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Biomedical subjects

John P Hanrahan

Publications and source records attributed to John P Hanrahan.

6 recordsLinked to original sources

A comparison of levalbuterol with racemic albuterol in the treatment of acute severe asthma exacerbations in adults.

UNLABELLED: This multicenter, randomized, double-blind trial compared nebulized levalbuterol (Lev) and racemic albuterol (Rac) in the treatment of acute asthma. METHODS: Adults with acute asthma exacerbations (FEV(1) 20%-55% predicted) received prednisone and either Lev (1.25 mg, n = 315) or Rac (2.5 mg, n = 312). Nebulized treatments were administered every 20 minutes in the first hour, then every 40 minutes for 3 additional doses, then as necessary for up to 24 hours. The primary end point was time to meet discharge criteria. Secondary end points included changes in lung function and hospitalization rates. A subset of 160 patients had plasma (S)-albuterol concentrations determined at study entry. RESULTS: Time to meet discharge criteria did not differ between the 2 treatments. FEV(1) improvement was greater following Lev compared with Rac, both after dose 1 and cumulatively over the entire treatment period (dose 1 in intent to treat [ITT] group: Lev 0.50 +/- 0.43 L, Rac 0.43 +/- 0.37 L; P = .02), particularly among the 60% of patients not on recent steroid therapy (dose 1: Lev 0.58 +/- 0.47 L, Rac 0.44 +/- 0.37 L; P < .01), and patients whose entry (S)-albuterol concentrations were in the highest quartile of those measured. A small and similar proportion of Lev-treated (7.0%) and Rac-treated (9.3%) patients required hospitalization (P = .28). Among patients not on steroids, fewer Lev- than Rac-treated patients required admission (3.8% vs 9.3%, P = .03), as was also the case for patients with high plasma (S)-albuterol concentrations. Asthma relapses (5% in 30 days) were lower than in previous reports and did not differ between groups. CONCLUSIONS: This study suggests that early, regular nebulized beta(2)-agonist and systemic corticosteroid therapy may reduce hospitalization and relapse rates in patients with acute severe asthma. Lev was well tolerated and compared favorably with Rac in improving airway function, particularly in those who were not on inhaled or oral corticosteroids and in those who had high plasma (S)-albuterol concentrations at presentation.

Acute Disease↗

Pore size engineering in mesoporous silicas using supercritical CO2.

In this paper we investigate the use of supercritical carbon dioxide (sc-CO(2)) for synthesizing calcined mesoporous silicas with tunable pore sizes, wall thickness, and d spacings. Small angle neutron scattering was used to probe the controlled swelling of the triblock copolymer surfactant templating agents, P123 (PEO(20)PPO(69)PEO(20)), P85 (PEO(26)PPO(39)PEO(26)), and F127 (PEO(106)PPO(70)PEO(106)), as a function of CO(2) pressure. The transition from the liquid crystal phase to the calcined mesoporous silicas, formed upon condensation and drying, was also studied in detail. Powder X-ray diffraction, transmission electron microscopy, and nitrogen adsorption techniques were used to establish pore diameters, silica wall widths, and the hexagonal packing of the pores within the calcined silicas. Using a direct templating method, the diameters of mesopores and the spacing between the pores could be tuned with a high level of precision. The swelling process was observed to have no detrimental effects on the quality of silica formed, a distinct advantage over conventional swelling techniques, and all of the silicas synthesized in this study were highly ordered over distances of at least 2000 A.

Adsorption↗

Water-in-CO2 emulsions: reaction vessels for the production of tetra-ethyl pyrone.

Water-in-CO2 (W/C) emulsions formed using a nickel Triton X-100 surfactant complex (Ni-surfactant) were used as microreactors for the carbon-carbon coupling reaction between hex-3-yne and CO2 to produce tetra-ethyl pyrone (TEP). The structure of the product, which was isolated in the CO2 phase, was determined using gas chromatography mass spectrometry (GC-MS) and infrared spectroscopy. The Ni-surfactant acted as both an emulsion forming agent and a water soluble catalyst for this carbon-carbon coupling reaction. The optimum yield of TEP was determined to be 69% after 72 h, at a temperature of 70 degrees C and a pressure of 206 bar. The ease with which the emulsion could be collapsed allowed the facile separation of products from the catalyst and any unreacted starting material. Product selectivity in the W/C emulsions was found to be greater than that obtained using conventional organic methodologies.

