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Biomedical subjects

D L Gilbert

Publications and source records attributed to D L Gilbert.

At least 37 records · Page 2Linked to original sources

Efficacy and mortality in treatment of refractory generalized convulsive status epilepticus in children: a meta-analysis.

There is no consensus on the choice of drug treatment for refractory generalized convulsive status epilepticus in children. The objective of this meta-analysis of the published literature was to determine the effects of drug treatments on efficacy (seizure cessation) and mortality in children with this condition, controlling for potential confounding factors. One hundred eleven children, treated with diazepam, midazolam, thiopental, pentobarbital, or isoflurane, met strict inclusion criteria. Diazepam was significantly less efficacious than other treatments (P = .006) stratifying for etiology. Overall mortality was 20% in symptomatic cases and 4% in idiopathic cases (P = .038). Mortality was less frequent in midazolam-treated patients (P = .021) stratifying for etiology. Midazolam appears to be a good choice for initial treatment of refractory generalized convulsive status epilepticus in children, but the attribution of differences in efficacy and mortality solely to drug effect is not possible based on the published literature.

Adolescent↗

The relationship between optic disc area and open-angle glaucoma: the Baltimore Eye Survey.

PURPOSE: To determine if eyes with larger optic disc area are more likely to have open-angle glaucoma or to have glaucoma at lower intraocular pressure (IOP). METHODS: Data were collected from a population-based sample of adults residing in East Baltimore, consisting of demographic information, ocular examinations, automated and static/kinetic visual field tests, IOP as measured by applanation tonometry, and image analysis of the optic disc. Optic disc area was calculated using refractive error to correct magnification. Open-angle glaucoma was defined by visual field and optic disc criteria. One eye from each of 75 patients with glaucoma was compared to those of 3,518 subjects without glaucoma. RESULTS: Although optic disc area was somewhat larger among patients with glaucoma than control subjects, in a regression model adjusting for age, gender, and race, the significance of this difference had a probability of 0.06. Among patients with glaucoma, disc area was not related to IOP level measured at study examination. CONCLUSION: Disc area is a weak risk factor for open-angle glaucoma. Disc area did not differ between patients with glaucoma who had lower IOP and those who had higher IOP among a group with glaucoma that were identified in a population survey.

Adult↗

Stability of cisatracurium besylate in vials, syringes, and infusion admixtures.

The stability of cisatracurium besylate was studied. Cisatracurium (as besylate) 2 mg/mL in 5- and 10-mL unopened vials and 10 mg/mL in 20-mL unopened vials, as well as 3 mL of solution from additional 2-mg/mL vials, repackaged in 3-mL sealed plastic syringes, was stored at 4 and 23 degrees C in the dark and in normal fluorescent room light. Admixtures of cisatracurium (as besylate) 0.1, 2, or 5 mg/mL in polyvinyl chloride (PVC) minibags of 5% dextrose injection or 0.9% sodium chloride injection were stored at 4 and 23 degrees C in normal fluorescent room light. Triplicate samples for each storage condition were taken initially and at 1, 3, 5, 7, 14, 21, and 30 days; samples from vials were also removed at 45 and 90 days. Solutions were stored in sterile vials at -70 degrees C and then thawed at room temperature before analysis of chemical stability by high-performance liquid chromatography. Physical stability was assessed as well. Cisatracurium besylate was physically stable in all samples throughout the study. Cisatracurium (as besylate) 2 mg/mL exhibited drug losses at 23 degrees C in vials at 45 days and in syringes at 30 days. Cisatracurium (as besylate) 0.1, 2, and 5 mg/mL in 5% dextrose injection and in 0.9% sodium chloride injection was stable for at least 30 days at 4 degrees C, but substantial drug losses occurred at 23 degrees C. Admixtures prepared with cisatracurium (as besylate) 0.1 mg/mL and with 5% dextrose injection exhibited the greatest losses. Cisatracurium besylate was stable in most samples for at least 30 days at 4 and 23 degrees C; admixtures containing cisatracurium (as besylate) 0.1 or 2 mg/mL exhibited substantial drug loss at 23 degrees C.

Atracurium↗

Compatibility and stability of paclitaxel combined with doxorubicin hydrochloride in infusion solutions.

