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Biomedical subjects

S L Spruance

Publications and source records attributed to S L Spruance.

At least 37 records · Page 2Linked to original sources
PubMed1995

Th1/Th2-like immunity and resistance to herpes simplex labialis.

To investigate potential immunologic mechanisms of resistance to recurrent herpes simplex labialis, we assayed serum antibody titers and cultured peripheral blood mononuclear cell (PBMC) cytokine production among patients with a history of frequent episodes (H+S+), herpes simplex virus (HSV)-seropositive individuals without a history of herpes labialis (H-S+) and HSV-seronegative persons (H-S-). In addition, H+S+ patients were exposed to experimental ultraviolet radiation (UVR) on the lips and the immunologic assay results compared among those who developed experimental lesions and those who did not. H+S+ patients were found to have higher median serum titers of HSV antibody and trends to lower levels of HSV-specific PBMC IFN-gamma and IL-2 than H-S+ control patients (123 vs 66, P = 0.04; 424 vs 548 pg/ml, P = 0.08; 14 vs 26 pg/ml, P = 0.14, respectively). Correlation of the results with the occurrence of experimental lesions showed the inverse: the subgroup of H+S+ patients with UVR-induced lesions had lower titers of antibody and trends to higher levels of IFN-gamma and IL-2 than H+S+ patients who could not be induced (93 vs 149, P = 0.02; 501 vs 347 pg/ml, P = NS; 26 vs 11 pg/ml, P = NS, respectively). The size and duration of UVR-induced lesions showed positive correlations with IFN-gamma and IL-2 levels (r = 0.60-0.67, P = 0.02-0.04). Although the small number of patients limited the power of this study, the overall pattern of the findings suggests that a Th1-like cytokine response (IFN-gamma and IL-2 production) may be associated with resistance to naturally occurring episodes of herpes labialis. The development and severity of experimental UVR-induced herpes labialis appears to be regulated differently and may involve an immunopathologic mechanism.

Antibodies, Viral↗
PubMed1995

Susceptibility to herpes labialis following multiple experimental exposures to ultraviolet radiation.

We studied susceptibility to herpes labialis by exposing 20 volunteers to experimental ultraviolet radiation (UVR) on three occasions at 3- to 4-month intervals. The number of patients who developed lesions after each session was 9/20 (45%), 9/20 (45%) and 14/20 (70%). Herpes simplex virus (HSV) was isolated from 21/29 (72%) of lesions sampled. Three patients never developed a lesion, 13 developed lesions on one or two of the three occasions, and 4 patients had a lesion following all three sessions. Seven of 33 (21%) lesions were 'immediate' lesions (developed within 48 h) and the others developed 3-7 days after UVR exposure (delayed lesions). Development of lesions correlated with historical susceptibility to sun-induced herpes labialis, but not with age, sex, years with herpes labialis, frequency of herpes labialis from all causes, or concurrent serum levels of cortisol, dehydroepiandrosterone, estradiol, progesterone or alpha 1-antitrypsin. Among normally menstruating females, a significant association was identified between the development of herpes labialis and the luteal phase of the menstrual cycle (8 cases of herpes labialis/11 attempts, RR = 14, P = 0.005). The lack of correlation between episodes of natural herpes labialis and susceptibility to experimental UVR-induced disease suggests that these events are controlled differently. The results of serial attempts to induce experimental herpes in each patient was most commonly inconsistent, indicating that individual patient susceptibility to UVR varies over time. While the explanation for this variation remains unclear, stages of the menstrual cycle may be important among women.

Adult↗
PubMed1994

Didanosine compared with continuation of zidovudine in HIV-infected patients with signs of clinical deterioration while receiving zidovudine. A randomized, double-blind clinical trial. The Bristol-Myers Squibb AI454-010 Study Group.

