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Biomedical subjects

M A Delaney

Publications and source records attributed to M A Delaney.

At least 19 recordsLinked to original sources
PubMed2001

Olanzapine versus haloperidol in children with autistic disorder: an open pilot study.

OBJECTIVES: Conventional neuroleptics ameliorate symptoms in children with autistic disorder; however, they are known to cause dyskinesias. Atypical neuroleptics, including olanzapine, may have less risk for dyskinesia, but their efficacy in autistic disorder is not established. This study was designed to investigate the safety and effectiveness of open-label olanzapine as a treatment for children with autistic disorder by using haloperidol as a standard comparator treatment. METHOD: In a parallel groups design, 12 children with DSM-IV autistic disorder (mean age 7.8+/-2.1 years) were randomized to 6 weeks of open treatment with olanzapine or haloperidol. Mean final dosages were 7.9+/-2.5 mg/day for olanzapine and 1.4+/-0.7 mg/day for haloperidol. Outcome measures included the Clinical Global Impressions (CGI) and the Children's Psychiatric Rating Scale (CPRS). RESULTS: Both groups had symptom reduction. Five of six in the olanzapine group and three of six in the haloperidol group were rated as responders according to the CGI Improvement item. Subjects showed improvement on the CPRS Autism Factor (F1,9 = 24.4, p = .0008). Side effects included drowsiness and weight gain. CONCLUSIONS: The findings suggest that olanzapine is a promising treatment for children with autistic disorder. Further placebo-controlled and long-term studies of olanzapine in autistic disorder are required.

Antipsychotic Agents↗
PubMed2001

Prognostic and pathologic significance of quantitative protein expression profiling in human gliomas.

PURPOSE: Analysis of tumor-derived genetic lesions has provided insights into molecular pathogenesis of human gliomas. Because these changes represent only one of several mechanisms that alter gene expression during tumorigenesis, it is likely that further information will be obtained from a careful analysis of important regulatory proteins present in these tumors. EXPERIMENTAL DESIGN: We have quantified the levels of key cell cycle/signaling proteins in 94 prospectively collected, meticulously preserved, "snap frozen" glioma specimens and have compared these levels with histopathological data and patient outcome. RESULTS: The results of these experiments confirm that the levels of wild-type tumor suppressor proteins, such as p53, pRB, PTEN, p14(ARF), and p16(INK4), are lost or severely reduced in most gliomas, and that epidermal growth factor receptor, 2human telomerase reverse transcriptase, and cyclin-dependent kinase 4 are overexpressed frequently and with a few exceptions, almost exclusively, in glioblastomas. In addition, we report frequent underexpression of E2F-1 (in 55% of gliomas) and cyclin E overexpression (in 26% of gliomas), which have not yet been reported on the genomic level. Several of these markers significantly correlated with histopathological grade, and the levels of five proteins showed significant association with patient outcome. In particular, overexpression of epidermal growth factor receptor, human telomerase reverse transcriptase, cyclin-dependent kinase 4, and cyclin E was largely restricted to glioblastomas and was significantly associated with reduced patient survivals. CONCLUSIONS: We conclude that the quantitation of cell cycle/signaling proteins from meticulously preserved glioma specimens provides further insights into the molecular pathogenesis of human gliomas and yields valuable prognostic information.

Blotting, Western↗
PubMed2000

A double-blind placebo-controlled study of lithium in hospitalized aggressive children and adolescents with conduct disorder.

