Farm animal exposure, respiratory illnesses, and nasal cell gene expression.

Background: Farm exposures in early life reduce the risks for childhood allergic diseases and asthma. There is less information about how farm exposures relate to respiratory illnesses and mucosal immune development.

Objective: We hypothesized that children raised in farm environments have a lower incidence of respiratory illnesses over the first 2 years of life than nonfarm children.

The association of allergic sensitization patterns in early childhood with disease manifestations and immunological reactivity at 10 years of age.

Background: Allergy to German cockroach (CR) is common in urban environments and is an important allergen in children with asthma.

Objective: We hypothesize that the evolution of allergic sensitization and clinical disease is associated with distinct patterns of allergen-specific T cell reactivity. To test this hypothesis, a subset of high-risk inner-city children participating in the URECA (Urban Environment and Childhood Asthma) birth cohort were selected to evaluate CR-specific T cell reactivity from three distinct groups based on acquisition of aeroallergen sensitivity from ages 2 to 10: low atopy with minimal to no sensitivity (n = 26), early-onset allergic sensitization (n = 25) and late-onset allergic sensitization (n = 25).

Patterns of immune development in urban preschoolers with recurrent wheeze and/or atopy.

Background: Disadvantaged urban children have high rates of allergic diseases and wheezing, which are diseases associated with type 2-biased immunity.

Objective: We sought to determine whether environmental exposures in early life influence cytokine responses that affect the development of recurrent wheezing illnesses and allergic sensitization.

Methods: A birth cohort of 560 urban families was recruited from neighborhoods with high rates of poverty, and 467 (83%) children were followed until 3 years of age.

The influence of atopy and asthma on immune responses in inner-city adults.

Asthma in the inner-city population is usually atopic in nature, and is associated with significant morbidity and mortality. However, the underlying immune abnormalities that underlie asthma in urban adults have not been well defined. We investigated the influence of atopy and asthma on cytokine responses of inner-city adult women to define immune abnormalities associated with asthma and atopy.

Relationships among environmental exposures, cord blood cytokine responses, allergy, and wheeze at 1 year of age in an inner-city birth cohort (Urban Environment and Childhood Asthma study).

Background: The Urban Environment and Childhood Asthma study was established to investigate the immunologic and environmental causes of asthma in inner-city children.

Objective: We sought to evaluate potential atopic outcomes in the first 12 months and their relationships to environmental exposures and immune development.

Methods: A birth cohort of 560 children with at least 1 parent with allergy or asthma was established in Baltimore, Boston, New York, and St Louis.

Phase II study of 1alpha-hydroxyvitamin D(2) in the treatment of advanced androgen-independent prostate cancer.

Purpose: In this single institution Phase II trial, we evaluated the efficacy of the vitamin D analogue, 1alpha-OH-D(2), in patients with advanced hormone-refractory prostate cancer.

Experimental Design: The patients initially received 1alpha-OH-D(2) at 12.5 micro g p.

Phase I pharmacokinetic and pharmacodynamic study of recombinant human endostatin in patients with advanced solid tumors.

Purpose: Endostatin is the first endogenous angiogenesis inhibitor to enter clinical trials. Laboratory investigations with endostatin have indicated broad antitumor activity coupled with remarkably low toxicity. A phase I trial of recombinant human endostatin was designed to evaluate toxicity and explore biologic effectiveness in patients with refractory solid tumors.

Phase I clinical and pharmacokinetic trial of the cyclin-dependent kinase inhibitor flavopiridol.

Purpose: Flavopiridol (NSC 649890) is a synthetic flavone possessing significant antitumor activity in preclinical models. Flavopiridol is capable of inducing cell cycle arrest and apoptosis, presumably through its potent, specific inhibition of cyclin-dependent kinases. We conducted a phase I trial and pharmacokinetic study of flavopiridol given as a 72-h continuous intravenous infusion repeated every 2 weeks.

Phase I clinical and pharmacokinetic study of NSC 655649, a rebeccamycin analogue, given in both single-dose and multiple-dose formats.

Purpose: NSC 655649 was given in both single- and multiple-dose formats, to characterize maximum tolerated dose (MTD), toxicity, and pharmacokinetic profile.

Experimental Design: Patients with advanced malignancies were treated with escalating doses of NSC 655649 in either a single-dose format (step 1) or a multiple-dose format (step 2). In step 1, NSC 655649 was given as a 30-60 min infusion.

Phase I clinical and pharmacokinetic study of oral penclomedine (NSC 338720) in adults with advanced solid malignancy.

Penclomedine is a synthetic alpha-picoline derivative that has shown antitumor activity both in preclinical development and in Phase I work using an i.v. preparation.

Phase I and pharmacokinetic study of a micronized formulation of carboxyamidotriazole, a calcium signal transduction inhibitor: toxicity, bioavailability and the effect of food.

Purpose: This Phase I study was conducted to evaluate the toxicity profile and determine the maximum tolerated dose (MTD) of an oral micronized formulation of the signal transduction inhibitor carboxyamidotriazole (CAI). Bioavailability of the micronized formulation relative to a gelatin capsule (gelcap) formulation was assessed. The effects of food intake and timing on CAI steady-state plasma concentrations (C(ss)) were also investigated.