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Biomedical subjects

C Lewis

Publications and source records attributed to C Lewis.

At least 55 records · Page 3Linked to original sources

The Otsego-Schoharie healthy heart program: prevention of cardiovascular disease in the rural US.

OBJECTIVES: To describe a rural, hospital-based public health intervention program and to evaluate its effectiveness in cardiovascular disease (CVD) risk reduction using cross-sectional studies and a panel study. METHODS: A rural population of 158,000 located in New York state comprised the intervention population. A similar but separate population was used for reference. A multifaceted, multimedia 5-year program provided health promotion and education initiatives to increase physical activity, decrease smoking, improve nutrition, and identify hypercholesterolemia and hypertension. To evaluate the effectiveness of the intervention, surveys were conducted at baseline in 1989 (cross-sectional) and at follow-up in 1994-95 (cross-sectional and panel). For cross-sectional studies, a random sample of adults was obtained using a three-stage cluster design. Self-reported and objective risk factor measurements were obtained. Comparison of pre- to post- changes in intervention versus reference populations was done using 2 x 2 randomized block ANOVA, 2 x 2 mixed ANOVA. and extension of the McNemar test. RESULTS: Smoking prevalence declined (from 27.9% to 17.6%) in the intervention population. Significant adverse trends were observed for high-density lipoprotein cholesterol and triglycerides. Systolic blood pressure was reduced while diastolic blood pressure remained stable. Body mass index increased significantly in both populations. CONCLUSIONS: This rural. 5-year CVD community intervention program decreased smoking. The risk reduction may be attributable to tailoring of a multifaceted approach (multiple risk factors, multiple messages, and multiple population subgroups) to a target rural population. The study period was too short to identify changes in CVD morbidity and mortality.

Adult↗

Design issues in the combination of international data from two rural community cardiovascular intervention programs.

OBJECTIVES: To compare and contrast two rural cardiovascular community intervention programs (CCIP) in northern Sweden and the US by discussing the methods used to select and combine similar data from two separately designed and implemented CCIP in order to describe and evaluate their effectiveness in reducing cardiovascular risk. METHODS: Two rural intervention populations and their reference populations were compared. A comparison was made of the intensity and duration of the intervention programs using an overall intervention intensity score. Population-based surveys were conducted at 5-year intervals in both countries. The methods used for data pooling and comparison are described. A description of statistical analyses using a mixed analysis of variance model is provided. RESULTS: The data were pooled. taking into consideration comparable ages. New variables were created in order to define the relationship between similar data that did not permit direct comparison. CONCLUSIONS: Combination and comparison of international data from two programs allowed evaluation of community intervention programs that were developed independently for similar communities. The effectiveness of interventions can be compared using such methods.

Adult↗

The Norsjö-Cooperstown healthy heart project: a case study combining data from different studies without the use of meta-analysis.

OBJECTIVES: This paper aims to develop and describe a method for combining. comparing, and maximizing the statistical power of two longitudinal studies of risk factors for cardiovascular disease that did not have identical data collection methodologies. METHODS: Subjects from a 1986 cross-sectional study (n = 180) were pair-matched with subjects of corresponding gender and age (+5 years) from a 1990 cross-sectional study. The methodology is described and results are calculated for various measures of cardiovascular risk or risk factors (e.g. cholesterol. Finnish Risk Score). RESULTS: Box's test of equality and symmetry of covariance matrices gave chi-square values of 223.8 and 710.0 for two cardiovascular risk factors (cholesterol and cardiac risk score, respectively); these values were highly significant (p=0.0001) For the North Karelia Risk Score, repeated measures ANOVA revealed a borderline significant interaction for treatment by time (p=0.054) and a significant interaction for treatment by time by country (p=0.035). These probabilities compared favorably with a randomized blocks model. CONCLUSIONS: Creation of a synthetic longitudinal control group resulted in a statistically valid ANOVA model that increased the statistical power of the study.

Adult↗

Different outcomes for different interventions with different focus!--A cross-country comparison of community interventions in rural Swedish and US populations.