BACKGROUND: A subgroup of children and adolescents with conduct disorder are characterized by severe and persistent aggression. Although there is no agreed on treatment for such aggression, lithium carbonate has shown promise in some studies involving children. Our study was designed to critically assess the efficacy of lithium in the treatment of aggression in children and adolescents using a measure specific for aggression. METHODS: Subjects were inpatients with conduct disorder hospitalized because of severe and chronic aggression. A parallel-groups design was used in this double-blind, placebo-controlled trial with randomization to lithium or placebo. Only those who met the aggression criterion during the 2-week placebo-baseline period were randomized to 4 weeks of treatment. Outcome measures included Clinical Global Impressions, the Global Clinical Judgements (Consensus) Scale, and the Overt Aggression Scale. RESULTS: Eighty-six inpatients enrolled in the study; 40 (33 male and 7 female; median age, 12.5 years) entered and completed the treatment phase. Lithium was statistically and clinically superior to placebo. Sixteen of 20 subjects in the lithium group were responders on the Consensus ratings vs 6 of 20 in the placebo group (P=.004). Ratings on the Overt Aggression Scale decreased significantly for the lithium group vs the placebo group (P=.04). More than half of the subjects in the lithium group experienced nausea, vomiting, and urinary frequency. CONCLUSIONS: Lithium is a safe and effective short-term treatment for aggression in inpatients with conduct disorder, although its use is associated with adverse effects.

Adolescent↗
PubMed1998

The nucleotide sequence and spliced pol mRNA levels of the nonprimate spumavirus bovine foamy virus.

We have determined the complete nucleotide sequence of a replication-competent clone of bovine foamy virus (BFV) and have quantitated the amount of splice pol mRNA processed early in infection. The 544-amino-acid Gag protein precursor has little sequence similarity with its primate foamy virus homologs, but the putative nucleocapsid (NC) protein, like the primate NCs, contains the three glycine-arginine-rich regions that are postulated to bind genomic RNA during virion assembly. The BFV gag and pol open reading frames overlap, with pro and pol in the same translational frame. As with the human foamy virus (HFV) and feline foamy virus, we have detected a spliced pol mRNA by PCR. Quantitatively, this mRNA approximates the level of full-length genomic RNA early in infection. The integrase (IN) domain of reverse transcriptase does not contain the canonical HH-CC zinc finger motif present in all characterized retroviral INs, but it does contain a nearby histidine residue that could conceivably participate as a member of the zinc finger. The env gene encodes a protein that is over 40% identical in sequence to the HFV Env. By comparison, the Gag precursor of BFV is predicted to be only 28% identical to the HFV protein.

Alternative Splicing↗
PubMed1998

Aggression classification and treatment response.

This preliminary study investigated whether the aggression subtypes derived from the Aggression Questionnaire (AQ) are related to treatment response. The subjects were 28 aggressive conduct-disordered children (25 males, 3 females), ranging in age from 9.8 to 17.0 years (mean age = 12.69 years), who participated in a double-blind, placebo-controlled study of lithium as a treatment for reducing aggression. We used the Predatory-Affective Index of the AQ to classify subjects into "predatory" (planned) or "affective" (explosive) subtypes of aggression and then related this classification to treatment response. This index did not differentiate placebo baseline responders from nonresponders. However, the Index did significantly differentiate responders and nonresponders during the experimental treatment period, regardless of whether they received lithium or placebo. Treatment response was associated with a more affective and less predatory subtype of aggression. To the best of our knowledge, this is the first study in children to show an association between the aggression subtype and treatment response.

Adolescent↗
PubMed1997

Nonpharmacological response in hospitalized children with conduct disorder.

OBJECTIVE: There is a paucity of research regarding the effects of hospitalization and/or the response to placebo in children with conduct disorder who are hospitalized for chronic and severe aggression. However, many children with this problem are hospitalized and immediately begin pharmacotherapy. In this report, the effects of hospitalization and placebo administration were examined. METHOD: Subjects were forty-four children (37 males, 7 females) with conduct disorder, aged 9.83 to 17.14 years, who were hospitalized for chronic and severe aggression. This was a 4-week double-blind and placebo-controlled study with a 2-week single-blind placebo lead-in period. During the 2-week placebo baseline period, aggression was measured on a 24-hour basis, using the Overt Aggression Scale. Only subjects meeting a specific aggression criterion were randomized to the treatment period of the trial. RESULTS: Of the 44 subjects enrolled, 23 (52.3%) met the aggression criteria for entering the treatment period (baseline nonresponders), while 21 (47.7%) did not (baseline responders). Thus, almost half of the subjects, while taking no active medication, benefited from the inpatient milieu/structure and/or placebo. CONCLUSION: This finding has important treatment and research implications. Medication to treat aggression should not be initiated immediately upon hospitalization because improvements associated with hospitalization may be attributed inaccurately to pharmacotherapy, resulting in unnecessarily medicating children. A placebo baseline period is essential to decrease the risk of a type II error in pharmacological research concerning aggression.

