PubMed Health⌕ Search

Biomedical subjects

D L Gilbert

Publications and source records attributed to D L Gilbert.

At least 19 recordsLinked to original sources
PubMed2006

Altered mesolimbocortical and thalamic dopamine in Tourette syndrome.

We used [F-18]fallypride PET in six adults with Tourette syndrome and age-matched controls to assess extrastriatal dopamine 2 (D2) receptors. D2 receptor availability was significantly lower in the orbitofrontal cortex, primary motor cortex, anterior cingulate gyrus, mediodorsal nucleus of thalamus, and hippocampus, areas important for motivation and reward, sensory gating, movement, and attention. Altered dopaminergic function in mesolimbocortical systems and thalamus may contribute to increased motivational salience of tics.

Adolescent↗
PubMed2005

Atomoxetine treatment in children and adolescents with ADHD and comorbid tic disorders.

OBJECTIVE: To test the hypothesis that atomoxetine does not significantly worsen tic severity relative to placebo in children and adolescents with attention deficit/hyperactivity disorder (ADHD) and comorbid tic disorders. METHODS: Study subjects were 7 to 17 years old, met Diagnostic and Statistical Manual of Mental Disorders-IV criteria for ADHD, and had concurrent Tourette syndrome or chronic motor tic disorder. Patients were randomly assigned to double-blind treatment with placebo (n = 72) or atomoxetine (0.5 to 1.5 mg/kg/day, n = 76) for up to 18 weeks. RESULTS: Atomoxetine treatment was associated with greater reduction of tic severity at endpoint relative to placebo, approaching significance on the Yale Global Tic Severity Scale total score (-5.5 +/- 6.9 vs -3.0 +/- 8.7, p = 0.063) and Tic Symptom Self-Report total score (-4.7 +/- 6.5 vs -2.9 +/- 5.2, p = 0.095) and achieving significance on the Clinical Global Impressions (CGI) tic/neurologic severity scale score (-0.7 +/- 1.2 vs -0.1 +/- 1.0, p = 0.002). Atomoxetine patients also showed greater improvement on the ADHD Rating Scale total score (-10.9 +/- 10.9 vs -4.9 +/- 10.3, p < 0.001) and CGI severity of ADHD/psychiatric symptoms scale score (-0.8 +/- 1.1 vs -0.3 +/- 1.0, p = 0.015). Discontinuation rates were not significantly different between treatment groups. Atomoxetine patients had greater increases in heart rate and decreases of body weight, and rates of treatment-emergent decreased appetite and nausea were higher. No other clinically relevant treatment differences were seen in any other vital sign, adverse event, or electrocardiographic or laboratory measures. CONCLUSIONS: Atomoxetine did not exacerbate tic symptoms. Rather, there was some evidence of reduction in tic severity with a significant reduction of attention deficit/hyperactivity disorder symptoms. Atomoxetine treatment appeared safe and well tolerated.

Adolescent↗
PubMed2004

Valproic acid blood genomic expression patterns in children with epilepsy - a pilot study.

OBJECTIVE: Valproic acid (VPA) is a commonly used anticonvulsant with multiple systemic effects. The purpose of this pilot study is to examine the blood genomic expression pattern associated with VPA therapy in general and secondly VPA efficacy in children with epilepsy. MATERIALS AND METHODS: Using oligonucleotide microarrays, gene expression in whole blood was assessed in pediatric epilepsy patients following treatment with VPA compared with children with epilepsy prior to initiation of anticonvulsant therapy (drug free patients). RESULTS: The expression of 461 genes was altered in VPA patients (n = 11) compared with drug free patients (n = 7), among which a significant number of serine threonine kinases were down-regulated. Expression patterns in children seizure free on VPA therapy (n = 8) demonstrated 434 up-regulated genes, many in mitochondria, compared with VPA children with continuing seizures (n = 3) and drug free seizure patients (n = 7). CONCLUSION: VPA therapy is associated with two significant and unique blood gene expression patterns: chronic VPA monotherapy in general and a separate blood genomic profile correlated with seizure freedom. These expression patterns provide new insight into previously undetected mechanisms of VPA anticonvulsant activity.

Adolescent↗
PubMed2003

Tic reduction with pergolide in a randomized controlled trial in children.

