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Biomedical subjects

C Lewis

Publications and source records attributed to C Lewis.

At least 19 recordsLinked to original sources
PubMed2001

Technique charts for EC film: direct optical measurements to account for the effects of X-ray scatter.

PURPOSE: To develop a method of measuring technique charts for enhanced contrast (EC) film, to demonstrate how X-ray scatter changes the response of EC film, and to generate technique charts for general use. METHODS AND MATERIALS: We have developed a "digital cassette"-consisting of a metal plate/phosphor screen, a light guide, a photodiode sensor, and an electrometer-that can be used to measure the light generated in the phosphor screen of the film cassette. In turn, these measurements can be used to generate technique charts for EC film. The digital cassette has been used to measure technique charts for 4-MV and 6-MV X-ray beams for a variety of different phantom thicknesses, field sizes, and phantom-to-cassette air gaps. RESULTS AND DISCUSSION: We have observed that the signals generated in an ionization chamber located 9.4 cm behind a 30-cm-thick water-equivalent phantom increase by a factor of 1.9 when the field size is increased from 4 x 4 cm(2) to 40 x 40 cm(2) when irradiated by a 6-MV X-ray beam. However, the change in EC film response is a factor of 3.5 under the same conditions. Irradiations to optimally expose the EC film predicted by the digital cassette differ by up to 82% compared to those predicted by ion chamber measurements. Nevertheless, the technique charts measured using the digital cassette predict the response of the EC film to +/- 0.2 optical density. The overresponse of the EC film is most likely due to low-energy scattered photons, which interact with the high atomic number (Z = 64) phosphor screen of the enhanced contrast localization cassette. Therefore, simple solutions, such as placing a high atomic number material above the enhanced contrast localization cassette, can reduce this contribution by scattered photons to the signal generated in the cassettes. CONCLUSIONS: We have developed a digital cassette that can make more accurate measurements of the technique charts for EC films. Our measurements show that under some conditions, X-ray scatter can generate a large fraction of the signals recorded by the EC film. Technique charts have been generated at 4 MV and 6 MV, and these charts should have universal applicability.

Film Dosimetry↗
PubMed2001

Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations.

Background Genetic predisposition to inflammatory bowel disease (IBD) has been shown by epidemiological and linkage studies. Genetic linkage of IBD to chromosome 16 has been previously observed and replicated in independent populations. The recently identified NOD2 gene is a good positional and functional candidate gene since it is located in the region of linkage on chromosome 16q12, and activates nuclear factor (NF) kappaB in response to bacterial lipopolysaccharides. Methods We sequenced the coding region of the NOD2 gene and genotyped an insertion polymorphism affecting the leucine-rich region of the protein product in 512 individuals with IBD from 309 German or British families, 369 German trios (ie, German patients with sporadic IBD and their unaffected parents), and 272 normal controls. We then tested for association with Crohn's disease and ulcerative colitis. Findings Family-based association analyses were consistently positive in 95 British and 99 German affected sibling pairs with Crohn's disease (combined p<0.0001); the association was confirmed in the 304 German trios with Crohn's disease. No association was seen in the 115 sibling pairs and 65 trios with ulcerative colitis. The genotype-specific disease risks conferred by heterozygous and homozygous mutant genotypes were 2.6 (95% CI 1.5-4.5) and 42.1 (4.3-infinity), respectively. Interpretation The insertion mutation in the NOD2 gene confers a substantially increased susceptibility to Crohn's disease but not to ulcerative colitis.

Alleles↗
PubMed2001

Sex, drugs, and hypertension: a methodological approach for studying a sensitive subject.

Sexual dysfunction is a recognized side effect of hypertension and antihypertensive medications in men, but is not established as a side effect in women, due to the lack of established methodology. An ambulatory medical record-based, case-control study was designed to study sexual function in treated and untreated hypertensive women and healthy controls. The research was performed in a teaching hospital with satellite clinics in upstate New York. There were 3312 medical records reviewed, 640 premenopausal Caucasian women in heterosexual relationships subjects were eligible for participatic diagnosis of mild hypertension (BP > or =140/90 mmHg and < 160/100 mmHg) for cases; no other significant medical history. A total of 241 women agreed to participate, 224 (35%) completed both a self-administered questionnaire and a telephone interview (112 healthy, 112 hypertensive). There was an initial 74% response rate among those eligible to participate, with 35% completing the entire study. Age and average blood pressure were not significant between 224 participants and 416 nonparticipants by 2-tailed t-test analysis. Seven composite variables were formed from a 47-item sexual response questionnaire. Initial unadjusted chi2 results reported women with hypertension had more difficulty than did healthy controls achieving lubrication and orgasm. Seven questions, each with the highest correlation to its respective composite variable (by Spearman's correlation), formed an abbreviated questionnaire. Quality of female sexual function was quantified in an ambulatory outpatient setting. A method was described to address hypertension, pharmacotherapy, and sexual functioning by employing self-administered questionnaires and telephone interviews. Initial analysis suggested that hypertensive women may have an impaired physiological sexual response. The abbreviated questionnaire generated from questions with the highest correlation to their respective composite variables may be useful in further evaluating this issue.

