The effect of hypoxemia on the disposition of theophylline was examined in 10 stable patients with chronic obstructive pulmonary disease (COPD) receiving chronic theophylline and supplemental home oxygen therapy. Pharmacokinetics after intravenous theophylline were estimated on the second day of supplemental oxygen (PaO2, 69 +/- 4 mmHg; mean +/- SEM) and on the second day of room air breathing (PaO2, 43 +/- 3) using a randomized cross-over design. On each occasion stable isotope-enriched theophylline (10 mg, m/z 183) was administered intravenously along with the regular oral dose of theophylline (m/z 180). Concentrations of both forms of theophylline in plasma samples obtained over 24 h were measured using mass spectrometry. Theophylline clearance during oxygen therapy (0.048 +/- 0.005 L/h/kg) was similar to that during room air breathing (0.050 +/- 0.004 L/h/kg). Values for elimination half-life (7.6 +/- 0.8 versus 6.8 +/- 0.6 h) and volume of distribution at steady state (0.450 +/- 0.021 versus 0.429 +/- 0.024 L/kg) were also unchanged. The volume of distribution of theophylline was inversely related to arterial pH during oxygen therapy (pH range, 7.32 to 7.44) and during room air breathing (pH range, 7.33 to 7.47). Although hypoxemia does not alter theophylline clearance in patients with COPD, theophylline loading doses may need adjustment according to arterial pH because of an effect on volume of distribution. 相似文献
Familial amyloidotic polyneuropathy (FAP) is a late-onset inherited disease characterized by the deposition of amyloid fibrils. FAP is associated with mutations on the transthyretin (TTR) gene. A monoclonal antibody, MAb 39-44, reacting with high molecular weight aggregates of TTR but not with tetrameric TTR has recently been generated and characterized. This antibody recognizes a cryptic epitope that is expressed in isolated recombinant amyloidogenic mutants and in ex vivo amyloid. In the present work we show that this amyloid-specific antibody specifically recognizes in a direct enzyme-linked immunoassay (ELISA) plasma TTR from carriers of various mutations associated with FAP, both in asymptomatic individuals and in patients. In contrast, it does not react with plasma TTR from healthy individuals or that from carriers of nonpathogenic mutations. Using the ELISA developed in this study we identified three different TTR mutations in Portuguese patients with neuropathy of unknown cause, later shown to have amyloid tissue deposition. This antibody recognizes conformations that express cryptic epitopes shared by amyloidogenic TTR variants associated with FAP, not present among nonpathogenic TTR molecules. This antibody will contribute to further identify and characterize intermediates of the amyloidogenic cascade. In addition, it will also be useful for screening amyloidogenic TTR mutations in patients with neuropathy of unknown cause, prior to precise molecular diagnosis using protein and/or DNA analysis. 相似文献
Four infants with congenital or acquired tracheobronchial stenosis were successfully treated with angioplasty balloon catheter dilation. The technical details and complications of these procedures are described. The authors believe balloon dilation therapy should be considered as the initial form of therapy for tracheal stenosis in infants, even in the presence of complex stenotic lesions. 相似文献
Mainstream oral care flavours are primarily designed to provide hedonic (taste) benefits and to promote breath freshness. In particular, a key criterion for a commercially successful toothpaste flavour is a long lasting reduction in the perception of mouth odour. Various additives can help deliver this benefit, in addition to flavours formulated according to patented guidelines. The residence time (substantivity) in the mouth of flavours and additives is clearly critical with respect to the longevity of the breath-freshening benefit, and little data are available in the literature to guide the selection of substantive components. The aim of this project was to investigate the dynamics of flavour loss from the buccal cavity following brushing using a mass spectrometer equipped with an atmospheric pressure headspace sampler which enabled real-time determination of flavour components in mouth air. A number of flavour ingredients found in peppermint- and spearmint-based oral care flavours were studied. The in vivo decay kinetics of flavour ingredient loss were quantified and found to be strongly related to the physicochemical properties of ingredients, except in the case of esters where a more complex dependence was observed arising from chemical transformation occurring in addition to physical transportation away from the mouth. Surprisingly, some materials were discovered to undergo rapid degradation with a half-life of minutes. Confirmatory studies of the decay kinetics of such materials were carried out in vitro, and structural features were identified which were associated with the observed hydrolytic vulnerability. This work has allowed the development of new guidelines to enable the creation of longer-lasting oral care flavours. 相似文献
Mark A. Schuster, MD, PhD; Paul J. Chung, MD, MS; Marc N. Elliott, PhD; Craig F. Garfield, MD, MAPP; Katherine D. Vestal, MPH; David J. Klein, MS
JAMA. 2008;300(9):1047-1055.
Context In 2004, California's Paid Family Leave InsuranceProgram (PFLI) became the first state program to provide paidleave to care for an ill family member.
Objective To assess awareness and use of the program byemployed parents of children with special health care needs,a population likely to need leave.
Design, Setting, and Participants Telephone interviewswith successive cohorts of employed parents before (November21, 2003-January 31, 2004; n = 754) and after (November18, 2005-January 31, 2006; n = 766) PFLI began, randomlysampled from 2 children's hospitals, one in California (withPFLI) and the other in Illinois (without PFLI). Response rateswere 82% before and 81% after (California), and 80% before and74% after (Illinois).
Main Outcome Measures Taking leave, length of leave, unmetneed for leave, and awareness and use of PFLI.
Results Similar percentages of parents at the Californiasite reported taking at least 1 day of leave to care for theirill child before (295 [81%]) and after (327 [79%]) PFLI, takingat least 4 weeks before (64 [21%]) and after (74 [19%]) PFLI,and at least once in the past year not missing work despitebelieving their child's illness necessitated it before (152[41%]) and after (156 [41%]) PFLI. Relative to Illinois, parentsat the California site reported no change from before to afterPFLI in taking at least 1 day of leave (difference of differences,–3%; 95% confidence interval [CI], –13% to 7%);taking at least 4 weeks of leave (1%; 95% CI, –9% to 10%);or not missing work, despite believing their child's illnessnecessitated it (–1%; 95% CI, –13% to 10%). Only77 parents (18%) had heard of PFLI approximately 18 months afterthe program began, and only 20 (5%) had used it. Even amongparents without other access to paid leave, awareness and useof PFLI were minimal.
Conclusions Parents of children with special health careneeds receiving care at a California hospital were generallyunaware of PFLI and rarely used it. Among parents of childrenwith special health care needs, taking leave in California didnot increase after PFLI implementation compared with Illinois.
BACKGROUND: The Surgeon General has called for an expansion of school-based extracurricular sports programs to address the obesity epidemic. However, little is known about the availability of and participation in high school extracurricular sports and how participation in these sports is related to high-risk behaviors. METHODS: We surveyed Los Angeles County public high schools in 2002 to determine the number of extracurricular sports programs offered and the percentage of students participating in those programs. We used community data on rates of arrests, births, and sexually transmitted diseases (STDs) among youth to examine associations between risk behaviors and participation in sports programs. RESULTS: The average school offered 14 sports programs, and the average participation rate was 39% for boys and 30% for girls. Smaller schools and schools with higher percentages of disadvantaged students offered fewer programs. The average school offering 13 or fewer programs had 14% of its students participating, while the average school offering 16 or more programs had 31% of its students participating in sports. Controlling for area-level demographics, juvenile arrest rates and teen birth rates, but not STD rates, were lower in areas where schools offered more extracurricular sports. CONCLUSIONS: Opportunities for participation in high school extracurricular sports are limited. Future studies should test whether increased opportunities will increase physical activity and impact the increasing overweight problem in youths. 相似文献