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Biomedical subjects

D Dougherty

Publications and source records attributed to D Dougherty.

At least 19 recordsLinked to original sources

Clonidine challenge in childhood anxiety disorder.

OBJECTIVE: To evaluate the neurohormonal and subjective mood response of children with anxiety disorder to clonidine challenge METHOD: Children with DSM-IV diagnoses of anxiety disorder (ANX) (n = 24) and normal controls (n = 15) were given a challenge of intravenous clonidine (1.3 micrograms/kg) and provided neurohormonal and mood self-report assessment over a 180-minute period. RESULTS: The ANX group differed from normal controls in Hamilton Anxiety Rating, Revised Children's Manifest Anxiety Scale score, and maximum change from baseline (delta max) in growth hormone (GH). Clonidine-stimulated GH concentration of the ANX group was significantly elevated compared with that of controls but returned to baseline within 2 hours. A subgroup with obsessive-compulsive disorder (OCD) (n = 9) had significantly higher delta max GH (17.5 +/- 10.1 ng/mL) than the group with other anxiety disorders (ANX-OCD) (9.1 +/- 5.8 ng/mL) and controls (5.7 +/- 4.1 ng/mL). CONCLUSION: GH response to clonidine challenge is not blunted in ANX subjects. This finding is in contrast to adult disorder and suggests that adrenergic postsynaptic receptor down-regulation is not a feature of childhood anxiety. These findings suggest enhanced central adrenergic sensitivity in ANX which is most pronounced in OCD and argue against a neurobiological continuum from childhood to adult anxiety disorder.

Adolescent

Platelet serotonin transporter in depressed children and adolescents: 3H-paroxetine platelet binding before and after sertraline.

OBJECTIVE: To evaluate serotonin transporter protein (5HTPR) binding in platelets from children and adolescents with major depression (MDD) compared to normal controls using the selective ligand 3H-paroxetine. METHOD: Children and adolescents with MDD (n = 24) defined by DSM-III-R criteria and normal controls (n = 22) were compared by platelet 5HTPR kinetic analysis with the hypothesis that 5HTPR is reduced in MDD. A subset of MDD subjects (n = 18) continued to participate in a fixed-dose, open-label sertraline trial for 6 weeks followed by drug-free washout and repeated 5HTPR analysis. RESULTS: Sex, prepubertal status, and age had no effect on 5HTPR. Medication-free MDD subjects differed from controls in reduced binding capacity (Bmax) (p < .001). Sertraline therapy decreased binding affinity from baseline non-selectively (p < .05), and Bmax elevation from baseline was associated with nonresponse and suicide attempt history. CONCLUSION: Earlier literature in this population is replicated with regard to reduced platelet 5HTPR Bmax in MDD. Findings support a continuum of 5HTPR involvement in MDD across the developmental spectrum.

1-Naphthylamine

Dopaminergic agents and stimulants as antidepressant augmentation strategies.

Dopaminergic agents and stimulants have been used to manage depression when conventional antidepressant treatments fail. We reviewed evidence for the role of dopaminergic dysfunction in depression, the use of dopaminergic agents as antidepressants, and the use of dopaminergic agents and stimulants as antidepressant adjuncts. Dopamine may be part of the pathophysiology of depression for a subset of patients. When used with caution and an appreciation of the potential risk of abuse, dopaminergic agents and stimulants may be useful for patients refractory to antidepressants alone.

Antidepressive Agents

Probing striatal function in obsessive-compulsive disorder: a PET study of implicit sequence learning.

Positron emission tomography was employed to contrast the brain activation pattern in patients with obsessive-compulsive disorder (OCD) to that of matched control subjects while they performed an implicit learning task. Although patients and control subjects evidenced comparable learning, imaging data from control subjects indicated bilateral inferior striatal activation, whereas OCD patients did not activate right or left inferior striatum and instead showed bilateral medial temporal activation. The findings further implicate corticostriatal dysfunction in obsessive-compulsive disorder. Furthermore, when OCD patients are confronted with stimuli that call for recruitment of corticostriatal systems, they instead appear to access brain regions normally associated with explicit (conscious) information processing.