Journal Article↗

A comparison of 5-day courses of dirithromycin and azithromycin in the treatment of acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Short-term use of antibiotics has become a common component of the management of acute exacerbations of chronic bronchitis (AECB), particularly in complex cases with productive cough or purulent phlegm. The macrolide antibiotics, particularly second-generation agents such as dirithromycin and azithromycin, are among the antibiotic classes frequently recommended and used to treat upper and lower respiratory infections, including AECB. OBJECTIVE: This study compared the clinical efficacy and tolerability of 5-day courses of dirithromycin and azithromycin given once daily for the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD). METHODS: This randomized, investigator-blinded, parallel-group clinical trial was conducted at 5 centers in the United States. Eligible patients were adult (age >35 years) smokers or ex-smokers (smoking history of at least 10 pack-years) with chronic bronchitis and an acute exacerbation, defined by the occurrence of increased dyspnea and/or productive cough and feverishness within 48 hours of enrollment. Before randomization, an attempt was made to obtain a sputum specimen from each patient for Gram's staining and culture. Patients were randomized to receive dirithromycin 500 mg QD for 5 days or azithromycin 500 mg QD on day 1 and 250 mg QD on days 2 to 5. Clinical efficacy was assessed separately by patients and physicians at early (days 7-10) and late (days 25-35) posttreatment visits. RESULTS: Eighty-six patients (48 women, 38 men; mean age, 55 years) with a mean smoking history of 31 pack-years were included in the intent-to-treat analysis. Forty-six (54%) patients were randomized to dirithromycin and 40 (47%) patients to azithromycin. Clinical efficacy was reported in a high proportion of patients in both treatment groups, both at the early posttreatment visit (84.8% dirithromycin, 75.7% azithromycin; difference dirithromycin - azithromycin, 9.1%; 95% CI, -8.2 to 26.4) and the late posttreatment visit (95.5% and 86.5%, respectively; difference dirithromycin - azithromycin, 9.0%; 95% CI, -3.7 to 21.6). A similar proportion of patients required a second course of antibiotics over the study period (20.5% dirithromycin, 27.0% azithromycin; difference dirithromycin - azithromycin, -6.6%; 95% CI, -25.2 to 12.1). Only 42 (48.8%) patients were able to produce a sputum sample before receiving study treatment, and of these, only 20 (47.6%) demonstrated a preponderance of neutrophils on Gram's staining. Both treatments were well tolerated. CONCLUSIONS: The results of this study suggest comparable clinical efficacy between 5-day courses of once-daily dirithromycin and azithromycin in acute exacerbations of COPD. There were insufficient data to permit meaningful comparison of the bacteriologic efficacy of these macrolide antibiotics.

Acute Disease↗

Sex-specific prediction equations for Vmax(FRC) in infancy: a multicenter collaborative study.

Measurements of maximal flow at functional residual capacity (Vmax(FRC)) from partial forced expiratory maneuvers remain the most popular method for assessing small airway function in infants and young children. However, the lack of appropriate reference data that are both applicable outside the centers that developed them and reflect the normal variability between healthy subjects has limited interpretation of Vmax(FRC) results in both clinical practice and research. To address this problem, we collated Vmax(FRC) data from 459 healthy infants (226 boys) tested on 654 occasions during the first 20 months of life from three collaborating centers. Multiple linear regression analysis indicated that sex, age, and length were important predictors of Vmax (FRC), which was, on average, 20% higher in girls than in boys during the first 9 months of life. (Vmax(FRC))0.5 (ml x second(-1)) = 4.22 + 0.00210 x length2 (cm) for boys (RSD = 3.01; R2 = 0.48), and -1.23 + 0.242 x length for girls (RSD = 2.72; R2 = 0.49). Alternative models incorporating both age and length z scores are also described. Failure to use sex-specific prediction equations for Vmax(FRC) may preclude detection of clinically significant changes in girls and lead to false reports of diminished airway function in boys. Appropriate use of z scores, which indicate a "normal" range (z scores of 0 +/- 2) for Vmax(FRC), during infancy should also improve interpretation of both clinical and research studies.

Body Constitution↗

Concordance of field and emergency department assessment in the prehospital management of patients with dyspnea.

OBJECTIVE: Dyspnea is a common complaint of patients treated by emergency medical services (EMS). Few studies have examined the ability of paramedics to distinguish between etiologies of dyspnea. The authors evaluated the degree of agreement related to cardiac versus noncardiac sources of dyspnea between field and emergency department (ED) assessment of patients transported at the advanced life support level. METHODS: This was a retrospective, cohort study of consecutive patients aged > or =35 years transported by paramedics with dyspnea. The authors compared the concordance between the EMS and ED diagnoses. They also investigated whether patients whose assessments were discordant had worse outcomes. RESULTS: Paramedics correctly assessed the cause of dyspnea in 172 of 222 (77%) patients (kappa=0.60; 95% confidence interval [CI]=0.51, 0.69). Among single-source (i.e., cardiac or noncardiac) dyspnea patients, prehospital providers correctly assessed 70 of 84 (83%) noncardiac causes and 98 of 114 (86%) cardiac causes (kappa=0.69; 95% CI=0.59, 0.79). When the ED diagnosis included both cardiac and noncardiac etiologies, paramedics treated seven of 24 (29%) patients as noncardiac, 13 of 24 (54%) as cardiac, and four of 24 (17%) as combined-source dyspnea. The authors did not observe any statistically significant differences in in-hospital mortality, intubation frequency, or hospital length of stay in patients whose prehospital dyspnea diagnosis was discordant. CONCLUSION: The authors conclude that in this EMS system, field assessment of dyspnea by paramedics is in agreement with that arrived at in the ED in a high proportion of patients with dyspnea from a single source. However, field assessment of dyspnea from multiple etiologies is less concordant.

Adult↗