OBJECTIVE: To determine whether pergolide, a mixed D1/D2/D3 dopamine agonist, is efficacious and safe in the treatment of children with chronic tic disorders and Tourette syndrome. BACKGROUND: Neuroleptics, which block dopamine transmission, are currently used to treat children with severe tics, but major side effects and limited efficacy reduce clinical utility. Prior open-label and crossover studies of pergolide suggest potential benefit. METHODS: The authors enrolled 57 children and adolescents, ages 7 to 17 years, randomizing them in a 2:1 ratio to either pergolide (0.15 to 0.45 mg per day) or placebo. Tic symptoms had to be >30 on the Yale Global Tic Severity Scale (YGTSS). The primary outcome measure was change in tic severity assessed by YGTSS. RESULTS: Compared to placebo treatment, pergolide treatment was associated with lower tic severity scores (treatment effect 8.8, pergolide vs placebo; 95% CI 0.1 to 17.6; p = 0.05) and attention-deficit hyperactivity disorder symptoms scores (treatment effect 3.8; 95% CI 0.7 to 6.8; p = 0.02). No patient had a serious adverse event and pergolide was well tolerated. CONCLUSIONS: In this randomized, placebo-controlled trial, pergolide appeared to be an efficacious and safe medication for tic reduction in children, and may also improve attention-deficit hyperactivity disorder symptoms.

Adolescent↗
PubMed2000

Cardiac complications in pediatric patients on the ketogenic diet.

Cardiac complications of the ketogenic diet, in the absence of selenium deficiency, have not been reported. Twenty patients on the ketogenic diet at one institution were investigated. Prolonged QT interval (QTc) was found in 3 patients (15%). There was a significant correlation between prolonged QTc and both low serum bicarbonate and high beta-hydroxybutyrate. In addition, three patients had evidence of cardiac chamber enlargement. One patient with severe dilated cardiomyopathy and prolonged QTc normalized when the diet was discontinued.

3-Hydroxybutyric Acid↗
PubMed2000

Effect of process parameters on compressibility of granulation manufactured in a high-shear mixer.

Various processing variables that can influence granulation characteristics of a lactose-based formulation were evaluated using a Plackett-Burman experimental design. These parameters were impeller speed, granulating solution addition rate, total amount of water added in the granulation step, wet massing time, moisture content of the granulation after drying, and screen size used for the dry milling. Results showed that granulation growth was enhanced by the increase in the amount of added water, high impeller speed, and short wet massing time. On the other hand, moisture content had the largest impact on granulation compressibility, followed by the wet massing time and impeller speed. Increasing moisture content of the granulation and decreasing wet massing time or impeller speed increased granulation compressibility. Increasing impeller speed and/or wet massing time decreased granule porosity and fragmentation propensity, which led to decreased granulation compressibility. Granulation compressibility was extremely sensitive to processing conditions. Tablets from all runs showed acceptable weight variation and friability, suggesting that the parameters evaluated had little effect on these responses in the ranges tested.

Drug Compounding↗
PubMed2000

Tourette's syndrome improvement with pergolide in a randomized, double-blind, crossover trial.

OBJECTIVE: To determine whether pergolide, a mixed D1-D2-D3 dopamine agonist, is efficacious and safe in the treatment of children with Tourette's syndrome. BACKGROUND: Neuroleptics, which block dopamine transmission, are currently used for treatment of children with severe tics, but major side effects and limited efficacy reduce clinical utility. Prior open-label reports of pergolide suggest potential benefit. METHODS: The authors enrolled 24 children age 7 to 17 years with Tourette's disorder, chronic motor tic disorder, or chronic vocal tic disorder by Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria, plus severity criteria on the Yale Global Tic Severity Scale (YGTSS) of > or =20, in a double-blind, placebo-controlled, crossover study. Children were randomized to receive either placebo or up to 300 microg/day pergolide for the first 6-week treatment period, with a 2-week placebo washout, followed by crossover to the alternate treatment. The primary outcome measure was tic severity assessed by YGTSS. RESULTS: Compared with placebo treatment, pergolide treatment was associated with significantly lower YGTSS scores (42.0 +/- 20.4 versus 23.5 +/- 18.7; F = 12.0, df = 1, 17, p = 0.0011). No patient had a serious adverse event and pergolide was well tolerated. CONCLUSIONS: In this randomized, placebo-controlled, crossover trial, pergolide appeared to be a safe and efficacious treatment for Tourette's syndrome in children.

Adolescent↗
PubMed2000

An EEG should not be obtained routinely after first unprovoked seizure in childhood.

OBJECTIVE: To quantify and analyze the value of expected information from an EEG after first unprovoked seizure in childhood. BACKGROUND: An EEG is often recommended as part of the standard diagnostic evaluation after first seizure. METHODS: A MEDLINE search from 1980 to 1998 was performed. From eligible studies, data on EEG results and seizure recurrence risk in children were abstracted, and sensitivity, specificity, and positive and negative predictive values of EEG in predicting recurrence were calculated. Linear information theory was used to quantify and compare the expected information from the EEG in all studies. Standard test-treat decision analysis with a treatment threshold at 80% recurrence risk was used to determine the range of pretest recurrence probabilities over which testing affects treatment decisions. RESULTS: Four studies involving 831 children were eligible for analysis. At best, the EEG had a sensitivity of 61%, a specificity of 71%, and an expected information of 0.16 out of a possible 0.50. The pretest probability of recurrence was less than the lower limit of the range for rational testing in all studies. CONCLUSIONS: In this analysis, the quantity of expected information from the EEG was too low to affect treatment recommendations in most patients. EEG should be ordered selectively, not routinely, after first unprovoked seizure in childhood.

