Safety of fexofenadine in children treated for seasonal allergic rhinitis.

BACKGROUND: The incidence of allergic rhinitis in children is increasing. OBJECTIVE: To evaluate the safety of fexofenadine HCI in children ages 6 through 11 years for treatment of seasonal allergic rhinitis. METHODS: Two large, double-blind, randomized, placebo-controlled, parallel studies with identical protocols included patients with a positive skin test to fall allergen(s) and allergic rhinitis symptoms. Patients were randomized to receive fexofenadine 15, 30, or 60 mg or placebo twice daily for 2 weeks after a 1-week placebo lead-in. Safety was evaluated through adverse event reporting, electrocardiograms, and pre- and posttreatment laboratory panels and physical examinations. RESULTS: A total of 875 patients from both studies were eligible for safety analyses. Ten patients (5 on placebo, 5 on fexofenadine) discontinued because of an adverse event; no event that resulted in discontinuation was judged to be caused by study medication. Incidence of adverse events was similar in active and placebo groups, and did not increase with increasing fexofenadine dose: 36.2% (83 of 229) in the placebo group versus 35.3% (79 of 224), 36.8% (77 of 209), and 34.7% (74 of 213) in the 15, 30, and 60 mg twice-daily fexofenadine groups, respectively. Headache was the most commonly reported adverse event (6.6%, 8.0%, 7.2%, and 9.4% in the placebo, 15, 30, 60 mg twice-daily fexofenadine groups, respectively). Clinical, vital sign, electrocardiogram, and laboratory measures were similar in active and placebo groups. There was no statistically significant mean change from baseline in any electrocardiogram parameter after fexofenadine treatment. CONCLUSIONS: Fexofenadine, 15, 30, and 60 mg twice daily, was safe and well tolerated in this large pediatric patient population.

Once-daily mometasone furoate dry powder inhaler in the treatment of patients with persistent asthma.

BACKGROUND: Although inhaled glucocorticoids are recommended for all stages of persistent asthma, compliance with long-term therapy is often poor, leading to significant morbidity and mortality. A simplified, once-daily dosing regimen may foster improved compliance. OBJECTIVE: To compare the efficacy and safety of once-daily (AM) administration of mometasone furoate dry powder inhaler (MF DPI) 200 microg and 400 microg with placebo in patients with asthma previously maintained only on short-acting inhaled beta-adrenergic receptor agonists. METHODS: This was a 12-week, double-blind, placebo-controlled, parallel group study. The mean change from baseline to endpoint (last treatment visit) for FEV1 was the primary efficacy variable. RESULTS: At endpoint, both doses of MF DPI were significantly more effective than placebo (P < or = .05) in improving FEV1. Based on morning peak expiratory flow rate, once-daily MF DPI 400 microg was more effective than placebo (P < or = .001) at endpoint. Both active treatments also demonstrated improvement at endpoint in asthma symptom scores, physician-evaluated response to therapy and use of rescue medication. Although both MF DPI dosages were efficacious, MF DPI 400 microg provided additional improvement in some measures of pulmonary function (eg, morning PEFR) when these agents were administered once daily in the morning. Both doses of MF DPI were well tolerated and treatment-related adverse events occurred at a similar incidence among the three treatment groups. CONCLUSIONS: The results of this study indicate that once-daily (AM) MF DPI provides a convenient and effective treatment option for patients with mild or moderate persistent asthma.

Prevalence of sensitization to aeroallergens in California patients with respiratory allergy. Allergy Skin Test Project Team.

BACKGROUND: The number of allergy skin tests required to evaluate patients with respiratory allergy has recently been challenged by the managed care community. OBJECTIVES: The purpose of this study was to determine which aeroallergens are prevalent in patients with respiratory allergy (allergic rhinitis and bronchial asthma) in California. METHODS: Utilizing aeroallergens thought to be relevant from recent aerobiologic and botanic data, 141 allergic and 17 asymptomatic control subjects were tested for the prevalence of 103 allergens. A standardized prick puncture technique and standardized interpretation of wheal/flare responses were utilized using the same lot of allergen for 13 allergy practices distributed throughout California. Frequency curves based on prevalence were established to determine the number of tests required to give up to 90% of positive responses for tree, weed and grass pollen, mold spores, and miscellaneous allergens which included house dust mite, cat, dog, and cockroach allergens. RESULTS: Positive responses in allergic subjects for grasses ranged from 46% to 54%, for weeds 19% to 37%, and for trees 10% to 42%. For molds the range was from 11% to 22%. The response rate for Dermatophagoides pteronyssinus was 53%, for Dermatophagoides farinae 42%, for cat pelt 39% and cat hair 37%, for cockroach 23% and dog dander 19%. Asymptomatic control subjects responded to only 4% of all allergens tested. Ninety percent of all positive tests required three miscellaneous allergens (house dust mite, cat, and cockroach), 9 molds, 2 grasses, 16 weeds, and 27 trees for a total of 57 allergens (56% of total tested). There was no clear relationship between locale and specific allergen response, probably related to the limited number of subjects tested and variability within the same geographic region. Several seldom tested tree and weed allergens showed a higher prevalence rate than several commonly tested for allergens. CONCLUSIONS: This preliminary study suggests that approximately 57 aeroalleroens might be adequate to detect 90% of all positive responses in patients with respiratory allergy in California. This study was limited by subject number and variability between study sites. It is hoped a standardized model can be developed from this pilot study to definitively determine which aeroallergens are relevant in the United States.