Adult

Prolactin monitoring of haloperidol and pimozide treatment in children with Tourette's syndrome.

Neuroleptic therapy of children and adolescents with Tourette's syndrome (GTS) is associated with unpredictable outcome and adverse drug responses (i.e., extrapyramidal symptoms). Assessing the potential outcomes in GTS from a physiologic marker such as plasma prolactin concentration is important in limiting exposure and optimizing therapy. In a double-blind, placebo-controlled, double crossover comparison of pimozide and haloperidol therapy, prolactin, tic severity, and extrapyramidal symptoms were assessed at a 6-week end point. Twenty-six GTS patients (10.5 +/- 2.6 years), experienced clinical response rates of 69% on 3.4 +/- 1.6 mg pimozide and 65% on 3.5 +/- 2.2 mg/day haloperidol. Pimozide responders demonstrate elevated prolactin (26.1 +/- 11.8 ng/mL) versus pimozide nonresponders (10.5 +/- 3.8 ng/mL) (p = .05) and haloperidol treated patients (p = .05). Prolactin may be a marker for tic response to pimozide, and conversely, a potential marker for haloperidol-related incidence of extrapyramidal symptoms during haloperidol therapy.

Adolescent

A comparison of structured versus guided preheart catheterization information on mood states and coping resources.

A rapid growth in outpatient surgical procedures has been necessary to help alleviate expensive health care costs. Because procedures, such as heart catheterization, require a short patient stay, preparatory information is often structured and delivered concisely. The purpose of this study was to determine if heart catheterization patients who receive guided precatheterization information had reduced stress compared with heart catheterization patients who received structured precatheterization information. Using a two-group pretest/posttest design, 89 subjects were randomly assigned to two different preparatory nursing interventions. Data were collected on outpatients' coping resources and mood states, which served as measures of stress. No significant differences in stress were found between the guided and structured preparatory information groups. The results indicated that a variety of approaches can be used to prepare patients for outpatient heart catheterization procedures.

Adaptation, Psychological

Long-term treatment of malignant gliomas with intramuscularly administered polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose: an open pilot study.

Polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC) (10-50 mcg/kg, administered intramuscularly one to three times weekly) was given for < or = 56 months to 38 patients with malignant gliomas. There was minimal or no toxicity. Twenty of 30 patients (66%) receiving at least twice weekly poly-ICLC showed regression or stabilization of gadolinium-enhancing tumor, as revealed by magnetic resonance imaging (median = 65% volume decrease). All but one patient with anaplastic astrocytomas who received continuous poly-ICLC remain alive, with a median progression-free survival of 54 months from diagnosis. Median Kaplan-Meier survival is 19 months for patients with glioblastomas who receive at least twice weekly poly-ICLC treatments. Tumor response was associated with 2',5' -oligoadenylate synthetase activation (P = 0.03) but not with serum interferon. We hypothesize clinical activation by poly-ICLC of a basic host tumor suppressor system. Prolonged, quality survival with tumor stabilization or regression confirmed by magnetic resonance imaging for most patients with anaplastic astrocytomas and glioblastomas suggests that more extensive laboratory and controlled clinical studies are warranted. The concept of long-term, broad spectrum stimulation of host defenses with nontoxic, inexpensive double-stranded ribonucleic acids, such as low-dose poly-ICLC, may be applicable to the treatment of other malignancies.

Adult

Nutrition care given new importance in JCAHO standards.

The 1995 standards developed by the Joint Commission on Accreditation of Healthcare Organizations are now in effect. In an unprecedented shift, the manual focuses on performance rather than structure and process. It emphasizes the interdisciplinary delivery of care, including nutrition care. This article describes the new standards as they relate to nutrition support professionals.

Joint Commission on Accreditation of Healthcare Or

Lymphocyte glucocorticoid receptor: predictor of sertraline response in adolescent major depressive disorder (MDD).

