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Biomedical subjects

S L Spruance

Publications and source records attributed to S L Spruance.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1985

Pathogenesis of herpes simplex labialis: experimental induction of lesions with UV light.

To develop a model system of herpes simplex labialis which would enable the study of patients before lesion onset, five patients were exposed to various doses of UV light from a sunlamp at their usual site of lesions. Six of 10 treatments resulted in the development of herpes labialis. Three of four treatments with the highest exposure levels led to large, vesicular, virus culture-positive sores. Side effects from sunlamp exposure were minimal.

Herpes Labialis↗
PubMed1984

Pathogenesis of recurrent herpes simplex labialis. IV. Maturation of lesions within 8 hours after onset and implications for antiviral treatment.

In order to define precisely the development of recurrent herpes simplex labialis, we studied 122 untreated or placebo-treated patients who were first seen when their lesions were less than 24 hours old. Subjects were divided into three groups with lesion ages of 0 to 8, 9 to 16, or 17 to 24 hours. Lesion pain, area, and virus titer were determined for each group at the time of the first clinic visit and again on the following day, and the change in lesion severity between visits was examined. The proportion of patients with increasing or decreasing lesion values was markedly influenced by lesion age. Among 0- to 8-hour-old lesions, area, pain, and virus titer increased in 27%, 21%, and 39% of the subjects, respectively, compared to 10%, 6%, and 0% among those lesions were 17 to 24 hours old at the first visit. A decrease in lesion area, pain, and virus titer was seen in 14%, 24%, and 12% of 0- to 8-hour-old lesions, compared with 35%, 65%, and 54% of the lesions in the 17- to 24-hour age group (p = 0.03, 0.006, and 0.0002). The majority of patients in each age group had mature lesions that remained unchanged or decreased in severity between visits. The possible benefits of antiviral chemotherapy to established lesions are limited because only a small number of untreated patients have progressive disease.

Herpes Labialis↗
PubMed1984

Penetration of guinea pig skin by acyclovir in different vehicles and correlation with the efficacy of topical therapy of experimental cutaneous herpes simplex virus infection.

Inadequate penetration of antiviral agents through the stratum corneum of the skin may be one of the limiting factors in the topical therapy of recurrent cutaneous herpes simplex virus infections in humans. In vitro studies of the penetration of the nucleoside analog acyclovir (ACV) through guinea pig skin demonstrated a marked increase in drug flux when ACV was formulated in dimethyl sulfoxide (DMSO), compared with water or polyethylene glycol (PEG) as the vehicle. To examine whether the increased transcutaneous flux of ACV effected by DMSO was meaningful in vivo, topical 5% ACV in DMSO was evaluated for the treatment of cutaneous herpes simplex virus infection in guinea pigs and compared with topical 5% ACV in PEG. When compared with infection sites treated with the vehicle alone, ACV in DMSO produced a greater percent reduction than did ACV in PEG in median lesion number (8 versus 58%; P less than 0.001), median lesion area (35 versus 73%; P = 0.001), and median lesion virus titer (21 versus 84%; P = 0.08). We conclude that DMSO is a highly effective vehicle for topical administration of ACV and is superior to PEG in our model. Careful choice of vehicle and consideration of transcutaneous penetration may be important for realization of the full potential of topical antiviral therapy in humans.

Acyclovir↗
PubMed1984

Early, patient-initiated treatment of herpes labialis with topical 10% acyclovir.

To determine whether topical acyclovir in polyethylene glycol could reduce the severity of herpes simplex labialis if applied immediately after onset of a recurrence, 10% acyclovir in polyethylene glycol ointment or polyethylene glycol alone was prospectively dispensed to 352 patients in a double-blind, randomized trial. Sixty-nine subjects initiated treatment in the prodrome (57%) or erythema (43%) stage and were followed by clinical and virological criteria. The healing time (6.0 days), maximum lesion area (42 mm2), vesicle or ulcer formation (91%), and maximum lesion virus titer (4.8 log10 PFU) in the drug recipients were not reduced in comparison with those who received the vehicle (5.2 days, 30 mm2, 75%, and 4.5 log10 PFU, respectively). Topical acyclovir in polyethylene glycol was ineffective for the treatment of herpes labialis despite an optimum therapeutic opportunity.

Acyclovir↗
PubMed1984

Effect of azone and propylene glycol on penetration of trifluorothymidine through skin and efficacy of different topical formulations against cutaneous herpes simplex virus infections in guinea pigs.

