Efficacy and safety of levocabastine nasal spray for seasonal allergic rhinitis.

This multicenter, double-blind, placebo-controlled trial evaluated the efficacy and safety of levocabastine nasal spray, a potent and selective H1-receptor antagonist, in the control of histamine-mediated symptoms of seasonal allergic rhinitis. Adults with > or = 2 year history of allergic rhinitis due to Mountain Cedar were randomized to treatment with levocabastine nasal spray (0.2 mg twice daily) or placebo for 28 days during the 1994-1995 Mountain Cedar allergy season. Patients assessed the severity of their rhinitis symptoms on a four-point scale twice daily. At the end of the trial, patients also performed a global evaluation of treatment efficacy on a five-point scale. Overall for the 4-week treatment period, levocabastine nasal spray significantly reduced major nasal (runny nose and sneezing) and primary rhinitis (runny nose, sneezing, and itchy/gritty eyes) symptoms compared with placebo on both repeated measures (p = 0.023; p = 0.01) and ANOVA (p = 0.003; p < 0.001) analyses. Global evaluations of treatment efficacy at the end of the trial significantly favored levocabastine over placebo (p = 0.002). Overall, the incidence of adverse events was similar for both treatment groups. In general, most adverse events were mild in intensity, with sinusitis (17% each group), headache (17% placebo, 14% levocabastine), and rhinitis (8% placebo, 2% levocabastine) most commonly reported. Levocabastine nasal spray 0.2 mg twice daily was significantly more effective than placebo in the relief of histamine-mediated symptoms in patients with seasonal allergic rhinitis and was well tolerated over the 28-day treatment period.

Undetectable interferon-alpha serum levels in a patient with atopic dermatitis.

A 3-year-old boy [corrected] was evaluated for the possible diagnosis of hyperimmunoglobulin E syndrome (HIES). From the age of 4 months he developed significant atopy and was subsequently diagnosed with severe atopic dermatitis, asthma, and allergic rhinitis, with moderately high total serum IgE levels. Because IgE production has been shown to be regulated by cytokines produced by the CD4+ helper T lymphocyte subsets, we measured the circulating levels of cytokines representative of these cellular subsets in this patient. We therefore measured serum levels of interleukin-4 (IL-4), the Th2 subset-derived cytokine that upregulates IgE synthesis, as well as the levels of interferon-gamma and interferon-alpha (IFN-gamma/alpha), cytokines produced by the Th1 subset that inhibit IL-4-mediated IgE upregulation. We found that in this patient, IL-4 levels were normal, indicating normal Th2 activity. The levels of IFN-gamma were higher than normal, but the serum IFN-alpha levels in this patient were undetectable and were actually below the normal range. Thus, even though both IFN-gamma and IFN-alpha have been shown to be necessary for controlling IL-4 actions, the selective absence of IFN-alpha, even in the presence of normal or increased amounts of IFN-gamma, could permit IL-4 induced IgE production. Lack of IFN-alpha may explain this patient's recurrent infections, as well as IgE-induced atopic conditions. Our data in this study with the patient showing selective deficiency of IFN-alpha but not of IFN-gamma provide support for the role of IFN-alpha in the pathogenesis of atopic dermatitis. The findings in this patient clearly warrant further studies of IFN-alpha in patients with atopic disorders.

Purified human fibroblast interferon in vivo: skin reactions and effect on bone marrow precursor cells.

Human interferon from normal diploid fibroblasts, purified by sequential chromatography on concanavalin A-agarose and phenyl-sepharose, was administered parenterally in 4 subjects. Fever, marked skin hypersensitivity reactions and suppression of marrow stem cells (estimated by the count of myeloid colony-forming cells), side-effects common for less purified fibroblast and leukocyte interferons, were absent. Purified fibroblast interferon retained antiviral and immunomodulatory activity, evidenced by reduction of the blastogenic response of peripheral lymphocytes and decrease of hepatitis B virus markers in a patient with chronic hepatitis B infection treated with this substance.

Fibroblast interferon treatment of a patient with chronic active hepatitis. Increased number of circulating T lymphocytes and elimination of rosette-inhibitory factor.

A 23 year old woman with chronic active hepatitis documented by liver biopsy demonstrated persistent hepatitis B surface antigen, hepatitis B virus specific DNA polymerase hepatitis B core antigen (HBcAg), for approximately one year. The number of circulating T lymphocytes that rosetted with sheep erythrocytes was decreased, and a rosette-inhibitory factor was present in her peripheral blood. Interferon treatment (1 X 10(6) U/day intramuscularly for 82 days) resulted in a decrease of HBsAg and disappearance of HBcAg, (HBeAg) and specific DNA polymerase. In addition, the number of T lymphocytes increased to normal, and the rosette-inhibitory factor disappeared from the circulation. These findings suggest that the effect of interferon in chronic active hepatitis is mediated in part through its action on the immune system.

Human fibroblast interferon in human neoplasia: clinical and laboratory study.

Human fibroblast interferon (HFIF) produced on a large scale from normal diploid cell strains was highly purified and then evaluated as to its safety clinical investigation. The selective antiproliferative activity of HFIF was observed in vitro against certain human malignant cell lines and in vivo against human bladder tumors grown in nude mice. Direct injections of HFIF into metastatic melanoma lesions of two patients resulted in either the disappearance of malignant cells or the significant reduction in tumor volume.

An improved micro-method for enumeration of human B-cell rosettes with mouse red blood cells.

A micro-method for enumerating B-lymphocytes in human peripheral blood is described, using formation of rosettes with mouse red blood cells as a B-cell marker. The optimal conditions for the enumeration of mouse red cell rosette forming cells have been defined. By this method, it was possible to utilize less than 1ml of peripheral blood (venous or capillary) for simultaneous enumeration of both T-cell and B-cell rosettes. Our study of human lymphoid cell lines, thymic cells, lymphocytes from agammaglobulinemia, and severe combined immunodeficiency has provided additional evidence that lymphocyte rosetting with mouse red blood cells represent B-lymphocytes.