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Relationship between routinization of daily behaviors and medication adherence in HIV-positive drug users.

Although lifestyle factors and routinization of daily activities are emerging as important variables in understanding and improving medication adherence, measures of these constructs remain crude and rudimentary. This study evaluated whether a brief, yet more comprehensive measure of the routinization of daily behaviors and activities is predictive of medication adherence. Participants with HIV and histories of drug dependency completed a 2-week practice trial that mimicked highly active antiretroviral therapy (HAART) (phase 1), followed by a 2-week observation of adherence to HAART (phase 2) for those who started antiretroviral therapy during the study. Fifty-one participants completed the study. Average electronic monitored adherence rate (proportion of prescribed doses taken) in the practice trial was 67% (standard deviation [SD] = 24), which was significantly correlated (r = 0.50; p< 0.05) with adherence to HAART. A high frequency of four daily activities (eating breakfast, watching favorite television program, attending meetings, sleeping at home) was associated with higher adherence, whereas a low frequency of having friends over to visit was associated with higher adherence; the composite score that combined these five activities, and represented the extent to which a patient's daily routine incorporated these specific behaviors, was highly correlated (r = 0.63, p < 0.001) with adherence. In a stepwise multiple regression analysis with several adherence correlates included as independent variables, the composite score was the best independent predictor of adherence, accounting for over one third (36%) of the variance. These findings suggest that the extent to which one's daily life is structured and routinized is an important factor in understanding medication adherence. The individual items of this scale as well as a composite measure may be used to predict adherence and inform strategies to enhance adherence via recommended changes in the patient's daily routine.

Activities of Daily Living↗

Adherence to therapy with oral antineoplastic agents.

With the rise in availability and increasing use of oral anticancer agents, concerns about adherence to prescribed regimens will become an increasingly important issue in oncology. Few published studies have focused on adherence to oral antineoplastic therapy, in part because the vast majority of chemotherapy is delivered intravenously in physicians' offices or hospitals. In this article, we review current knowledge of adherence behavior with regard to oral medications in general, including factors associated with adherence and methods for measuring adherence. We also review published studies of adherence to oral antineoplastic agents in adult and pediatric populations and adherence issues in cancer prevention. The available evidence reveals that patient adherence to oral chemotherapy recommendations is variable and not easily predicted. Adherence rates ranging from less than 20% to 100% have been reported, and certain populations, such as adolescents, pose particular challenges. Future efforts should focus on improving measurement and prediction of adherence and on developing interventions to improve adherence for both patients in clinical trials and patients being treated outside of the research setting. Assessment of adherence among individuals with cancer and implementation of interventions in situations of poor adherence should improve clinical outcomes.

Administration, Oral↗

Poor antipsychotic adherence among patients with schizophrenia: medication and patient factors.

Many patients with schizophrenia are poorly adherent with antipsychotic medications. The newer, atypical antipsychotics may be more acceptable to patients and result in increased adherence. We used national Department of Veterans Affairs (VA) pharmacy data to examine whether patients receiving atypical agents are more adherent with their medication and explored patient factors associated with adherence. Patients who received a diagnosis of schizophrenia or schizoaffective disorder between October 1, 1998, and September 30, 1999, were identified in the VA National Psychosis Registry. We calculated medication possession ratios (MPRs) for patients filling prescriptions for one (n = 49,003) or two (n = 14,211) antipsychotics during the year. We examined cross-sectional relationships among adherence, type of antipsychotic, and patient characteristics and explored adherence among patients switching antipsychotics during the year. Among patients receiving one antipsychotic, 40 percent had MPRs < 0.8, indicating poor adherence. African-Americans and younger patients were more likely to be poorly adherent. Cross-sectionally, patients on atypical agents were more likely to be poorly adherent (41.5%) than patients on conventional agents (37.8%). However, among a small group of patients switching from a conventional to an atypical agent (n = 1,661) during the year, the percentage who were poorly adherent decreased from 46 percent to 40 percent. We describe the continuum of antipsychotic adherence among a large sample of patients with schizophrenia and confirm that poor adherence is common. African-Americans and younger patients are particularly at risk. Unfortunately, atypical antipsychotics may not be associated with substantial improvements in adherence. More intensive interventions are likely needed.

Adult↗

Oral medication adherence in pediatric inflammatory bowel disease.

