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Biomedical subjects

D J Freeman

Publications and source records attributed to D J Freeman.

At least 73 records · Page 4Linked to original sources
PubMed1986

Comparison of foscarnet cream, acyclovir cream, and acyclovir ointment in the topical treatment of experimental cutaneous herpes simplex virus type 1 infection.

Topical foscarnet (PFA) and acyclovir (ACV) were compared in the dorsal cutaneous guinea pig model of herpes simplex virus type 1 infection. The relative order of efficacy was PFA cream greater than ACV cream greater than ACV ointment. In vitro studies demonstrated that PFA and ACV formulated in cream vehicles penetrated through guinea pig skin 7- to 10-fold faster than did ACV in ointment.

Acyclovir↗
PubMed1986

Simplified liquid-chromatographic assay of amiodarone and desethylamiodarone after solid-phase extraction.

We describe a rapid, simplified isocratic "high-performance" liquid-chromatographic method for simultaneous measurement of the antiarrhythmic drug amiodarone and its major metabolite, desethylamiodarone, in small volumes of sera (100 microL). Compared with liquid-liquid extraction, the solid-phase method of extraction saves time and glassware and improves reproducibility for small sample volumes. Amiodarone and desethylamiodarone could be measured at concentrations as low as 250 micrograms/L. Standard curves for the drug and metabolite are linear over the range of concentrations found in our patients. Within-run CVs (n = 6) ranged from 2.7% to 4.5% for amiodarone and from 4.0% to 5.7% for desethylamiodarone over the range of 250 to 4000 micrograms/L. Between-run CVs (n = 12) were 8.3% and 5.7% for amiodarone and desethylamiodarone, respectively. Commonly used cardiovascular medications do not interfere with the assay.

Amiodarone↗
PubMed1985

Preclinical assessment of topical treatments of herpes simplex virus infection: 5% (E)-5-(2-bromovinyl)-2'-deoxyuridine cream.

The potential efficacy of topical therapy with (E)-5-w-bromovinyl)-2'-deoxyuridine (BVDU) for cutaneous herpesvirus infection was evaluated in vitro and in guinea pigs. Drug sensitivity testing against herpes simplex virus type 1 strain E115 revealed an ID50 of 0.008 microgram/ml for BVDU and 0.19 microgram/ml for acyclovir (ACV). In vitro drug diffusion studies showed poor penetration of guinea pig skin by BVDU from the cream compared to BVDU from dimethylsulfoxide (DMSO) (0.04 vs. 1.5 microgram/cm2 per h). 5% BVDU cream, 5% BVDU/DMSO, and 5% ACV in polyethylene glycol (PEG) were then compared in the treatment of experimental dorsal cutaneous HSV-1 infection in guinea pigs. Lesion number, total lesion area and virus titer were reduced by all three formulations compared to control sites treated with the corresponding drug vehicles (P less than or equal to 0.01). BVDU cream effected a greater reduction in lesion number (20+ vs. 13%) and total lesion area (40% vs. 28%) than did ACV/PEG and a significantly greater decrease in virus titer (990% vs. 55%, P less than 0.002). BVDU/DMSO was clinically twice as effective as BVDU cream (P less than or equal to 0.01) and reduced lesion virus titers to a similar degree. The results of these studies show that BVDU is a more potent virus-inhibitory agent than ACV in vitro and is superior to topical ACV in vivo when formulated in a simple aqueous cream. The marked efficacy of BVDU/DMSO in the animal model demonstrates the potential of this antiviral if drug delivery is improved.

Absorption↗
PubMed1985

Treatment of recurrent herpes simplex labialis with topical butylated hydroxytoluene.

Butylated hydroxytoluene (BHT) is a hydrophobic compound with in vitro activity against many enveloped viruses, including herpes simplex virus. The effect of topical therapy with 15% BHT in mineral oil on the course of recurrent herpes simplex labialis was examined in 30 patients in a double-blind, placebo-controlled pilot study in which treatment was initiated by the physician. Sixteen patients received BHT and 14 received the placebo mineral oil vehicle. The time from lesion onset to dry crust formation was slightly shorter among BHT recipients than among placebo recipients (2.0 and 2.4 days; P = 0.01). Duration of the vesicle-ulcer stages was likewise shorter (1.2 and 2.0 days; P = 0.09), and lesion virus excretion appeared to be less in the subjects who received BHT than in the controls, but these differences were not significant. There was no clinical or laboratory evidence of toxicity.

