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Biomedical subjects

S M Butler

Publications and source records attributed to S M Butler.

At least 19 recordsLinked to original sources
PubMed2005

Epidemiology of cystic fibrosis-related diabetes.

OBJECTIVES: Cystic fibrosis-related diabetes (CFRD) has emerged as an important complication of CF. To better understand who is at risk of developing CFRD, to gain insight into the impact of CFRD on pulmonary and nutritional status, and to assess the association of CFRD with various practice patterns and comorbid conditions, we characterized the Epidemiologic Study of Cystic Fibrosis (ESCF) patient population. STUDY DESIGN: Analyses were performed on the 8247 adolescents and adults who were evaluated at one of 204 participating sites during 1998. CFRD was defined as the use of insulin or an oral hypoglycemic agent at any time during the year. RESULTS: Previously reported risk factors for CFRD including age, gender (female), and pancreatic insufficiency were confirmed in this study. Patients with CFRD had more severe pulmonary disease, more frequent pulmonary exacerbations, and poorer nutritional status as compared with those without diabetes. CFRD also was associated with liver disease. CONCLUSIONS: CFRD is a common complication in adolescents and adults that is associated with more severe disease.

Adolescent↗
PubMed2001

Selection for in vivo regulators of bacterial virulence.

We devised a noninvasive genetic selection strategy to identify positive regulators of bacterial virulence genes during actual infection of an intact animal host. This strategy combines random mutagenesis with a switch-like reporter of transcription that confers antibiotic resistance in the off state and sensitivity in the on state. Application of this technology to the human intestinal pathogen Vibrio cholerae identified several regulators of cholera toxin and a central virulence gene regulator that are operative during infection. These regulators function in chemotaxis, signaling pathways, transport across the cell envelope, biosynthesis, and adherence. We show that phenotypes that appear genetically independent in cell culture become interrelated in the host milieu.

Animals↗
PubMed1999

Adsorption of serum albumin to thin films of poly(lactide-co-glycolide).

Protein adsorption has been implicated in the variability of drug release from biodegradable microspheres. We used optical reflectometry to measure the extent and kinetics of bovine serum albumin (BSA) adsorption to smooth spin-cast films prepared from two poly(lactide-co-glycolide) (PLG) samples that have different end-groups, one being a hydrophilic carboxylic end group and the other a hydrophobic ester end group. One of us has previously shown that these end-groups influence microsphere degradation (Tracy et al. , 1998, Factors affecting the degradation rate of poly(lactide-co-glycolide) microspheres in vivo and in vitro. Biomaterials: submitted for publication.). Both films were moderately hydrophobic, and their wettability was independent of the type of end-group. BSA adsorbed readily to both native PLG films, attaining as much as 50% surface coverage by area and was insensitive to the type of end-group. Aging the films in water for 24 h prior to BSA exposure decreased the hydrophobicity of the films and this in turn correlated with a significant decrease in the initial BSA adsorption rate. This was consistent with the often-observed trend that surface hydrophobicity favors protein adsorption. In spite of the lower adsorption affinity revealed by this decreased initial adsorption rate, the final adsorbed amounts on the aged films exceeded those attained on native films, presumably due to the increase in total surface area produced by partial PLG erosion.

Adsorption↗
PubMed1999

Epidemiologic study of cystic fibrosis: design and implementation of a prospective, multicenter, observational study of patients with cystic fibrosis in the U.S. and Canada.

Cystic fibrosis (CF) is a complex illness characterized by chronic lung infection leading to deterioration in function and respiratory failure in over 85% of patients. An understanding of the risk factors for that progression and the interaction of these factors with current therapeutic strategies should materially improve the prevention of this progressive lung disease. The Epidemiologic Study of Cystic Fibrosis (ESCF) was therefore designed as a multicenter, longitudinal, observational study to prospectively collect detailed clinical, therapeutic, microbiologic, and lung function data from a large number of CF treatment sites in the U.S. and Canada. The ESCF also serves an important role as a phase-IV study of dornase alfa. To be eligible for enrollment, subjects must have the diagnosis of CF and receive the majority of their care at an ESCF site. In this paper, the authors present the ESCF study design in detail. Further, enrollment data collected at 194 study sites in 18,411 subjects enrolled from December 1, 1993 to December 31, 1995 are presented in summary form. This comprehensive study is unique in the detail of clinical data collected regarding patient monitoring and therapeutic practices in CF care. Two companion articles present data regarding practice patterns in cystic fibrosis care, including data on resource utilization and prescribing practices.

Adolescent↗
PubMed1999

Patterns of medical practice in cystic fibrosis: part I. Evaluation and monitoring of health status of patients. Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis.