OBJECTIVES: There is a need among healthcare providers to acquire more knowledge about small-scale and low budget community intervention programmes. This paper compares risk factor outcomes in Swedish and US intervention programmes for the prevention of cardiovascular disease (CVD). The aim was to explore how different intervention programme profiles affect outcome. METHODS: Using a quasi-experimental design, trends in risk factors and estimated CVD risk in two intervention areas (Norsjö. Sweden and Otsego-Schoharie County, New York state) are compared with those in reference areas (Northern Sweden region and Herkimer County, New York state) using serial cross-sectional studies and panel studies. RESULTS: The programmes were able to achieve significant changes in CVD risk factors that the local communities recognized as major concerns: changing eating habits in the Swedish population and reducing smoking in the US population. For the Swedish cross-sectional follow-up study cholesterol reduction was 12%, compared to 5% in the reference population (p for trend differences <0.000). The significantly higher estimated CVD risk (as assessed by risk scores) at baseline in the intervention population was below that of the Swedish reference population after 5 years of intervention. The Swedish panel study provided the same results. In the US, both the serial cross-sectional and panel studies showed a > 10% decline in smoking prevalence in the intervention population, while it increased slightly in the reference population. When pooling the serial cross-sectional studies the estimated risk reduction (using the Framingham risk equation) was significantly greater in the intervention populations compared to the reference populations. CONCLUSIONS: The overall pattern of risk reduction is consistent and suggests that the two different models of rural county intervention can contribute to significant risk reduction. The Swedish programme had its greatest effect on reduction of serum cholesterol levels whereas the US programme had its greatest effect on smoking prevention and cessation. These outcomes are consistent with programmatic emphases. Socially less privileged groups in these rural areas benefited as much or more from the interventions as those with greater social resources.

Adult↗

Bioaerosol emissions from a suburban yard waste composting facility.

The purpose of this study was to assess worker and community exposure to bioaerosols emitted from a suburban yard waste composting facility in northern Illinois, USA. Characterization of on- and off-site viable bioaerosols was undertaken through a total of 288 on- and off-site Andersen samples conducted over 10 sampling days. A total of 46 dust samples and 38 Kramer-Collins spore samples were also collected in this period. Evaluation of the impact of the facility on community bioaerosol concentrations was undertaken by comparing on- and off-site measurements by sampling locations, wind direction, and site activity. On-site concentrations of total spores, Aspergillus/Penicillium spores, total bacteria, Gram-positive bacteria, Gram-negative bacteria, actinomycetes, total particulates, endotoxin, and beta-1,3 glucans were higher than off-site concentrations. Total fungal spores averaged 13,451 spores/m3 (range 5,223-26,067) on-site and 8,772 spores/m3 (range 243-18,276) off-site. Viable bacterial airborne concentrations (in cfu/m3) averaged 11,879 on-site (range 480-78,880) and 3,204 off-site (range 160-17,600). Mean levels of endotoxins (in ng/m3) were 1.94 on-site (range 0.12-6.06) and 0.14 off-site (range 0.01-0.41). Mean levels of beta-1,3 glucans (in ng/m3) were 2.17 on-site (range 0.12-14.45) and 0.24 off-site (range 0.01-0.78). Mean total viable fungi, on the other hand, were higher off-site than on-site (8,651 vs 3,068 cfu/m3). On-site concentrations of total bacteria, Gram-positive bacteria, Gram-negative bacteria, and actinomycetes demonstrated a statistically significant pattern of decreasing concentration with distance from pile and higher downwind vs upwind concentrations. Mean on-site concentrations of viable bacteria, viable fungi, and endotoxins were significantly higher during periods of activity compared to periods of no activity. Off-site concentrations of bacteria were also significantly higher during periods of activity compared to no activity. The highest concentrations of total particulates, endotoxin, and beta-1,3-glucans were observed in the personal samplers worn by workers at the facility. One personal sampler measured an Asp f1 exposure of 22.17 ng/m3 during turning activity. Peak exposures to several bioaerosol constituents were sufficiently high to warrant use of respirators by workers during periods of pile activity that lead to dust generation.

Aerosols↗

Association of complementation group and mutation type with clinical outcome in fanconi anemia. European Fanconi Anemia Research Group.

Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder. Clinical care is complicated by variable age at onset and severity of hematologic symptoms. Recent advances in the molecular biology of FA have allowed us to investigate the relationship between FA genotype and the nature and severity of the clinical phenotype. Two hundred forty-five patients from all 7 known complementation groups (FA-A to FA-G) were studied. Mutations were detected in one of the cloned FANC genes in 169 patients; in the remainder the complementation group was assigned by cell fusion or Western blotting. A range of qualitative and quantitative clinical parameters was compared for each complementation group and for different classes of mutation. Significant phenotypic differences were found. FA-G patients had more severe cytopenia and a higher incidence of leukemia. Somatic abnormalities were less prevalent in FA-C, but more common in the rare groups FA-D, FA-E, and FA-F. In FA-A, patients homozygous for null mutations had an earlier onset of anemia and a higher incidence of leukemia than those with mutations producing an altered protein. In FA-C, there was a later age of onset of aplastic anemia and fewer somatic abnormalities in patients with the 322delG mutation, but there were more somatic abnormalities in patients with IVS4 + 4A --> T. This study indicates that FA patients with mutations in the FANCG gene and patients homozygous for null mutations in FANCA are high-risk groups with a poor hematologic outcome and should be considered as candidates both for frequent monitoring and early therapeutic intervention. (Blood. 2000;96:4064-4070)

Abnormalities, Multiple↗

Insights from a large rural population laboratory. Health census '89 and '99.

