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Biomedical subjects

K Crawford

Publications and source records attributed to K Crawford.

67 records · Page 4Linked to original sources
PubMed1987

Effects of topical PGF2 alpha on aqueous humor dynamics in cynomolgus monkeys.

Single topical applications of prostaglandin F2 alpha (PGF2 alpha) tromethamine salt to living cynomolgus monkey eyes reduced intraocular pressure (IOP). Twice daily topical application was far more effective, so that after the 7th 50 micrograms or 100 micrograms dose on day 4, IOP fell 40-50%, to 8-10 mm Hg. Following twice daily application of 50 or 100 micrograms for greater than 3 days: (1) no increase in total outflow facility could be demonstrated by 2-level constant pressure perfusion or Schiotz tonography; (2) no decrease in aqueous humor formation rate could be demonstrated by fluorophotometry--rather, aqueous flow may have increased; (3) anterior chamber aqueous humor protein concentration was unaltered, but entry of intravenously injected fluorescein into the cornea and anterior chamber tended to increase; (4) there was a weak but sometimes statistically significant miosis of up to approximately 0.5 mm. We conclude that in the cynomolgus monkey: (1) PGF2 alpha is a potent ocular hypotensive agent with only very weak miotic and blood-aqueous barrier-disrupting effects; (2) the ocular hypotensive action of PGF2 alpha is definitely not due to increased conventional outflow facility or decreased aqueous production, but probably to increased uveoscleral drainage of aqueous humor.

Administration, Topical↗
PubMed1983

Hypnosis and lateral cerebral function as assessed by dichotic listening.

In a replication of Frumkin et al. we investigated the hypothesis that hypnosis may facilitate a shift in brain hemispheric dominance, as assessed by right-ear dominance shifts in a dichotic listening paradigm. Eight low, 13 medium, and 8 high hypnotizables, as assessed by the Stanford Hypnotic Susceptibility Scale, Form C, were given the Berlin et al. dichotic tape during two waking conditions and following an alert hypnotic induction. Results contradicted Frumkin et al. In contrast, low hypnotizables showed a significant reduction in right-ear dominance, suggestive of greater participation of the right cerebral hemisphere following hypnotic induction. Highs and mediums did not change. Discussion centers around procedural differences between the two studies (particularly type of hypnotic induction and instructions to attend to one or both ears) and the possible influence of relaxation/anxiety levels upon lateral shifts in cerebral function.

Adult↗
PubMed1979

Prevention of the mutagenic activation of an antischistosomal isothiocyanate in primates by an antibiotic.

Administration of 4 nitro-4' isothiocyano-diphenylamine (CGP 4540, amoscanate) to two nonhuman primates, Macaca mulatta and Cebus apella, resulted in the appearance of mutagenic material in the urines of these animals. Mutagenic metabolites of this drug could also be detected in the urines when the drug was administered to primates infected with Schistosoma mansoni and Schistosoma japonicum. As observed previously in mice, the mutagenic activation of amoscanate can be prevented in primates by coadministration of a single oral dose of erythromycin with no concomitant reduction in antischistosomal activity. The protective effect of erythromycin was confirmed in several crossover experiments. This dissociation of mutagenic from chemotherapeutic effects provides an opportunity to reduce serious potential long-term risks of this antischistosomal drug.

Aniline Compounds↗
PubMed1976

Kinetic properties of Serratia marcescens adenosine 5'-diphosphate glucose pyrophosphorylase.

The regulatory properties of partially purified adenosine 5'-diphosphate-(ADP) glucose pyrophosphorylase from two Serratia marcescens strains (ATCC 274 and ATCC 15365) have been studied. Slight or negligible activation by fructose-P2, pyridoxal-phosphate, or reduced nicotinamide adenine dinucleotide phosphate (NADPH) was observed. These compounds were previously shown to be potent activators of the ADPglucose pyrophosphorylases from the enterics, Salmonella typhimurium, Enterobacter aerogenes, Enterobacter cloacae, Citrobacter freundii, Escherichia aurescens, Shigella dysenteriae, and Escherichia coli. Phosphoenolpyruvate stimulated the rate of ADPglucose synthesis catalyzed by Serratia ADPglucose pyrophosphorylase about 1.5- to 2-fold but did not affect the S0.5 values (concentration of substrate required for 50% maximal stimulation) of the substrates, alpha-glucose-1-phosphate, and adenosine 5'-triphosphate. Adenosine 5'-monophosphate (AMP), a potent inhibitor of the enteric ADPglucose pyrophosphorylase, is an effective inhibitor of the S. marcescens enzyme. ADP also inhibits but is not as effective as AMP. Activators of the enteric enzyme counteract the inhibition caused by AMP. This is in contrast to what is observed for the S. marcescens enzyme. Neither phosphoenolpyruvate, fructose-diphosphate, pyridoxal-phosphate, NADPH, 3-phosphoglycerate, fructose-6-phosphate, nor pyruvate effect the inhibition caused by AMP. The properties of the S. marcescens HY strain and Serratia liquefaciens ADPglucose pyrophosphorylase were found to be similar to the above two S. marcescens enzymes with respect to activation and inhibition. These observations provide another example where the properties of an enzyme found in the genus Serratia have been found to be different from the properties of the same enzyme present in the enteric genera Escherichia, Salmonella, Shigella, Citrobacter, and Enterobacter.