Adolescent↗
PubMed2000

Fifty years of radical ideas.

My role in the free radical theory of oxygen toxicity is discussed. Rebeca Gerschman and I published several papers on this subject. This sparked my interest in geochemistry and I developed the idea that oxygen was the best qualified biological potential energy source for the following reasons: great abundance, easily accessible, possession of a high thermodynamic potential, and its slow reaction rate. Ionization radiation can be viewed as a catalyst for reactive oxygen species since a killing dose imparts an infinitesimal small amount of energy. Next, Carol A. Colton and I showed that in the mammalian brain that stimulated microglia produce the superoxide radical anion and its implications in Alzheimer's disease is discussed. More recently, I have become interested in the role of sulfhydryl groups in transcription factors.

Alzheimer Disease↗
PubMed2000

Microglial contribution to oxidative stress in Alzheimer's disease.

Microglia are the CNS macrophage and are a primary cellular component of plaques in Alzheimer's disease (AD) that may contribute to the oxidative stress associated with chronic neurodegeneration. We now report that superoxide anion production in microglia or macrophages from 3 different species is increased by long term exposure (24 hours) to A beta peptides. Since A beta competes for the uptake of opsonized latex beads and for the production of superoxide anion by opsonized zymosan, a likely site of action are membrane receptors associated with the uptake of opsonized particles or fibers. The neurotoxic fibrillar peptides A beta (1-42) and human amylin increase radical production whereas a non-toxic, non-fibrillar peptide, rat amylin, does not. We also report that the effect of A beta peptides on superoxide anion production is not associated with a concomitant increase in nitric oxide (NO) production in either human monocyte derived macrophages (MDM) or hamster microglia from primary cultures. Since NO is known to protect membrane lipids and scavenge superoxide anion, the lack of A beta-mediated induction of NO production in human microglia and macrophages may be as deleterious as the over-production of superoxide anion induced by chronic exposure to A beta peptides.

Alzheimer Disease↗
PubMed2000

The ketogenic diet: seizure control correlates better with serum beta-hydroxybutyrate than with urine ketones.

The objective of this study was to determine the relationship between beta-hydroxybutyrate levels and seizure control in children on the ketogenic diet. Seventy-four children on the ketogenic diet presenting for routine follow-up visits had blood levels of beta-hydroxybutyrate correlated with their seizure control. Forty-two children admitted for initiation of the ketogenic diet had urine ketones measured by dipstick and correlated with simultaneous blood levels of beta-hydroxybutyrate. Blood beta-hydroxybutyrate levels statistically correlated with seizure control (P = .003). Children with blood beta-hydroxybutyrate levels greater than 4 mmol/L were significantly more likely to have a decrease in seizure frequency than those with levels less than 4 mmol/L. Urine ketones of 4+ (160 mmol/L) were found on dipstick when blood beta-hydroxybutyrate levels exceeded 2 mmol/L. Seizure control correlates with blood beta-hydroxybutyrate levels and is more likely when blood beta-hydroxybutyrate levels are greater than 4 mmo/L. The traditional measurement of urine ketones by dipsticks in children on the ketogenic diet provides a less than optimal assessment of the degree of blood ketosis. Three to four plus (80-160 mmol/L) urine ketones are necessary, but not necessarily sufficient, to achieve optimal seizure control in children on the ketogenic diet. At present, however, urine ketones are the only readily available inexpensive approach to ketone assessment.

3-Hydroxybutyric Acid↗
PubMed2000

Adequacy of a new chlorhexidine-bearing polyurethane central venous catheter for administration of 82 selected parenteral drugs.

