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Biomedical subjects

D C Pearson

Publications and source records attributed to D C Pearson.

At least 19 recordsLinked to original sources

Azathioprine for maintaining remission of Crohn's disease.

OBJECTIVES: To assess the effectiveness of azathioprine in maintaining remission of quiescent Crohn's disease. SEARCH STRATEGY: Pertinent studies were selected using the MEDLINE data base (1966 - May 1998), the Cochrane Controlled Trials Register, the Inflammatory Bowel Disease Trials Register, as well as abstracts from major gastrointestinal research meetings and references from published articles and reviews. SELECTION CRITERIA: Five randomized, double-blind, placebo-controlled trials of azathioprine therapy were identified. Two of these trials consisted solely of patients with quiescent Crohn's disease. Three trials had multiple therapeutic arms for both induction of remission and maintenance of remission. DATA COLLECTION AND ANALYSIS: Data were extracted by three independent observers (GRM, GF, LRS) based on the intention to treat principle. Peto odds ratios for the overall maintenance of remission, steroid sparing, and withdrawals due to adverse effects were calculated, and from these, 95% confidence intervals were derived. Numbers needed to treat or harm (NNT, NNH respectively) for the maintenance of remission, steroid sparing, and withdrawals due to adverse effects were also determined. MAIN RESULTS: Azathioprine had a positive effect on maintaining remission. The Peto odds ratio for maintenance of remission was 2.16 (CI 1.35 - 3.47) with an NNT of 7. A higher dose improved response. A steroid sparing effect was noted, with a Peto odds ratio of 5.22 (CI 1.06 - 25.68) and NNT of 3 for quiescent disease. The Peto odds ratio for withdrawals due to adverse events was 4.36 (CI 1.63 - 11.67), the NNH (Number Needed to Harm) was 19. REVIEWER'S CONCLUSIONS: Azathioprine is effective in maintaining remission. There is evidence for a steroid sparing effect.

Azathioprine↗

Familial idiopathic adulthood ductopenia: a report of five cases in three generations.

BACKGROUND/AIMS: Idiopathic adulthood ductopenia is a cholestatic liver disease of unknown etiology. Although most cases are sporadic, familial cases do occur. METHODS: We describe a series of adult-onset bile duct depletion involving five members of an extended family spanning three generations. The proband, a 49-year-old man, presented in 1989 with asymptomatic elevation of liver enzyme tests. Investigations for chronic liver disease, including endoscopic retrograde cholangiopancreatography, were negative. Findings on liver biopsy progressed from normal in 1989 to striking loss of interlobular bile ducts in 1992. Ursodeoxycholic acid has resulted in improvement of liver enzyme tests. The proband's brother required a liver transplant at age 35 for cryptogenic cirrhosis. The proband's sister, age 42, has had intermittent jaundice and elevation of liver enzyme tests since 1971. Her liver biopsy findings progressed from normal in 1975, to striking bile duct damage by 1997. The proband's 21-year-old son has elevated liver enzyme tests and a liver biopsy consistent with idiopathic adulthood ductopenia. The proband's father had a liver biopsy at age 70 for investigation of a liver mass. It revealed extensive fibrosis and striking bile duct destruction. RESULTS/CONCLUSIONS: This is the largest series of familial idiopathic adulthood ductopenia reported, and the first with multiple generations described. Genetics appears to play a role in some cases of adulthood ductopenia. Ursodeoxycholic acid may be beneficial in the treatment of this condition.

Adult↗

The Kaiser Family Foundation Community Health Promotion Grants Program: findings from an outcome evaluation.

OBJECTIVES: To present results from an outcome evaluation of the Henry J. Kaiser Family Foundation's Community Health Promotion Grants Program (CHPGP) in the West, which represented a major community-based initiative designed to promote improved health by changing community norms, environmental conditions, and individual behavior in 11 western communities. METHODS: The evaluation design: 14 randomly assigned intervention and control communities, 4 intervention communities selected on special merit, and 4 matched controls. Data for the outcome evaluation were obtained from surveys, administered every two years at three points in time, of community leaders and representative adults and adolescents, and from specially designed surveys of grocery stores. Outcomes for each of the 11 intervention communities were compared with outcomes in control communities. RESULTS: With the exception of two intervention communities-a largely Hispanic community and a Native American reservation-we found little evidence of positive changes in the outcomes targeted by the 11 intervention communities. The programs that demonstrated positive outcomes targeted dietary behavior and adolescent substance abuse. CONCLUSIONS: Improvement of health through community-based interventions remains a critical public health challenge. The CHPGP, like other prominent community-based initiatives, generally failed to produce measurable changes in the targeted health outcomes. Efforts should focus on developing theories and methods that can improve the design and evaluation of community-based interventions.

