The use of plethysmography and oscillometry to compare long-acting bronchodilators in patients with COPD.

What Is Already Known About This Subject: Forced expiratory volume in 1 s (FEV(1)) is the standard measurement used to measure drug effects in chronic obstructive pulmonary disease (COPD) clinical trials. Having previously shown that specific airway conductance (sGaw) measured using body plethysmography and impulse oscillometry (IOS) are more sensitive than FEV(1) for assessing short-acting bronchodilator effects in patients with COPD, we conducted the first randomized, placebo-controlled study to compare long-acting bronchodilators in COPD patients using these techniques.

What This Study Adds: sGaw and IOS sensitively differentiated between the effects of tiotropium and salmeterol when FEV(1) measurements were similar.

Bronchodilating effect of combined therapy with ipratropium bromide and ondansetron in patients with COPD.

The objectives of this study were to determine the effect of single and repeat dosing with oral ondansetron, a 5-HT3-specific receptor blocker, on the degree and duration of bronchodilation induced by inhaled ipratropium bromide in patients with COPD. Five clinics and university medical centers in four countries participated in the study; 47 patients with COPD were randomized to treatment; 44 completed all treatments. Patients had a baseline (pre-bronchodilator) FEV1>1L and post-bronchodilator (200 mcg salbutamol) FEV1<90% of predicted, with FEV1 reversibility (to 80 mcg inhaled ipratropium bromide and 400 mcg salbutamol) of at least 12% or 200 mL over baseline.

A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma.

Rationale: Accumulation of eosinophils in the bronchial mucosa of individuals with asthma is considered to be a central event in the pathogenesis of asthma. In animal models, airway eosinophil recruitment and airway hyperresponsiveness in response to allergen challenge are reduced by specific targeting of interleukin-5. A previous small dose-finding study found that mepolizumab, a humanized anti-interleukin-5 monoclonal antibody, had no effect on allergen challenge in humans.

Plethysmography and impulse oscillometry assessment of tiotropium and ipratropium bromide; a randomized, double-blind, placebo-controlled, cross-over study in healthy subjects.

Aims: Spirometry, plethysmography and impulse oscillometry (IOS) measure different aspects of lung function. These methods have not been compared for their ability to assess long- and short-acting anticholinergic agents. We therefore performed a double-blind, placebo-controlled, four-way cross-over study in 30 healthy subjects.

Pranlukast, a cysteinyl leukotriene receptor antagonist, attenuates allergen-induced early- and late-phase bronchoconstriction and airway hyperresponsiveness in asthmatic subjects.

Background: The cysteinyl leukotrienes (cysLTs) have been implicated in the pathogenesis of allergen-induced airway responses. The purpose of this study was to evaluate the effects of pretreatment with the cysLT receptor antagonist pranlukast on allergen-induced early asthmatic responses (EARs) and late asthmatic responses (LARs) and on allergen-induced airway hyperresponsiveness (AHR).

Methods: Ten atopic, nonsmoking patients with mild asthma and previously demonstrated early- and late-phase allergen-induced asthmatic responses participated in a double-blind, placebo-controlled, cross-over study, comparing treatment with either 450 mg pranlukast given twice daily or placebo for 5.

Results of the first U.S. double-blind, placebo-controlled, multicenter clinical study in asthma with pranlukast, a novel leukotriene receptor antagonist.

Pranlukast (SB 205312; ONO-1078), a potent, orally active selective cysteinyl-leukotriene receptor antagonist (LTRA), was developed in Japan for the treatment of asthma. This article reports results of the initial U.S.

A placebo-controlled multicenter study of auranofin in the treatment of patients with corticosteroid-dependent asthma. Auranofin Multicenter Drug Trial.

Background: Previous clinical studies have demonstrated that injectable gold salts and the oral gold compound, auranofin, possess significant steroid-sparing effects in the treatment of asthma.

Objectives: The objectives of this investigation were to determine whether auranofin could reduce oral corticosteroid requirements and to evaluate the safety of auranofin in the treatment of chronic corticosteroid-dependent asthma.

Methods: Patients with asthma were eligible if they required at least 10 mg of prednisone per day for control and prevention of asthma exacerbations.

Reaction of antipolynucleotide antibody from systemic lupus erythematosus patient serum with double-stranded DNA complexed to protein.

Antipolynucleotide antibody from systemic lupus erythematosus patient serum was found to interact with common determinants of double-stranded DNA (dsDNA) complexed to protein within nucleosomes, and with protein-free denatured DNA. In contrast, purified dsDNA isolated from nucleosomes manifested decreased reactivity with antipolynucleotide antibody. These data suggest that immunoassays using denatured DNA antigen substrate are useful for identifying a broad spectrum of antipolynucleotide antibodies that are reactive with dsDNA complexed to protein.

Inhibition of leukocyte adherence by potassium chloride extract of allogeneic squamous cell carcinoma of the human uterine cervix.

Leukocyte adherence inhibition (LAI) assay was used to evaluate cell-mediated immunity in patients with invasive squamous cell carcinoma of the cervix. The reactivity of the peripheral blood leukocytes of these patients was evaluated after incubation with pooled extracts of allogeneic squamous cell carcinoma of the cervix. One hundred sixty-seven sets of LAI assays were performed on 54 individuals, including 23 patients with Stage I squamous cell carcinoma of the cervix, 9 patients with other stages of this tumor, 9 patients with unrelated tumors and 13 normal healthy volunteers.

