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Biomedical subjects

R J Roberts

Publications and source records attributed to R J Roberts.

At least 181 records · Page 10Linked to original sources
PubMed1986

Phenytoin metabolism in infants following intravenous and oral administration.

The disposition of phenytoin was examined in 7 infants with a mean age of 22 days and a mean weight of 3,756 g. Multiple doses of phenytoin were administered intravenously and/or orally as a part of required medical care. Gas chromatography/mass spectrometry was employed for analyses of phenytoin and three metabolites - 5-(4-hydroxyphenyl)-5-phenylhydantoin, methylated 3,4-catechol, and 3,4-dihydrodiol - in blood, urine, and feces. Data from identical studies previously conducted in adults were utilized for comparison with the infants. The mean phenytoin dose (+/- SD) in infants was 8.1 +/- 4.4 mg/kg/day, and the mean serum concentration (+/- SD) was 4.8 +/- 4.6 micrograms/ml. In adults, the mean dose was 5.3 +/- 0.6 mg/kg/day, and the mean serum concentration was 12.0 +/- 1.9 micrograms/ml. No significant differences were found between infants and adults in the pattern of urinary metabolites or in the total recovery of phenytoin and metabolites in 24-hour urine samples. These results indicate that pathways for phenytoin metabolism are the same in infants and adults. Absorption of an oral dose of phenytoin in infants appeared to be completely based on recoveries of drug and metabolites in urine and on the fact that less than 3% of an oral dose could be found in stools. The results of these studies indicate that the low blood concentrations of phenytoin resulting from the relatively high daily dosage of phenytoin in infants, when compared to adults, cannot be explained on the basis of poor oral absorption of phenytoin. These age-related differences must be due to a relatively high metabolic clearance of the drug in infants.

Administration, Oral↗
PubMed1986

Lipid peroxidation in newborn rabbits: effects of oxygen, lipid emulsion, and vitamin E.

The extent of in vivo lipid peroxidation and the in vivo antioxidant effects of alpha-tocopherol and alpha-tocopheryl acetate were studied in newborn rabbits exposed to one of two oxidant stresses: hyperoxia (FIO2 greater than 0.9) or parenteral lipid emulsion infusion. Lipid peroxidation was monitored by measurement of expired ethane and pentane, tissue thiobarbituric acid (TBA) reactants, and tissue lipid peroxides. Seventy-two h of hyperoxia did not increase any of the parameters of lipid peroxidation although mortality was higher in oxygen exposed animals. alpha-Tocopherol (100 mg/kg, intravenous) lowered expired hydrocarbons and tissue TBA reactants, but raised liver lipid peroxides in both air and hyperoxia exposed pups. Infusion of soybean oil emulsion increased production of ethane and pentane, liver TBA reactants, and lung lipid peroxides. Both alpha-tocopherol and alpha-tocopheryl acetate prevented the soybean oil emulsion induced increase in volatile hydrocarbons. alpha-Tocopherol (100 mg/kg, intravenous) administration also prevented the increase in liver TBA reactants and lung lipid peroxides. In identically treated animals, alpha-tocopheryl acetate administration decreased liver TBA reactants but had no effect on lung lipid peroxides. We conclude that alpha-tocopherol reduces lipid peroxidation in newborn rabbits including animals exposed to hyperoxia or infused with lipid emulsions. alpha-Tocopheryl acetate results in lower tissue alpha-tocopherol concentrations and is less effective as an antioxidant in lipid emulsion infused rabbits.

Animals↗
PubMed1986

An approach to the management of the poisoned patient.

Our systematic approach to the evaluation and treatment of the acutely poisoned patient involves establishing an accurate diagnosis and prognosis that often may be based on quantitation of the blood concentration of the toxic substance. The major feature of this approach is the proper selection of treatment(s) for the poisoned patient, ie, decontamination and supportive care and, in some cases, antidotal therapy and/or active removal of the toxic substance. Invasive, expensive methods of active removal (eg, hemodialysis or hemoperfusion) are generally recommended only if specific criteria are satisfied. Noninvasive, inexpensive methods of active removal (eg, manipulation of urinary pH or the oral administration of multiple doses of activated charcoal) may have significant utility in the treatment of poisoned patients not requiring invasive methods. This systematic approach to the poisoned patient should lead to an effective use of treatment modalities with minimal risks and optimal clinical results.

