Drop weight variation in an automated collection procedure and its relationship to apparent surface tension.

A drop counter-regulated fraction collector yields samples containing equal numbers of drops. Such fractions vary slightly in weight depending on experimental conditions such as surface tension. Provided that variables such as flow rate and eluate density remain constant, apparent surface tension may be estimated directly from the weights of eluate fractions obtained from gel filtration experiments. The detergents sodium cholate and sodium lauryl sulphate significantly decreased drop weights in this system. Following gel filtration on Sepharose 4B, sodium cholate eluted in the fractions containing low molecular weight material. It eluted in the same position when pre-mixed with human plasma. Normal plasma was found to contain two surface tension-reducing components with apparent molecular weights of 3-10(6) and 1-10(5). The apparent surface tension of whole human plasma was found to be time dependent and decreased as the flow rate was reduced.

Human bone marrow progenitor cells stimulated by cord blood.

Agar cultures of human bone marrow cells stimulated by cord plasma or irradiated cord blood feeder layers demonstrated the presence of a multilineage hemopoietic growth factor in cord blood. When bone marrow cultures stimulated with giant cell tumor-conditioned medium (GCT-CM) were supplemented with this cord blood-derived growth factor, total colony numbers increased by more than 50% after day 23 and persisted in culture for approximately 40 days. Marrow cultures stimulated by the cord blood-derived growth factor formed colonies of neutrophils, monocyte-macrophages, eosinophils, mast cells, and a few colonies containing a mixed cell population. The results suggest that, while GCT-CM contains granulocyte-monocyte colony-stimulating factor (GM-CSF), cord blood contains a high concentration of a multilineage hemopoietic growth factor, which may be multi-CSF.

Immunophenotypic analyses of cultured hemopoietic mast cells.

Immunophenotypic analyses of immature stage (day 19-23), intermediate stage (day 28-32), mature stage (day 34-37), and older stage (day 42-44) human hemopoietic mast cells from colonies grown in semi-solid agar cultures were performed to study the ontogeny and identity of this cell type and its relationship to other leukocytes. Intermediate to mature stage mast cells were positive with the YB5.B8 mouse monoclonal antibody, (McAb) specific for human mast cells, whereas the reactivity of immature mast cells with this McAb was inconsistent and older cells were generally negative. Mast cells at all stages of maturation were strongly positive for IgE receptor sites and negative with the Bsp-1 McAb, specific for human basophils. Mast cells at all stages of maturation were also strongly positive with the monocyte McAbs RPA-M1 (CD11), positive with the monocyte McAb OKM5 and the monocyte/granulocyte McAbs BMA-210 and MY7 (CD13), strongly positive with the B-cell markers J5 (CD10) and anti-IgM, and positive with the plasma cell marker PCA-1 and to a lesser extent with the activated B-cell marker CD23. The mast cells were also strongly positive with anti-CD45 to the common leukocyte antigen and positive with an antibody to HLA-DR and an antibody to FVIIIC. They were negative for specific T-cell markers. The diversity of this phenotype supports the current concept that mast cells originate from the pluripotential progenitor cells in the bone marrow.

Identification and characterization of human hemopoietic mast cell colonies.

Persisting mast cell colonies from human bone marrow and cord blood cells grown in semisolid agar cultures for over 56 days have been positively identified and characterized using morphology and cytochemistry. Mast cells demonstrated the following features: Cytoplasmic granules frequently contained the specific and characteristic papyrus rolls (transmission electron microscopy); mature cells were positive to the mouse monoclonal antibody YB5.B8 specific for human mast cells (raised against acute myeloid leukemia cells) and RPA-M1 specific for human monocytes but negative to the human basophil monoclonal antibody Bsp-1; morphologically the cells were large (diameter 20-25 micron), deeply basophilic, and contained granules that measured up to 2 micron in diameter (May-Grünwald-Giemsa stain); the presence of heparin by the thrombin clotting time and positive staining with toluidine blue and alcian blue; the presence of histamine by a positive fluorescent o-phthalaldehyde stain; the presence of IgE receptor sites with human IgE and a rabbit anti-human IgE second antibody; and a unique zone of lysis around mast cell colonies occurred when cultured on peripheral blood feeder layers in agar plates that was not present around monocytic, neutrophilic, or eosinophilic colonies under the same culture conditions. Our results identify the cells in persisting colonies as mast cells and describe some specific characteristics that distinguish these cells from basophils.