The effectiveness of once-daily dosing of inhaled flunisolide in maintaining asthma control.

OBJECTIVE: The purpose of this study was to evaluate the feasibility of switching to once-daily (qd) administration of flunisolide in patients with asthma that was controlled by twice-daily (bid) dosing of this inhaled steroid. METHODS: Three hundred sixty-six adults and children with bronchial asthma that was controlled with inhaled steroids were recruited for this prospective, double-blind, parallel-group study. After a 4-week, stable baseline period of flunisolide administration, 2 inhalations (500 microg) twice daily, each patient was randomized into one of four 12-week flunisolide treatment groups: group 1, 2 inhalations (500 microg) bid; group 2, 4 inhalations (1000 microg) qd in the morning; group 3, 4 inhalations (1000 microg) qd in the evening; or group 4, 2 inhalations (500 microg) qd in the morning. Outcome measures included morning and evening asthma symptoms (scale of 0 to 3), daytime and nighttime albuterol use, morning and evening peak expiratory flow rate (PEFR), FEV1, and methacholine PC20. In addition, a subset of patients in each group had 24-hour urinary cortisol levels measured before and after randomization. RESULTS: Outcome measures in the four groups were not significantly different at baseline before randomization. The three groups that received maintenance therapy with flunisolide, 1000 microg daily, did not show significant changes from baseline values and remained comparable in all outcome areas. Asthma control in the group randomized to flunisolide 500 microg qd, however, deteriorated significantly: morning symptoms increased by 0.21 units (48%), evening symptoms increased by 0.15 units (31%), daytime albuterol use increased by 0.42 inhalations per day (37%), nighttime albuterol use increased by 0.48 inhalations per night (91%), morning PEFR decreased by 17.1 L/min (4%), and evening PEFR decreased by 12.6 L/min (3%). There were no significant changes in PC20 or 24-hour urinary cortisol levels in any group. CONCLUSIONS: For patients with asthma that was stabilized by 2 inhalations of flunisolide (500 microg) bid, switching to 4 inhalations (1000 microg) qd in either the morning or evening is effective in maintaining asthma control. Reducing the dose to 2 inhalations (500 microg) qd in the morning, however, leads to a deterioration in asthma control.

Once versus twice daily dosing of terfenadine in the treatment of seasonal allergic rhinitis: US and European studies.

Terfenadine was compared for efficacy in treatment regimens of 120 mg once daily (qd) and 60 mg twice daily (bid) in patients with seasonal allergic rhinitis in double blind, randomized, parallel 1-week studies, three in Europe (one multicenter study, three sites; n = 191) and one in the US (single center; n = 201). Patients had moderate or severe symptoms for 2 or more years and positive skin tests to relevant pollen antigens. On entry and final visit individual symptoms were rated by physicians on a visual analog scale in Europe and a numerical scale in the US. Most patients filled out daily symptom diaries during the studies. Individual symptom scores and total symptom scores, (calculated by adding individual symptom scores together) as assessed by physicians and patients, were similar at baseline for both treatment regimens on entry, with improvement during the week. There were more patients with complete and marked relief in Europe than in the US. (Total symptom scores as assessed by physicians, for instance, improved from baseline ratings of 407 for the 60 bid regimen and 431 for the 120 qd regimen in Europe to 102 and 95 at final visit, and in the US from 8.8 for 60 bid and 8.5 for the 120 qd to 4.5 and 4.1). There was no statistical difference between the two treatment regimens in Europe or the US. Terfenadine, 120 mg once daily, is as effective as the currently approved dosage of 60 mg twice daily in the treatment of seasonal allergic rhinitis, and terfenadine, 120 mg once daily, has the added convenience of allowing the patient once a day dosing.

Bone marrow transplantation in DiGeorge syndrome.

