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Biomedical subjects

D Dougherty

Publications and source records attributed to D Dougherty.

At least 19 recordsLinked to original sources

Use of the Multiple Sclerosis Functional Composite to predict disability in relapsing MS.

OBJECTIVE: To determine whether the MS Functional Composite (MSFC) can predict future disease progression in patients with relapsing remitting MS (RR-MS). BACKGROUND: The MSFC was recommended by the Clinical Outcomes Assessment Task Force of the National MS Society as a new clinical outcome measure for clinical trials. The MSFC, which contains a test of walking speed, arm dexterity, and cognitive function, is expressed as a single score on a continuous scale. It was thought to offer improved reliability and responsiveness compared with traditional clinical MS outcome measures. The predictive value of MSFC scores in RR-MS has not been determined. METHODS: The authors conducted a follow-up study of patients with RR-MS who participated in a phase III study of interferon beta-1a (AVONEX) to determine the predictive value of MSFC scores. MSFC scores were constructed from data obtained during the phase III trial. Patients were evaluated by neurologic and MRI examinations after an average interval of 8.1 years from the start of the clinical trial. The relationships between MSFC scores during the clinical trial and follow-up status were determined. RESULTS: MSFC scores from the phase III clinical trial strongly predicted clinical and MRI status at the follow-up visit. Baseline MSFC scores, and change in MSFC score over 2 years correlated with both disability status and the severity of whole brain atrophy at follow-up. There were also significant correlations between MSFC scores during the clinical trial and patient-reported quality of life at follow-up. The correlation with whole brain atrophy at follow-up was stronger for baseline MSFC than for baseline EDSS. CONCLUSION: MSFC scores in patients with RR-MS predict the level of disability and extent of brain atrophy 6 to 8 years later. MSFC scores may prove useful to assign prognosis, monitor patients during early stages of MS, and to assess treatment effects.

Adult↗

Photodynamic therapy for chest wall progression from breast carcinoma is an underutilized treatment modality.

BACKGROUND: Chest wall progression of breast carcinoma after failure of salvage surgery, radiation, and chemohormonal therapy is a quagmire with limited therapeutic options. Because photodynamic therapy (PDT) offers excellent results in cutaneous lesions, PDT may play a role in this indication. However, to the authors' knowledge, published data for this subgroup of patients using the only commercially available photosensitizing agent, Photofrin, often show high treatment morbidity, limiting PDT's usefulness. The authors report the feasibility of decreasing the photosensitizer drug dose as a means of exploiting photobleaching kinetics to improve the therapeutic ratio for these individuals. METHODS: One hundred two chest wall sites were treated with PDT after failure of multimodality salvage therapy. In these 9 patients, lesion size ranged from 0.57 to 9 cm. Photodynamic therapy consisted of outpatient intravenous infusion of 0.8 mg/kg of Photofrin, followed 48 hours later by 630 nm light treatment of 135-170 J/cm2 delivered by a KTP:YAG laser coupled to dye unit. Two patients underwent a second PDT procedure due to new lesion formation. All patients were observed for a minimum of 6 months, and none was lost to follow-up. RESULTS: Photodynamic therapy was well tolerated with no photosensitivity reported. Despite all patients having failed surgery, full dose radiation and multiagent chemohormonal therapy, chest wall lesions healed with no scarring. Only 1 (9 cm) lesion took longer than 3 months to granulate over. The authors were able to evaluate all treatment sites, and complete response, defined as total lesion elimination, was noted in 89% of the lesions; reduction without regrowth occurred in 8% with no response in 3% of the lesions. CONCLUSIONS: Despite having prior treatment and fragile tissues, low dose Photofrin-induced PDT offers excellent clinical response with minimal morbidity. These results show that PDT should play an important role in the management of chest wall failure from breast carcinoma.

Adult↗

A report card on quality improvement for children's health care.

OBJECTIVE: Improving the quality of health care is a national priority. Nonetheless, no systematic effort has assessed the status of quality improvement (QI) initiatives for children or reviewed past research in child health care QI. This assessment is necessary to establish priorities for QI programs and research. METHODS: To assess the status of QI initiatives and research, we reviewed the literature and interviewed experts experienced in QI for child health services. We defined QI as activities intended to close the gap between desired processes and outcomes of care and what is actually delivered. We classified reports published between 1985 and 1997 by publication characteristics, study design, clinical problem addressed, site of intervention, the QI method(s) used, and explicit association with a continuous quality improvement program. RESULTS: We reviewed 68 reports meeting our definition of QI. More than half (48) were published after 1994. The reviewed reports included controlled evaluations in 36% of all identified interventions, and 3% of the reports were associated with continuous quality improvement. QI methods demonstrating some effectiveness included reminder systems for office-based preventive services and inpatient pathways for complex care. Reportedly successful QI initiatives more commonly described improvement in administrative measures such as rate of hospitalization or length of stay rather than functional status or quality of life. Interviews found that barriers to QI for children were similar to those for adults, but were compounded by difficulties in measuring child health outcomes, limited resources among public organizations and small provider groups, and relative lack of competition for pediatric tertiary care providers. Research and dissemination of QI for children were seen as less well developed than for adults. CONCLUSIONS: Attempts to improve the quality of child health services have been increasing, and the evidence we reviewed suggests that it is possible to improve the quality of care for children. Nonetheless, numerous gaps remain in the understanding of QI for children, and widespread improvement in the quality of health services for children faces significant barriers.

Acute Disease↗

From breast to baby: quality assurance for breast milk management.

Breast milk is a body fluid capable of transmitting blood-borne pathogens when ingested. High-risk infants are frequently fed mother's expressed breast milk and may be at risk if they receive the wrong mother's milk. A multidisciplinary team at this 42-bed Level III regional NICU developed a quality assurance program and audit aimed at reducing the risk of feeding expressed breast milk (EBM) to the wrong high-risk infant in the unit. Changes to the old system included modernizing the handling, storing, and distribution of EBM. Elimination of feeding errors was the priority. A specific protocol to minimize EBM feeding errors became part of the quality assurance program and is consistent with the recommendations of the NICU multidisciplinary team.

Breast Feeding↗

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↗