OBJECTIVE: To determine the benefits of switching to didanosine compared with continuing zidovudine among patients infected with human immunodeficiency virus (HIV) who have previously used zidovudine and have signs of clinical deterioration. DESIGN: Randomized, double-blind, two-armed, parallel, comparative clinical trial with a blinded, compassionate crossover provision at 12 weeks. SETTING: Outpatient clinics at 19 tertiary care medical centers. PATIENTS: 312 patients infected with HIV who had received zidovudine for 6 months or more, had CD4 cell counts of 300/mm3 or less, and had signs of clinical deterioration within 12 weeks before study entry. INTERVENTION: Peroral didanosine tablets (600 mg/d adjusted for weight, "high dose") or zidovudine capsules (600 mg/d). MEASUREMENTS: Primary study end points were death, a new acquired immunodeficiency syndrome (AIDS)--defining event, or the combination of two new or recurrent HIV-related diagnoses with a 50% decrease in CD4 cells. RESULTS: Switching to didanosine was associated with fewer end points than continuing zidovudine (relative risk [RR] for zidovudine:didanosine = 1.5; 95% Cl, 1.1 to 2.0). This benefit was consistent across subgroups of patients with either AIDS-related complex or AIDS and was most apparent among those with a CD4 count at entry of 100/mm3 or more (RR = 2.2; Cl, 1.1 to 4.4). CONCLUSIONS: This study shows a positive treatment effect for switching from zidovudine to didanosine among patients with either AIDS-related complex or AIDS and validates the common practice of using clinical signs or a decrease in the CD4 count as an indication for changing therapy.

AIDS-Related Complex↗
PubMed1994

Treatment of acyclovir-unresponsive cutaneous herpes simplex virus infection with topically applied SP-303.

The naturally occurring polyphenolic biopolymer SP-303 has in vitro activity against both HSV-1 and HSV-2, including strains that are resistant to acyclovir. Nine AIDS patients with acyclovir-unresponsive mucocutaneous herpes simplex virus infection were treated with thrice daily topical SP-303T ointment in an open-label pilot study. Although a transient decrease in lesion size was observed in 4 patients during study drug therapy, and 3 patients sustained a quantitative decrease in virus burden, neither complete healing nor cessation of virus shedding occurred in any patient. Seven patients complained of pain or burning upon application of the study ointment, causing 1 patient to terminate the study. In summary, application of SP-303T ointment effected no significant improvement in the clinical course of 9 AIDS patients with acyclovir-unresponsive HSV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Correlation between detection of herpes simplex virus in oral secretions by PCR and susceptibility to experimental UV radiation-induced herpes labialis.

We examined the oral secretions of 25 patients for herpes simplex virus (HSV) at the time of and following experimental UV radiation (UVR). HSV was detected in one or more oral secretion specimens in 5 of 12 (42%) cases by cell culture and in 8 of 12 (67%) cases by PCR. On the day of UVR, HSV was detected in 1 of 12 (8%) patients who developed a lip lesion and 2 of 16 (13%) patients who did not (the difference is not significant). We conclude that PCR is more sensitive than culture in the detection of HSV and that HSV is not shed with increased frequency from the oral cavity before the development of UVR-induced herpes labialis.

DNA, Viral↗
PubMed1993

Prophylactic chemotherapy with acyclovir for recurrent herpes simplex labialis.

The medical literature was reviewed and 11 clinical trials of prophylactic topical or peroral acyclovir for the suppression of recurrent herpes simplex labialis were identified. The results of these trials showed that prophylactic topical acyclovir was mostly ineffective, but that prophylactic peroral acyclovir, in doses ranging from 400 to 1,000 mg/day, reduced the frequency of herpes labialis during treatment by 50-78%. The reduction in the frequency of episodes of herpes labialis with acyclovir prophylaxis is less than the suppressive effect that has been reported for herpes genitalis (50-78% vs. 80-90%). In trials of prophylactic acyclovir for herpes labialis induced by experimental ultraviolet radiation, 26% of induced lesions developed within 48 hours of radiation exposure ("immediate" lesions) and, in contrast to "delayed" lesions that developed 2-7 days post-irradiation, were not suppressed by the antiviral compound. It is proposed that these treatment-unresponsive immediate lesions have an atypical pathogenesis, possibly involving latency of herpes simplex virus in the labial epithelium, and that these may be responsible for the apparent difference between herpes labialis and genitalis in the degree of benefit from prophylactic acyclovir therapy.

Acyclovir↗
PubMed1992

The presence of a dehydroepiandrosterone-specific receptor binding complex in murine T cells.