PURPOSE: Data are limited on health status behaviors and use of health services for rural residents. Yet rural areas now have higher rates of chronic diseases, such as coronary heart disease, than urban areas.METHODS: A population laboratory (Health Census) was established in rural Central NY (Otsego County) to study these variables in this population. HC '89 was a door-to-door enumeration of all permanent households in the country. In 1989, 44,500 adults in 18,000 households provided data on individual health screenings, cancer and cardiovascular risk factors, health behaviors, chronic disease, access to care, preventive services use, health insurance and emergency department utilization. Data collection for HC '99 will identify 10-year trends; it also includes baseline data for children. Also, households in six surrounding rural counties (N = 10,000) were sampled; cost benefits of different survey methods were assessed. Questions about perceived health status, and special health and pediatric preventive care needs were included. After 10 years of social change, many limitations of traditional survey methods became apparent; much more varied and frequent types of follow-up were needed to achieve adequate response rates.RESULTS: The HC '89 final response rate was 86%. There were significant socioeconomic gradients in use of preventive services (blood pressure screening, rectal exams, mammograms and Pap smears). Adults without health insurance or Medicaid had much lower utilization rates of screening tests and higher rates of cigarette smoking and obesity. Several community intervention programs were implemented as a result of HC '89. HC '99 provides additional analyses to examine change in preventive service use, self-reported chronic disease, and health services use; it will likely verify the persistence of socioeconomic gradients. Response rates are similar to '89, but achieved only with more intensive reinforcement.CONCLUSIONS: HC '89 confirmed a lag in positive health indices in rural populations in Central NY. Both newer methodologies now needed and results of HC '99 will serve as guides for smaller rural counties to develop affordable local health surveys and plan intervention strategies.

Journal Article↗

Crystal structure of the IMP-1 metallo beta-lactamase from Pseudomonas aeruginosa and its complex with a mercaptocarboxylate inhibitor: binding determinants of a potent, broad-spectrum inhibitor.

Metallo beta-lactamase enzymes confer antibiotic resistance to bacteria by catalyzing the hydrolysis of beta-lactam antibiotics. This relatively new form of resistance is spreading unchallenged as there is a current lack of potent and selective inhibitors of metallo beta-lactamases. Reported here are the crystal structures of the native IMP-1 metallo beta-lactamase from Pseudomonas aeruginosa and its complex with a mercaptocarboxylate inhibitor, 2-[5-(1-tetrazolylmethyl)thien-3-yl]-N-[2-(mercaptomethyl)-4 -(phenylb utyrylglycine)]. The structures were determined by molecular replacement, and refined to 3.1 A (native) and 2.0 A (complex) resolution. Binding of the inhibitor in the active site induces a conformational change that results in closing of the flap and transforms the active site groove into a tunnel-shaped cavity enclosing 83% of the solvent accessible surface area of the inhibitor. The inhibitor binds in the active site through interactions with residues that are conserved among metallo beta-lactamases; the inhibitor's carboxylate group interacts with Lys161, and the main chain amide nitrogen of Asn167. In the "oxyanion hole", the amide carbonyl oxygen of the inhibitor interacts through a water molecule with the side chain of Asn167, the inhibitor's thiolate bridges the two Zn(II) ions in the active site displacing the bridging water, and the phenylbutyryl side chain binds in a hydrophobic pocket (S1) at the base of the flap. The flap is displaced 2.9 A compared to the unbound structure, allowing Trp28 to interact edge-to-face with the inhibitor's thiophene ring. The similarities between this inhibitor and the beta-lactam substrates suggest a mode of substrate binding and the role of the conserved residues in the active site. It appears that the metallo beta-lactamases bind their substrates by establishing a subset of binding interactions near the catalytic center with conserved characteristic chemical groups of the beta-lactam substrates. These interactions are complemented by additional nonspecific binding between the more variable groups in the substrates and the flexible flap. This unique mode of binding of the mercaptocarboxylate inhibitor in the enzyme active site provides a binding model for metallo beta-lactamase inhibition with utility for future drug design.