Acute Disease↗
PubMed1985

Nucleotide sequence of the BsuRI restriction-modification system.

The genes of the 5'-GGCC specific BsuRI restriction-modification system of Bacillus subtilis have been cloned and expressed in E. coli and their nucleotide sequence has been determined. The restriction and modification genes code for polypeptides with calculated molecular weights of 66,314 and 49,642, respectively. Both enzymes are coded by the same DNA strand. The restriction gene is upstream of the methylase gene and the coding regions are separated by 780 bp. Analysis of the RNA transcripts by S1-nuclease mapping indicates that the restriction and modification genes are transcribed from different promoters. Comparison of the amino acid sequences revealed no homology between the BsuRI restriction and modification enzymes. There are, however, regions of homology between the BsuRI methylase and two other GGCC specific modification enzymes, the BspRI and SPR methylases.

Bacillus subtilis↗
PubMed1985

Memory for recent U.S. presidents in patients with cerebral disease.

Four tasks were developed to assess memory for recent U.S. presidents: free recall of presidents' names, naming their photographs, and temporal ordering of their printed names and photographs. The tasks were standardized on a sample of 250 hospital control subjects and administered to 55 patients with cerebral disease. Recall of the presidents' names, a task frequently advocated for mental status examination, was relatively difficult for hospital control patients and was least sensitive to brain disease. None of the brain-damaged patients manifested an isolated retrieval defect. Generalized memory impairment for recent presidents was not found with focal lesions. In the context of a diffuse or bilateral disease, generalized memory impairment for recent presidents was a frequent concomitant of substantial intellectual loss. This brief, multi-task assessment of memory for recent presidents may prove a more useful adjunct to neurobehavioral evaluation than testing simple recall of presidents' names.

Adult↗
PubMed1985

The effect of punch velocity on the compaction of a variety of materials.

The effect of punch velocity over the range 0.033-400 mms-1 on the compaction of a variety of materials has been studied using constants derived from the Heckel equation as criteria to describe their behaviour. For materials known to deform plastically, e.g. maize starch and polymeric materials, there was an increase in the yield pressure with punch velocity attributable to a change either from ductile to brittle behaviour or a reduction in the amount of plastic deformation due to the time dependent nature of plastic flow. For materials known to consolidate by fragmentation, e.g. magnesium and calcium carbonates, there was no change in yield pressure with increasing punch velocity. The data has been analysed in terms of the strain rate sensitivity of the materials calculated from their yield pressure at low and high punch velocities.

Acetaminophen↗
PubMed1985

Tissue vitamin E levels in newborn rabbits after pharmacologic dosing. Influence of dose, dosage form, and route of administration.

Tissue levels of alpha-tocopherol and alpha-tocopheryl acetate were measured in neonatal rabbits using high-performance liquid chromatography after administration of 100 mg/kg once or daily of either alpha-tocopherol or alpha-tocopheryl acetate subcutaneously, orally, or intravenously. Tissues were analyzed at 1, 3, and 6 days after daily dosing was begun. Tissue levels of alpha-tocopherol increased after each dose of alpha-tocopherol; the liver had much higher concentrations than other tissues after subcutaneous or oral administration. Alpha-tocopherol and alpha-tocopheryl acetate given orally produced similar tissue levels of alpha-tocopherol. Intravenous administration of alpha-tocopherol resulted in high concentrations of alpha-tocopherol in the liver, whereas intravenously administered alpha-tocopheryl acetate produced high concentrations of alpha-tocopheryl acetate in the lung. Following intravenous administration of alpha-tocopheryl acetate, only 2-4% of the total vitamin E present in the lung was alpha-tocopherol. From these results we conclude that total dose, dosage form, and route of administration of vitamin E have major influences on tissue vitamin E levels and whether the predominant molecular form is alpha-tocopherol or alpha-tocopheryl acetate. Assuming vitamin E tissue levels and molecular form determine tissue antioxidant activity, total dose, dosage form, and route of administration of vitamin E affect the potential clinical benefits that may result from pharmacologic vitamin E therapy in newborn infants.

