Tumors of the skin. VI. Study on effects of local administration of 5-fluorouracil in basal cell carcinoma.

Exploratory studies on topical administration of 20% 5-Fluorouracil in hydrophilic base were carried out in 36 solitary nodular basal cell carcinomas. Under the conditions of this study, tumor resolution lasting through an observation period of 20 months was observed in 21 study sites, although changes in the natural course of lesions were present in all the tumors. Topical administration of anti-tumor agents is not suitable for clinical management of solitary basal cell carcinoma at the present. Further evaluation as an investigative approach in studies on chemotherapy and tumor biology may be warranted.

Antibody-dependent cellular cytotoxicity to target cells infected with herpes simplex viruses: functional adequacy in the neonate.

The functional adequacy of antibody-dependent cellular cytotoxicity (ADCC) in the human neonate was evaluated in a 51Cr release assay which employs tissue culture cells acutely infected with type 1 or type 2 herpes simplex virus (HSV) as targets. Two aspects of ADCC were assessed: cytotoxic effector activity in cord blood mononuclear cells (MC) and the ability of the antibody mediating ADCC to pass the placenta. Although effector cell activity was readily detected in all 13 cord blood specimens tested, cord blood MC showed moderately reduced cytotoxic activity when compared with blood MC from normal adults at the same effector cell:target cell ratio. This finding suggests that effector cells in cord blood make up a reduced proportion of the total circulating MC population and may be of relevance to the newborn's increased susceptibility to HSV infection. On the other hand, the number of MC in cord blood was found to be almost twice that of adult blood, suggesting that the absolute number of ADCC effector cells in cord blood was within the adult range. The antibody mediating ADCC to HSV-infected cells was shown to be transferred quantitatively across the placenta, providing further evidence that it is an IgG immunoglobulin.

Werner's syndrome with associated malignant neoplasms.

Werner's syndrome is an autosomal recessive disease characterized by juvenile cataracts, scleroderma-like skin changes, and a high incidence of neoplasms. A 57-year-old man had Werner's syndrome associated with a fibrosarcoma of the mediastinum and multiple basal cell epitheliomas. In two of these basal cell epitheliomas, since the sclerotic skin made it difficult to assess the extent of the tumor, microscopically controlled excision (Mohs' chemosurgery technique) was employed.

Immunotherapy for accessible tumors utilizing delayed hypersensitivity reactions and separated components of the immune system.

Courses of repeated delayed hypersensitivity challenge reactions at the sites of tumors have been shown to eradicate malignant and premalignant epidermal neoplasms. Local immunotherapy produces therapeutic responses in malignant and premalignant lesions before they are clinically detectable. This leads to a reduced incidence and prevention of tumors. Immunotherapeutic approaches are effective in controlling the early stages of mycosis fungoides and may aid in the management of the cutaneous manifestations in the late stages of the disease. Immunotherapeutic methods induce regressions of soft tissue lesions of a number of multifocal or metastatic malignant diseases with or without concurrent chemotherapy. Immunotherapeutic effects on tumors are similar with primary and recall antigens. Separated components of the cell-mediated immune system induce regressions of tumors following intralesional or perilesional administration, indicating common factors in host defenses against malignant diseases.

Adding omalizumab to the therapy of adolescents with persistent uncontrolled moderate--severe allergic asthma.

OBJECTIVE: This study aimed to evaluate the effectiveness of omalizumab among adolescents with moderate-severe allergic asthma inadequately controlled with inhaled corticosteroids. PATIENTS AND METHODS: Data from patients 12 to 17 years of age were pooled from 5 placebo-controlled registration trials of omalizumab. Impact on asthma control was assessed by need for rescue bursts of oral corticosteroids, lung function, symptom scores, and unscheduled office visits. RESULTS: In adolescents (n = 146), addition of omalizumab decreased mean number of rescue bursts (0.3 vs 0.9) versus placebo; relative risk 0.47 (95% confidence interval [CI], 0.22-0.99; P = .047). At study conclusion, mean forced expiratory volume in 1 second increased 268 mL (13.8%) in omalizumab-treated subjects versus 98 mL (5.5%) for placebo (least squares mean treatment difference 146 mL [95% CI, 19.4-272.6; P = .024]). Omalizumab significantly improved asthma symptom scores and reduced unscheduled office visits. CONCLUSION: Omalizumab added to baseline therapy improves measures of asthma control in adolescents with persistent moderate-severe allergic asthma.