Binding Sites↗

Representation of the cardinality principle: early conception of error in a counterfactual test.

There is debate over how the integration of non-verbal quantifying and verbal counting relates to the representation of number principles. A stringent representational test would be one in which a child obeyed a number principle where it ran counter to a characteristic procedure. We devised a test relying on the uniqueness principle for using evidence from a miscount in inferring a counterfactual cardinal number. All the 5-year-olds passed, as did half the preschoolers. Subtests probed associated number-skills. We suggest that a crucial preschool step is to start conceptualising error by categorising relations between counting and miscounting. That step is taken at a similar age to passing a representational theory of mind test but the two were uncorrelated.

Child Development↗

Correlates of physicians' prevention-related practices. Findings from the Women Physicians' Health Study.

BACKGROUND: Determinants of physicians' prevention-related counseling and screening practices are not well understood. Such determinants are worth knowing because we can then intervene on malleable variables and produce physicians with stronger prevention-related skills. Of the few such variables that have been examined, they have typically only been studied in univariate analyses or in small or otherwise limited populations and have been especially sparsely studied in women physicians. OBJECTIVE: To explore the effect of potential counseling- and screening-related variables in 4501 respondents to the Women Physicians' Health Study, a questionnaire-based study of a representative sample of US women MDs. RESULTS: Being a primary care practitioner and practicing a related health habit oneself were significantly correlated with reporting counseling and screening for all prevention-related variables examined. Current attempts to improve a related habit oneself, ethnicity, region, practice site, and amount of continuing medical education were sometimes significantly correlated with counseling and screening; most other variables studied (i.e., personal health status, a personal or family history of disease, control of work environment, and career satisfaction) were rarely significantly correlated. CONCLUSIONS: Being a primary care practitioner and having related healthy habits oneself were the most significant correlates of US women physicians' self-reported prevention-related counseling and screening practices. These findings suggest potential new directions for physician training.

Adult↗

Bronchiectasis in Alaska Native children: causes and clinical courses.

Although bronchiectasis has become a rare condition in U.S. children, it is still commonly diagnosed in Alaska Native children in the Yukon Kuskokwim Delta. The prevalence of bronchiectasis has not decreased in persons born during the 1980s as compared with those born in the 1940s. We reviewed case histories of 46 children with bronchiectasis. We observed that recurrent pneumonia was the major preceding medical condition in 85% of patients. There was an association between the lobes affected by pneumonia and the lobes affected by bronchiectasis. Eight (17%) patients had surgical resection of involved lobes. We conclude that the continued high prevalence of bronchiectasis appears to be related to extremely high rates of infant and childhood pneumonia. Pediatr Pulmonol. 2000;29:182-187. Published 2000 Wiley-Liss, Inc.

Adolescent↗

Large-scale purification of myeloperoxidase from HL60 promyelocytic cells: characterization and comparison to human neutrophil myeloperoxidase.

A large-scale purification procedure was developed for the isolation of myeloperoxidase from HL60 promyelocytic cells in culture. Initial studies showed the bulk of peroxidase-positive myeloperoxidase activity to be located in the cetyltrimethylammonium bromide solubilized particulate fraction of cell homogenates. The myeloperoxidase was then chromatographically purified using concanavalin A followed by gel filtration. SDS-PAGE analysis of the final preparation showed the presence of only two proteins with molecular masses of approximately 55 and 15 kDa, corresponding to the large and small subunits of myeloperoxidase. These data, along with Reinheit Zahl (RZ) values (A(430)/A(280)) of greater than or equal to 0.72, indicate that the myeloperoxidase prepared by this method is apparently homogeneous. Preparations routinely yielded 12-20 mg of pure myeloperoxidase per 10 ml of cell pellet. The HL60 myeloperoxidase was shown to be indistinguishable from purified human neutrophil myeloperoxidase by size exclusion chromatography, analytical ultracentrifugation, SDS-PAGE, Western blot, and NH(2)-terminal sequence analysis. The activities of the two myeloperoxidase samples, as measured using either the tetramethylbenzidine or the taurine chloramine assay, were indistinguishable. Finally, both enzymes responded identically to dapsone and aminobenzoic acid hydrazide, known inhibitors of myeloperoxidase. A protocol is presented here for the rapid, large-scale purification of myeloperoxidase from cultured HL60 cells, as well as evidence for the interchangeability of this myeloperoxidase and that purified from human neutrophils.

Benzidines↗

Does hypertension and its pharmacotherapy affect the quality of sexual function in women?

