A double-blind, placebo-controlled study of topical tetracaine in the treatment of herpes labialis.

BACKGROUND: Before the September 1996 approval of 1% penciclovir cream for the treatment of herpes labialis, no other prescription topical therapy was approved for the treatment of this recurrent viral disease affecting approximately 20% of the adult population of the United States. Local anesthetics, such as tetracaine, have been used in over-the-counter topical products, but are only labeled for the relief of pain and itching associated with cold sores and fever blisters. OBJECTIVE: The purpose of this study was to determine whether a topical preparation of a tetracaine cream is safe and effective in the treatment of recurrent herpes labialis in immunocompetent patients. METHODS: A double-blind, placebo-controlled study was conducted to assess the relative effectiveness and safety of 1.8% tetracaine equivalent in a cream base versus placebo in the treatment of herpes labialis in immunocompetent adults. In this study, patients applied medication up to 6 times daily until the lesions healed (scab loss), but for no more than 12 days. The patients were monitored on the day of enrollment, once during the course of treatment, and at a final visit after the lesions had healed. Patients assessed themselves the day of scab formation and the day the scab fell off. They also graded, on a daily basis, their perception of relief from itching and pain and the overall benefit. RESULTS: The results from 72 patients (35 = placebo; 37 = active) showed that scab formation occurred in a mean of 2.4 +/- 0.27 days for the placebo group and 2. 3 +/- 0.26 days for the active group. Healing time (scab loss) occurred in a mean 7.2 +/- 0.36 days for the placebo group and in 5. 1 +/- 0.35 days in the active group. The difference observed for healing time between the placebo and the active tetracaine cream was statistically significant (P =.0002). This represents an approximately 30% reduction in the healing time for the active group compared with the placebo group. In addition, the study patients ranked the benefit of their treatment on a daily basis and graded the overall benefit of the therapy at their final visit. The ranking was on a 1 to 10 index scale (1 = no benefit at all; 10 = very effective treatment). At the final visit there was a statistically significant difference in the benefit index for active preparation versus placebo for this subjective evaluation (placebo index, 5.9 +/- 0.6; active index, 7.3 +/- 0.48 [P =.0359]). The subjects also evaluated relief from itching and pain on a daily basis. Relief from itching was significantly greater in the active group than in the placebo group on days 2 and 3 after initiation of the treatment. Pain was not found to be severe in either the placebo or active treatment groups. At day 2 of treatment and beyond, pain scores never were greater than 3.2 +/- 0.28 for active on a scale in which 1.0 represented "no pain at all" and 10 represented "most severe pain imaginable." Although mean values for pain were always less for the active therapy, lesional pain scores never reached statistically significant lower values for active compared with placebo. CONCLUSION: Our findings indicate that a 1.8% topical tetracaine cream, when applied frequently, significantly reduces the healing time of recurrent herpes labialis lesions. Additionally, it is perceived by the study subjects to reduce itching of the lesions and to have a beneficial overall effect.

Seven patients with respiratory infections due to Corynebacterium pseudodiphtheriticum.

Seven cases of lower respiratory tract infection due to Corynebacterium pseudodiphtheriticum are described. Lower respiratory tract infections with C. pseudodiphtheriticum in immunocompetent patients are usually associated with pre-existing chronic pulmonary disease, and are sometimes associated with endotracheal intubation. Antimicrobial susceptibility testing of these isolates showed uniform sensitivity to penicillin and variable results to erythromycin.

Cervical carcinoma antigen: distribution in neoplastic lesions of the uterine cervix and comparison to other tumor markers.

Four antibodies (anti-CCA, anti-CEA, Ca-l, and anti-EMA) were used to study the distribution of antibody-binding sites in normal endocervical mucosa, metaplastic squamous epithelium, squamous epithelium exhibiting varying grades of intraepithelial neoplasia, and invasive squamous cell carcinoma. Anti-CCA, a novel monoclonal antibody raised against an extract of squamous cell carcinoma of the cervix, recognizes dysplastic, neoplastic, and metaplastic cervical epithelial cells. While anti-CCA and Ca-l rarely stained normal glandular epithelium, 31.4 and 45.7% of the samples stained positively for CEA and EMA, respectively. There did not appear to be significant differences between anti-CCA and the other antibodies in the frequency with which neoplastic conditions were stained. Based upon these observations, it appears that none of the antibodies tested can be regarded as a specific tumor marker.

Inhibition of herpes simplex virus replication by cobra alpha-neurotoxoid.

A peptide, prepared by gentle oxidative detoxification of a methionine-free cobra alpha-neurotoxin, was evaluated for antiviral activities in vivo and in vitro. When added to BHK cells before infection the peptide reduced herpes simplex virus type 1 (HSV-1)-induced TCD50 in a dose- and time-dependent manner. The antiviral effect was also expressed on initiation of cell treatment 1 h after infection if the peptide was left in contact with cells. Single, intracerebral doses of the toxoid in suckling mice significantly increased 50% survival times, and reduced virus replication in the infected brain tissues. Cutaneous lesions and resultant scar formation induced by HSV-1 in hairless mice were also significantly reduced by subcutaneous peptide injections.

The antigenicity and immunology of human cervical squamous cell carcinoma: a review.

