PubMed Health⌕ Search

Biomedical subjects

J Elia

Publications and source records attributed to J Elia.

12 recordsLinked to original sources
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

B cells in autoimmune (NZB x NZW)F1 mice show altered IgG isotype switching upon T cell-dependent antigenic stimulation in vitro.

Humoral immune responses of (NZB x NZW)F1 (BWF1) autoimmune mice to T cell-dependent antigens often exhibit a predominance of IgG2 antibodies, while normal mice produce IgG1 antibodies. In order to determine whether this results from differences in properties of the B cells or the T cells involved, the responses of both primary and secondary BWF1 B cells to the antigen DNP-hemocyanin (Hy) were measured in limiting dilution splenic fragment cultures in the presence of normal T cell help. Furthermore, the capacity of Hy-primed lymph node T cells from BWF1 mice to provide help to BALB/c nu/nu B cells was determined in modified splenic fragment cultures. These experiments indicated that (a) stimulation of primary BWF1 B cells with DNP-Hy and normal T cell help failed to yield significant numbers of clones which produced any of the IgG isotypes; (b) antigenic stimulation of BWF1 secondary B cell clones also demonstrated a paucity of IgG1, but elevated production of IgG2 isotypes; and (c) Hy-primed BWF1 lymph node T cells were comparable to those derived from BALB/c mice in their capacity to provide both help for nu/nu B cell responses and modulation of IgG isotype switching. BWF1 B cells apparently differ from normal murine B cells in their capacity to produce IgG antibodies upon T cell-dependent antigenic stimulation.

Animals↗
PubMed1991

Methylphenidate and dextroamphetamine treatments of hyperactivity: are there true nonresponders?

The response to stimulant drugs of 48 boys with attention deficit/hyperactivity disorder was measured following dextroamphetamine, methylphenidate, and placebo in a double-blind crossover study. To distinguish lack of behavioral improvement from adverse drug effects, a day hospital setting and a wide dose range were used. Both drugs were highly and equally efficacious for the group as a whole, and frequently one drug or the other was superior for an individual child, or adverse effects occurred only on one of the stimulants. Only one of the 48 boys (2%) was discharged without the recommendation for continued stimulant drug treatment. "Nonresponse" appears to be extremely rare when both stimulants and a wide range of doses are given.

Analysis of Variance↗
PubMed1991

Stimulants and antidepressant pharmacokinetics in hyperactive children.

Psychopharmacological treatment of attention-deficit hyperactivity disorder (ADHD), is well established. The central nervous system stimulants, especially dextroamphetamine and methylphenidate, are the drugs of choice. Response is rapid, consistent and predictable. Most children respond to one or the other when a trial of both stimulants are given across wide dose ranges (Elia et al. 1991). The efficacy of pemoline is also well established, but its variable onset and duration of action in children has made it a secondary treatment. Tricyclic antidepressants also produce rapid behavioral effects in ADHD, at doses less than those used for depression. Adverse effects are a limiting factor for continued treatment as well as the fact that beneficial effects are often short-lived.

Antidepressive Agents↗
PubMed1991

P.r.n. medications in child psychiatric patients: a pilot placebo-controlled study.

BACKGROUND: The administration p.r.n. (as needed) of sedative medications is a widespread practice in the management of acute dyscontrol of child psychiatric inpatients. Its efficacy, however, has never been tested in a controlled clinical trial. METHOD: Twenty-one male inpatients, aged 5-13 years, participated in a double-blind, placebo-controlled study of the p.r.n. use of diphenhydramine, a sedative antihistaminic often used in child psychiatry wards. The patients' DSM-III-R diagnoses were conduct disorder, attention-deficit hyperactivity, and major depression. Each patient in acute dyscontrol blindly received either oral or intramuscular doses of diphenhydramine 25-50 mg (N = 9) or placebo (N = 12). The Conners Abbreviated 10-Item Teacher Rating Scale and the Clinical Global Impressions scale were completed before and 0.5, 1, and 2 hours after the dose. RESULTS: Repeated measures ANOVA showed significant time effects, but no difference due to drug. The intramuscular route tended to be more effective than the oral, regardless of whether active drug or placebo was given. CONCLUSION: The data indicate that if p.r.n. administrations are effective, this is a placebo effect. Likewise, intramuscular administrations are more effective because of a route effect ("the needle") and not because of a specific pharmacologic activity.