Tropical formulations of 5-trifluoromethyl-2'-deoxyuridine (TFT) containing different concentrations of TFT, Azone (Nelson Research and Development, Irvine, Calif.), and propylene glycol were evaluated for their potential efficacy in the treatment of cutaneous herpes simplex virus infections by in vitro studies of TFT penetration through skin and in vivo studies of therapeutic activity against herpes simplex virus type 1 infections in the dorsal cutaneous guinea pig model. Azone dramatically increased TFT penetration through human and guinea pig skin. Unexpectedly, high concentrations of propylene glycol were also associated with increased penetration. Studies in the guinea pig model revealed increased efficacy with Azone-propylene glycol-containing formulations, consistent with the in vitro drug diffusion results. A formulation containing 1% TFT, 5% Azone, and 80% propylene glycol decreased lesion area, in comparison to the drug vehicle control, more effectively than 5% acyclovir in polyethylene glycol (reduction of 70 versus 46%, P = 0.03). These studies demonstrate the value of penetration-enhancing agents and the need for careful preclinical evaluations in the development of topical antiviral agents.

Administration, Topical↗
PubMed1984

Pathogenesis of herpes simplex labialis: excretion of virus in the oral cavity.

Excretion of herpes simplex virus (HSV) in the oral cavity was studied in eight human subjects with a history of herpes labialis. Serial intraoral specimens were obtained by gargling broth and examined for virus by centrifugal inoculation of primary human amnion cells. Forty-seven of 637 specimens (7.4%) contained HSV. The majority of isolates (62%) were found in clusters, and the rate of excretion was significantly increased during the common cold (21%) and after oral trauma (17%) (P = 0.001 and 0.04, respectively). Oral HSV excretion often occurred in parallel with episodes of herpes labialis but could not be attributed to viral contamination from a labial lesion. Each patient excreted only one strain of HSV type 1 as determined by restriction endonuclease analysis with KpnI and BamHI. Unexpectedly, prodromal symptoms of herpes labialis were commonly not followed by development of a lesion (false prodrome). False prodromes were associated with a high rate of oral HSV excretion (60%). Intraoral ulcers on the gingivae and hard palate were frequently associated with oral HSV excretion (31%) and are the most likely source of HSV in the oral cavity.

Adult↗
PubMed1983

Spontaneous and induced interferon production by peripheral blood mononuclear leukocytes from humans with herpes labialis.

Peripheral blood mononuclear leukocytes (PBML) were obtained from 44 individual human subjects within 1 to 66 days after the onset of an episode of recurrent herpes labialis. PBML did not spontaneously produce interferon (IFN) when maintained in cultures that contained medium only. Absence of detectable IFN could not be explained by delayed kinetics of production because no appreciable IFN was present in medium from 5-day-old cultures. IFN was produced when PBML were exposed to Newcastle's disease virus or to phytohemagglutinin. These findings suggest that spontaneous IFN production may not occur predictably after an episode of herpes labialis.

Cells, Cultured↗
PubMed1982

Topical 5 percent acyclovir in polyethylene glycol for herpes simplex labialis. Antiviral effect without clinical benefit.

A double-blind, placebo-controlled trial of topical 5 percent acyclovir in polyethylene glycol was conducted among 208 patients with herpes simplex labialis. Reduced excretion of virus from lesions was seen in the subgroup of patients who entered the study within eight hours of lesion onset, but no differences were noted in the patients who began treatment nine to 25 hours after onset. No clinical benefit from treatment with acyclovir was observed.

Acyclovir↗
PubMed1982

Treatment of herpes simplex labialis with topical acyclovir in polyethylene glycol.

A double-blind, placebo-controlled trial of topical 5% acyclovir (ACV) in polyethylene glycol (PEG) was carried out among 208 patients who had an episode of herpes simplex labialis. Patients who were treated with ACV had a greater decrease in median titers of virus in lesions between the first and second visits to the clinic than did patients who were treated with placebo (-1.5 log pfu [plaque-forming units] vs. -0.2 log pfu; P = 0.04). The antiviral effect occurred in the subgroup of patients who entered the study 0-8 hr after the onset of lesions. No differences were noted in the remaining patients who began treatment 9-25 hr after onset. An examination of the subgroup who had virus-positive specimens before treatment revealed prominent and more statistically significant virologic differences between treatment groups. No clinical benefit from treatment with ACV was observed; however, the present study describes the first antiviral effect of topical treatment for recurrent herpes labialis and identifies treatment strategies for future studies.