The purpose of this study was to examine reports of adherence to oral medications, parent-child concordance in reports of adherence, and factors associated with poor adherence in adolescents with inflammatory bowel disease (IBD). Participants were 50 children with IBD 11 to 17 years of age and their parents. Parents completed an adherence interview and the Child Behavior Checklist, Family Assessment Device, and demographics questionnaires. Separately, adolescents completed the adherence interview and the Piers Harris Self-Concept Scale, Children's Depression Inventory, and Coping Strategies Inventory questionnaires. The treating gastroenterologists of participating children completed the Pediatric Crohn's Disease Activity Index during a clinic visit within a week of completion of the questionnaires. Mean parent- and child-reported adherence scores fell between the "most of the time" and "always" categories, although perfect adherence was low. Among IBD-specific medications (5-ASAs, immunomodulators, steroids), 48% of children and 38% of parents reported being always adherent to all medications. Parent-child concordance was high. Family dysfunction and poor child coping strategies were associated with worse adherence. The correlation between more behavioral/emotional problems and lower adherence approached significance. Adherence should be monitored in families that lack appropriate child discipline and in children who cope by simply wishing stressors would go away. Because these issues are associated with poor adherence, it has been suggested that psychotherapy addressing these areas may contribute to improved adherence.

Adaptation, Psychological↗

Effect of a brief antiretroviral adherence intervention delivered by HIV care providers.

Antiretroviral therapy (ART) is effective in controlling viral load in many people infected with HIV, but high levels of adherence to ART are needed for prolonged viral suppression. This study evaluated a brief adherence intervention delivered to HIV-positive patients by primary care providers during routine medical examinations. Six clinics were randomly allocated to deliver an intervention focusing on ART adherence (2 clinics) or safer sex (4 clinics). Interventions included written information (posters, brochures, and flyers) and brief counseling from providers and were evaluated with cohorts of randomly selected patients (n = 437) measured before and after a 10-month intervention. Among those 95% or greater adherent at baseline, 91% of patients who received the adherence intervention remained 95% or greater adherent at follow-up compared with 75% of the patients who received the safer sex intervention (chi = 12.59, P < 0.01). This difference was significant in a logistic regression analysis (odds ratio = 2.26; 95% confidence interval = 1.27-4.04), adjusting for baseline adherence, demographics, and HIV medical status. The adherence intervention did not significantly increase the prevalence of 95% or greater adherence among patients less than 95% adherent at baseline. Similar but nonsignificant results were observed for viral load. A brief intervention delivered to HIV patients by their primary providers helped to maintain adequate adherence to ART regimens. More intensive intervention is needed to improve adherence among patients who are initially less than 95% adherent.

Anti-Retroviral Agents↗

A practical method to calibrate self-reported adherence to antiretroviral therapy.

OBJECTIVE: Self-report of antiretroviral medications adherence is inexpensive and simple to use in clinical settings but grossly overestimates adherence. We investigated methods to calibrate patients' self-reported adherence to match objectively measured adherence more closely for the purpose of developing a practical and more accurate self-reported adherence measure. DESIGN: Longitudinal cohort design. METHODS: Using data from 2 prospective longitudinal clinical investigations conducted at 5 HIV clinics, we examined the discrepancy between self-reported adherence and objectively measured adherence. We evaluated the relation between attitudinal measures and the degree of discrepancy and used a cross-validation approach to propose candidate items to improve adherence survey methodology. RESULTS: Among 330 patients, self-reported adherence was consistently higher than objectively measured adherence. The best calibration models included the patient's self-reported adherence, duration of the antiretroviral regimen, and attitudinal measures (ability to take medication as instructed, believing medication can help one to live longer, whether or not it is too troublesome to take antiretrovirals, and feeling things are going the right way). CONCLUSION: The method efficiently identified survey items to improve self-reported adherence measurement. The calibrated measure more closely approximates objectively measured adherence and is more sensitive for detecting nonadherence. These models merit evaluation in other settings.

Adult↗

Helicobacter pylori adherence to gastric epithelial cells: a role for non-adhesin virulence genes.