OBJECTIVE: To evaluate the physical compatibility and chemical stability of paclitaxel at concentrations of 300 and 1200 micrograms/mL with doxorubicin hydrochloride 200 micrograms/mL in NaCl 0.9% injection and dextrose 5% injection over 7 days at 4, 23, and 32 degrees C. DESIGN: The test samples were prepared in polyolefin bags of the infusion solutions at the required drug concentrations. Evaluations were performed initially and after 4 hours, and 1, 3, 5, and 7 days of storage at 4, 23, and 32 degrees C for physical and chemical stability. Physical stability was assessed by using visual observation in normal fluorescent light and a high-intensity monodirectional light beam. In addition, turbidity and particle content were measured electronically. Chemical stability of the two drugs was evaluated by using two stability-indicating HPLC analytic techniques. RESULTS: All samples were physically stable through 1 day. However, microcrystalline precipitation of paclitaxel occurred within 3 days in some samples and within 5 days in all samples. Paclitaxel concentrations remained at more than 97% in all samples throughout the study. Doxorubicin hydrochloride also was stable throughout the study period, remaining above 90% in all samples at all storage temperatures. CONCLUSIONS: Admixtures of paclitaxel 300 and 1200 micrograms/mL with doxorubicin hydrochloride are limited in their utility time by paclitaxel microcrystalline precipitation. All combinations were physically and chemically stable for at least 24 hours at 4, 23, and 32 degrees C.

Antineoplastic Combined Chemotherapy Protocols↗

Compatibility of doxorubicin hydrochloride liposome injection with selected other drugs during simulated Y-site administration.

The compatibility of doxorubicin hydrochloride liposome injection with selected other drugs during simulated Y-site administration was studied. Five milliliters of doxorubicin hydrochloride liposome injection 0.4 mg/mL in 5% dextrose injection was combined with 5 mL of each of 82 other drugs in 5% dextrose injection or, if necessary to avoid incompatibilities with the diluent, 0.9% sodium chloride injection. The combinations were examined with the unaided eye in fluorescent light and in high-intensity monodirectional light to enhance visualization of small particles and low-level turbidity. The turbidity of each combination was measured as well. Particle sizing and counting were performed on selected combinations. Evaluations were performed initially and at one and four hours. All combinations were stored at room temperature (approximately 23 degrees C). Most of the test drugs were compatible with doxorubicin hydrochloride liposome injection during the four-hour observation period. However, practitioners should be cautious in administering any drug simultaneously with doxorubicin hydrochloride liposome injection until the integrity of the liposomes can be verified. Eighteen drugs exhibited unacceptable increases or decreases in measured turbidity or particulate formation within four hours. During simulated Y-site administration, doxorubicin hydrochloride 0.4 mg/mL (as the liposomal injection) in 5% dextrose injection was compatible with 64 of 82 other drugs for four hours at approximately 23 degrees C and was incompatible with 18 of the test drugs.

Antibiotics, Antineoplastic↗

Compatibility of remifentanil hydrochloride with selected drugs during simulated Y-site administration.

The compatibility of remifentanil hydrochloride with 90 other drugs during simulated Y-site administration was studied. Five milliliters of remifentanil 25 and 250 micrograms/mL (as hydrochloride) in 0.9% sodium chloride injection or 5% dextrose injection was combined with 5 mL of each of 90 other drugs in 5% dextrose injection of 0.9% sodium chloride injection. Each combination was prepared in duplicate. The combinations were stored at approximately 23 degrees C under fluorescent light and examined with the unaided eye and in high-intensity monodirectional light during the first 15 minutes after preparation and at one and four hours. The turbidity of each combination was measured as well. Particle sizing and counting were performed for selected combinations. Most of the combinations exhibited no haze, turbidity, or color change throughout the study period. Remifentanil 25 micrograms/mL combined with chlorpromazine hydrochloride showed a small increase in haze within four hours. One of the combinations of remifentanil 250 micrograms/mL with cefoperazone sodium was unacceptably hazy within one hour. The combination of remifentanil 250 micrograms/mL with amphotericin B formed a gross precipitate upon mixing. Remifentanil 25 and 250 microgram/mL (as hydrochloride) in 0.9% sodium chloride injection was compatible for four hours at approximately 23 degrees C with all the drugs studied except chlorpromazine hydrochloride (with remifentanil 25 micrograms/mL), cefoperazone sodium (with remifentanil 250 micrograms/mL), and amphotericin B (with remifentanil 250 micrograms/mL in 5% dextrose injection).

Amphotericin B↗

Compatibility of cisatracurium besylate with selected drugs during simulated Y-site administration.