A Hispanic infant girl with DiGeorge syndrome underwent successful bone marrow transplantation (BMT) at age 28 1/2 weeks. She had typical facies, a cardiac defect, hypoparathyroidism, severe T and B cell immunodeficiency, and low levels of facteur thymique serique (FTS). In vitro incubation of the peripheral blood lymphocytes with thymosin alpha 1 showed no increase in the number of T cells on two occasions. A fetal thymus for transplantation was not available, and further review of past experience with thymic cells or factors revealed inconsistent and incomplete responses. Because of the patient's worsening clinical and immunologic status, BMT was performed, with her histocompatible brother as donor. The patient has had a good clinical and immunologic response to BMT, with evidence of T cell engraftment, improved B cell function, and increased levels of serum FTS. This experience indicates that minimal thymic influence is necessary for successful BMT and that patients with DiGeorge syndrome with significant T cell deficiency may benefit from this treatment.

Efficacy of doxepin in the treatment of chronic idiopathic urticaria.

Doxepin hydrochloride, a tricyclic antidepressant, was evaluated in a double-blind, placebo-controlled crossover trial for the treatment of chronic idiopathic urticaria in 16 adults. Efficacy was evaluated by symptom scores, concomitant antihistamine use, and suppression of histamine- and codeine-induced wheal response. Doxepin-treated subjects experienced fewer lesions (p less than 0.001), less waking hours with lesions (p less than 0.01), lesser degree of itch and/or discomfort (p less than 0.001), and less swelling or angioedema (p less than 0.001) as compared to placebo-treated subjects. Doxepin-treated subjects required less daily concomitant antihistamine use (mean 0.13 tablets versus 1.48 tablets, p less than 0.05). Doxepin also significantly suppressed histamine- and codeine-induced cutaneous wheal response as compared to placebo. Lethargy was commonly observed but diminished with continued use. Dry mouth and constipation were also commonly observed. We conclude that doxepin is an effective agent for the treatment of chronic idiopathic urticaria.

Phenotypic and cytotoxic characteristics of the immune cells of the human placenta.

Despite some functional impairment of the newborn's T-cell immune system, most infants survive the intrauterine and perinatal period without succumbing to infection or maternal lymphocyte engraftment. The placenta may play a crucial role in protecting the infant from microbial and histocompatibility antigens. Accordingly, we studied phenotypic and functional capacities of placental cells. Placentas were obtained from uncomplicated pregnancies. Matched cord blood and maternal peripheral blood were also obtained in many instances. Fresh minced placental tissue was washed and digested with collagenase and DNase and mononuclear cells were obtained by density gradient centrifugation. The average yield was 10(6) cells/g of tissue with greater than 80% viability. Chromosome analysis of five placental preparations indicated that these cells were of fetal rather than maternal origin. The isolated placental cells consisted of trophoblasts, lymphocytes (74 +/- 3%), monocytes (16 +/- 3%), and granulocytes (8 +/- 2%). E-rosette forming cells (T cells) made up 65 +/- 2% and surface membrane immunoglobulin positive cells made up 8 +/- 1% of the placental mononuclear cells. Fluorescent activated analysis of the mononuclear cells indicated less Leu 4-positive cells (Pan-T) 43 +/- 3%, and less Leu 3-positive (T-helper cells) (25 +/- 2%), than cord and maternal cell preparations. Leu-2, DR, and B1 positive cells were similar to those in cord and maternal blood. Leu 7 and especially Leu 11 positive cells, markers for natural killer cells, were abundant in placental cells, making up 4 +/- 0.7% and 20 +/- 3%, respectively. The Leu 7/Leu 11 ratio of the placental cells was different from either the maternal or cord blood cells. Natural killer activity of placental cells against a K562 natural killer target was low, despite the abundance of cells with NK markers. The K562 activity was low in the placental cells, similar to the low NK activity of maternal and cord cells. Molt 4f killer activity was near normal. Lectin-dependent cytotoxicity using an EL-4 cell target plus PHA was low in placentas, compared to normal, maternal, or cord cell cytotoxicity. Matched samples indicated that LDCC activity was mother greater than cord greater than placenta. Antibody-dependent cytotoxicity (Raji target) of placental cells showed low activity, and again the paired studies indicated that normal controls greater than maternal greater than cord greater than placenta cytotoxicity.(ABSTRACT TRUNCATED AT 400 WORDS)

The use of sodium 2-mercaptoethane sulfonate to prevent cyclophosphamide cystitis.

In 2 patients receiving bone marrow transplantation sodium 2-mercaptoethane sulfonate has proved efficacious in preventing the serious problem of cyclophosphamide cystitis by regional detoxification of acrolein. We detail the first use of sodium 2-mercaptoethane sulfonate in the United States. We are cautiously enthusiastic and optimistic that the simultaneous administration of sodium 2-mercaptoethane sulfonate and cyclophosphamide will decrease if not eliminate cyclophosphamide-induced carcinoma.

Congenital stiff-man syndrome.

A second large family with a dominantly inherited benign disorder resembling the stiff-man syndrome is reported. The infants are markedly hypertonic at birth, but their tone becomes almost normal by 3 years of age. Stiffness reappears at adolescence, often precipitated by sudden movement or cold, but remains mild when compared with the sporadic disorder.