This report characterizes patterns of evaluation and monitoring of the health status of patients with cystic fibrosis (CF) as observed in the Epidemiologic Study of Cystic Fibrosis (ESCF), and compares these practices to published guidelines. All patients (18,411) who enrolled in ESCF at 194 study sites in the United States and Canada from December 1, 1993 to December 31, 1995 were considered for study. Patients enrolled before January 1, 1995 with >/=1 healthcare encounters during 1995 (12,631) were included in the analysis. Patients enrolled after January 1, 1995 (5,266), or who died (354), withdrew from the study (128), or were lost to follow-up (21) were excluded. Frequency of encounters (outpatient and hospital), spirometry, respiratory tract cultures, and chest radiographs were recorded during a 1-year period (1995) and analyzed by gender, age, severity of lung disease, and presence of any Pseudomonas species in the respiratory tract. The 12,631 patients had 53,024 outpatient visits. In 57.5% of patients, the recommended criteria of >/=4 total visits per year were met. Only 27.4% of all patients had >/=4 routine visits; 3.1% had only sick visits, and 59.0% had no sick visits. One third (34.6%) were hospitalized at least once, for a total of 8,561 hospitalizations. Older patients with lower pulmonary function and Pseudomonas in their respiratory tract had fewer routine visits and more sick visits, and were hospitalized more than were younger patients. In three fourths (75.8%) of patients the recommended criterion of two spirometry assessments per year was met, whereas in 79.3% the criterion of one culture was met, and in 68.3% the criterion of one radiograph/year was met. We conclude that in the majority of CF patients, the recommended criteria for routine evaluation and monitoring were met. However, in a rather substantial number they were not. An increase in the utilization of healthcare resources was observed in patients with more severe disease. This information will help to establish benchmarks for future quality assessment programs.

Adolescent↗
PubMed1999

Patterns of medical practice in cystic fibrosis: part II. Use of therapies. Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis.

This report describes the prescribing pattern of therapeutic interventions in the management of patients with cystic fibrosis (CF), as observed in the Epidemiologic Study of Cystic Fibrosis (ESCF). Use of 20 therapies by 12,622 patients was recorded from each health care encounter (53,024 outpatient visits and 8,561 hospitalizations) during a 1-year period (1995), and analyzed by gender, age, severity of lung disease, and presence of any Pseudomonas species in the respiratory tract. The percentage of patients using the following pulmonary therapies was observed (in descending order): airway clearance techniques (88.2%); inhaled bronchodilators (82.2%); oral antibiotics (excluding quinolones) (68. 2%); dornase alfa (52.9%); intravenous antibiotics (34.4%); oral quinolones (34.4%); inhaled antibiotics (34.3%); mast cell stabilizers (29.5%); inhaled corticosteroids (25.9%); oral corticosteroids (17.1%); oral bronchodilators (16.2%); oxygen (8. 1%); inhaled mucolytic agent acetyl cysteine (6.5%); and diuretics (1.4%). The percentage of patients using nutritional therapies was: pancreatic enzymes (96%); oral nutritional supplements (31.1%); enteral nutrition (7.3%); and parenteral nutrition (0.7%). The percentage of patients using other therapies was: nonsteroidal anti-inflammatory drugs (7.9%); and insulin or oral hypoglycemic agents (6.1%). The general trend was for therapies to be used more by older patients, those with lower pulmonary function, and by those with Pseudomonas in their respiratory tract. Exceptions to this trend occurred for airway clearance, oral antibiotics, mast cell stabilizers, and pancreatic enzymes. Four therapies (oral nutritional supplements, parenteral nutrition, diuretics, and pancreatic enzymes) were used more by males than females. However, there was no gender difference for this group of therapies on pulmonary or nutritional status.

Adolescent↗
PubMed1999

Estimating effectiveness in an observational study: a case study of dornase alfa in cystic fibrosis. The Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis.

Patients with cystic fibrosis (CF) receiving dornase-alfa had improved pulmonary function relative to a control group in a large randomized phase III controlled study. We reviewed data from a large observational phase IV study to estimate the observed drug effect in patients receiving dornase alfa as part of their routine care. Patients 6 years or older and with a baseline forced expiratory volume in 1 second (FEV1) of at least 40% predicted who had been enrolled for at least 18 months were included (n = 283). The control group consisted of 2382 patients who had never received dornase alfa. Patients in the study had a baseline spirometry and a second spirometry recorded 12 months later; a baseline observation period of 6 months preceded the initial spirometry, and dornase alfa had to have been started after the baseline spirometry (within 3 months) and to have continued through the 12-month follow-up spirometry. Patients treated with dornase alfa had lower pulmonary functions, more bacterial colonization, and more exacerbations at baseline (FEV1 : 76.0% vs 87.6%, Pseudomonas aeruginosa : 64.1% vs 46.7%, pulmonary exacerbations during the previous 6 months: 56.4% vs 22. 2%). Mean values of FEV1 for patients treated with dornase alfa improved by 3.9% of predicted compared with a decline of 1.6% in the untreated cohort. Covariate adjustment provided an estimated benefit of dornase alfa of 4.3% predicted FEV1 (SE = 0.9, P <.0001). This analysis provides evidence for the effectiveness of dornase alfa therapy in clinical practice.