Is there a role for treatment of asthma with omalizumab?

The allergic response is distinct from other immune reactions in its reliance on IgE, its high affinity receptor, Fc epsilon RI, and the primary effector cell--the tissue mast cell. Positive skin tests or raised concentrations of specific immunoglobulin E (IgE) in the serum define IgE sensitisation or "atopy". IgE participates both in immediate hypersensitivity response and in the induction of chronic allergic inflammation. It enhances allergen capture and Th2 cell activation, and may trigger other immunoregulatory pathways. Considerable effort in therapeutic research has focused on interference with IgE function because of its position high in the allergic cascade. Therapy with anti-IgE is one such approach that shows much promise.

Anti-IgE therapy in children with asthma.

The prevalence of asthma continues to grow rapidly among children in areas undergoing urbanization. Current pharmacotherapy for asthma reduces inflammation and provides symptomatic relief, but it does not work for all patients and it does not entirely suppress the underlying disease. For these reasons new therapeutic approaches are still needed. Anti-IgE, the newest therapeutic modality for asthma, a biologic agent to control allergic disorders, represents a fundamentally new concept in treatment.

Asthma--something old, something new ....

Asthma is an inflammatory disease characterized by infiltration of the airways by eosinophils and ensuing bronchial hyperresponsiveness. The activation of eosinophils and their recruitment to the airways are strongly influenced by T-lymphocytes and their products. There is now evidence that successful therapy of asthma results in changes in the ratios of helper and suppressor T-lymphocytes both in the circulation and in bronchoalveolar lavage fluid. Theophylline, a drug which has been used in asthma therapy for many years, provides additional benefit for patients already treated with effective doses of beta-agonists and/or corticosteroids. The effects of theophylline on lymphocyte traffic and function have not been studied extensively. However, there is evidence from studies conducted in renal transplant recipients and patients with asthma that theophylline increases the numbers and activity of suppressor T-lymphocytes in the peripheral circulation. This property of theophylline may provide a therapeutic benefit in the treatment of asthma, one that is distinct from its activity as a bronchodilator.

Adverse effects of medications for rhinitis.

LEARNING OBJECTIVES: Reading this article will reinforce the reader's awareness of the adverse effects of medications used for the treatment of rhinitis. DATA SOURCES: Articles on therapy of rhinitis and reports of associated side effects were reviewed. A MEDLINE database using subject keywords was searched from 1992 through 1997. STUDY SELECTION: Pertinent articles were chosen. A distinction was made in the text between controlled studies and case reports. RESULTS: Antihistamines, decongestants, anticholinergic agents, and corticosteroids, alone or in combination are used in the treatment of rhinitis. Reported side effects include sedation, psychosis, impaired learning and memory, and cardiac arrhythmias. CONCLUSION: Rhinitis and its complications are important medical conditions. Adverse reactions are often difficult to diagnose and assess. Side effects may arise from the use of individual drugs or from drug combinations. There is insufficient cause to abandon these medications, but physicians must be mindful of the inherent risks of the drugs that they prescribe and of others that their patients may be taking without the physicians' knowledge or approval.

Nonadherence to asthma treatment and failure of therapy.

Adherence to clinical regimens is paramount in determining their effectiveness. Asthma is a chronic illness that requires consistent, anti-inflammatory therapy. A "high risk" profile for fatal or near-fatal asthma has emerged that includes suboptimal pharmacotherapy in conjunction with severe disease, psychologic dysfunction, black race or Hispanic-American ethnicity, and residence in an urban area with a high concentration of poverty. Collaboration between physicians and patients is necessary to allow individuals to make choices informed by medical facts and the physician's experience. Objective monitoring of adherence and pulmonary function and acceptance by the clinicians of the National Asthma Education and Prevention Program guidelines to control airway inflammation are essential in order to reduce the unacceptable rates of morbidity and mortality associated with asthma.