Effectiveness of enteral and parenteral nutrition in the nutritional management of children with Wilms' tumors.

The effectiveness of enteral and parenteral feeding in supporting a satisfactory nutrition status and/or reversing protein-energy malnutrition was evaluated in nine children, ages 1 to 7 years (eight female), with Wilms' tumors. At the onset of treatment, eight patients received comprehensive enteral nutrition (CEN) which included intense nutritional counseling and oral supplements while one received total parenteral nutrition (TPN). Despite CEN, the initial, intense treatment period was associated with a decreased energy intake (64 +/- 27% Recommended Dietary Allowances), dramatic weight loss (22 +/- 7% by 26 +/- 17 days from the beginning of treatment), decreased skinfold thickness (< 10th percentile), and decreased albumin concentrations (< 3.2 g/dl). Four of those who initially received CEN subsequently required TPN. A total of five patients received TPN for a mean of 31 days (range 11 to 60); kcal averaged 105 +/- 9% Recommended Dietary Allowances during weight gain. At onset of TPN, the mean albumin, transferrin, total lymphocyte count were 3.02 +/- 0.45 g/dl, 155 +/- 40 mg/dl, and, 655 +/- 437/mm3, respectively; all children had abnormal anthropometric measurements and anergy to recall skin test antigens. TPN for 28 or more days supported weight gain (+ 2.44 kg), increased serum albumin (+ 0.58 +/- 0.47 g/dl) and transferrin (+ 76 +/- 34 mg/dl), and reversed anergy despite low total lymphocyte counts. During maintenance treatment, nutritional status was maintained or restored with CEN in the group who responded. These preliminary data document the severity of protein-energy malnutrition which accompanies initial, intense treatment of children with Wilms' tumors, the nutritional and immunological benefits of TPN during continuing intense treatment and the effectiveness of CEN in maintaining a satisfactory nutritional status during maintenance treatment.

Effectiveness of central parenteral nutrition versus peripheral parenteral nutrition plus enteral nutrition in reversing protein-energy malnutrition in children with advanced neuroblastoma and Wilms' tumor: a prospective randomized study.

The effectiveness of central parenteral nutrition (CPN) versus peripheral parenteral nutrition (PPN) plus enteral nutrition in reversing protein-energy malnutrition was evaluated in 19 children (nine CPN, 10 PPN) with advanced neuroblastoma or Wilms' tumor. Weekly dietary, anthropometric, and biochemical measurements were compared for 15 patients (eight CPN, seven PPN) who completed more than 25 days of nutrition support. The groups had similar mean energy and protein intakes (CPN: 95 +/- 5% of healthy children, 2.5 +/- 0.3 g/kg; PPN: 102 +/- 5% of healthy children, 2.9 +/- 0.3 g/kg). Increases in weight (p less than 0.001), subscapular skinfold thickness (p less than 0.001), albumin (p less than 0.05), and transferrin (p less than 0.05) for the first 28 days were significant and did not differ between groups. Fever, sepsis, elevated SGOT, and severe anemia occurred with both CPN and PPN. PPN resulted in subcutaneous infiltrations and more psychological trauma. PPN with enteral nutrition seems most appropriate for short term intravenous nutrition support or as a temporary substitute for CPN; CPN is preferred for long-term support.

Lack of improved growth outcome related to nonnutritive sucking in very low birth weight premature infants fed a controlled nutrient intake: a randomized prospective study.