Major depressive disorder (MDD) in adolescents demonstrates resistance to tricyclic antidepressants and absence of hypercortisolemia. The efficacy of serotonin reuptake inhibitors (SRIs) is uncertain, and response predictors are unavailable. Abnormal fast feedback and negative feedback of the hypothalamic-pituitary-adrenal axis implicates a dampened limbic-hippocampal glucocorticoid type II receptor (GCII). We hypothesized that lymphocyte GCII is altered in adolescent MDD and could serve as a marker for response to SRIs. In an open-label study, adolescents (n = 20) meeting DSM-III-R criteria for MDD showed baseline lymphocyte GCII sites per cell (sites/cell) values of 793 +/- 106 versus 2,563 +/- 499 (+/- SEM) for matched controls (n = 18) (t = 3.5; df = 36; p < .001). GCII was bimodally distributed, with SRI responders differing from nonresponders (t = 3.9; df = 14; p < .001). GCII accurately classified 90 percent of sertraline responders and 80 percent of nonresponders. Only SRI responders showed GCII sites/cell upregulated after 6 weeks of treatment (t = 2.1, df = 10; p < .05).

1-Naphthylamine

Development of a non-selecting, non-perturbing method to study human brain tumor cell invasion in murine brain.

The infiltrative nature of glial and some meningeal neoplasms is responsible for the failure of surgical removal and high recurrence rate of these tumors. Modeling of this process in vitro and in vivo will lead to a better understanding of the pathophysiology of this process and identify targets for novel therapy directed towards this phenotype. We present the results of the development and refinement of two model systems of tumor invasion: one in vitro barrier assay using the basement membrane extract Matrigel, and one in vivo where molecular detection of tumor cells allows single cell discrimination by in situ hybridization histochemistry. These techniques have strong correlations which validate their utility as measures of nervous system tumor invasion.

Animals

Adolescent health: a report to the U.S. Congress.

This article reports findings from an assessment by the Office of Technology Assessment (OTA), an analytical arm of the U.S. Congress. In brief, OTA found the conventional wisdom that American adolescents as a group are so healthy that they do not require health and related services is not justified. Even more disturbing, U.S. adolescents often face formidable barriers in trying to obtain health care. OTA suggested that Congress could act to 1) increase adolescents' access to health care, most effectively by supporting school- or community-based comprehensive health services specifically for adolescents, 2) restructure and reinvigorate the federal role in adolescent health, most visibly by creating an office of adolescent health in the U.S. Executive branch, and 3) improve adolescents' social environments, by providing more support to the families of adolescents, limiting adolescents' access to firearms, supporting the expansion of recreational opportunities for adolescents, and further supporting opportunities for community service. Congressional actions taken since the release of OTA's report are summarized.

Adolescent

Isolation and partial purification of growth factors with TGF-like activity from human malignant gliomas.

The effect of concentrated conditioned medium from each of eight human malignant glioma cell lines on the growth of indicator cells (normal rat kidney fibroblasts (NRK), clone 14) was determined in monolayer and in soft agar assay systems. The conditioned medium from all cell lines was mitogenic in the monolayer assay, but only SF-210, U-343 MG-A, and U-251 MG produced soluble factors that caused NRK cells to grow in soft agar. The soluble growth-promoting factors from these three cell lines were acid- and heat-stable (60 degrees C for 30 minutes) but were inactivated by trypsin (100 microns/ml) and dithiothreitol (50 microM). The growth factors from SF-210 and U-343 MG-A were further purified by molecular-sieve chromatography. The partially purified growth factor from U-343 MG-A retained transforming growth factor (TGF)-like activity, had a molecular weight of 9 kD, was potentiated by TGF-beta in the soft agar assay, competed effectively with 125I-epidermal growth factor (EGF) radiolabeled for the EGF receptor on A 431 epidermoid carcinoma cells, and was completely inhibited by monoclonal antibodies to TGF-alpha. The partially purified growth factor from SF-210 had a molecular weight of 17 kD, was not inhibited by monoclonal antibodies to platelet-derived growth factor (PDGF) or TGF-alpha, and did not bind to a heparin-Sepharose column. These results imply that U-343 MG-A secretes a growth factor with TGF-alpha-like activity, and SF-210 secretes a TGF with neither TGF-alpha nor TGF-beta activity.

Agar