OBJECTIVE: To screen 82 commonly used parenteral medications for compatibility with a new chlorhexidine-bearing central venous catheter, the ARROWg+ard Blue Plus. Evaluations were performed for completeness of drug delivery and impact, if any, of the drugs on the amount of chlorhexidine removed from the internal lumens. DESIGN: Drug solutions were prepared in dextrose 5% injection or NaCl 0.9% at common concentrations. Three 10-mL aliquots of each drug solution were delivered over 10 minutes, one aliquot through each lumen of the triple-lumen catheter. The initial drug concentrations of the admixtures and the effluent samples were analyzed by HPLC for chlorhexidine content and for the amount of drug delivered relative to its initial concentration. RESULTS: The delivery of the infusion solutions alone through sample catheters resulted in no more than trace amounts of chlorhexidine in the solution. Background amounts ranged from < 2.5 to 6.1 micrograms/mL in the first 10 mL of solution. Administration of none of the drugs tested resulted in a substantial increase in chlorhexidine delivery. Furthermore, delivery of most of the drugs was at least 95% and usually was in excess of 97% of the initial concentration. Concentrations of five drugs, amikacin sulfate, cefoperazone sodium, cefotaxime sodium, cefepime HCl, and netilmicin sulfate were somewhat lower than the initial concentration (range 91-95%), but were still considered acceptable. CONCLUSIONS: The ARROWg+ard Blue Plus central venous catheter can be recommended for use with all of the 82 parenteral drugs tested.

Catheterization↗
PubMed1999

Chemical stability of an ester prodrug of a glycoprotein IIb/IIIa receptor antagonist in solid dosage forms.

DMP 754 is an ester prodrug of a glycoprotein IIb/IIIa receptor antagonist that undergoes ester and amidine hydrolysis in the presence of excipients. A means for the stabilization of DMP 754 was needed for the formulation of a stable drug product. Incorporation of a pH modifier in the formulation was used to control the microenvironment pH to coincide with that of maximum stability for DMP 754. Stability of tablets and capsules manufactured by (a) trituration process, (b) dry granulation process, and (c) wet granulation process was evaluated in HDPE bottles. Formulations manufactured by the dry and wet granulation processes contained disodium citrate as the pH modifier. Although aqueous wet granulation of a hydrolyzable drug is usually avoided, tablets and capsules manufactured by wet granulation were more stable in this case than those manufactured by the dry granulation process. This was attributed to the more uniform distribution of the pH modifier. Although the compression process resulted in enhanced degradation of the binary blend of DMP 754 and anhydrous lactose, tablets manufactured by the wet granulation process were more stable than capsules manufactured by the same process. Decreasing excipient-to-drug ratio enhanced the stability of tablets manufactured by the wet granulation process.

Amino Acids↗
PubMed1999

Effect of different acids on solid-state stability of an ester prodrug of a IIb/IIIa glycoprotein receptor antagonist.

DMP 754 is an ester prodrug of a fibrinogen glycoprotein IIb/IIIa receptor antagonist. The purpose of this study was to determine whether the addition of acids to blends containing DMP 754 and anhydrous lactose could improve the stability at 40 degrees C/75% relative humidity. DMP 754 drug substance was stable at this accelerated condition. Blending of DMP 754 with anhydrous lactose accelerated the hydrolysis of both the ester and the amidine groups. The pH of a saturated solution of lactose is approximately 6, whereas the pH of maximum solution stability for the drug substance is approximately 4. Acids were incorporated into the blend so that the microenvironment would be more acidic and afford improved drug stability. Addition of acids decreased the rate of hydrolysis of the amidine group and this effect was more pronounced with stronger acids. However, the more acidic ingredients led to more rapid hydrolysis of the ester group.

Amino Acids↗
PubMed1999

Medication cost reduction in children on the ketogenic diet: data from a prospective study.

In a prospective study of the efficacy of the ketogenic diet in children with severe, refractory epilepsy, data were collected on medication changes over 1 year. Cost reductions in medications were calculated over the first year and estimated for a second year. Fifty-seven percent of the children stayed on the diet for 1 year, and 74% of these children had their number of medications reduced. Forty-eight percent of children who stayed on the diet were on no medications at 12 months follow-up. Daily medication costs were reduced by nearly 70%.

Adolescent↗
PubMed1999

Complications and costs of treatment of refractory generalized convulsive status epilepticus in children.

Multiple case series in the literature suggest that benzodiazepines and barbiturates are highly efficacious at stopping seizures. Apparent differences in mortality might not be due solely to drug effect. In this systematic review of the medical literature, we assessed the complications and costs of treatment of refractory status epilepticus in 111 children who met strict inclusion criteria, as part of an effort to provide an evidenced-based recommendation for optimal therapy. All children treated with barbiturates required mechanical ventilation, versus 13% of patients treated with benzodiazepines. Benzodiazepine treatment was associated with pressor use in 3.5% of cases, versus 35% with barbiturate treatment. Midazolam treatment was for the shortest duration and allowed the most rapid return to consciousness. Differences in mean 24-hour drug costs were small compared to savings produced by shorter length of treatment and return to consciousness. Benzodiazepines appear to have higher drug costs but lower complications and overall costs than barbiturates.

Adolescent↗