tryptophan via the kynurenine pathway and thereby has the potential of mediating N-methyl-D-aspartate neuronal damage and dysfunction. Conversely, the related metabolite, kynurenic acid, is an antagonist of N-methyl-D-aspartate receptors and could modulate the neurotoxic effects of QUIN as well as disrupt excitatory amino acid neurotransmission. In the present study, markedly increased concentrations of QUIN were found in both lumbar cerebrospinal fluid (CSF) and post-mortem brain tissue of patients with inflammatory diseases (bacterial, viral, fungal and parasitic infections, meningitis, autoimmune diseases and septicaemia) independent of breakdown of the blood-brain barrier. The concentrations of kynurenic acid were also increased, but generally to a lesser degree than the increases in QUIN. In contrast, no increases in CSF QUIN were found in chronic neurodegenerative disorders, depression or myoclonic seizure disorders, while CSF kynurenic acid concentrations were significantly lower in Huntington's disease and Alzheimer's disease. In inflammatory disease patients, proportional increases in CSF L-kynurenine and reduced L-tryptophan accompanied the increases in CSF QUIN and kynurenic acid. These responses are consistent with induction of indoleamine-2,3-dioxygenase, the first enzyme of the kynurenine pathway which converts L-tryptophan to kynurenic acid and QUIN. Indeed, increases in both indoleamine-2,3-dioxygenase activity and QUIN concentrations were observed in the cerebral cortex of macaques infected with retrovirus, particularly those with local inflammatory lesions. Correlations between CSF QUIN, kynurenic acid and L-kynurenine with markers of immune stimulation (neopterin, white blood cell counts and IgG levels) indicate a relationship between accelerated kynurenine pathway metabolism and the degree of intracerebral immune stimulation. We conclude that inflammatory diseases are associated with accumulation of QUIN, kynurenic acid and L-kynurenine within the central nervous system, but that the available data do not support a role for QUIN in the aetiology of Huntington's disease or Alzheimer's disease. In conjunction with our previous reports that CSF QUIN concentrations are correlated to objective measures of neuropsychological deficits in HIV-1-infected patients, we hypothesize that QUIN and kynurenic acid are mediators of neuronal dysfunction and nerve cell death in inflammatory diseases. Therefore, strategies to attenuate the neurological effects of kynurenine pathway metabolites or attenuate the rate of their synthesis offer new approaches to therapy.
Aged↗
B cell precursors are decreased in senescent BALB/c mice, but retain normal mitotic activity in vivo and in vitro.
The numbers of phenotypic (sIg- Ly5[220]+) and functional B cell precursors were significantly reduced in the bone marrow of senescent (22-24 months old) BALB/c mice when compared to their young (2-4 months old) cohorts. Little alteration in the numbers of B cell precursors occurred during the first 12 months of life in this strain. In contrast, an accelerated loss of B cell precursors between 15 and 18 months of age was observed. In particular, the levels of small Ly5(220)+ B cell precursors were decreased with advanced age, although a decline in numbers of large sIg- Ly5(220)+ B cell precursors was also evident. The percentages of large sIg- Ly5(220)+ B cell precursors in (S + G2/M) stages of cell cycle were similar (e.g., 60-80%) in aged and young BALB/c mice. Importantly, Ly5(220)+ pre-B cells from both young and aged BALB/c mice, either present in vivo or derived from Ly5(220)- cells in vitro, were capable of proliferation in response to rIL-7. These observations suggest that the aging process results in a progressive decline in the numbers of pre-B cells; however, this apparently is not due to failure of B lineage precursor cells to respond to growth mediators either in vivo or in vitro.
Aging↗