We have investigated the ability of dehydroepiandrosterone (DHEA) to alter the production of interleukin-2 (IL-2) and to bind to a specific binding complex in antiCD3 epsilon activated T cells. Binding activity correlated with the presence of a specific DHEA binding complex in the cytosol and nuclei of DHEA-responsive T-cell hybridomas, as well as in CD4+ and CD8+ cells isolated from peripheral lymph nodes of normal mice. Scatchard analysis determined that intact lymphocytes and cytosolic fractions contained high affinity binding for [3H]DHEA (approx. 2.6 nM) with 1000-7000 binding sites existing per cell. Five of the T-cell hybridomas tested both responded to DHEA treatment with increased production of IL-2 and also contained specific high affinity [3H]DHEA binding. Four additional T-cell hybridomas were found to contain no specific [3H]DHEA binding and were also unresponsive to DHEA influences on IL-2 production. Sucrose density gradients demonstrated a 3-4s [3H]DHEA binding complex in high salt and a 7-8s binding complex in low salt. Specific binding was inhibited by preincubation of the cytosol fractions with either trypsin or chymotrypsin, or by heating to 60 degrees C for 1 h (less than 15% of control). [3H]DHEA binding was unaffected by preincubation of the cytosol fractions with ribonuclease, deoxyribonuclease, or phospholipase A. The DHEA-protein complexes bound to DNA-cellulose with the amount of binding being slightly increased by preincubation at 25 degrees C as compared to 4 degrees C. As expected, [3H]DHEA binding was inhibited by the addition of unlabeled DHEA, but was also modestly inhibited by dihydrotestosterone and cortisol. Binding of DHEA was unaffected by progesterone, dexamethasone, estradiol, androsterone, DHEAS, and beta-etiocholanolone at all concentrations tested. DHEA was incapable of inhibiting the binding of [3H]DHT to the androgen receptor or [3H]dexamethasone to the glucocorticoid receptor. Collectively, these findings suggest that murine T cells contain a specific DHEA receptor. We believe that DHEA is a steroid hormone that is directly involved in the regulation of IL-2 production by both normal and some T-cell hybridomas.

Animals↗
PubMed1992

Ofloxacin versus doxycycline for treatment of cervical infection with Chlamydia trachomatis.

Women with culture-proven Chlamydia trachomatis cervical infection were randomized to receive either ofloxacin (300 mg) or doxycycline (100 mg), orally twice daily for 7 days. All 56 had negative cultures 5 to 9 days after treatment. Four weeks after treatment, 26 (93%) of 28 ofloxacin-treated patients and all 22 doxycycline-treated patients were cured. We conclude that 300 mg of ofloxacin given twice daily for 7 days provides effective therapy for chlamydial infection of the cervix.

Chlamydia Infections↗
PubMed1992

The natural history of recurrent oral-facial herpes simplex virus infection.

Oral-facial herpes simplex virus infection is a common, worldwide affliction on which neither public health procedures, vaccines, nor antiviral chemotherapy have yet to have a significant clinical impact. Careful examination of the pathogenesis and clinical features of this illness could lead to insights and a rationale for new and more effective preventive and therapeutic measures. The resistance of recurrent herpes simplex labialis to antiviral chemotherapy may be caused in part by inoculation of the skin simultaneously at multiple foci, such that only a few cycles of virus replication are needed before there is coalescence of the foci, destruction of the epidermis, and clinical lesion formation. Studies of herpes simplex labialis induced by ultraviolet radiation have suggested that there is a subpopulation of lesions that develop immediately after irradiation and that are refractory to chemotherapy. The difficulty finding a treatment for herpes simplex labialis may in part be methodological. Clinical trial protocols for antiviral drugs should target susceptible lesion subgroups and specific stages of the disease.

Antiviral Agents↗
PubMed1991

The natural history of ultraviolet radiation-induced herpes simplex labialis and response to therapy with peroral and topical formulations of acyclovir.

The lips of 196 patients with a history of sun-induced herpes labialis were exposed to experimental ultraviolet radiation (UVR) and treated with acyclovir (ACV) or placebo at different times and by different routes. Of 98 placebo recipients, 39 (40%) developed 43 lesions inside or within 10 mm of the irradiated zone. The temporal distribution of lesions was bimodal. 11 (26%) occurring within 48 h (immediate) and 32 (72%) 2-7 days after UVR exposure (delayed). Prophylactic peroral ACV begun 7 days before or 5 min after UVR prevented the development of the delayed but not the immediate lesions (P less than .001). When peroral ACV was started 48 h after UVR, delayed lesions developed but were less severe (P = .01-.05). Prophylactic topical ACV begun 5 min after UVR did not reduce lesion frequency or severity. ACV therapy can be efficacious, but some rapidly developing lesions are unresponsive to treatment. This suggests that more than one process may contribute to the pathogenesis of herpes labialis.