Acyclovir↗
PubMed1982

Pathogenesis of herpes simplex labialis: correlation of vesicle fluid interferon with lesion age and virus titer.

Of 51 patients with herpes simplex labialis, 50 had detectable interferon (IFN) in samples of lesion vesicle fluid. The median titer of vesicle fluid IFN was 8,200 U. and the range of values was 400 to 63,600 U. The amount of vesicle fluid IFN was correlated with lesion age (r = 0.32, P = 0.024) and vesicle fluid virus titer (r = 0.59, P = 0.00004), but not with the clinical severity of the disease. The presence of vesicle fluid IFN (1,500 to 28,600 U) in 15 lesions less than 12 h old emphasizes the need for early treatment in studies of antiviral agents for herpes simplex labialis.

Adult↗
PubMed1982

Typing of herpes simplex virus with type-specific human immunoglobulin M in an indirect immunofluorescence assay.

Sera from nine individuals with suspected primary herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) infection were screened to identify those containing HSV type-specific immunoglobulin M (IgM). Selected sera were then utilized in an IgM-specific indirect immunofluorescent-antibody HSV-typing assay (patent pending). To evaluate the procedure, 29 HSV isolates were grown in cultures of continuous human amnion cells, fixed, and used as substrates for indirect immunofluorescence. Determination of virus type was based on intensity of fluorescence of the substrate with HSV-1- and HSV-2-specific antisera after staining with fluorescein-conjugated anti-human IgM. Typing of the isolates by restriction endonuclease digestion showed that of 29, 18 were HSV-2 and 11 were HSV-1. Results by IgM-specific indirect immunofluorescent-antibody assay were identical to those by restriction endonuclease digestion for 27 of the isolates; 2 isolates failed to replicate adequately in the test cells. The IgM-specific indirect immunofluorescent-antibody procedure appears to be a simple, rapid, and accurate technique which could be of use to clinical virology laboratories.

Fluorescent Antibody Technique↗
PubMed1981

The histopathologic evolution of recurrent herpes simplex labialis.

In a study of the natural history of recurrent herpes simplex labialis, we examined hematoxylin and eosin-stained sections of biopsies taken from lesions at various clinical stages. The earliest specific findings which could be recognized were changes within the epidermal cell nuclei, including peripheral clumping of chromatin, development of homogeneous "ground glass" appearance, and ballooning of nuclei. Eosinophilic intranuclear inclusion bodies were unusual and occurred in late lesions. Vacuolization was the earliest cytoplasmic alteration within keratinocytes. The herpes-induced changes began focally along the basal cell layer, but the entire epidermis was rapidly altered. Pilosebaceous units were commonly affected. Within the dermis, no cells with typical herpesvirus-induced changes were seen. In early lesions, mononuclear and polymorphonuclear inflammatory cells were equally prominent; in later lesions neutrophils were most numerous. Histopathologic changes of recurrent herpes simplex begin multicentrically within the epidermis and are present prior to the onset of physical findings.

Biopsy↗
PubMed1981

Viral-induced leukocyte interferon in vesicle fluid from lesions of recurrent herpes labialis.

Antiviral activity characterized as human interferon (HuIFN) was demonstrated in vesicle fluid from lesions of recurrent herpes labialis in 18 of 19 otherwise healthy patients. High titers (geometric mean, 29,200 units) were present during the early course of lesion development. Antiviral activity in vesicle fluid was neutralized by antibody to leukocyte (types I) HuIFN (HuIFN-alpha) in the eight patients in whom it was tested. These results indicate that HuIFN-alpha is present in the local lesions of recurrent herpes labialis. HuIFN may have a role in the pathogenesis of recurrent herpesvirus infections.

Adult↗
PubMed1980

Topical ether and herpes simplex labialis.

In a double-blind, placebo-controlled study, 51 patients with recurrent herpes simplex labialis were treated with topical ether or placebo within 24 hours of onset of a lesion. There was no noteworthy difference between groups given ether and placebo in progression of lesions, healing time, duration or intensity of pain, and duration or quantity of virus excretion. The ether also failed to reduce appreciably lesion virus titer, even when lesions were cultured immediately after topical application. Despite these results, 75% of the patients receiving ether and 77% of those receiving placebo reported effective reduction of the severity and duration of lesions. The marked placebo effect in the treatment of recurrent herpes infection helps to emphasize the need for objective measurements and placebo-controlled studies.

Administration, Topical↗