1,4-alpha-Glucan Branching Enzyme↗
PubMedDate not supplied

Polymer-supported tetrafluorophenol: a new activated resin for chemical library synthesis.

A new tetrafluorophenol activated resin that facilitates the use of 19F NMR to quantitate loading is presented. This new resin provides a useful tool for acylation, and a novel activated polymeric sulfonate ester to generate sulfonamides. This activated resin reacts with a wide scope of N-nucleophiles including primary and secondary amines, and anilines. This new activated resin methodology provides a powerful tool for pure single-compound library synthesis.

Journal Article↗
PubMedDate not supplied

Severe lumbar lordosis after dorsal rhizotomy.

Two children with spastic quadriplegia who developed excessive lumbar lordosis after selective dorsal rhizotomy are described. The rhizotomy did not change the ambulatory status of either child (one nonambulator, one household ambulator). Preservation of unopposed hip flexion in the presence of multiple laminectomies may lead to the development of a lordotic deformity in children who sit most of the time. Excessive lumbar lordosis may cause pain and difficulty in sitting. Surgical correction of this deformity is complex because of the removal of posterior elements during the rhizotomy.

Adolescent↗
PubMedDate not supplied

The development of human fetal dorsal root ganglia in vitro: the first 20 days.

Human fetal dorsal root ganglia aged from 8 to 12 weeks post-menstrual were grown in vitro for up to 20 days. Outgrowth of Schwann cells, axons and fibroblasts occurred after 4 h. By the 7th day in vitro Schwann cells enclosed bundles of axons and after 10 days some Schwann cells were seen to enclose individual axons. By the 20th day in vitro there was still a predominance of Schwann cells enclosing axonal bundles, but there were more individual axons ensheathed by three or four turns of Schwann cells. This arrangement mimics the early development in vivo of human dorsal root ganglia and provides the potential for an experimental system utilizing human nervous tissue rather than non-human animal models.

Axons↗
PubMedDate not supplied

Emerging role of the pediatric nurse practitioner in acute care.

The pediatric nurse practitioner role in the tertiary setting is one of several emerging roles gaining recognition in the various groups of advanced practice nursing programs today. The advanced practice nurse (APN) who is a pediatric nurse practitioner (PNP) in an acute care setting helps to provide cost-effective, quality patient care for critically and chronically ill children who are in these settings. The foundation of advanced practice nursing in this role incorporates the general role expectations of advanced nursing preparation, including case management, clinical pathway development, consultation and education, research, and collaboration, with the specific knowledge and skills of the pediatric nurse practitioner to function effectively with sick children in the acute care areas.

Case Management↗
PubMedDate not supplied

Terfenadine metabolism in human liver. In vitro inhibition by macrolide antibiotics and azole antifungals.

To determine whether the clinical adverse interactions of terfenadine with azole antifungals and macrolide antibiotics may be related to inhibition of terfenadine biotransformation, an in vitro system was developed to follow the metabolism of terfenadine by rat liver S9 or human liver microsomes. When test compounds were coincubated with terfenadine, the metabolites formed and unchanged terfenadine was quantitatively analyzed by HPLC. Five metabolites of terfenadine were formed by rat liver S9: predominantly alcohol metabolite (III), with four minor metabolites--azacyclonol (I), acid metabolite (II), an unidentified metabolite (IV), and a new ketone metabolite (V). By human liver microsomes, two major metabolites were formed: azacyclonol (I) and alcohol metabolite (III). Ketoconazole, fluconazole, itraconazole, erythromycin, clarithromycin, and troleandomycin potently inhibited terfenadine metabolism by human liver (IC50 = 4-10 microM), but inhibition by rat liver was weaker (IC50 = 87-218 microM) and 18% maximally for troleandomycin. Other CYP3A substrates (cyclosporin A, naringenin, and midazolam) also demonstrated potent inhibition of terfenadine biotransformation in human liver microsomes (IC50 = 17-24 microM). Substrates of other P450 families [sparteine (CYP2D6), caffeine (CYP1A), and diclofenac (CYP2C)] only very weakly inhibited terfenadine metabolism. Dixon plot analyses for human liver revealed competitive/reversible inhibition by the azole antifungals and macrolide antibiotics of azacyclonol and alcohol metabolite formations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Effects of restricting levothyroxine dosage strength availability.

We conducted a prospective, randomized, controlled trial to assess whether hospital formulary restrictions involving limiting dosage strengths of levothyroxine affect physicians' ability to manage patients effectively and provide pharmacy cost savings in a tertiary care federal government research hospital. Thirty-three endocrinologists were randomly assigned to prescribe levothyroxine from a restrictive (dosage strengths of 25, 50, 100, 125, and 150 micrograms) or a nonrestrictive (dosage strengths of 25, 50, 75, 100, 112, 125, 150, 175, 200, and 300 micrograms) formulary through a central computer system. Their 241 respective outpatients' laboratory results and drug compliance were outcome measures. Achievement of treatment objectives was measured by thyroid function tests (free and total thyroxine, total triiodothyronine, thyrotropin), number of clinic visits, and compliance (survey method). Additional measures were drug distribution patterns, drug costs, and pharmacy inventory costs. Restriction of levothyroxine's dosage strength did not significantly alter therapeutic outcomes. However, the restricted formulary was associated with more complex dosing regimens, and resulted in no significant cost savings. It is not known whether such restriction would adversely affect the care of patients of nonspecialists. Prospective studies are required to verify presumed cost-containment measures before such measures are adopted for widespread application.

Adult↗