Considerable research has been conducted into the effects of antihypertensive drugs on male sexual functioning. This remains underexplored in women, even though almost half of treated hypertensives are women. An ambulatory medical record-based, case-control study was designed to study sexual function in treated and untreated hypertensive women and healthy controls. We conducted this study at a teaching hospital with satellite clinics in upstate New York. Of 3312 medical records reviewed, 640 premenopausal white women with or without mild hypertension (defined as blood pressure [BP] > or = 140/90 and < 160/110 mmHg), in heterosexual relationships, with no other significant medical history, were eligible. Of these, 241 women agreed to participate, and 224 (35%) completed both a self-administered questionnaire and a telephone interview. Analysis was conducted on 211 women (107 healthy controls, and 104 mild hypertensives, of whom 37 were unmedicated and 67 medicated). Questions on sexuality were classified into seven composite variables and later further divided. There were no demographic differences between participants and nonparticipants. Cases and controls differed only by age (P < .01); therefore, subsequent analysis was age-adjusted. Current smokers reported a significantly lower mean score for orgasm than did nonsmokers (P = .04). Women with unmedicated and medicated hypertension did not differ significantly on sexuality scores and were subsequently combined. Using age-adjusted ANOVA, women with hypertension reported significantly decreased lubrication and orgasm and increased pain compared to nonhypertensive women. There were no significant differences by ANOVA in the quality of sexual functioning between six treatment groups. In conclusion, the quality of female sexual functioning was quantified in an ambulatory outpatient setting. Hypertensive women, regardless of type of treatment, reported age-adjusted decrease in vaginal lubrication, less frequent orgasm, and more frequent pain when compared to nonhypertensive women. Emotional aspects of sexual functioning in hypertensive women do not appear to be impaired. These areas require further investigation. An incidental finding indicated diminished orgasm reported in current smokers, compared to nonsmokers, which was not associated with age or hypertension.

Adult↗

Epidemiology of erectile dysfunction: a community-based study in rural New York State.

PURPOSE: Few published population-based studies that deal with the prevalence of erectile dysfunction (ED) involve rural populations. This study determined the prevalence and determinants of ED among a rural population. It also evaluated the relevance of some major predictors of help-seeking decisions. METHODS: A self-administered survey was conducted by mail among 5198 randomly selected men 50-76 years old, living in four rural counties in Central New York State. RESULTS: The response rate was 44.7% and the participation rate among respondents was 71.0%. Mean ages of men reporting and those not reporting ED were 64.5 7.2 and 59.8 7.2 years respectively. The mean duration of self-reported ED was 4.9 4.6 years. The overall prevalence of ED was 46.3% while the minimum prevalence was estimated as 21.3%. Age-specific prevalence was 26.0%, 34.9%, 46.9%, 57.8% and 69.4% among men 50-54, 55-59, 60-64, 65-69, and 70-76 years old respectively. There was a statistically significant relationship between age, socio-economic status, perceived state of health and erectile function status (p < 0.001). However, socio-economic status, marital status, perceived state of health and age were not significant predictors of help-seeking decisions. CONCLUSIONS: The prevalence of ED among men 50-76 years old in rural Central New York State is at least 21.3% and may be as high as 46.3%. Age, perceived state of health and socio-economic status were found to be important determinants of erectile dysfunction among this population. For purposes of comparative analyses, future epidemiological studies should report both the overall and minimum rates among men with clinically relevant erectile dysfunction.

Aged↗

Stability and haplotype analysis of the FRAXE region.

FRAXE full mutations are rare and appear to be associated with mild mental retardation. As part of a screening survey of boys with learning difficulties to determine the frequency of full and premutations, we have collected data on the frequency of instability at FRAXE for about 4000 transmissions and the haplotype for over 7000 chromosomes. The distribution of FRAXE repeats was similar to other English populations but differed from two North American Caucasian series. Observed instability at FRAXE was rare but increased with increasing repeat number, and there were no expansions into the full mutation range, except in pedigrees ascertained through a full mutation. Haplotype analysis suggested division into five groups with each group having a characteristic distribution of FRAXE repeats. Fourteen of the 15 full mutations occurred on a single haplotype and this haplotype also had a significant excess of intermediate-sized alleles, suggesting that full mutations originate from large normal alleles. However, a related haplotype also had a significant excess of intermediates but we observed no full mutations on this haplotype, suggesting either loss or gain of stability determinants on it. We suggest that whilst triplet repeat size is a significant predisposing factor for expansion at FRAXE other genetic determinants are also likely to be important.

Alleles↗