The effect of nonnutritive sucking during gavage feeding on nutritional outcome and gastrointestinal transit time was evaluated in 18 premature appropriate for gestational age infants whose birth weights were less than or equal to 1,400 g and gestational ages were less than or equal to 30 weeks. Infants were randomized to a treatment (nonnutritive sucking infants received a pacifier for 30 minutes with each feeding, 12 times per day until they reached a weight of 1,500 g, eight times per day thereafter) or control (no pacifier) group. The nine nonnutritive sucking (five girls, four boys) and nine control (five girls, four boys) infants were treated for 14 days. Infants were without medical complications and were fed a single premature formula by intermittent gastric gavage at exactly 120 kcal/kg/d throughout the study period. Weight gain, linear growth, subscapular and triceps skinfold, and arm circumference accretions were assessed weekly. Serum proteins (albumin, prealbumin, retinol-binding protein, and transferrin) were measured weekly. Gastrointestinal transit times were measured weekly using carmine red markers. In contrast to previous studies, these data indicate no apparent effect of nonnutritive sucking on growth outcome, serum proteins, or gastrointestinal transit time in growing, very low birth weight infants when nutrient intake was controlled. In a subgroup of eight boys (four nonnutritive sucking, four control), energy and fat excretions were determined from 72-hour fecal collections and energy expenditure was estimated from six-hour cumulative heart rate measurements. Neither excretion of fat and calories nor estimated energy expenditure was affected significantly by nonnutritive sucking in this subgroup of baby boys. Fat excretion correlated well (r = .987) with energy excretion.

Haemophilia in Australia.

The major problems currently facing haemophilia management in Australia relate to (1) a need for better co-ordination of our entire national effort for haemophilia therapy and (2) a need to improve the efficiency of our preparation of factor VII concentrates. If we could simply double or treble our factor VIII yields from the same volume of donor plasma many of our urgent treatment problems could be solved.

Persisting colonies in agar cultures containing serum from patients with CML in blastic transformation.

Addition of serum from patients with chronic myeloid leukemia (CML) in both chronic phase and blastic transformation, to agar cultures of normal human marrow cells stimulated the growth of persisting colonies (day 35) containing either eosinophils or mast cells. Chronic phase serum stimulated an 800% increase in the total number of these colonies of which only 16% were mast cells. Serial studies using serum from 2 patients demonstrated that the proportion of mast cells increased during the progression to blastic transformation. The emergence of a greater proportion of persisting mast cell colonies and a decrease in absolute number of eosinophil colonies in agar cultures of normal marrow cells containing serum from patients with CML coincides with the emergence of blastic transformation and suggests that a significant change occurs in the absolute and relative concentration of hemopoietic growth factors in these patients.

Salmeterol powder provides significantly better benefit than montelukast in asthmatic patients receiving concomitant inhaled corticosteroid therapy.

STUDY OBJECTIVES: Comparison of inhaled salmeterol powder vs oral montelukast treatment in patients with persistent asthma who remained symptomatic while receiving inhaled corticosteroids. DESIGN: Randomized, double-blind, double-dummy, parallel-group, multicenter trials of 12-week duration. SETTING: Outpatients in private and university-affiliated clinics. PATIENTS: Male and female patients > or = 15 years of age with a diagnosis of asthma (baseline FEV(1) of 50 to 80% of predicted) and symptomatic despite receiving inhaled corticosteroids. INTERVENTIONS: Inhaled salmeterol xinafoate powder, 50 microg bid, or oral montelukast, 10 mg qd. MEASUREMENTS AND RESULTS: Treatment with salmeterol powder resulted in significantly greater improvements from baseline compared with montelukast for most efficacy measurements, including morning peak expiratory flow (35.0 L/min vs 21.7 L/min; p < 0.001), percentage of symptom-free days (24% vs 16%; p < 0.001), and the percentage of rescue-free days (27% vs 20%; p = 0.002). Total supplemental albuterol use was decreased significantly more in the salmeterol group compared with the montelukast group (- 1.90 puffs per day vs - 1.66 puffs per day; p = 0.004) and nighttime awakenings per week decreased significantly more with salmeterol than with montelukast (- 1.42 vs - 1.32; p = 0.015). Patients treated with inhaled salmeterol were significantly more satisfied with their treatment regimen and how well, how fast, and how long it worked than were patients who were treated with oral montelukast. The safety profiles for the two treatments were similar. CONCLUSION: In patients with persistent asthma who remain symptomatic while receiving inhaled corticosteroids, adding inhaled salmeterol powder provided significantly greater improvement in lung function and asthma symptoms and was preferred by patients over oral montelukast.