Administration, Oral↗
PubMed1990

Motor/vocal tics and compulsive behaviors on stimulant drugs: is there a common vulnerability?

The occurrence of abnormal movements or perserverative/compulsive behaviors was noted in 34 (76%) of a group of 45 hyperactive boys during a double-blind crossover treatment trial of methylphenidate and dextroamphetamine given in a wide range of doses. These adverse effects were often subtle and transient, and they usually occurred only on one drug. There was only one case where treatment was discontinued due to the severity of the tic the subject developed during his initial treatment phase. Dextroamphetamine tended to produce more compulsive behaviors, which were also more likely to resemble clinical obsessive-compulsive disorder (OCD), than did methylphenidate. Abnormal movements and compulsive behaviors tended to co-occur on methylphenidate only; no general "Tourette-OCD diathesis" was found for this population.

Attention Deficit Disorder with Hyperactivity↗
PubMed1990

Stimulant drug treatment of hyperactivity: biochemical correlates.

To compare the effects of the stimulant drugs dextroamphetamine and methylphenidate on urinary and plasma monoamines and metabolites within the same clinical sample, thirty-one children with attention-deficit disorder with hyperactivity were treated with dextroamphetamine (up to 1.5 mg/kg/day), methylphenidate (up to 3.0 mg/kg/day), and placebo in an 11-week double-blind crossover trial. As expected, both drugs showed striking clinical efficacy, and within a subsample of the group, earlier findings were confirmed, that dextroamphetamine but not methylphenidate lowered urinary and plasma 3-methoxy-4-hydroxyphenylglycol and whole body norepinephrine turnover, and that urinary and plasma concentration of homovanillic acid was unaltered by either drug. Methylphenidate but not dextroamphetamine increased plasma norepinephrine. Urinary epinephrine and metanephrine were increased with both drugs, but this increase did not correlate significantly with clinical improvement.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Attention-deficit hyperactivity disorder.

The epidemiology, etiology, pathogenesis, clinical presentation, diagnostic criteria, and clinical course of attention-deficit hyperactivity disorder (ADHD) are described and the role of pharmacotherapy in the management of this disorder is discussed. ADHD is a behavioral disorder of unknown etiology characterized by inattention, impulsiveness, and hyperactivity. The behavior, which may be manifest at home, at school, or in social situations, is generally worse in settings requiring sustained attention; as a result, academic underachievement is frequently an associated problem. Although the onset usually occurs before the age of four years, ADHD is most commonly diagnosed when the child enters school. It is up to six times more common in boys than in girls. Nearly one third of all children with ADHD continue to show symptoms of the disorder in adulthood. While many questions about the pathophysiology of ADHD remain unanswered and a cure has not yet been found, pharmacotherapy can effectively control the symptoms of the disorder in most patients. Three psychostimulant medications--dextroamphetamine sulfate, methylphenidate hydrochloride, and pemoline--are considered the drugs of first choice for management of the behavioral manifestations of ADHD. Dextroamphetamine and methylphenidate are equally effective in improving the symptoms of ADHD. Pemoline, a newer agent, may be tried in patients who cannot tolerate or do not respond to these two first-line agents. Common adverse effects associated with stimulant medications include anorexia, insomnia, stomach pain, and weight loss; these are generally transient and decrease with time. Imipramine hydrochloride and desipramine hydrochloride are less effective and may produce more serious adverse effects than the psychostimulants and are therefore considered second-line agents for the treatment of ADHD. Dextroamphetamine sulfate, methylphenidate hydrochloride, and pemoline have been shown to effectively control the behavioral symptoms of ADHD. For maximum impact, pharmacotherapy should be accompanied by behavioral, educational, and psychosocial intervention.

Attention Deficit Disorder with Hyperactivity↗