Numerous studies have demonstrated an altered antigenicity in the carcinomatous cervix. Whether the neoplasia-associated antigens are of viral origin, are actually normal antigens expressed in elevated levels, or are true tumor-associated antigens has not been precisely determined, since evidence has been presented for all of these possibilities. These antigens associated with cervical squamous cell carcinoma have been demonstrated not only biochemically and by raising antisera to the tumors in animals but also by studies of the humoral and cell-mediated immune responses of cervical cancer patients. Immunodiagnosis of cervical cancer with the use of these antigens has, to date, not been feasible, although several of the assays appear potentially useful.

Cervical carcinoma antigens in the diagnosis of human squamous cell carcinoma of the cervix.

The use of tumor-associated antigens (TAA) in the diagnosis of human squamous cell carcinoma of the cervix was evaluated by immunofluorescence staining of second cervical scrapes and touch preparations of normal and carcinomatous tissue. Rabbit antisera, prepared against human cervical squamous cell carcinoma homogenates and absorbed with normal human cervix and plasma, were used to stain 103 second cervical scrapes by indirect immunofluorescence. Of these specimens, 59 were positive by immunofluorescence, whereas the remaining 44 were negative. Compared with conventional cytologic diagnosis, positive immunofluorescence was detected in 100% (49/49) of the second scrapes from patients with cervical dysplasia or carcinoma (for a false-negative rate of zero). Of the second cervical scrapes from 57 patients negative by cytology, 13 were positive by immunofluorescence (for a false-positive rate of 22.8%). Indirect immunofluorescence tests on tumor touch preparations also revealed cervical TAA in other types of gynecologic tumors.

Monoclonal antibodies specific for dengue virus type 3.

Mouse lymphocyte hybridomas were prepared by polyethylene glycol-mediated fusion of cells from a mouse plasmacytoma line with lymphocytes from a mouse hyperimmunized with dengue virus type 3 (dengue-3). Media from 50 hybrid colonies were screened; 46 of them showed antibody activity against dengue-3-infected cells as determined by an indirect immunofluorescent antibody technique. Dengue monoclonal antibody obtained after cloning one of these colonies demonstrated activity in hemagglutination inhibition and indirect immunofluorescent antibody assays with dengue-3 antigen, but not type 1, 2, and 4 antigens. In addition, this antibody activity could be removed from culture media only by absorption with dengue-3 antigen.

Tumor-bound immunoglobulin in human gynecologic cancers.

By the use of immunofluorescence techniques, immunoglobulin of the IgG class was consistently found in touch preparations and in frozen sections of squamous cell carcinomas of the uterine cervix (both keratinizing and nonkeratinizing) and in an adenosquamous cell carcinoma of the cervix, an adenocarcinoma of the cervix, a mixed mesodermal-uterine tumor, and a uterine adenocarcinoma metastasized to the ovaries. Trace amountsof IgM were found in 1 squamous cell carcinoma and in 1 adenocarcinoma of the cervix. Except for 1 tumor specimen consisting primarily of infiltrating lymphocytes that stained positive for human IgG, IgM, IgA, and C3, the tumors were consistently negative for IgA and C3. Specimens made from normal cervical tissue were uniformly negative for all immunoglobulins and complement. Positive staining for human IgG could be eliminated by incubation of the tumor preparations with unconjugated goat antihuman IgG before the preparations were stained with fluorescein isothiocyanate-conjugated goat antihuman IgG. Attempts to elute the tumor-bound IgG with glycine-HCl buffer (pH 2.2) were most successful with the use of unfixed tissue, although the positive staining for IgG could not be entirely eliminated. The elution effects of the low-pH buffer on tissue fixed over 2 hours in 10% Formalin were minimal.

Biochemical characteristics of rat C-type virus WF-1.

The non-oncogenic rat C-type virus WF-1, isolated from a Wistar-Furth rat embryo cell line, was characterized biochemically. The purified virus has a buoyant density of 1.15 to 1.16 g/cm3 in sucrose, RNA-dependent DNA polymerase (reverse transcriptase) activity, and RNA with a sedimentation coefficient of 62 to 68 S. The viral RNA is single-stranded, and, upon treatment with heat, yields components with sedimentation coefficients of 36 S, 18 to 20 S, and 4 to 12 S.

Characteristics of rat carcinoma in culture.

Rat chloroma cells have been propagated in permanent suspension cultures and are grown in Dulbecco's modified Eagle's medium with 10% fetal calf serum and 2.5% horse serum. Several lines have been established; the one of longest duration, Mia C51, has been maintained for over 18 months and has undergone over 100 transfers. Mia C51 cells have a doubling time of 12 hr and maintain many of the properties of the parent tumor, including the characteristic greenish color with high myeloperoxidase activity, an an aneuploid chromosomal pattern, and intact tumorigenicity. They will uniformly produce greenish chloroma tumors when injected into newborn rats. Electron microscopic examination of chloroma tumors and the cultured cells derived from them reveal the presence of extracellular mature and immature type C virus particles morphologically typical of oncornaviruses. Chloroma cells obtained from tumors that lost their alkaline phosphatase activity after repeated transfer regain full activity in culture. Studies using the antigen-antibody crossed electrophoresis indicate that the loss of alkaline phosphatase activity represents a true decrease in alkaline phosphatase protein, which is restored under culture conditions. The availability of a permanent chloroma cell line in culture that maintains the biological properties of the parent tumor provides a useful model for the study of myeloid leukemia.