Salmeterol vs theophylline: sleep and efficacy outcomes in patients with nocturnal asthma.

STUDY OBJECTIVES: To compare the efficacy, safety, and effects on sleep quality of salmeterol and extended-release theophylline in patients with nocturnal asthma. DESIGN: Randomized, double-blind, double-dummy, three-period crossover. SETTING: Outpatients at a single center. Patients spent 1 night during screening and 2 nights during each study period in a sleep laboratory for completion of sleep studies. PATIENTS: Male and female patients who were at least 18 years old with nocturnal asthma (baseline FEV1, 50 to 90% of predicted) and who required regular bronchodilator therapy. Patients on inhaled corticosteroids, cromolyn, and nedocromil were allowed into the study if their dosing remained constant throughout the study. INTERVENTIONS: Inhaled salmeterol (42 microg per actuation), extended-release oral theophylline (titrated to serum levels of 10 to 20 microg/mL), and placebo taken twice daily. MEASUREMENTS AND RESULTS: Efficacy measurements included nocturnal spirometry, nocturnal polysomnography, sleep questionnaires, and daily measurements of lung function and symptoms. Salmeterol was superior to theophylline (p < or = 0.05) in maintaining nocturnal FEV1 levels and was superior to placebo (p < or = 0.05) in improving morning and evening peak expiratory flow (PEF) and in decreasing nighttime albuterol use. The use of salmeterol significantly increased the percentage of days and nights with no albuterol use and decreased daytime albuterol use compared with theophylline and placebo (p < or = 0.05). Sleep quality global scores significantly improved with salmeterol and placebo (p < 0.001) but not with theophylline. The effects on sleep architecture were similar across treatment groups. CONCLUSIONS: Salmeterol (but not theophylline) was associated with sustained improvements in morning PEF, protection from nighttime lung function deterioration, reductions in albuterol use, and improvements in patient perceptions of sleep. No differences were seen in polysomnographic measures of sleep quality.

Effect of long-term salmeterol therapy compared with as-needed albuterol use on airway hyperresponsiveness.

STUDY OBJECTIVES: To determine the effect of long-term salmeterol aerosol therapy on airway hyperresponsiveness measured by methacholine challenge. DESIGN: Randomized, double-blind, placebo-controlled, multicenter study. SETTING: Thirty-one clinical centers in the United States. PATIENTS: Four hundred eight asthmatic patients > or = 12 years of age with baseline FEV1 of > or = 70% of predicted values. Patients were not using inhaled corticosteroids. INTERVENTIONS: Twice-daily salmeterol aerosol, 42 microg, or placebo via metered-dose inhaler for 24 weeks. Backup albuterol was available. MEASUREMENTS AND RESULTS: Pulmonary function tests were performed before, during, and after treatment. Subjects recorded asthma-related symptoms, morning and evening peak expiratory flow (PEF) levels, and use of supplemental albuterol daily on diary cards. Methacholine challenges were performed 10 to 14 h postdose at weeks 4, 12, and 24, and 3 and 7 days posttreatment. Over 24 weeks of treatment, salmeterol provided significant (p < 0.001) protection against methacholine-induced bronchoconstriction of approximately one doubling dose of methacholine when compared to placebo with no evidence for a progressive decrease in protection. A rebound increase in airway hyperresponsiveness was not observed 3 and 7 days after cessation of salmeterol therapy. Salmeterol treatment resulted in sustained improvements of 0.21 to 0.26 L in morning premedication FEV1 and an improvement of 26.2 L/min in morning PEF when compared to placebo (p < 0.001). The use of salmeterol significantly reduced combined daytime asthma symptoms by 20% when compared to placebo (p = 0.005). A total of 34 and 48 exacerbations, respectively, were reported in the Salmeterol and placebo groups, and no evidence was present for a difference in the severity of asthma exacerbations between groups. Adverse event profiles were similar for the salmeterol and placebo groups. CONCLUSIONS: Regular long-term use of salmeterol aerosol resulted in sustained improvements in pulmonary function and asthma symptom control over the 24-week treatment period. There was no increase in bronchial hyperresponsiveness or loss of bronchoprotection at 24 weeks from that seen following 4 weeks of therapy. There was no evidence of rebound airway hyperresponsiveness after cessation of salmeterol treatment. Regular treatment with the long-acting beta-agonist salmeterol does not lead to clinical instability or vulnerability to unpredictable asthma attacks.