Adolescent↗

Brownian dynamics study of the interaction between plastocyanin and cytochrome f.

The electrostatic interaction between plastocyanin (PC) and cytochrome f (cyt f), electron transfer partners in photosynthesis was studied using Brownian dynamics (BD) simulations. By using the software package MacroDox, which implements the BD algorithm of Northrup et al. (Northrup, S. H., J. O. Boles, and J. C. L. Reynolds. 1987. J. Phys. Chem. 91:5991-5998), we have modeled the interaction of the two proteins based on crystal structures of poplar PC and turnip cyt f at pH 7 and a variety of ionic strengths. We find that the electrostatic attraction between positively charged residues (K58, K65, K187, and R209, among others) on cyt f and negatively charged residues (E43, D44, E59, and E60, among others) on PC steers PC into a single dominant orientation with respect to cyt f, and furthermore, that the single dominant orientation that we observe is one that we had predicted in our previous work (Pearson, D. C., E. L. Gross, and E. S. David. 1996. Biophys. J. 71:64-76). This dominant orientation permits the formation of hydrophobic interactions, which are not implemented in the MacroDox algorithm. This proposed complex between PC and cyt f implicates H87, a copper ligand on PC, as the residue that accepts electrons from the heme on cyt f (and possibly through Y1 as we proposed previously). We argue for the existence of this single dominant complex on the basis of observations that the most favorable orientations of the interaction between PC and cyt f, as determined by grouping successful BD trajectories on the basis of closest contacts of charged residues, tend to overlap one another and have very close distances between the metal centers on the two proteins (copper on PC, iron on cyt f). We use this knowledge to develop a model for PC/cyt f interaction that places a reaction between the two proteins occurring when the copper-to-iron distance is between 16 and 17 A. This reaction distance gives a good estimate of the experimentally observed rate constant for PC-cyt f interaction. Analysis of BD results as a function of ionic strength predicts an interaction that happens less frequently and becomes less specific as ionic strength increases.

Algorithms↗

A comprehensive influenza campaign in a managed care setting.

Group Health Cooperative, a large, membership-governed, staff model health maintenance organization (HMO), has designed a comprehensive influenza campaign for identifying, recruiting and vaccinating enrollees at increased risk for influenza-related complications. The Cooperative's Centre for Health Promotion is responsible for the overall planning, implementation and evaluation of the influenza campaign. The model for delivering influenza immunizations has been designed to build on the strengths and capabilities of a staff model HMO with sophisticated automated information systems. The model permits area medical centres (AMCs) and physicians to use the materials and intervention strategies generated by the Centre for Health Promotion, while at the same time allowing them flexibility to design and use their own intervention strategies to increase compliance. More importantly, the model reduces resource requirements on AMCs and physicians to plan and maintain internal immunization efforts. Recommendations for improving the influenza campaign are discussed.

Aged↗

Superior vena cava thrombosis associated with a central venous access device: a case report.

A case report is presented that illustrates the signs, symptoms, and treatment of superior vena cava thrombosis (SVCT) related to a venous access device (VAD). SVCT is a rare complication associated with VADs; its symptoms can be very subtle, which makes diagnosis difficult. Knowing who is at risk, assessing these patients closely, and providing patient education will help to identify early complications. Because patients spend most of their time away from healthcare providers, education is needed to increase patients' awareness of the subtle signs and symptoms of SVCT. Patients need to know what to report to their oncology team members so that early treatment can be initiated.

Catheters, Indwelling↗

The anti-oxidant properties of 5-aminosalicylic acid.