Adolescent↗
PubMed1995

The working alliance and consumer case management.

The Working Alliance Inventory was used to measure the strength of the therapeutic relationship between seriously mentally disabled case management clients and their case managers in a randomized trial of consumer-provided case management services. It was found that while there was no difference in the strength of the alliance between the consumer and nonconsumer teams of case managers, there were positive relationships between alliance and some outcomes, including quality of life, symptomatology, attitudes toward medication compliance, and satisfaction with mental health treatment.

Assertiveness↗
PubMed1995

The lithium test dose prediction method in aggressive children.

Cooper and associates (1973) developed a method of ascertaining the lithium dosage required to attain a therapeutic serum level of 0.6 to 1.2 mEq/L. However, reports about the safety and accuracy of their method in children are limited (Geller & Fetner 1989). This study relates our experience with using this method in children. Subjects were 16 conduct-disordered children (13 males, 3 females), ages 8.97 to 17.14 years (mean, 12.73 +/- 2.12), who were treated with lithium to decrease aggressive behavior. Following a lithium 600-mg loading dose, a 24-hour serum lithium level was drawn from which a "predicted" lithium dosage was established. These dosages ranged from 600 to 1,800 mg/day (mean, 1,312.5 +/- 450) and the corresponding serum lithium levels at steady-state ranged from 0.58 to 1.13 mEq/L (mean, 0.87 +/- 0.15). No severe side effects were encountered. This suggests that the method is safe and useful for predicting lithium dosages in children.

Adolescent↗
PubMed1994

The Overt Aggression Scale in a study of lithium in aggressive conduct disorder.

This article describes an open study of lithium carbonate in conduct-disordered children. The objective of the study was to investigate the effectiveness of lithium in reducing aggression and the usefulness of the Overt Aggression Scale (OAS), as a measure of treatment effect. The subjects, 8 children, ages 9.2 to 16.9 years (mean +/- standard deviation [SD] = 12.48 +/- 2.97), were treated for 4 weeks with lithium. Optimal dosages ranged from 1200 to 1800 mg/day (mean = 1350 +/- 227) with corresponding serum lithium levels ranging from 0.86 to 1.39 mEq/L (mean = 1.05 +/- 0.17). OAS results indicated that aggression decreased significantly over time. The findings from the OAS agreed with findings from a more general measure, the Global Clinical Consensus Rating, leading to the conclusion that the OAS is a promising outcome measure for treatment studies of aggression in children. Further placebo-controlled studies of lithium carbonate in reducing aggressive behavior in conduct-disordered children, employing a specific measure such as the OAS, are warranted.

Adolescent↗
PubMed1993

Community service utilization by youths hospitalized in a state psychiatric facility.

A majority of a cohort of 62 children and adolescents who had been hospitalized in a state psychiatric facility was found to have received less restrictive services such as outpatient mental health services prior to their index admission. Also, a number had been involved with the juvenile justice system and almost two-thirds had been placed out-of-home. Ninety percent had at least one prior psychiatric hospitalization. Just over half of the cohort received case management and individual counseling post release. About a third received family counseling, and a few received other types of services. At least a third were rehospitalized within a year of release. Although 90% of the cohort received some type of service post release, a higher proportion of non service receivers were rehospitalized than service receivers. Even those who received services had a high rate of rehospitalization. These findings raise questions as to the appropriateness of service provision during and following hospitalization.