The compatibility of cisatracurium besylate with 91 other drugs during simulated Y-site injection was studied. Five milliliters of cisatracurium 0.1, 2, and 5 mg/mL (as besylate) in 5% dextrose injection was combined with 5 mL of each of 91 drugs in 5% dextrose injection or 0.9% sodium chloride injection. All combinations were prepared in duplicate and stored at approximately 23 degrees C. Samples were visually examined under normal laboratory fluorescent light and, if there was no obvious visual incompatibility, under high-intensity monodirectional light. Turbidity was measured as well. Particle sizing and counting was performed for selected combinations. All evaluations were performed at intervals up to four hours. Cisatracurium besylate at all three concentrations was compatible with most of the drugs tested. However, one drug (cefoperazone) was incompatible with cisatracurium besylate at all three concentrations, 14 (including many cephalosporins) were incompatible with cisatracurium besylate 2 and 5 mg/ mL, and 12 were incompatible with cisatracurium 5 mg/ mL. During simulated Y-site administration, cisatracurium 0.1, 2, and 5 mg/mL (as besylate) in 5% dextrose injection was compatible with 64 of 91 drugs for four hours at approximately 23 degrees C. Twenty-seven drugs were incompatible with cisatracurium besylate at one or more concentrations.

Anti-Infective Agents↗

Compatibility of propofol injectable emulsion with selected drugs during simulated Y-site administration.

The compatibility of a new formulation of injectable propofol with selected other drugs during simulated Y-site injection was studied. Two milliliters of undiluted propofol injectable emulsion was combined with 2 mL of each of 112 other drugs in 5% dextrose injection or 0.9% sodium chloride injection. The liquids were diluted with 6 mL of particle-free high-performance liquid chromatography (HPLC)-grade water and centrifuged for 20 minutes. A pipette connected to a vacuum line was used to remove the fat layer at the top and most of the aqueous phase. The remaining liquid was diluted with 9 mL of particle-free HPLC-grade water to facilitate visualization of any precipitate. The liquids were examined with the unaided eye in fluorescent light and with a Tyndall beam to enhance visualization of small particles. Samples were evaluated during the first 15 minutes and one hour after mixing. Propofol injectable emulsion was compatible with 98 of the 112 drugs testes. Fourteen drugs demonstrated incompatibilities, including precipitation, gel formation, and oiling out of cracked emulsions. During simulated Y-site injection, propofol injectable emulsion was compatible with most other drugs tested for one hour at approximately 23 degrees C

Anesthetics, Intravenous↗

Compatibility of parenteral nutrient solutions with selected drugs during simulated Y-site administration.

The compatibility of 102 drugs with parenteral nutrient (PN) solutions during simulated Y-site administration was studied. Five milliliters of each of four representative PN solutions was combined in duplicate in a 1:1 ratio with 5-mL samples of solutions of 102 drugs in 5% dextrose injection or 0.9% sodium chloride injection. Visual examinations were performed in fluorescent laboratory light and under high-intensity monodirectional light, and turbidity was measured. Particle sizing and counting were performed for selected solutions. All evaluations were performed at intervals up to four hours; storage was at 23 degrees C. Most of the drugs tested were compatible with the PN solutions. However, 20 drugs exhibited various incompatibilities with one or more of the PN solutions. During simulated Y-site administration, four PN solutions were compatible with 82 of 102 drugs for four hours at 23 degrees C. Twenty drugs were incompatible with one or more of the PN solutions.

Drug Incompatibility↗

Compatibility of granisetron hydrochloride with selected drugs during simulated Y-site administration.

The compatibility of granisetron hydrochloride with selected other drugs during simulated Y-site administration was studied. Five milliliters of granisetron 50 micrograms/mL (as the hydrochloride) in 5% dextrose injection was combined with 5 mL of each of 91 secondary additives, including antineoplastics, anti-infectives, and supportive care drugs, in 5% dextrose injection or (if necessary to avoid incompatibility with the diluent) 0.9% sodium chloride injection. Visual examinations were performed with the unaided eye in fluorescent light and in high-intensity monodirectional light to enhance visualization of small particles and low-level turbidity. The turbidity of each solution was measured as well. Particle sizing and counting were performed for selected solutions. Evaluations were performed initially and at one and four hours. Nearly all the test drugs were compatible with granisetron during the four-hour observation period. The granisetron-amphotericin B combination had an unacceptable increase in turbidity upon being mixed. During simulated Y-site administration, granisetron 50 micrograms/mL (as the hydrochloride) in 5% dextrose injection was compatible with 90 of 91 drugs and combination drugs for four hours at room temperature; the exception was amphotericin B.

Antiemetics↗

Polyribonucleotides induce nitric oxide production by human monocyte-derived macrophages.