Adult↗
PubMed2001

IL-4, IL-13, and dexamethasone augment fibroblast proliferation in asthma.

BACKGROUND: IL-4 and IL-13 have been shown to be critical for expression of the asthma phenotype in a murine model and may modulate human fibroblast function. OBJECTIVE: We hypothesized that IL-4 and IL-13 would increase airway fibroblast proliferation and reduce the ability of dexamethasone to decrease this proliferation. METHODS: Six subjects with severe asthma, 5 subjects with mild asthma, and 5 healthy subjects underwent bronchoscopy with endobronchial biopsy. Biopsy specimens were placed in Dulbecco modified Eagle medium and cultured, and only fibro-blasts from the first and second passages were evaluated. Cells were incubated with IL-4 (50 ng/mL), IL-13 (10 ng/mL), and the combination for 48 hours in the presence and absence of dexamethasone, 10(-7) mol/L, and 10(-8) mol/L. Fibroblasts were also incubated with IFN-gamma at 50 ng/mL to assess the response of a T(H)1 cytokine on proliferation. RESULTS: Fibroblast proliferation, determined by (3)H-thymidine incorporation, was significantly increased by IL-4 in subjects with mild asthma as compared with IL-4 in subjects with severe asthma and healthy subjects (P =.003), IL-13 (P =.011), and the combination (P =.004). Dexamethasone also increased proliferation in the group with mild asthma as compared with the group with severe asthma and the healthy group (10(-7) mol/L, P =.02; 10(-8) mol/L, P =.02). IFN-gamma did not significantly alter airway fibroblast proliferation. CONCLUSION: IL-4, IL-13, and dexamethasone all significantly increased fibroblast proliferation in subjects with mild asthma.

Adult↗
PubMed2001

A normative reference database study for Pronosco X-posure System.

Cortical width from radiographs has been used for more than 40 yr as a means of estimating bone strength. In the last 5-10 yr, increased availability of computers and the development of automated algorithms for image assessment have led to an increased interest in radiogrammetry. In this study, we examined a new radiogrammetry device, the Pronosco X-posure System, which estimates bone mineral density (BMD) from forearm/hand radiographs. We obtained hand and forearm radiographs and performed dual X-ray absorptiometry (DXA) at the wrist and hip on 832 women ages 20-79 at four clinical centers across the United States. We then used the X-posure System to estimate BMD (DXR-BMD). The goal of the study was to establish reference ranges for the method and to compare the measurement to DXA measurements of BMD at the wrist and hip. Using statistical models, we estimated that the peak value for DXR-BMD occurred at age 38 (mean = 0.598 g/cm2, standard deviation = 0.034 g/cm2). The correlation between DXR-BMD and DXA was 0.90 at the wrist and 0.61 at the hip. The relationship of DXR-BMD to reported history of fracture was of similar magnitude to that for DXA at the wrist and hip. The strong correlation of DXR-BMD from the X-posure System with DXA at the wrist from the Hologic machine suggests that the X-posure System may be an alternative to DXA at the wrist for the assessment of osteoporosis.

Absorptiometry, Photon↗
PubMed2001

The lifetime cost of bipolar disorder in the US: an estimate for new cases in 1998.

OBJECTIVE: To develop a cost model that estimates the total and per case lifetime cost of bipolar disorder for 1998 incident cases in the US. STUDY DESIGN: Lifetime cost simulation model. PERSPECTIVE: Societal. METHODS: Age- and gender-specific incidence of bipolar disorder in 1998 was estimated by simulation based on existing prevalence data. The course of illness and mental health service cost of 6 clinically defined prognostic groups was estimated based on the research literature and the judgement of panels of experts. Excess cost of general medical care was estimated based on claims data from a large insurer. Indirect cost was projected including excess unemployment and reduced earnings reported in the National Comorbidity Survey. Comorbidity treatment and indirect cost related to alcohol (ethanol) and drug abuse was added based on a National Institute on Drug Abuse study. RESULTS: The present value of the lifetime cost of persons with onset of bipolar disorder in 1998 was estimated at 24 billion US dollars ($US). Average cost per case ranged from $US11,720 for persons with a single manic episode to $US624,785 for persons with nonresponsive/chronic episodes. CONCLUSION: The model indicates the potential cost savings of preventing a case of bipolar disorder and underscores the importance of achieving a stable outcome in new cases to limit the economic consequences of the disorder.

Adolescent↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