Child↗
PubMed1996

Antioxidants and reduced functional capacity in the elderly: findings from the Nun Study.

BACKGROUND: This study investigated the relationship of plasma antioxidants to reduced functional capacity in the elderly. A hallmark of reduced functional capacity in the elderly is dependence in self-care (i.e., requiring assistance with bathing, walking, dressing, standing, toileting, and feeding). METHODS: This relationship was assessed in a cross-sectional study of 88 Catholic sisters (nuns). These 77- to 98-year-old women lived in the same building, ate food prepared in the same kitchen, and had all nursing services provided by the same staff. In 1993, ability to perform self-care was assessed, and blood was drawn to determine plasma carotenoids (lycopene, beta carotene, alpha carotene, zeaxanthin and lutein combined, and beta cryptoxanthin) and alpha tocopherol. RESULTS: Dependence in self-care had a strong negative association with lycopene, but was not clearly related to other carotenoids or alpha tocopherol. Results from age-adjusted least squares regression indicated that a 30 micrograms/dl decrease in lycopene was associated with 2.4 additional dependencies in self-care (95% confidence interval = 1.5, 3.3; p < .001). Lycopene's relationship to dependence was modified by plasma LDL-cholesterol, the predominant carrier of lycopene in the blood. Women with low lycopene and low LDL-cholesterol had 3.6 dependencies (95% confidence interval = 3.1, 4.2; p < .001), compared to 1.0 dependency (95% confidence interval = 0.3, 1.8) in those with high lycopene and low LDL-cholesterol. CONCLUSIONS: This is the first study to report an association between lycopene and functional status. This finding needs to be replicated in other human and animal studies before the association is accepted as real.

Aged↗
PubMed1996

Trends in mortality in older women: findings from the Nun Study.

During this century, Catholic sisters have remained constant in many life-style characteristics such as smoking and reproduction (Catholic sisters are nonsmoking and nulliparous). It is therefore of interest to compare trends in the health of elderly Catholic sisters to those in the general population. In this study, mortality rates at ages 50 to 84 years in a population of 2,573 Catholic sisters were compared to those in the general population during the years 1965 to 1989. The Catholic sisters had a mortality advantage that increased dramatically over calendar time, and from early to more recent birth cohorts. This coincided with increases in smoking by U.S. women, while during the same time period the Catholic sisters had very low rates of mortality from smoking-related diseases. The Catholic sisters had high rates of mortality from cancers of the breast and reproductive organs, suggesting an effect of nulliparity manifested in older women.

Aged↗
PubMed1996

Age, education, and changes in the Mini-Mental State Exam scores of older women: findings from the Nun Study.

OBJECTIVE: To describe the relationship of Mini-Mental State Exam (MMSE) scores and changes over time in MMSE scores to age and education in a population of older women. DESIGN: A prospective study of a defined population. SETTING: Various motherhouses and church-run health care facilities in the Eastern, Midwestern, and Southern regions of the United States. PARTICIPANTS: Catholic sisters (nuns) participating in the Nun Study, a study of aging and Alzheimer's Disease. The 678 participants were 75 to 102 years old (mean 83.3, standard deviation 5.5, median 82.3) at the time of the first functional assessment. Second assessments were obtained an average of 1.6 years later on 575 survivors. MEASUREMENTS: The outcome variables were MMSE scores at the first assessment (Time-one), and MMSE scores at the second assessment (Time-two). The independent variables were age at Time-one, and education (bachelor's degree or no bachelor's degree). RESULTS: Time-one MMSE scores decreased with age at Time-one. The decrease in MMSE scores with age was less in sisters with bachelor's degrees than in sisters without bachelor's degrees. The changes in MMSE scores had a "U-shaped" relationship with Time-one score, where the greatest declines occurred in sisters with intermediate Time-one scores. Stratified analysis by age, education, and Time-one MMSE scores of 20 or greater because of the small numbers of sisters with Time-one scores less than 20. In sisters with Time-one MMSE scores in the categories 20 to 23, 24 to 26, or 27 to 30, older ages at Time-one were associated with greater decline in those with bachelor's degrees, but not in those without bachelor's degrees. Also, lower education was associated with greater decline in sisters aged 75 to 84 years at Time-one, but this education effect disappeared or reversed in sisters who were 85 years of age or older at Time-one. CONCLUSIONS: Cognitive function as measured by the MMSE decreased with age at Time-one, most steeply as a function of age in those without bachelor's degrees. Cognitive function declined over 1.6 years within individuals, and the extent of decline increased with age in the sisters with bachelor's degrees. The extent of decline varied with age and education in an interactive manner, which may have been attributable to a hardy survivor effect in lower educated sisters. It may be necessary to consider such interactions whenever changes in function are studied, particularly when analyses are stratified by the initial level of function.