Helicobacter pylori is a major aetiological agent in gastroduodenal disorders and adherence of the bacteria to the gastric mucosa is one of the initial stages of infection. Although a number of specific adhesins has been identified, other H. pylori virulence factors may play a role in adherence to gastric epithelial cells directly or through interaction with other adhesins. This study assessed the effect of 16 H. pylori virulence factors on the adherence of the bacteria to gastric AGS cells and on gastric epithelial cell cycle distribution. Defined isogenic H. pylori SS1 mutants were used. After co-incubation of gastric AGS cells and bacteria, adherence of H. pylori to AGS cells was visualised by immunofluorescence microscopy and quantified by flow cytometry. Cell cycle phase distribution was analysed by flow cytometry with propidium iodide staining. Mutants were tested for their ability to adhere to AGS cells and compared with the wild-type SS1 strain. Mutations in genes in the cag pathogenicity island showed that cagP and cagE mutants adhered less than the wild-type strain to AGS cells, whereas a cagF mutant showed no reduction in adherence. Mutations in genes involved in flagellar biosynthesis showed that the adherence ability of fliQ, fliM and fliS mutants was reduced, but a flhB mutant possessed wild-type levels of adherence. Mutations in genes coding for the urease (ureB) and phospholipase (pldA) enzymes did not affect adherence, but mutation of the tlyA gene encoding an H. pylori haemolysin resulted in a reduced adherence. A fliQ mutant, with reduced adherence to AGS cells, was less able to induce AGS cell apoptosis than SS1. The ability to induce G0G1 cell cycle arrest was also abolished in the fliQ mutant. However, an increased cell number in S phase was observed when AGS cells were exposed to the fliQ mutant compared with SS1, suggesting that unattached bacteria may still be able to stimulate cell proliferation. In addition to known adhesins, other bacterial virulence factors such as CagE, CagP, FliQ, FliM, FliS and TlyA appear to play a role in H. pylori adherence to gastric epithelial cells. Mutations in these genes may affect H. pylori pathogenicity by reducing either the ability of the bacteria to attach to gastric epithelial cells or the intensity of bacteria-host cell interactions.

Apoptosis↗

Role of agr (RNAIII) in Staphylococcus aureus adherence to fibrinogen, fibronectin, platelets and endothelial cells under static and flow conditions.

In the present study, the adherence of Staphylococcus aureus (strain 83254) and its RNAIII mutant (WA400) to immobilised fibrinogen and fibronectin, and to human endothelial cells (EC), was studied. [3H]Thymidine-labelled bacteria in stationary phase were incubated on the test surfaces for 20 min under static or flow (200/s) conditions. The results showed: (a) increased adherence of the RNAIII mutant to fibrinogen under static conditions, and decreased adherence of the mutant to fibronectin and EC under both static and flow conditions compared with the parental strain; (b) stronger ability of the mutant compared with the parental strain to induce platelet aggregation in suspension; (c) greater adherence of the parental strain and the mutant to EC pre-treated with platelet-rich plasma compared with platelet-poor plasma, and to EC pre-treated with platelet-poor plasma compared with control; (d) increased adherence of S. aureus to EC pre-treated with PMA-activated platelets and decreased adherence to EC pre-treated with tirofiban, a platelet glycoprotein IIb-IlIa inhibitor, which paralleled with increased adherence of PMA-activated platelets and decreased adherence of glycoprotein IIb-IIIa-blocked platelets to EC in the absence of bacteria; and (e) adherence of the mutant was more sensitive to pre-treatment of EC with plasma and PMA-activated platelets. In conclusion, RNAIII down-regulates S. aureus adherence to fibrinogen under static condition and up-regulates S. aureus adherence to fibronectin and EC under both static and flow conditions. The potentiating role of activated platelets in the presence of plasma in S. aureus adherence to EC is down-regulated by RNAIII, probably due to down-regulation of adherence to fibrinogen, the important plasma protein bridging S. aureus, platelets and EC.

Bacterial Adhesion↗

Adherence of Candida albicans to epithelial cells: studies using fluorescently labelled yeasts and flow cytometry.