Acyclovir↗
PubMed1990

Topical treatment of cutaneous herpes simplex virus infections.

Topical antiviral chemotherapy has a number of potential advantages over systemic drug delivery for the treatment of cutaneous herpes simplex virus infections, including convenience; higher target tissue drug levels and greater efficacy; and specific targeting of the drug to the site of infection, with reduced cost and reduced exposure of the remainder of the body to drug side effects. Realization of these possibilities has been slow in part because of the paucity of 'active' topical drug formulations with effective penetration-enhancing agents and a technical barrier-our failure as yet to measure drug levels in the epidermis, which could guide formulation development. Recent success with a topical treatment for herpes simplex labialis should stimulate continued laboratory and clinical research in this field.

Administration, Topical↗
PubMed1990

Treatment of recurrent herpes simplex labialis with oral acyclovir.

In a double-blind, randomized, patient-initiated clinical trial, 174 nonimmunocompromised patients with a history of virus-culture-confirmed herpes simplex labialis were treated with acyclovir capsules, 400 mg five times daily for 5 days, or placebo capsules. For 97% of the patients, treatment started within 1 h of the first sign or symptom of a recurrence. The frequency of positive lesion virus cultures was significantly lower among acyclovir-treated subjects (29/114, 25%) than among placebo-treated subjects (29/60, 48%; P = .004). Drug treatment did not affect the development of lesions, measured by the frequency of macular and papular (aborted) lesions and mean maximum lesion size. However, acyclovir hastened lesion resolution among the patients who could start treatment in the prodrome or erythema lesion stage. For this group, the mean duration of pain was reduced by 36% (P = .02) and the mean healing time to loss of crust by 27% (P = .03). Thus, oral acyclovir alleviated some of the clinical manifestations of herpes simplex labialis.

Acyclovir↗
PubMed1990

Early application of topical 15% idoxuridine in dimethyl sulfoxide shortens the course of herpes simplex labialis: a multicenter placebo-controlled trial.

In a double-blind, randomized, patient-initiated treatment study at five medical centers, 301 immunocompetent patients experiencing a recurrence of herpes labialis were treated with topical 15% idoxuridine (IDU) in dimethyl sulfoxide (DMSO), 80% DMSO control solution, or 2% DMSO control solution. IDU did not prevent the development of lesions but significantly accelerated lesion resolution in comparison with the combined control groups. For the total population, the mean duration of pain was reduced by 1.3 days (35%, P = .01) and the mean healing time to loss of crust by 1.7 days (21%, P = .004). Analysis of subpopulations revealed that the beneficial activity of the treatment was concentrated among the patients who began treatment in the prodrome or erythema lesion stage. For these patients, the mean duration of pain was reduced by 1.8 days (42%, P = .08) and the mean healing time to loss of crust by 3.3 days (38%, P less than .001). If only patients with classic herpes lesions (vesicle, ulcer, or crust formation) were considered, there was a greater drug effect on the duration of pain (reduction by 2.6 days, 49%; P = .03) and the mean healing time to normal skin was significantly shortened (reduction by 2.3 days, 23%; P = .004). Adverse reactions to the medication were minimal.

Administration, Topical↗
PubMed1989

Lack of ocular changes with dimethyl sulfoxide therapy of scleroderma.

Eighty-four patients with scleroderma hand ulcers were treated 3 times daily for 3 months in a randomized, double-blind clinical trial by immersing their hands into bags of topical 70% dimethyl sulfoxide (DMSO), topical 2% DMSO, or 0.85% normal saline. Fifty-five of the patients completed the study, 46 of whom received blinded initial (0 days) and final (12 weeks) full ophthalmologic examinations. This evaluation included past ocular history, past drug history, family ocular history, pupillary examination, cycloplegic refraction, motility study, applanation tension, indirect dilated funduscopic examination, and slit-lamp examination. No statistical difference in these ocular variables, including visual acuity, lenticular changes, and cataract development, were noted among the three groups, and in no patients were the DMSO-related lenticular changes reported in numerous animal studies found. The maximum theoretical dosage of DMSO administered was 2.6 g/kg/day, which is comparable to those used in the animal studies.

Administration, Topical↗