Oxidative damage to biological membranes is an important cause of tissue injury in inflammatory bowel disease. 5-Aminosalicylic Acid (5ASA) has therapeutic efficacy in Ulcerative colitis, which may be based on its antioxidant properties. We used Parinaric acid as a fluorescent marker of oxidation in an intestinal microvillous brush border membrane preparation. Various concentrations of the antioxidants 5ASA, ascorbate, and tocopherol were added, and oxidation was initiated from within the membrane by 2,2' azobis (2.4-dimethylvaleronitrile) (AMVN) and from solution by 2,2' azobis (2-amidinopropane) hydrochloride (AAPH). Tocopherol was able to inhibit oxidation from either source. Ascorbate was only able to inhibit oxidation initiated from solution. 5ASA was able to inhibit oxidation initiated from either site, and was more effective than tocopherol against AAPH, but similarly effective against AMVN. We postulate that water soluble 5ASA preferentially associates with membrane surface, allowing chain-breaking antioxidant activity when peroxidation is initiated within the membrane. Likewise, it is effective against aqueous oxidants because its position allows it to interact with AAPH before lipid peroxidation can be initiated as well as breaking the lipid peroxidation chain once it is initiated. This dual capacity may be important for therapeutic effect of 5ASA and may suggest other candidate antioxidants for clinical trials.

Amidines↗

Electrostatic properties of cytochrome f: implications for docking with plastocyanin.

The electrostatic properties of cytochrome f (cyt f), a member of the cytochrome b6f complex and reaction partner with plastocyanin (PC) in photosynthetic electron transport, are qualitatively studied with the goal of determining the mechanism of electron transfer between cyt f and PC. A crystal structure for cyt f was analyzed with the software package GRASP, revealing a large region of positive potential generated by a patch of positively charged residues (including K58, K65, K66, K122, K185, K187, and R209) and reinforced by the iron center of the heme. This positive field attracts the negative charges of the two acidic patches on the mobile electron carrier PC. Three docked complexes are obtained for the two proteins, based on electrostatic or hydrophobic interactions or both and on steric fits by manual docking methods. The first of these three complexes shows strong electrostatic interactions between K187 on cyt f and D44 on PC and between E59 on PC and K58 on cyt f. Two other manually docked complexes are proposed, implicating H87 on PC as the electron-accepting site from the iron center of cyt f through Y1. The second complex maintains the D44/K187 cross-link (but not the E59/K58 link) while increasing hydrophobic interactions between PC and cyt f. Hydrophobic interactions are increased still further in the third complex, whereas the link between K187 on cyt f and D44 on PC is broken. The proposed reaction mechanism, therefore, involves an initial electrostatic docking complex that gives rise to a nonpolar attraction between the regions surrounding H87 on PC and Y1 on cyt f, providing for an electron-transfer active complex.

Binding Sites↗

The effects of heparin flush on patency of the Groshong catheter: a pilot study.

PURPOSE/OBJECTIVES: To determine whether the addition or a heparinized saline flush would decrease clot formation and persistent withdrawal occlusion (PWO) in Groshong (Bard Access Systems, Salt Lake City, UT) catheters. DESIGN: A prospective, nonrandomized study using a historical control group of patients with Groshong catheters that had been flushed weekly with 5 ml normal saline compared to data from patients with Groshong catheters flushed weekly with 2.5 ml heparinized saline (100 U/ml). A retrospective chart review was performed to determine the incidence of PWO. In both groups, the presence of liquid blood and adherent or nonadherent clot in explanted catheters was recorded. SETTING: Oncology inpatient and outpatient units of a cancer research center located in a mid-Atlantic city in the United States. SAMPLE CONTROL GROUP: Twenty-eight 9.5 Fr. double-lumen Groshong catheters maintained with a saline flush. Experimental group: Twenty-three double-lumen Groshong catheters maintained with a heparin flush. At the time of this report, 12 of these 23 catheters had been explanted and 11 remained in place. METHODS: The frequency of PWO was measured in a retrospective chart review and determined by the number of urokinase instillations required for each catheter. All 28 catheters in the saline flush group and 8 catheters in the heparin flush group were examined immediately after removal for intraluminal liquid blood and adherent or nonadherent clot. MAIN RESEARCH VARIABLES: Urokinase usage, intra-luminal blood or clot, and PWO. FINDINGS: PWO occurred less frequently in the heparin flush group (p = 0.006) than in the saline fush group. All 28 of the saline flush catheters developed an adherent clot in one or both lumens, whereas no adherent clots were found in the heparin flush catheters (p < 0.0001). CONCLUSIONS: The addition of a heparinized saline weekly flush to maintain Groshong catheters decreased the presence of intraluminal adherent clots and improved the catheter function. IMPLICATIONS FOR NURSING PRACTICE: The safe delivery of medication and the ability to obtain blood specimens are vital for patients who depend on functioning venous access catheters. Flushing Groshong catheters with heparinized saline decreases the likelihood of intraluminal clot formation and catheter malfunction.