Animals↗
PubMed1985

Assessment of lipid peroxidation in newborn infants and rabbits by measurements of expired ethane and pentane: influence of parenteral lipid infusion.

Peroxidation of the unsaturated fatty acid constituents of tissue is one proposed mechanism of in vivo oxidant damage. Products of unsaturated fatty acid peroxidation include the volatile hydrocarbons ethane and pentane. These volatile hydrocarbons are eliminated in expired air and reflect in vivo lipid peroxidation. Newborn infants excrete 16 pmol of ethane per kilogram body weight per minute and 15 pmol of pentane per kilogram body weight per minute. This compares with 1.4 pmol of ethane per kilogram body weight per minute and 1.3 pmol of pentane per kilogram body weight per minute in healthy adult men. Infants receiving total parenteral nutrition including intravenous lipid emulsion excrete more than 100 pmol of pentane per kilogram body weight per minute. Newborn rabbits, delivered at term, also excrete more pentane while receiving lipid emulsion infusion. In the newborn rabbit, the amount of pentane exhaled increases linearly with the dose of lipid emulsion. Blood and tissue thiobarbituric acid reactants are also increased in newborn rabbits after administration of lipid emulsion. These results indicate that lipid peroxidation is quantitatively greater in infants than in adult humans and can be significantly increased by parenteral administration of lipid emulsion.

Adult↗
PubMed1985

Evaluation of an extension set for intermittent intravenous drug delivery to infants.

An intravenous administration set designed for delivery of drug doses to pediatric patients was tested in vitro for the effect of fluid density and flow rate on drug delivery, and delivery of drug by this extension set was compared in vivo with delivery by other methods. Gentamicin (as the sulfate salt) and penicillin G potassium were used to represent low-density and high-density drugs, respectively; a 1-mL solution of each drug, labeled with carbon 14, was tested with each of two primary infusion solutions: 0.45% sodium chloride injection and 10% dextrose injection. The drug dose was injected via a port into a piston-containing chamber from which an equivalent amount of the primary fluid was displaced. Serial samples collected from the end of the filter-containing extension set were analyzed for drug concentration using a liquid scintillation technique. In 12 infants receiving i.v. gentamicin, this delivery method was compared in a randomized crossover trial with delivery by a syringe pump and by i.v. push. Each delivery system was used on one of three consecutive days, and serum gentamicin concentrations were measured by enzyme-multiplied immunoassay. The time required for in vitro delivery of the dose was dependent on flow rate. Density of the drug solution or the primary i.v. fluid did not significantly affect drug delivery. Serum gentamicin concentrations were not significantly different for the three delivery methods, but variability of drug delivery was greatest with the pediatric extension set. This pediatric extension set provides accurate and reliable drug delivery at primary infusion flow rates slower than 10 mL/hr when the drug dosage volume is 2-3 mL or less.

Evaluation Studies as Topic↗
PubMed1985

Factors affecting drug delivery from a syringe-pump infusion set.

In vitro testing of drug delivery via dual-lumen, small-volume i.v. extension tubing designed for use with a syringe pump was conducted. From a dual-lumen extension set with intraluminal diameters of 0.020 inch, effluent samples were collected at 5, 10, and 20 minutes after injection of a 1-mL volume of drug solution intended for delivery over 20 minutes by a syringe infusion pump. Variables were flow rate (5 or 25 mL/hr) of the primary infusion, tubing position (vertical or horizontal), and density of the drug solution (penicillin G potassium 250,000 units/mL and aminophylline 25 mg/mL represented high and low specific gravities, respectively). Each drug solution was labeled with radioactive carbon and the drug content of the effluent was analyzed by liquid scintillation. For each set of variables, samples were also tested after the tubing was flushed with 5% dextrose injection 0.2-0.6 mL. Similar procedures were followed to determine delivery of the labeled penicillin G potassium solution via a dual-lumen extension set with intraluminal diameters of 0.020 inch (for drug) and 0.060 inch (for the primary infusion); a 13-mm-diameter, 0.2 micron filter was attached to the smaller-lumen tubing. A primary infusion flow rate of 5 mL/hr and flush volumes of 0.3 and 0.6 mL were used in this study. To determine the influence of intraluminal diameter on the flush volume required for delivery of a dose of aminophylline (1-mL volume), single-lumen extension tubings with different diameters were tested. The final percentage of the drug dose delivered via the dual-lumen extension set with 0.020-inch lumens was affected only by flush volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Infusions, Parenteral↗
PubMed1984

DNA sequences from the adenovirus 2 genome.