Administration, Topical↗
PubMed1985

Comparison of topically applied 5-ethyl-2'-deoxyuridine and acyclovir in the treatment of cutaneous herpes simplex virus infection in guinea pigs.

Three percent 5-ethyl-2'-deoxyuridine (EdU) in an aqueous cream base was compared with 5% acyclovir (ACV) in polyethylene glycol ointment and 3% EdU in 95% dimethyl sulfoxide (DMSO) for efficacy in the topical treatment of an experimental dorsal cutaneous herpes simplex virus type 1 infection in guinea pigs. Topical ACV treatment reduced the mean lesion number by 15%, the lesion area by 32%, and the lesion virus titer by 60% when compared with measurements at contralateral sites treated with the vehicle alone. Application of 3% EdU cream was more beneficial, effecting reductions of 29, 44, and 68% in the same measurements. EdU in DMSO was even more effective, reducing the lesion measurements by 39, 60, and 90%, respectively. The penetration of EdU and ACV through guinea pig skin was compared in single-chamber diffusion cells. In the aqueous cream, EdU readily penetrated excised skin and exhibited rates of flux 10-fold greater than those shown by ACV in ointment formulation (0.56 versus 0.05 microgram/cm2 per h; P = 0.05). The flux of EdU in DMSO was 3.39 micrograms/cm2 per h, six times higher than the flux in the cream vehicle. EdU was more effective than ACV in this experimental animal model, most likely due to better percutaneous drug delivery of EdU from the cream and DMSO vehicles.

Acyclovir↗
PubMed1984

Evaluation of cyclosporin-phenytoin interaction with observations on cyclosporin metabolites.

We have observed that patients on concurrent cyclosporin and phenytoin therapy required increased doses of cyclosporin to maintain therapeutic concentrations of this novel immunosuppressive drug. We have, therefore, studied the influence of phenytoin on the pharmacokinetics of oral cyclosporin in six healthy male subjects. Cyclosporin concentrations in serum and whole blood were measured by high pressure liquid chromatography (h.p.l.c.) and radioimmunoassay (RIA). Concentrations of cyclosporin in whole blood were consistently higher than corresponding values in serum. Concentrations of cyclosporin determined by RIA were also consistently higher than those determined by h.p.l.c. Irrespective of the biological fluid (serum or whole blood) or the type of drug analysis (h.p.l.c. or RIA), changes in cyclosporin kinetics following phenytoin administration exhibited similar patterns. Phenytoin significantly reduced the maximum concentration and the area under the concentration-time curve and significantly increased total body clearance of cyclosporin. There was a statistically significant reduction of cyclosporin half-life (t 1/2) in whole blood using h.p.l.c. analysis. However, there was no significant change in cyclosporin t 1/2 in serum following phenytoin administration, using either form of drug analysis. Cyclosporin metabolites 17 and 18 were measured by h.p.l.c. in whole blood samples only, since these metabolites were found almost entirely in red blood cells. Phenytoin significantly reduced the Cmax and AUC of both metabolites, but no significant change was observed in the t 1/2 of either. Phenytoin enhanced the metabolism of antipyrine which was co-administered with cyclosporin to assess oxidative enzyme activity. We conclude that patients undergoing organ transplantation should be carefully monitored if they require phenytoin or other drugs known to accelerate oxidative metabolism.

Adult↗
PubMed1983

Estrogen sulfotransferase activity in guinea pig uterus and chorion.