Adult↗

Azathioprine and 6-mercaptopurine in Crohn disease. A meta-analysis.

PURPOSE: To assess the effectiveness of azathioprine and 6-mercaptopurine in inducing remission of active Crohn disease and the effectiveness of azathioprine in maintaining remission of quiescent disease. DATA SOURCES: Pertinent studies were selected from the MEDLINE database (1966 to May 1994), abstracts from major gastrointestinal meetings, and references from published articles and reviews. STUDY SELECTION: Nine randomized, placebo-controlled trials of azathioprine or 6-mercaptopurine therapy were identified: Four addressed active disease, two addressed quiescent disease, and three had multiple therapeutic arms. DATA EXTRACTION: Data were extracted by three independent observers on the basis of the intention-to-treat principle and were analyzed with logistic regression. Each study was given a quality score on the basis of predetermined criteria. DATA SYNTHESIS: Compared with placebo, azathioprine or 6-mercaptopurine therapy had an odds ratio of response of 3.09 (95% CI, 2.45 to 3.91) in patients with active Crohn disease. When the single trial that used 6-mercaptopurine in active disease was excluded from the analysis, the odds ratio of response was 1.45 (CI, 1.12 to 1.87). No trials of quiescent disease used 6-mercaptopurine; the odds ratio of response in these trials of quiescent disease was 2.27 (CI, 1.76 to 2.93). For active disease, continuation of therapy for at least 17 weeks improved response (P = 0.03). For quiescent disease, a higher dose improved response (P = 0.008). Increased cumulative dose improved response in both groups (P < 0.001 for active disease and P = 0.01 for quiescent disease). A steroid-sparing effect was seen in active disease (odds ratio, 3.69 (CI, 2.12 to 6.42) and in quiescent disease (odds ratio, 4.64 [CI, 1.00 to 21.54]). Fistulae improved with therapy (odds ratio, 4.44 [CI, 1.50 to 13.20]). Adverse events requiring withdrawal from a trial, primarily allergy, leukopenia, pancreatitis, and nausea, were increased with therapy (odds ratio, 5.26 [CI, 2.20 to 12.60]). CONCLUSIONS: Azathioprine and 6-mercaptopurine are effective in treating active Crohn disease and in maintaining remission. Cumulative dose was an important factor in predicting response. Adverse effects were more common among patients receiving therapy.

Azathioprine↗

Chemotherapy extravasation: a consequence of fibrin sheath formation around venous access devices.

PURPOSE/OBJECTIVES: To describe, using two case studies, chemotherapy drug extravasation as a consequence of fibrin sheath formation. DATA SOURCES: Journal articles, textbooks, medical records, and personal experiences. DATA SYNTHESIS: Fibrin sheath formation around venous access devices (VADs) frequently leads to persistent withdrawal occlusion (PWO). While PWO often is easily managed with small doses of thrombolytic therapy (e.g., urokinase), it may result in a more serious complication, such as chemotherapy extravasation. CONCLUSIONS: Chemotherapy should not be administered through a VAD unless a free-flowing blood return can be demonstrated. IMPLICATIONS FOR NURSING PRACTICE: Careful nursing assessment of all VADs is important to identify complications such as fibrin sheath formation. To rule out fibrin sheath formation, nurses must obtain catheter dye studies when fibrinolytic therapy fails to restore catheter function.

Adult↗

Race- and ethnicity-specific characteristics of participants lost to follow-up in a telephone cohort.

The purpose of this study was to describe race- and ethnicity-specific characteristics of subjects lost to follow-up. For a study of community-based health interventions, adult subjects from 11 US communities were initially recruited by random digit dialing and interviewed by telephone in 1988; 2 years later, they were recontacted, and the same survey was administered a second time. Associations with loss to follow-up were assessed in separate models for whites, African Americans, Hispanic Americans, and Asian Americans. After 2 years, 40.8% of the 5,851 participants were lost to follow-up; cohort attrition was highest among African Americans (51.3%) and lowest among whites (37.5%). Age, aspects of employment, education, marital status, and income were significant independent predictors of loss to follow-up for one or more of the four racial and ethnic groups. Characteristics of subjects lost to follow-up in this telephone cohort differed among various racial and ethnic groups. After adjustment for demographic, socioeconomic, and health status variables, the important behavioral predictors of loss to follow-up were current smoking for whites (p < 0.05), having a high fat diet for African Americans (p < 0.10), consuming one or more alcoholic drinks per day for Hispanic Americans (p < 0.10), and high levels of physical activity for Asian Americans (p < 0.05).

