High susceptibility to bacterial infection, but no liver dysfunction, in mice compromised for hepatocyte NF-kappaB activation.

Based on the essential involvement of NF-kappaB in immune and inflammatory responses and its apoptosis-rescue function in normal and malignant cells, inhibitors of this transcription factor are potential therapeutics for the treatment of a wide range of diseases, from bronchial asthma to cancer. Yet, given the essential function of NF-kappaB in the embryonic liver, it is important to determine its necessity in the liver beyond embryogenesis. NF-kappaB is normally retained in the cytoplasm by its inhibitor IkappaB, which is eliminated upon cell stimulation through phosphorylation-dependent ubiquitin degradation. Here, we directed a degradation-resistant IkappaBalpha transgene to mouse hepatocytes in an inducible manner and showed substantial tissue specificity using various means, including a new method for live-animal imaging. Transgene expression resulted in obstruction of NF-kappaB activation, yet produced no signs of liver dysfunction, even when implemented over 15 months. However, the transgene-expressing mice were very vulnerable both to a severe immune challenge and to a systemic bacterial infection. Despite having intact immunocytes and inflammatory cells, these mice were unable to clear Listeria monocytogenes from the liver and succumbed to sepsis. These findings indicate the essential function of the hepatocyte through NF-kappaB activation in certain systemic infections, possibly by coordinating innate immunity in the liver.

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.

Infantile myofibromatosis: a case report.

A male infant had three nodules on the left cheek, right forearm, and right neck. Biopsy specimen revealed infantile myofibromatosis (IM). Further evaluation revealed a solitary pulmonary nodule in the right middle lobe located far from mediastinal structures, which had no evidence of tumor enlargement on follow-up tomographic scan. Immunoperoxidase studies were negative for desmin and positive for actin. This is a potentially life-threatening multiorgan system disease; however, if lesions are limited mainly to the skin and soft tissues, the prognosis becomes more favorable. Although many reports suggest spontaneous and complete healing of the cutaneous lesions, our patient had profound atrophy at lesion sites as resolution occurred.

Adjuncts to scalp reduction surgery. Intraoperative tissue expanders and hyaluronidase.

Scalp reduction has become an important part of the cosmetic surgeon's armamentarium in the treatment of male pattern alopecia. Recently, the use of two-stage tissue expansion has been advocated for scalp reduction. Intraoperative tissue expansion obviates many of the disadvantages of delayed expansion and increases the yield of excised scalp by 20-30% over standard reduction techniques in the 20 patients studied. The addition of hyaluronidase to the local anesthetic facilitates its diffusion, enhancing anesthesia and the ease of dissection. Therefore, the use of intraoperative tissue expansion and the addition of hyaluronidase to the local anesthetic are two separate adjuncts to scalp reduction surgery.

Ocular dominance and the interocular suppression of blur in monovision.

Presbyopic contact lens patients with monocular corrections (monovision) see clearly at all distances by virtue of an interocular suppression of anisometropic blur that occurs regionally between corresponding retinal areas. This suppression fails to occur with small high-contrast targets viewed under low luminance conditions. The effect of target size and contrast upon interocular suppression of blur was quantified by reducing contrast of a bright test spot, viewed binocularly while wearing various plus lenses monocularly, until the out-of-focus image was suppressed. The strength of interocular suppression was equivalent when the plus lens was before either eye. However, after subjects wore a plus lens over their nonsighting eye for one day, interocular suppression of blur became enhanced when the nonsighting eye was blurred, and it became reduced when the sighting eye was blurred. Successful monovision subjects suppressed blur at higher contrast levels than did unsuccessful subjects. These results suggest a possible clinical test for quantifying adaptation to monovision.

Multiple dermatofibromas and systemic lupus erythematosus.

We report on three black women with multiple dermatofibromas and systemic lupus erythematosus. In one patient occurrence of new dermatofibromas was definitely related to increases in corticosteroid dosage, but in another the dermatofibromas predated all treatment. Histopathologic, ultrastructural, and direct immunofluorescence studies of lesions of two of the patients showed characteristic changes of dermatofibroma but did not reveal a specific cause. This finding in patients with systemic lupus erythematosus is probably much more common than has previously been appreciated.

Acrokeratosis paraneoplastica (Bazex' syndrome). Report of a case and review of the literature.

Acrokeratosis paraneoplastica (Bazex' syndrome) is a rare but clinically distinctive dermatosis that has been associated in all reported cases, to our knowledge, with either a primary malignant neoplasm of the upper aerodigestive tract or metastatic cancer to the lymph nodes of the neck. Acrokeratosis paraneoplastica was found in a 53-year-old black man with squamous cell carcinoma of the tonsil. A distinctive series of changes was found on histopathologic examination of biopsy specimens taken from his skin lesions, and direct immunofluorescence microscopy of both lesional and nonlesional skin specimens showed immunoglobulin and complement deposition on the epidermal basement membrane. The skin lesions largely resolved following radiation therapy of the neoplasm and of the presumably involved lymph nodes.