Candida albicans adherence to epithelial cells is the first step in the infectious process, but in spite of its importance, current methods for the quantitative measurement of adherence of C. albicans to epithelial cells in vitro have some serious limitations. They are based on filtration assays and either microscopic or radiometric analysis. The adherence reaction is usually carried out with a large excess of yeasts (100-fold) over epithelial cells in order to perform the microscopic analysis, which is slow, subjective and limited to 100-200 cells and thus lacks statistical power. The radiometric analysis fails to measure individual cells. A method for measuring yeast adherence that overcomes these problems has been developed. It is based on labelling the yeasts with the fluorogenic marker 2',7'-bis-(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester (BCECF) prior to the adherence reaction, and analysing 10(4) epithelial cells by flow cytometry, while nonbound yeasts are excluded by gating. Two subpopulations of buccal epithelial cells (BECs) which differ in their mean fluorescence intensities per cell (MFIs) were observed: one with MFI which did not exceed nonspecific fluorescence, and the other with MFI as high or higher than the MFI of labelled yeasts. The two subpopulations represent yeast-free and yeast-binding epithelial cells, respectively, and the MFI increment of the BECs is a quantitative measure of the extent of yeast adherence. Control experiments confirming previously described basic features of adherence, such as enhanced adherence at increasing yeast excess, diminished adherence of trypsin-treated or heat-inactivated yeasts, and the differential adherence of various Candida species, supported the validity of the assay. The possibility of studying adherence reliably at low yeast:epithelial cell ratios, which better mimic adhesion as it occurs in vivo, is an important advantage of the assay. New findings, using this method, included the observation that exfoliated BECs from diabetic patients exhibited the same capacity for C. albicans adherence as cells from healthy controls, and that epithelial cells from early human ontogenic stages had a significantly lower adherence level than those from later stages.

Adult↗

Treatment adherence with antipsychotic medications in bipolar disorder.

OBJECTIVES: Atypical antipsychotic medications are a relatively new, increasingly prominent component of the treatment armamentarium for bipolar disorder. Information on adherence with antipsychotics among individuals with bipolar disorder in general, and atypical antipsychotics in particular, is currently quite limited. Using data from the VA National Psychosis Registry, we examined adherence with antipsychotic medications among patients with bipolar disorder (n = 73,964). METHODS: Antipsychotic medication adherence among veterans with bipolar disorder was evaluated using the medication possession ratio and categorizing patients into three groups: fully adherent, partially adherent and non-adherent. We compared characteristics of bipolar patients who received versus those who did not receive antipsychotic medication, and also identified predictors of poor adherence with antipsychotic medications. RESULTS: Approximately 45% (n = 32,993) of all individuals with bipolar disorder were prescribed antipsychotic medication. Individuals who were prescribed antipsychotic medications were younger and more often had comorbid substance abuse or post-traumatic stress disorder compared to individuals with bipolar disorder who were not prescribed antipsychotic medication. Just over half (51.9%) of individuals appear to be fully adherent with antipsychotic medications, while 48.1% of individuals are either partially adherent or non-adherent with antipsychotic medications. Factors associated with treatment non-adherence were younger age, minority ethnicity, comorbid substance abuse and homelessness. CONCLUSIONS: Treatment non-adherence is a major issue for close to half of individuals with bipolar disorder prescribed antipsychotic medication. Additional studies are needed to better understand treatment adherence within the full range of pharmacologic therapies among individuals with bipolar disorder.

Antipsychotic Agents↗

Adherence of Candida albicans and other Candida species to mucosal epithelial cells.

To study the possible involvement of candidal adherence in mucosal colonization, we examined the in vitro adherence capabilities of seven Candida species. Adherence was evaluated by direct microscopic examination and by a quantitative radiometric adherence test. The results indicate that C. albicans adheres to vaginal and buccal epithelial cells to a significantly greater degree (P less than 0.01) than the other species tested. C. tropicalis and C. stellatoidea demonstrated moderate adherence capabilities, while C. parapsilosis adhered only to a slight degree. Other species failed to interact with isolated mucosal cells. These findings suggest that there is a relationship between the adherence capabilities of the Candida species and their abilities to colonize mucosal surfaces, since those species which adhere are those which most frequently colonize mucosal surfaces. C. albicans was found to be adherent under a variety of environmental conditions. Stationary-phase blastospores of C. albicans were found to be more adherent than logarithmic-phase yeasts, and larger blastospore cell-to-epithelial cell ratios resulted in greater adherence values. The actual number of adherent yeasts varied considerably when epithelial cells were obtained from different donors.

Adhesiveness↗

Mannose-sensitive and mannose-resistant adherence to human uroepithelial cells and urinary virulence of Escherichia coli.