The sequence of 5,839 nucleotides from the adenovirus 2 genome has been determined and includes the regions between coordinates 32-44% and 66-71%. These regions contain the coding sequences for the 52,55K polypeptide, polypeptide IIIa, penton base, and the N terminus of the 100K polypeptide. Several additional unidentified open reading frames are present, including examples which overlap identified reading frames on the complementary strand and on the same strand. In conjunction with previously published sequences and those described in the accompanying papers (Akusjärvi, G., Aleström, P., Pettersson, M., Lager, M., Jöurnvall, H., and Pettersson, U. (1984) J. Biol. Chem. 259, 13976-13979; Aleström, P., Akusjärvi, G., Lager, M., Yeh-kai, L., and Pettersson, U. (1984) J. Biol. Chem. 259, 13980-13985) a complete sequence of 35,937 nucleotide pairs can now be reconstructed for the adenovirus 2 genome.

Adenoviruses, Human↗
PubMed1984

Effect of hyperoxia on phosphatidylcholine synthesis, secretion, uptake and stability in the newborn rabbit lung.

The effects of breathing greater than 95% oxygen from birth for 48 h of life on surfactant phosphatidylcholine synthesis and secretion, as well as uptake and stability of exogenous phosphatidylcholine were studied using rabbit lung tissue slices. Lung slices from animals breathing greater than 95% oxygen for 48 h exhibited a decreased rate of [14C]phosphatidylcholine release (30%) in comparison to lung slices from air-exposed controls. In vitro incorporation of [14C]choline into phosphatidylcholine was decreased by a similar amount in lung slices from pups exposed to greater than 95% oxygen. Uptake of exogenous [14C]phosphatidylcholine by lung slices from hyperoxic-exposed and control groups was not different, and the stability of extracellular phosphatidylcholine was likewise unaffected by hyperoxia. Turnover of labelled phosphatidylcholine taken up by tissue slices from medium was apparently decreased in association with hyperoxic exposure. These results are consistent with multiple sites of effect of hyperoxia on the pulmonary surfactant system in the newborn. These effects of hyperoxia on the lung surfactant system occur at a time of critical adaption to extrauterine life, and thus may have major consequences on lung function and ultimate survival of the premature infant with respiratory distress syndrome.

Animals↗
PubMed1984

Characterization of the major mRNAs from adenovirus 2 early region 4 by cDNA cloning and sequencing.

The sequences at the splice junctions of many early region 4 (E4) mRNAs from adenovirus 2 (Ad2) were determined by analysis of cDNA clones. The cDNAs were synthesized from poly(A)+ mRNA isolated from HeLa cells early during Ad2 infection. A standard library was constructed, in pBR322, from double stranded cDNAs initiated by oligo-dT priming. Approximately 1% of total recombinants contained E4 sequences, however among eighty clones analyzed in detail, only four contained the 5' leader sequence. A second library was prepared using a new method that led to a greatly increased representation of desired clones. This method employed oligo-dT to prime the synthesis of the first strand and an oligonucleotide ligated to pBR322, whose sequence was present in the 5' leader, to prime the synthesis of the second strand. With this method the percentage of recombinants containing E4 sequences ranged between 15 and 50% of the total colonies. Virtually all of these E4 cDNA clones contained the 5' leader sequence and several hundred were analyzed by comparing the results from single channel dideoxy sequencing reactions. Nine unique sequence patterns were identified and representative clones were completely sequenced.

Adenoviruses, Human↗
PubMed1984

Computer programs for handling nucleic acid sequences.

Programs have been developed that will accurately display restriction enzyme maps, open translational reading frames and the results of specific searches on a high resolution graphics terminal (Retrographics VT640). Many of our earlier programs have been upgraded to allow online access to GENBANK, the NIH data bank of DNA sequences and also to deal with sequences of any length. Progress has also been made in the automation of the DNA assembly programs.

Amino Acid Sequence↗
PubMed1984

Preface.

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Journal Article↗