Aged↗
PubMed1995

Delayed elevation of platelet activating factor in ischemic hippocampus.

We used in vivo microdialysis to define the chronological relationship between release of thromboxane and platelet activating factor (PAF) into the extracellular space of ischemic hippocampus. The thromboxane level peaked after 20 min of postischemic reperfusion, followed by a delayed PAF response 120 min later. We conclude that cerebral ischemia causes delayed elevation of PAF in the extracellular space, long after the immediate synthesis and release of thromboxane metabolites.

Analysis of Variance↗
PubMed1995

Prosodic characteristics of speech pre- and post-right hemisphere stroke.

Case-control studies have shown right hemisphere specialization in the production of intonation in speech. We examined spontaneous prosody in audiotapes of interviews with a 77-year-old right-handed woman recorded 6 months before and 6 weeks after she suffered a stroke affecting the right frontotemporo-parietal regions and the right basal ganglia. Post-stroke, the patient had a normal Mini-Mental Status Examination Score of 29, hemispatial neglect, and impairments in the comprehension of facial expression and prosody. Self-rated mood was within normal limits. We compared beginning, peak, and ending fundamental frequencies (fo) in breath groups, the timing of these fo changes, rate of speech, pause duration, and breath-group duration. We found that post-stroke, the patient had a more restricted fo contour, no changes in the timing of peak fo, an increased rate of speech, less variability in pause duration, and no changes in breath-group duration.

Affect↗
PubMed1995

Elevated thiobarbituric acid-reactive substances and antioxidant enzyme activity in the brain in Alzheimer's disease.

We determined levels of thiobarbituric acid-reactive substances (TBARS), a measure of lipid peroxidation, and the activity of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), and catalase (CAT) in the amygdala, hippocampus, pyriform cortex, superior and middle temporal gyri, inferior parietal lobule, middle frontal gyrus, occipital pole, and cerebellum of 13 Alzheimer's disease (AD) and 10 control brains. Levels of TBARS were elevated in all AD brain regions except the middle frontal gyrus, and elevation levels reached statistical significance in the hippocampus and pyriform cortex and marginal significance in the amygdala of AD subjects compared with age-matched controls. Significant elevation of GSH-Px activity was present in AD hippocampus compared with control. Moderate but statistically insignificant elevations of GSH-Px activity also were present in the amygdala and pyriform cortex in AD. GSSG-R activity was significantly elevated in the amygdala and hippocampus in AD subjects compared with controls. CAT activity was significantly elevated in AD hippocampus and superior and middle temporal gyri. SOD levels were elevated in all brain regions in AD patients compared with controls, although none of these elevations reached statistical significance. Antioxidant enzyme activities were significantly elevated where lipid peroxidation was most pronounced, suggesting a compensatory rise in antioxidant activity in response to increased free radical formation. This study supports the concept that the brain in AD is under increased oxidative stress and demonstrates that the oxidative changes are most pronounced in the medial temporal lobe, where histopathologic alterations are most severe.

Aged↗
PubMed1995

The FEHBP as a model for a new Medicare program.

The deficiencies of the Medicare program are rooted in its defined-benefit structure and in its use of price controls. Medicare should be transformed into a defined cash contribution made to beneficiaries' private plans or to the traditional Medicare program. The Federal Employees Health Benefits Program (FEHBP) is essentially such a system and is a good model for Medicare reform. The FEHBP has been highly successful at holding down costs while offering a wide range of benefits and types of plans. Its features for consumer information and plan standards also would be useful in a reformed Medicare program.

Aged↗
PubMed1994

Maternal compliance to court-ordered assessment in cases of child maltreatment.

Parental compliance to court-ordered assessment was examined in 82 mothers whose children had been removed from the home due to child maltreatment. Compliant (n = 52) and Noncompliant (n = 30) mothers were compared on parental and psychosocial risk factors previously documented in child maltreatment research. The results indicate that noncompliant mothers tend to be younger, lead more transient lifestyles, show a greater degree of antisocial behavior, and experience more violence in their spousal relationships. The implications of these data for clinical and legal involvement with these families is discussed.

Adult↗