The adherence to human uroepithelial cells of 23 Escherichia coli strains belonging to three groups with different levels of virulence was investigated, and the mechanism of adherence was studied. It was found that strains belonging to the most virulent group adhered better to human uroepithelial cells than did avirulent strains. Adherence of loss virulent but supposedly nephropathogenic strains was more variable. These results suggest that adherence is an important virulence factor, especially in the group of strains with the highest but a more general virulence. Piliated strains adhered better than did nonpiliated strains. We found strong evidence for the existence of at least two different mechanisms of adherence: (i) mannose-sensitive adherence by piliated strains, very likely mediated by type I pili because this mannose-sensitive adherence was associated with mannose-sensitive hemagglutination of guinea pig erythrocytes by broth cultures of the strains; (ii) mannose-resistant adherence by piliated strains, very likely mediated by non-type I pili because this mannose-resistant adherence was invariably associated with mannose-resistant hemagglutination of human group A erythrocytes by the strains, whether grown in broth or on plates. Additionally, one strain without pili and without hemagglutinating activity adhered well. Thus in most cases adherence seemed to be mediated by bacterial pili, although different types might be involved.

Adult↗

Eikenella corrodens adherence to human buccal epithelial cells.

The mechanism of Eikenella corrodens adherence to human buccal epithelial cells in vitro was studied. Initial experiments to determine the optimal conditions for adherence of E. corrodens to buccal epithelial cells showed that adherence was dependent on time, temperature, bacterial concentration, and pH. Different strains of E. corrodens varied in their ability to adhere, and strain 1073 showed the greatest ability in adherence. Strain 1073 was selected for studies of adherence mechanisms. Trypsin treatment or heating (100 degrees C, 10 min) of the bacterial cells abolished their capacity to adhere to buccal epithelial cells. Treatment of buccal epithelial cells with trypsin also abolished adherence of E. corrodens 1073, whereas neuraminidase treatment of buccal epithelial cells enhanced the adherence. The adherence was inhibited by ethylenediaminetetraacetic acid and restored by adding Ca2+. The adherence was remarkably inhibited by sugars containing D-galactose and n-acetyl-D-galactosamine. Treatment of neuraminidase-treated epithelial cells with sodium metaperiodate or alpha- and beta-galactosidase did not decrease the adherence. These data suggest that adherence of E. corrodens 1073 to human buccal epithelial cells may require the interaction of lectin-like proteins on the bacterial surface with galactose-like receptors on the surface of epithelial cells.

Bacteroides↗

Adherence of Streptococcus sanguis to hydroxyapatite coated with lysozyme and lysozyme-supplemented saliva.

The adherence of [3H]thymidine-labeled Streptococcus sanguis strains to bare hydroxyapatite and to hydroxyapatite coated with a range of concentrations of lysozyme, poly-L-lysine, poly-L-glutamic acid, whole saliva supernatant, and combinations of some of the above was studied. Adherence of several strains of S. sanguis to bare hydroxyapatite and saliva-coated hydroxyapatite was compared. Saliva present as a pellicle on the hydroxyapatite inhibited adherence of some strains (903, M-5, 73X11) and stimulated that of others (S35, B-4, 66X49). Strains 903 and S35 were chosen for further study. Adherence of both strains was stimulated up to fivefold by the presence of adsorbed lysozyme or poly-L-lysine on the hydroxyapatite, whereas poly-L-glutamic acid inhibited adherence (80 to 95%). Adherence of strain S35 to hydroxyapatite coated with combinations of saliva and (i) lysozyme, (ii) poly-L-lysine, or (iii) poly-L-glutamic acid was unaffected compared with adherence to hydroxyapatite coated with saliva alone. In contrast, adherence of strain 903 to hydroxyapatite coated with combinations of saliva and either lysozyme or poly-L-lysine was inhibited up to ca. 90% compared with hydroxyapatite coated with saliva alone. Strain 903 was also unaffected by combinations of poly-L-glutamic acid and saliva on the hydroxyapatite. Adherent cells of both strains were completely (greater than 90%) eluted with high-ionic-strength buffer from either bare hydroxyapatite or hydroxyapatite coated with lysozyme alone. Adherent cells of strain S35 were only poorly eluted (25%) from hydroxyapatite coated with either saliva alone or saliva and lysozyme. Strain 903 elution from hydroxyapatite coated with either saliva alone or saliva and lysozyme was essentially complete. These observations were taken to indicate that the two test strains adhered to saliva-coated hydroxyapatite by different mechanisms. Protein-coated hydroxyapatite was shown not to be saturated under the conditions described here. Examination by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the variously supplemented salivary pellicles formed on the hydroxyapatite demonstrated that major changes in salivary protein composition did not occur when lysozyme, poly-L-lysine, or poly-L-glutamic acid was used to supplement saliva. Lysozyme-dependent aggregation of strain 903 was shown not to occur under the conditions of our experiments. We suggest that the basis for stimulation of adherence to hydroxyapatite coated only with lysozyme is an increase in the cationic surface area available for electrostatic adherence of the microorganisms.(ABSTRACT TRUNCATED AT 400 WORDS)

Adhesiveness↗

Participation of yeast cell surface hydrophobicity in adherence of Candida albicans to human epithelial cells.