Sequential in vitro reactivity of lymphocytes from patients with cervical squamous malignancy in a cytotoxicity assay.

The in vitro reactivity of peripheral blood lymphocytes from patients with cervical squamous malignancy was prospectively followed over a relatively long period of time. In 12 of 14 patients with preinvasive cervical lesions, reactivity was present at the time of initial diagnosis. Three months after treatment, reactivity was still present in only one of 12 (8%).

Partial characterization of serum suppressor factors in patients with cervical squamous carcinoma.

A cell-mediated cytotoxicity system was used to characterize the suppressor factors in sera from patients with invasive squamous cell carcinoma of the uterine cervix. The immunoglobulin-M fraction of the sera of 17 patients with different stages of invasive squamous cell carcinoma of the cervix, separated by Sephadex gel filtration, were tested. All showed marked cytotoxic suppressor activity, including two cases in which sera showed only mild activity.

Pathology of metastasizing tumors in nitrosomethyl urea-induced rat mammary carcinoma.

The metastatic capacity of rat mammary tumors induced with N-nitrosomethyl urea was tested in BUF/N inbred female rats by successive transplantation. After the first and second passage, tumor cells appeared diffusely distributed throughout the bone marrow and spleen, confirming results reported by others; no other metastases were observed. After six successive transplantations, large, well-defined tumor nodules were observed in the liver, spleen, lung, and the peritoneal surface of the intestines in 40% of the injected animals.

Cytotoxic blocking activity in invasive squamous cell carcinoma of the human uterine cervix.

A cell-mediated cytotoxicity assay was used to evaluate the specific reactivity of patients with squamous cell carcinoma to an established cell line derived from squamous cell carcinoma of the cervix. Heat inactivated sera from patients with squamous cell carcinoma could very effectively nullify this specific cytotoxicity (P less than 0.01).

Cell-mediated cytotoxicity in preinvasive and invasive squamous cell carcinoma of the cervix.

Cell-mediated immunity was tested by coincubation of target cell line (2043) of human squamous cell carcinoma and peripheral blood leukocytes (PBL) of 22 patients with squamous cell neoplasia of the uterine cervix, 9 patients with other tumors, and 9 normal females. The percentage of cell reduction in mild dysplasia was 90.1 +/- 6.

Isolation and characterization of a human liver and kidney-specific protein: the hepato-renal (H-R) antigen.

This paper reports the isolation and characterization of a soluble antigen shared by the liver and kidney of human and some other animal species. Homogenates of human liver in saline were centrifugated at 27,000 g and the supernatants were fractionated by preparative polyacrylamide gel electrophoresis. The gels were divided in sections and each was injected into rabbits; after absorption with polymerized normal human serum, the antiserum obtained by injecting one of the sections reacted only with saline extracts of human liver and kidney when tested against a variety of human tissue extracts.

Isolation and characterization of a human pancreas-specific protein.

Homogenates of human pancreas in saline were centrifuged at 27 000 X g and the supernates were fractionated by preparative polyacrylamide gel electrophoresis. The gels were divided into sections and each section was injected into rabbits; after absorption with polymerized serum from apparently normal humans, the antiserum obtained by injecting one of the sections was tested against a variety of human tissue extracts but reacted only with saline extracts of human pancreas. The absorbed antiserum, polymerized and made insoluble with glutaraldehyde, was used to purify a pancreas-specific antigen by immunoaffinity batch technique.

Leukocyte migration in ovarian carcinoma: comparison of inhibitory activity of tumor extracts.

Inhibition of migration of leukocytes from patients with serous cystadenocarcinoma of the ovary was studied by the use of several different types of ovarian carcinoma extract as antigen. KCl extract of an ovarian carconoma was found to be the most effective antigen preparation in comparison with saline, deoxycholate, and perchloric acid extracts. Low concentrations of KCl ovarian carcinoma extract significantly inhibited migration of leukocytes from 11 of 17 patients with ovarian carcinoma (migration index, less than 0.

Radioimmunoassay for antibodies to cytoplasmic ribosomes in human serum.

A radioimmunoassay for the detection of antibodies in human serum to tritium-labeled HeLa cell cytoplasmic ribosomes was developed with the use of Macaloid for the inhibition of endogenous ribonuclease activity. Antibodies were observed in the serum of patients with systemic lupus erythematosus in high incidence and titer. Patients with rheumatoid arthritis and chronic active hepatitis manifested a lower incidence and titer of antibodies to ribosomes, whereas serums from normal individuals and from patients with sarcoidosis, chronic glomerulonephritis, and malignant tumors showed no significant reactivity with cytoplasmic ribosomes.

Avidity of anti-DNA antibodies in serum and IgG glomerular eluates from patients with systemic lupus erythematosus. Association of high avidity antinative DNA antibody with glomerulonephritis.

Significant differences in both specificity and avidity of anti-DNA antibodies were observed in the sera of groups of patients with active systemic lupus erythematosus glomerulonephritis, active systemic lupus erythematosus without nephritis, and in IgG eluates obtained by DNAase digestion of isolated glomeruli from glomerulonephritic kidneys. With methylated albumin-kieselguhr fractionated 3H-HeLa DNA as a source of native or single-strand DNA antigen in a modified Farr assay, an increased level of antibody to native DNA was associated with active systemic lupus erythematosus, particularly active nephritis. The avidity of antinative DNA estimated from plots of the reciprocals of bound and free antigen according to the Sips distribution formula was significanly lower in active glomerulonephritis sera than in sera from patients with active systemic lupus erythematosus without nephritis.