Fluticasone alone or in combination with salmeterol vs triamcinolone in asthma.

OBJECTIVES: To compare the efficacies of medium-dose fluticasone propionate (FP), medium-dose triamcinolone acetonide (TAA), and combined low-dose FP plus salmeterol (SL). DESIGN: Randomized, double-blind, triple-dummy, multicenter, 12-week clinical trial. SETTING: Allergy/respiratory care clinics. PATIENTS: Six hundred eighty patients with asthma previously uncontrolled with low-dose inhaled corticosteroids. INTERVENTIONS: FP, 220 microg bid; TAA, 600 microg bid; or FP, 88 microg plus SL, 42 microg bid. MEASUREMENTS AND RESULTS: Outcome measures included FEV1, peak expiratory flow (PEF), supplemental albuterol use, nighttime awakenings, asthma symptoms, and physician global assessment. Compared with TAA, 600 microg bid, treatment with FP 220, microg bid, significantly increased FEV1, morning and evening PEF, and percent symptom-free days, and significantly reduced rescue albuterol use, number of nighttime awakenings, and overall asthma symptom scores (p < or = 0.035). Improvements with low-dose FP, 88 microg, plus SL, 42 microg bid, were significantly (p < or = 0.004) greater than TAA, 600 microg bid, in all the aforementioned efficacy measures as well as percent of rescue-free days. Combined low-dose FP, 88 microg, plus SL, 42 microg bid, also significantly increased FEV1 and percent of rescue-free days, and significantly reduced albuterol use compared with medium-dose FP, 220 microg bid (p < or = 0.018). At endpoint, both FP, 220 microg bid, and FP, 88 microg, plus SL, 42 microg bid, significantly increased FEV1 by 0.48 L and 0.58 L, respectively, compared with 0.34 L with TAA, 600 microg bid. CONCLUSION: In patients who are symptomatic while taking low-dose inhaled corticosteroids, medium-dose FP (440 microg/d) and combination treatment with low-dose FP (176 microg/d) plus SL (84 microg/d) are both more effective than medium-dose TAA (1200 microg/d) in improving pulmonary function and asthma symptom control.

Efficacy of salmeterol xinafoate in the treatment of COPD.

STUDY OBJECTIVES: To examine and compare the efficacy and safety of salmeterol xinafoate, a long-acting inhaled beta2-adrenergic agonist, with inhaled ipratropium bromide and inhaled placebo in patients with COPD. DESIGN: A stratified, randomized, double-blind, double-dummy, placebo-controlled, parallel group clinical trial. SETTING: Multiple sites at clinics and university medical centers throughout the United States. PATIENTS: Four hundred eleven symptomatic patients with COPD with FEV1 < or = 65% predicted and no clinically significant concurrent disease. INTERVENTIONS: Comparison of inhaled salmeterol (42 microg twice daily), inhaled ipratropium bromide (36 microg four times a day), and inhaled placebo (2 puffs four times a day) over 12 weeks. RESULTS: Salmeterol xinafoate was significantly (p < 0.0001) better than placebo and ipratropium in improving lung function at the recommended doses over the 12-week trial. Both salmeterol and ipratropium reduced dyspnea related to activities of daily living compared with placebo; this improvement was associated with reduced use of supplemental albuterol. Analyses of time to first COPD exacerbation revealed salmeterol to be superior to placebo and ipratropium (p < 0.05). Adverse effects were similar among the three treatments. CONCLUSIONS: These collective data support the use of salmeterol as first-line bronchodilator therapy for the long-term treatment of airflow obstruction in patients with COPD.