An estrogen sulfotransferase (ST) is detectable in high speed supernatants of pregnant guinea-pig uterus and shows maximum activity between about 47 and 55 days of gestation, with a decrease toward term. No appreciable activity was apparent in the non-pregnant state or before at least 43 days of pregnancy. A considerably higher ST activity is present in chorion as early as 30 days of gestation, and this also decreases toward term. The two ST's exhibit similar KM (0.1-0.13 microM with estrone as substrate) and pI (5.8) values, as well as similar specificities. Estradiol-17 beta and estriol are sulfurylated 82 and 6% that of estrone at equimolar concn. Neither p-nitrophenol nor several neutral steroids are substrates for the enzymes. Enzyme activity is poorly expressed in the absence of thiol groups, the presence of monothioglycerol stimulating uterine and chorion enzymes by 5- and 15-fold, respectively. Stimulation is also observed in the presence of Mg2+, Ca2+ or Mn2+. Chromatofocusing on a poly buffer ion-exchanger from pH 7.4 to 4.0 resulted in elution of a sharp peak of enzyme activity, at pH = 5.8, from both tissues provided that the eluting buffer contained thiol groups and 0.25 M sucrose. This single step resulted in at least a 35- to 100-fold increase in specific activity. The partially purified enzyme from chorion exhibited a KM for estrone of 0.13 microM.

Animals↗
PubMed1983

Simplified liquid-chromotographic analysis for cyclosporin A, and comparison with radioimmunoassay.

We describe a simplified isocratic "high-performance" liquid-chromatographic method for measuring a new immunosuppressive drug, cyclosporin A, in biological fluids with use of its analogs cyclosporin C and cyclosporin D as internal standards. The method is reproducible and accurate and appears to be specific for cyclosporin A; the detection limit is 31 micrograms/L. The chromatographic measurements of the concentration of cyclosporin A in serum of patients receiving the drug were invariably lower than those by radioimmunoassay and the difference became more pronounced the greater the period of time after dosing. Because measurements of cyclosporin A in serum standards were almost identical with both techniques, the differences between the two sets of results for patients' samples suggests that the radioimmunoassay is nonspecific and measures metabolites of cyclosporin A.

Adult↗
PubMed1981

New family of preformed left atrial-coronary catheters for retrograde left atrial catheterization and coronary and/or aortocoronary bypass angiography via brachial artery cutdown.

A previously described preformed No. 7 Ducor catheter for retrograde left atrial catheterization was modified for coronary angiography and used in 358 consecutive patients, 22 of whom had 26 of 51 previous aortocoronary bypass grafts still patent. In 42 patients these catheters were also employed for retrograde left atrial catheterization. Sixty percent of right coronary, 96% of left coronary, and 96% of aortocoronary bypass angiography attempts were successful. Complete left heart study and angiography were accomplished with one catheter in ten patients (2.8%), with two catheters in 200 patients (55.9%), with three catheters in 132 patients (36.9%), and with more than three catheters in 16 patients (4.5%). Except in 4 of 12 patients with aortic valve deformities, left catheterization was achieved whenever attempted. The complication rate was within acceptable limits. Average left heart and angiography procedure and fluoroscopy times were respectively 29.4 and 6.5 minutes. In addition to reconfirming usefulness for retrograde left atrial catheterization, these data demonstrate this family of catheters is useful for coronary-particularly left-and aortocoronary bypass angiography.

Adult↗
PubMed1981

Heparin assay and protamine titration.

By utilizing the fact that heparin and protamine sulfate directly neutralize each other, it is possible to quickly detect excess levels of protamine (anti-heparin activity) by back-titrating a plasma specimen with predetermined amounts of heparin. The approach suggested allows for the simultaneous definition of low levels of heparin, and incorporates an equally rapid and accurate measurement of high heparin concentrations. The methodology presented employs heparin assays using the "Protopath" technic. The concept appears to be applicable to other test systems currently designed to monitor heparin activity.

Blood Coagulation Tests↗
PubMed1980

Analysis of dolichol in human tissues by high pressure liquid chromatography.

Dolichol from human liver was shown by reverse-phase high pressure liquid chromatography to consist of a series of homologues ranging in length from 17 to 23 isoprene units. The two major components, corresponding to 19 and 20 isoprene units, respectively, were isolated and identified by mass spectrometry. Dolichyl palmitate, synthesized from liver dolichol, showed an identical series of peaks with longer retention times. Attempts to chromatography dolichyl phosphate under similar conditions were unsuccessful. Dolichol from uterine tissue and several other human tissues showed a shift toward shorter chain length, with a predominance of homologues containing 18 and 19 isoprene units.

Chromatography, High Pressure Liquid↗