Adolescent↗
PubMed1992

Assessment of therapeutic relationship of community-agency workers.

This article reports on the ratings of the personal and professional characteristics of community-based workers for children and adolescents who had recently been released from a psychiatric inpatient service. The child/adolescent's family members/caregivers and the community workers both responded to the same items of a questionnaire. Families/caregivers rated the community workers with whom they were the most and the least satisfied. Community workers rated themselves in relation to these study children and/or their families. Findings indicate that both family members/caregivers and the community workers themselves saw community workers performing relatively well in the areas of providing information and offering support to families. Likewise, both assessed the service providers as having the greatest deficits in the area of teaching skills for child/adolescent home management. Suggestions for meeting the needs of the families and for ensuring that a system of care for child/adolescents is child-centered and family-focused are discussed.

Adolescent↗
PubMed1992

Replication of DHBV genomes with mutations at the sites of initiation of minus- and plus-strand DNA synthesis.

We have examined the consequences on duck hepatitis B virus DNA synthesis of deleting the 5' and 3' copies of the 12 base sequence, DR1, from the viral pregenome. With the wild-type virus, reverse transcription initiates at nt 2537 within the 3' copy of DR1. When this sequence was deleted, initiation of reverse transcription was found at two other sites located closer to the 3' end of the pregenome (nt 2576 and nt 2644). The 3-base motif UUA was the only sequence common to these sites as well as the wild-type initiation site in DR1. Deletion of the 5' copy of DR1 did not alter minus strand synthesis, but led to aberrant priming of plus strand synthesis to generate predominantly linear rather than relaxed circular, double-stranded viral DNA, in agreement with the recent report by Loeb et al. (EMBO J. 10, 3533-3540, 1991). A mutant lacking only the 3' copy of DR1 rapidly converted to wild type in transfected cells. This apparently occurred as a consequence of conversion of newly synthesized relaxed circular to covalently closed circular (CCC) DNA, which might then serve as a template for the synthesis of wild-type viral RNAs. A mutant lacking only the 5' copy of DR1 did not exhibit this behavior. These results support the conclusion that amplified CCC DNA serves as transcriptional template.

Animals↗
PubMed1990

Reliability of DSM-III diagnoses of hospitalized children.

The reliability of diagnoses of 46 child psychiatric inpatients made using three independent instruments--an unstructured interview with the parent and child that produced the chart diagnosis, a structured interview with the parent, and a structured interview with the child--was assessed. These diagnoses were then compared with a review diagnosis, which was based on all information available at the patient's discharge. Substantial disagreement between the diagnoses resulting from the structured and unstructured interviews was found in one-third of the cases. The review diagnosis disagreed with the chart diagnosis in 33 percent of the cases but disagreed with the diagnosis resulting from the structured interview with the parent in 13 percent of the cases. While structured interviews can contribute to the standardization of diagnoses, the reliability and validity of child psychiatric diagnoses remain problematic.

Adolescent↗
PubMed1988

Pharmacokinetics of lithium carbonate in children.

The pharmacokinetics in both serum and saliva of a single oral dose of lithium carbonate 300 mg was investigated in nine children aged 9 to 12 years. The serum and saliva concentration-time curves were parallel and biexponential, with a fast distribution phase after the peak at the second hour and a slow elimination phase starting from the 12th hour. The fast phase half-life was 6.0 +/- 1.8 hour in the serum, and 5.8 +/- 1.9 hour in the saliva. The slow phase half-life was 17.9 +/- 7.4 hour in the serum and 15.6 +/- 8.2 hour in the saliva. Lithium was 2.84 +/- 0.86 times higher in the saliva than in the serum, with a saliva/serum r coefficient of correlation of 0.93. A relatively large error was found in predicting serum levels from saliva. There were significant intersubject differences in the saliva/serum ratio, which point to the need for individual ratios in clinical use. On the whole, the pharmacokinetics of lithium in children had the same features as in adults, with a trend toward a shorter elimination half-life and higher total clearance.

Child↗