Recent studies have revealed that hydrophobic cells of the opportunistic pathogenic fungus Candida albicans are more virulent than hydrophilic cells. One critical step in the pathogenic process is adherence to host tissues. Adherence of C. albicans to epithelial tissues is mediated primarily by specific adhesin-receptor interactions, but whether cell surface hydrophobicity (CSH) of the yeast cells may also contribute has not been definitively demonstrated. Nineteen isolates of C. albicans were grown in Sabouraud dextrose broth at either 23 or 37 degrees C and tested for CSH by a polystyrene microsphere assay and for the ability to adhere to HeLa cells, a human cervical epithelioid carcinoma cell line. For 13 isolates, growth at 23 degrees C resulted in significantly higher levels of CSH than did growth at 37 degrees C. Three isolates were hydrophobic and two were hydrophilic regardless of growth temperature. One isolate was more hydrophobic after growth at 37 degrees C. Of the isolates that were more hydrophobic after growth at 23 degrees C, 86.5% (11 of 13) were also more adherent to HeLa cells. Growth temperature did not appear to determine adherence ability, as all isolates that did not differ in CSH after growth at either temperature also did not differ in ability to adhere. No correlation (r = 0.44) was obtained between CSH and adherence when the isolates grown at 23 degrees C were evaluated as a group. Higher correlation (r = 0.65) was obtained when the isolates were grown at 37 degrees C. Interestingly, a significantly positive correlation between CSH and adherence was obtained when individual isolates were analyzed. To accomplish this analysis, the isolates were allowed to vary in CSH over time in tissue culture medium without serum, and the corresponding adherence values determined. Only isolates that varied in CSH by greater than 10% were used. Correlation statistical analysis in which the coefficient of determination (r2) was calculated indicated that poor correlation between CSH and adherence for the isolates evaluated as a group was likely due to the fact that CSH had little effect on adherence once a moderately high level of CSH was attained. These results indicate that CSH is involved in adherence but is not the predominant mechanism and that the effect of CSH on adherence is isolate dependent.

Adhesiveness↗

Adherence of oral "Streptococcus milleri" cells to surfaces in broth cultures.

Cells of representative strains of oral "Streptococcus milleri" firmly adhered to glass surfaces when grown in glucose broths as well as in fructose and sucrose broths. Cellular adherence occurred on saliva-coated glass surfaces as well as uncoated surfaces, but the cells of only a few (6 of 69) tested adherent strains agglutinated upon the addition of human whole-saliva supernatant. Thus, the firm adherence of growing "S. milleri" cells is independent of sucrose and salivary macromolecules. Two macroscopic forms of cell adherence were observed: one was a coarse-granule type and one was a tiny-granule type covered with a thin homogeneous membranous material. Scanning electron microscopy revealed that, in both types, a stringy substance interconnected the cells and connected the cells to glass surfaces, with amorphous flocklike materials present in the intercellular space. Of the 154 tested strains, 128 were adherent, of which 90 were firmly and extensively (+2 or +3) adherent. Most strains of the serovars f/F, g, h, i, j, g-, and gj- were extensively adherent. Generally, cells of the more strongly adherent strains were more hydrophobic and spontaneously aggregating. However, there also existed a few hydrophilic and nonaggregating but extensively adherent strains. The presence of trypsin or pronase completely inhibited the adherence of some strains (mostly nonaggregating) but did not at all inhibit that of others (mostly aggregating). The adhering groups did not significantly differ in their cell surface hydrophobicities. Therefore, at least two factors, one proteinaceous and one nonproteinaceous, appear to be principally involved in the firm surface adherence of "S. milleri."

Bacterial Adhesion↗

Adherence properties of Staphylococcus aureus under static and flow conditions: roles of agr and sar loci, platelets, and plasma ligands.

