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.

Use of behavioral risk factor surveys to predict alcohol-related motor vehicle events.

The relationship between acute alcohol intoxication and increased risk of traffic violations, crashes, and injuries is well known. We designed this study to investigate the usefulness of behavioral risk factor surveys (BRFSs) in identifying drivers at risk for subsequent motor vehicle violations and crashes. We carried out a retrospective cohort study in a random sample of members of a health maintenance organization, who were followed for five years after ascertainment of alcohol use. Reported problem drinking behavior increased the risk of motor vehicle violations or crashes for women drivers and older drivers (older than 65 years of age) of both sexes. Women "binge drinkers" had an age-adjusted relative risk (RR) for violations of 1.7 (95% confidence interval [CI] = 1.1, 2.8) and an age-adjusted RR for crashes of 1.9 (95% CI = 1.1, 3.2). Older drivers reporting drinking and driving or multiple drinking problems had an increased risk of motor vehicle crashes (sex-adjusted RR = 2.7; 95% CI = 1.2, 5.8, and 3.0; 95% CI = 1.1, 8.4). A CAGE score of 2 or more identified older drivers at increased risk for both violations and crashes. We found no increased risk for male drivers under 65 years of age for any of the problem drinking behaviors. We conclude that BRFSs in a general population can help identify high-risk drivers among women and drivers older than 65 years of age.

Participation in a smoking cessation program: a population-based perspective.

We examined factors associated with participation in an HMO-based, self-help smoking cessation trial by comparing participants with nonparticipating smokers who responded to a prior health survey. Recruitment to the trial was accomplished through the HMO's monthly magazine sent to all enrollee households, and the health survey involved a random sample of the enrollee population. Participants were more likely to be female, older, better educated, and heavier smokers with more attempts to quit in the past. Participants consistently reported poorer levels of health status (self-perceived health and energy, life satisfaction, depression, and symptoms), less healthy lifestyles (exercise and dietary fat), and a greater conviction that smoking cessation would improve how they feel than nonparticipants. These findings confirm previous suggestions that formal cessation programs attract those with a more extensive history of addiction, prior failure, and pathophysiologic effects and may provide clues to increasing motivation among smokers with a greater likelihood of treatment success.

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.

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.

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.

Evaluation of Group Health Cooperative of Puget Sound's Senior Influenza Immunization Program.

The goal of this study was to identify areas in which an influenza immunization campaign for seniors, sponsored by a health maintenance organization (HMO), could be improved. This study was conducted at Group Health Cooperative of Puget Sound (GHC), serving approximately 470,000 enrollees in Washington State. A survey was administered to two groups of seniors drawn at random--those who received influenza vaccine and those who did not, during the fall and winter of 1991. Immunization rates were almost 75 percent for "well" seniors and 85 percent for "chronically ill" seniors. Bivariant analysis showed that two activities of the influenza campaign were associated with vaccine compliance: a provider-generated recruitment letter and exposure to an immunization article in the enrollee newsletter. Using a broader framework for predicting vaccine compliance, logistic regression showed that vaccine compliance was associated positively with previous immunizations and belief that "my doctor wants me to get a shot," and negatively with fear of adverse reaction and belief that the vaccine is ineffective. There were few suggestions for improving the immunization program, among both vaccinated and unvaccinated enrollees. Approximately two-thirds of unvaccinated enrollees said there was nothing GHC could do to convince them to be vaccinated. These findings suggest high vaccine compliance and satisfaction with an HMO-sponsored influenza campaign. Strategies and potential to further increase vaccination rates are discussed.

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.

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. 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.

Resorption beneath silastic mandibular implants. Effects of placement and pressure.

OBJECTIVE: To evaluate the extent to which silicone rubber mandibular implant (Silastic; Dow Corning, Midland, Mich) pressure and placement (supraperiosteal or subperiosteal) affect underlying mandibular resorption. DESIGN: A randomized, controlled animal trial. SUBJECTS: Ten mixed-breed adult hounds. INTERVENTIONS: Each animal's mandible was implanted with 6 Silastic blocks, 3 inserted supraperiosteally and 3 subperiosteally. Within each grouping of 3 implants, pressure was varied from "minimum" to "moderate" to "maximum" by compressing the implant with titanium miniplates. After 4 months, the animals were killed and their mandibles sectioned for microscopic examination. RESULTS: Mandibular resorption occurred in varying degrees beneath all implants by the end of the study period. The extent of resorption was consistent with retrospective studies in humans. No statistically significant difference was found between supraperiosteal or subperiosteal placement of the implants. However, higher-pressure implants tended to produce less resorption than lower-pressure implants. CONCLUSIONS: While some bone resorption seems inevitable with Silastic mandibular implants, these results would seem to suggest that the placement of implants above or below the periosteum need not be a concern for the surgeon attempting to minimize this consequence. On the other hand, increased pressure may actually decrease resorption, contrary to current assumptions.

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.

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.

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.

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.

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.

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.

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.

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.

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.