The bronchitis index. A semiquantitative visual scale for the assessment of airways inflammation.

Flexible fiberoptic bronchoscopy has been proven to be an effective tool for the assessment and characterization of airway inflammation. Visual inspection of airways affected by chronic bronchitis discloses an abnormal appearance characterized by erythema, edema, secretions, and friability. It was hypothesized that the visual appearance of airway inflammation could be assessed in a semiquantitative manner. A bronchitis index (BI) was developed that scores the visual appearance of airways according to the presence or absence of abnormal edema, erythema, secretions, and friability (0 = normal, 3 = remarkably abnormal). The BI was determined in three study groups: 86 subjects with chronic bronchitis, 15 subjects who smoked cigarettes, but did not have chronic bronchitis, and 25 normal, nonsmoking control subjects. The reproducibility of the BI was determined by comparing the results from pairs of two independent observers assessing 249 subjects undergoing fiberoptic bronchoscopy under various investigative protocols. In total, nine investigators scored the airways. For the three observer pairs with more than six observations, there were no differences noted in the BI (p = 0.43, 0.67, 0.82). To control for the effect of cough upon the BI, lidocaine usage was recorded. No correlation was found between lidocaine usage and BI. As previously noted for a smaller group of subjects, the BI was found to be elevated in those with chronic bronchitis (13.2 +/- 0.53) compared with both asymptomatic smokers (8.5 +/- 0.89, p < 0.0005) and normal volunteers (2.3 +/- 0.55, p < 0.0001); the latter two groups also differed significantly (p < 0.0001). The BI was also found to correlate significantly with bronchial sample lavage fluid neutrophil content in lavage fluid obtained after determination of the BI and with cigarette smoking as quantitated by pack years. Conversely, the BI correlated negatively with the spirometric measures of airway obstruction, FEV1, FEV1/FVC, FEV25-75, and FEFmax. Thus, the BI appears to be a reproducible, semiquantitative assessment of the visual appearance of airway inflammation. It may be a useful bronchoscopic adjunct for the assessment of airway inflammation in clinical investigations.

Post bone marrow transplant sera and persisting mast cell colonies.

Serum samples were collected from eight recipients of allogeneic bone marrow transplants (BMT) following the normalization of peripheral blood counts. Three patients (11 samples) were in the early engraftment period (less than 6 months post-BMT) and still receiving cyclosporin A or methotrexate and the remaining five patients (18 samples) were in stable engraftment (12-84 months post-BMT) and not on immunosuppressive therapy. All post-BMT serum samples supported the growth of increased numbers of mast cell colonies in long-term agar cultures when compared with normal controls (p less than 0.025-0.005), irrespective of the time from BMT or the presence of clinical graft-versus-host disease (GVHD). In contrast, the numbers of neutrophil, monocyte and eosinophil colonies were equivalent in test and control groups. It is proposed that post-BMT sera contain higher levels of a mast cell stimulating activity(s) than does normal sera. Such increased levels might be associated with clinical or subclinical GVHD.

Fibrin powder turbidity measurement for rapid assessment of antiplasmins.

Fibrinolytic activity was determined from the rate of disappearance of turbidity in a suspension of heat-treated fibrin powder. Using this method for estimating residual fibrinolytic activity in mixtures of serum and plasmin, antiplasmin behaviors of specimens from patients with various clinical disorders were determined after long and short preincubation times. Slow-acting antiplasmins were found to be increased in a variety of conditions among these patients, while immediate acting antiplasmins were generally decreased, compared with those in specimens from a large pool of normal, healthy vounteers. Normal women taking oral contraceptives had consitently high levels of slow antiplasmins. Tests in vitro showed that the antifibrinolytic agents epsilon-aminocaproic acid, Trasylol and soybean trypsin inhibitor act only as fast antiplasmins.