Global regulatory genes in Staphylococcus aureus, including agr and sar, are known to regulate the expression of multiple virulence factors, including cell wall adhesins. In the present study, the adherence of S. aureus RN6390 (wild type), RN6911 (agr), ALC136 (sar), and ALC135 (agr sar) to immobilized fibrinogen, fibronectin, von Willebrand factor (vWF), extracellular matrix (ECM), and human endothelial cells (EC) EAhy.926 was studied. Bacteria grown to postexponential phase were subjected to light oscillation (static condition) or to shear stress at 200 s(-1) (flow condition) on tissue culture polystyrene plates coated with either protein ligands, ECM, or EC. Adherence of nonlabeled bacteria to immobilized ligands was measured by an image analysis system, while adherence of [(3)H]thymidine-labeled S. aureus to ECM and EC was measured by a beta-scintillation counter. The results showed increased adherence of agr and agr sar mutants to immobilized fibrinogen and higher potential of these mutants to induce platelet aggregation in suspension, decreased adherence of sar and agr sar mutants to immobilized fibronectin and vWF as well as to ECM and EC, increased adherence of both S. aureus wild type and sar mutant to EC treated with platelet-rich plasma (PRP) compared to platelet-poor plasma (PPP) and to EC treated with PPP compared to the control, and increased adherence of S. aureus wild type to EC coated with PRP in which platelets were activated with phorbol 12-myristate 13-acetate compared to intact PRP. This finding paralleled the increased adherence to EC of activated compared to intact platelets. It is suggested that platelet-mediated S. aureus adherence to EC depends on platelet activation and the number of adherent platelets and available receptors on the platelet membrane. In conclusion, the agr locus downregulates S. aureus adherence to fibrinogen, while the sar locus upregulates S. aureus adherence to fibronectin, vWF, ECM, and EC. The effect of both agr and sar on S. aureus adherence properties develops primarily under flow conditions, which suggests different adhesion mechanisms in static and flow conditions.

Animals↗

Predictors of adherence and virologic outcome in HIV-infected patients treated with abacavir- or indinavir-based triple combination HAART also containing lamivudine/zidovudine.

OBJECTIVES: To compare dosing convenience and adherence with abacavir (ABC) 300 mg plus a fixed-dose lamivudine 150 mg/zidovudine 300 mg combination tablet (COM) twice daily versus indinavir (IDV) plus COM twice daily in treatment-naïve, HIV-1-infected adults; and to evaluate the association among difficulty taking antiretroviral regimens, adherence, and virologic efficacy. METHODS: An open-label, randomized, multicenter, international study compared the COM/ABC and IDV/COM regimens with respect to self-reported adherence and regimen convenience over 48 weeks. Logistic regression analysis (LRA) was done on a patient sub-sample from both groups to evaluate predictors of adherence and virologic response at last time-point on randomized therapy (LTORT). RESULTS: The study population was diverse with respect to ethnicity (38% Asian, 27% Hispanic, 28% white, 3% black, 4% other) and gender (39% women, 61% men). Baseline median HIV-1 RNA was 4.80 log(10) copies/mL and CD4+ cell count was 315 cells/mm(3). Of 329 patients who were randomized and received treatment, 315 (96%) provided adherence data. Significantly more patients in the ABC/COM group than in the IDV/COM group reported > or = 95% adherence to therapy (76 vs 58%, p < 0.001) and no difficulty in taking their regimen (91 vs 61%, p < 0.001). In both groups, the highest probability of HIV-1 RNA < 400 copies/mL occurred when median adherence was > or = 95%. The probability of HIV-1 RNA < 400 copies/mL declined more rapidly in the IDV/COM group as adherence rates decreased. LRA showed that no difficulty taking any of the drugs in the regimen, ABC/COM treatment group, and male gender were independent significant predictors of > or = 95% adherence (p < 0.05). Median adherence and baseline HIV-1 RNA were significant predictors of HIV-1 RNA < 400 copies/mL (p < 0.05). CONCLUSIONS: Patients reported greater ease of use and superior adherence to ABC/COM than IDV/COM. Patient-reported difficulty taking drugs in a regimen was predictive of reduced adherence, and both of the latter factors were predictive of poorer virologic outcome. Adherence levels of > or = 95% in both treatment groups maximized the probability of patients achieving an HIV-1 RNA < 400 copies/mL.

Adult↗