Cytokine-mediated activation of inducible nitric oxide synthase (iNOS) in monocytes or macrophages is species specific. In contrast to rat or mouse, human macrophages do not produce measurable levels of nitric oxide (NO) when induced by inflammatory mediators. Exposure to noncytokine mediators such as tumor cells or viruses, however, has recently been shown to activate human iNOS. NO production in response to these mediators is much lower than that seen for rat or mouse cells and often requires several days of stimulation. We have found that the synthetic, doublestranded polyribonucleotide polyinosinic-polycytidilic acid (Poly I:C), commonly used to mimic viral exposure, activated iNOS in human monocyte-derived macrophages (MDM). The production of NO, measured by nitrite accumulation, was detected after 24 h of stimulation with Poly I:C. The single-stranded polyribonucleotide Poly I, but not Poly C, also increased NO production. Nitrite production was enhanced when the MDM were primed (pretreated) with gamma or alpha interferon or other immune mediators such as IL-4 and was reduced by the iNOS inhibitor, N-methyl-L-arginine (L-NMMA). The use of Poly I:C to initiate NO production in human macrophages provides a useful tool to study the differences between the commonly used animal models and human cells and may provide insight into the pathophysiological significance of these differences.

Cells, Cultured↗

Compatibility and stability of paclitaxel combined with cisplatin and with carboplatin in infusion solutions.

OBJECTIVE: To evaluate the physical compatibility and chemical stability of paclitaxel at concentrations of 0.3 and 1.2 mg/mL with cisplatin 0.2 mg/mL in NaCl 0.9% injection and with carboplatin 2 mg/mL in NaCl 0.9% injection and dextrose 5% injection over 7 days at 4, 23, and 32 degrees C. DESIGN: The test samples were prepared in polyolefin bags of the infusion solutions at the required drug concentrations. Evaluations were performed initially and after 4 hours, and 1, 3, 5, and 7 days of storage at temperatures of 4, 23, and 32 degrees C for physical and chemical stability. Physical stability was assessed by using visual observation in normal light and using a high-intensity monodirectional light beam. In addition, turbidity and particle content were measured electronically. Chemical stability of the three drugs was evaluated by using three stability-indicating HPLC analytical techniques. RESULTS: All samples were physically stable through 1 day. However, microcrystalline precipitation of paclitaxel occurred in 3 days in some samples and within 5 days in all samples. Paclitaxel concentrations remained above 90% in all samples throughout the study. Cisplatin admixtures exhibited paclitaxel concentration-dependent decomposition with cisplatin losses of approximately 5-8% in 4 hours and approximately 20% in 1 day at 23 and 32 degrees C in the paclitaxel 1.2 mg/mL admixtures. With paclitaxel 0.3 mg/mL in the admixtures, cisplatin losses were about 10% in 7 days at these temperatures. Carboplatin in admixtures with both concentrations of paclitaxel was stable for 7 days at 4 degrees C, but sustained losses of about 10% and 12% in 3 days at 23 and 32 degrees C, respectively. CONCLUSIONS: Admixtures of paclitaxel 0.3 and 1.2 mg/mL with cisplatin and carboplatin are limited in their utility time by both paclitaxel microcrystalline precipitation and decomposition of cisplatin and carboplatin. The admixture of paclitaxel 1.2 mg/mL with cisplatin 0.2 mg/mL in NaCl 0.9% injection exhibits unacceptable cisplatin loss in 24 hours. All other combinations were physically and chemically stable for at least 24 hours at 4, 23, and 32 degrees C.

Antineoplastic Agents↗

Stability of thiotepa (lyophilized) in 5% dextrose injection at 4 and 23 degrees C.

The stability of thiotepa (lyophilized) 0.5 and 5 mg/mL in 5% dextrose injection was studied. Vials of lyophilized thiotepa were reconstituted with sterile water for injection to yield a solution with a nominal 10-mg/mL drug concentration. The reconstituted solution was filtered and diluted in 5% dextrose injection in polyvinyl chloride and polyolefin bags to nominal thiotepa concentrations of 0.5 and 5 mg/mL. Triplicate test admixtures were prepared and stored at 4 or 23 degrees C in normal fluorescent light. Initially and after four and eight hours and 1, 3, 7, and 14 days, samples were removed for visual evaluation, turbidimetry, and stability-indicating high-performance liquid chromatography. No incompatibilities were observed. Admixtures containing thiotepa 0.5 mg/mL retained at least 90% of the initial drug concentration for eight hours at either temperature in either type of container; after 24 hours, losses ranged from 10% to 17%. Thiotepa in the 5-mg/mL admixtures was stable for 3 days at 23 degrees C and 14 days at 4 degrees C in both container types. Thiotepa (lyophilized) 0.5 mg/mL in 5% dextrose injection was stable for eight hours at 4 or 23 degrees C. Thiotepa (lyophilized) 5 mg/mL in 5% dextrose injection was stable for 3 days at 23 degrees C and 14 days at 4 degrees C.

Antineoplastic Agents, Alkylating↗