An evaluation of currently available methods for plasma fibrinogen.

Fibrinogen levels in a variety of clinical plasma samples were assessed concurrently by several methods. Technics that appeared to provide the best improvements over the basic varieties of methods for fibrinogen assay were used. Results were correlated against a reference method based on Ancrod clottable fibrinogen and calibrated by ultraviolet absorbance with alkaline solutions of carefully dried fibrin standard. The best correlations with the reference method were achieved by an immunologic method using the Centrifichem principle and by heat precipitation with quantitation by packing in microhematocrit tubes. A modified clot opacity method also gave acceptable results. The turbidimetric ammonium sulfate and sodium sulfite precipitation methods correlated less well with the reference method, and in particular, the sodium sulfite technic gave high apparent fibrinogen levels with jaundiced plasmas. Neither of the turbidimetric methods were useful for fibrinogen levels below 50 mg/dl. The thrombin time method showed excellent sensitivity to fibrinogen, even at very low fibrinogen levels, but did not correlate well with the reference method.

Use of changes in symptoms to predict changes in lung function in assessing the response to asthma therapy.

BACKGROUND: The majority of adult patients with asthma are managed by primary care providers. Although there is no generally accepted gold standard for the assessment of asthma severity in general practice, treatment decisions and modifications to therapy are strongly influenced by patients' symptoms and history of asthma medication use. OBJECTIVES: The primary goal of this study was to determine whether there is a correlation between changes in asthma symptoms during treatment and changes in lung function, as measured by peak expiratory flow (PEF). A secondary goal was to compare the relative efficacy (in terms of improvement in asthma symptoms and lung function) of 3 commonly used asthma treatments: inhaled fluticasone propionate, inhaled salmeterol xinafoate, and oral zafirlukast. METHODS: This was a retrospective comparison employing regression analyses of asthma symptom and lung function data from 2890 male and female adolescent and adult patients with persistent asthma who were enrolled in 8 randomized, double-blind, double-dummy, parallel-group studies. Data on patients' self-rated symptoms, PEF, supplemental albuterol use, nighttime awakenings, and frequency of asthma exacerbations were used to ascertain whether there was a correlation between changes in asthma symptoms and changes in pulmonary function, and to compare treatment effects. RESULTS: Changes in patients' ratings of asthma symptoms after treatment with study medications showed a strong correlation with changes in lung function. Similarly, changes in lung function were strongly correlated with changes in supplemental beta-agonist use and quality of life. In addition, fluticasone or salmeterol treatment resulted in significantly greater increases in mean morning PEF (P < 0.001), significantly greater decreases in symptom scores (P < or = 0.004), significantly fewer nights with awakenings due to symptoms (P < or = 0.017), and significantly greater reductions in supplemental beta-agonist use (P < 0.001) compared with zafirlukast treatment or placebo. Patients treated with fluticasone or salmeterol also experienced significantly lower rates of asthma exacerbation (3%) during treatment than did those receiving zafirlukast (7%) or placebo (12%) (P < 0.001 and P = 0.015, fluticasone and salmeterol, respectively). CONCLUSION: These findings support the validity of primary care practitioners' basing asthma-management decisions on patients' symptoms.

Contact activation by ellagic acid - the concept of soluble activator disputed.

Concentrated, true solutions of ellagic acid (EA) prepared by pH reduction had only a small effect on contact activation initially. However when the EA formed a fine microcrystalline dispersion there was concurrent development of contact activity with turbidity. The dependence of contact activity on EA concentration was found to be a log-log relationship. After relatively low speed centrifugation contact activity-promoting material was decreased from supernatant layers at all concentrations. These findings suggest that EA is not effective as a contact activator when in true solution, but is active only when present as a solid.