Adolescent↗

Group Health Cooperative's community services initiative.

Service to the broader community is an important component of Group Health Cooperative's (GHC's) tradition, values, and mission. The role and potential of community services in a staff model HMO requires consensus, careful planning and communication, and attention to results. This paper describes GHC's efforts to define, implement, and sustain its community services initiative.

Community Health Services↗

Self-help quit smoking interventions: effects of self-help materials, social support instructions, and telephone counseling.

Smokers requesting self-help materials for smoking cessation (N = 2,021) were randomized to receive (a) an experimental self-quitting guide emphasizing nicotine fading and other nonaversive behavioral strategies, (b) the same self-quitting guide with a support guide for the quitter's family and friends, (c) self-quitting and support guides along with four brief counselor calls, or (d) a control guide providing motivational and quit tips and referral to locally available guides and programs. Subjects were predominantly moderate to heavy smokers with a history of multiple previous quit attempts and treatments. Control subjects achieved quit rates similar to those of smokers using the experimental quitting guide, with fewer behavioral prequitting strategies and more outside treatments. Social support guides had no effect on perceived support for quitting or on 8- and 16-month quit rates. Telephone counseling increased adherence to the quitting protocol and quit rates.

Behavior Therapy↗

Factors associated with participation in a community senior health promotion program: a pilot study.

Factors associated with participation in a community senior health promotion program were studied in 103 participants and a population-based control group of 531 non-participants. Compared to controls, participants had similar physical health status, but lower mental and social health status. Both men and women participants reported more depressive symptoms, lower positive affect, and lower social participation. Mental and social health may be important yet under-studied factors influencing participation in community health promotion programs.

Aged↗

Smokers and drinkers in a health maintenance organization population: lifestyles and health status.

This study examines, among a large health maintenance organization population, the prevalence of two high-risk lifestyle practices (smoking and problem drinking), their interrelationships, and their relationships with other lifestyle practices, sociodemographic characteristics, and health status measures. Results, based on a random sample of 1,133 adults, showed that smoking and problem drinking are strongly correlated. Individuals with no drinking problems had an age-, sex-, and education-adjusted smoking prevalence of approximately 20%, while problem drinkers smoked at about twice that rate. In addition, reporting one type of problem drinking behavior (binge, chronic, or drinking and driving) at least doubled, and in one instance increased by sixfold, the likelihood of reporting another type of problem drinking behavior. Smokers and problem drinkers were more likely to be younger than age 65, to be irregular seat belt users (smokers and binge drinkers only), and not to belong to voluntary organizations. Results of the analysis suggest that detection, prevention, and treatment of drug use, in general, might prove more beneficial than only focusing on smoking and problem drinking. In addition, because binge drinking and drinking and driving were so widespread among younger age groups, it might prove more beneficial to consider preventive strategies that change the sale and distribution of alcohol and make the environment safer in which to drink, such as providing transportation to get drinkers back home.

Adult↗

Chemical mechanisms for cytochrome P-450 hydroxylation: evidence for acylation of heme-bound dioxygen.

Using isotopic tracer methods, we have shown that dihydrolipoic acid (2,3-thioctic acid) acylates the distal oxygen of ferrous oxygenated Pseudomonas cytochrome P-450, forming a transient acyl peroxide intermediate that facilitates oxygen-oxygen bond cleavage. Single-turnover studies with 18O2 indicate one oxygen-18 atom incorporated into the carboxylate group of lipoic acid for each oxygen-18 inserted into the substrate, camphor, forming the product, exo-5-hydroxycamphor. Such a branching ratio for label indicates that water is initially released from an unlageled position and illustrates that the general P-450 mixed-function oxidase stoichiometry generates H218O from 18O2 only after multiple-turnover equilibration with the acylating carboxylate oxygen. Formation of an acyl peroxide state is a natural intermediate in peracid, "oxene", or radical mechanisms for methylene carbone oxygenation.

Acylation↗