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Cytokine production by adherent and non-adherent mononuclear cells in chronic fatigue syndrome.

It has been suggested that cytokines play a role in certain clinical manifestations of chronic fatigue syndrome (CFS). In this study adherent (monocytes) and non-adherent (lymphocytes) mononuclear cells were stimulated in the presence or absence of phytohemagglutinin (PHA) or lipopolysaccharide (LPS), respectively, and supernatants were assayed for IL-6, TNF-alpha, and IL-10 by ELISA. IL-6 was also measured at the mRNA level by polymerase chain reaction. The levels of spontaneously (unstimulated) produced TNF-alpha by non-adherent lymphocytes and spontaneously produced IL-6 by both adherent monocytes and non-adherent lymphocytes were significantly increased as compared to simultaneously studied matched controls. The abnormality of IL-6 was also observed at mRNA level. In contrast, spontaneously produced IL-10 by both adherent and non-adherent cells and by PHA-activated non-adherent cells were decreased. This preliminary study suggests that an aberrant production of cytokines in CFS may play a role in the pathogenesis and in some of the clinical manifestations of CFS.

Adult↗

Determinants of adherence to methylphenidate and the impact of poor adherence on maternal and family measures.

OBJECTIVE: The aim of this study was to examine the association between adherence to immediate-release methylphenidate (IR MPH) and maternal psychological distress, parenting style, parent- child relationship, and perceived family support. METHODS: The sample consisted of 307 children with attention-deficit hyperactivity disorder (ADHD) (271 boys and 36 girls), 6-17 years of age, who had been treated with IR MPH for the past 6 months. The measures included the Chinese Health Questionnaire, Parental Bonding Instrument, Family APGAR, and Home Behaviors of the Social Adjustment Inventory for Children and Adolescents. RESULTS: Reasons for poor adherence (n = 79; 25.7%) included forgetting medication (72.7%), the medication having no effect (20.0%), and refusing medication (12.7%). Increased age and three-times-daily administration were the major predictors for poor adherence to IR MPH. Poor adherence was associated with increased degree of maternal psychological distress, indifferent parenting, maternal overprotection/control, poor family support, decreased interaction with parents, and increased problems at home. CONCLUSIONS: Findings indicate that multiple daily dosing of MPH increases the likelihood of poor adherence, particularly in adolescents, and that poor adherence is associated with impaired maternal/family process. Once-daily administration of MPH is necessary to improve adherence and to decrease the possible exacerbation of tense parent-child relationships caused by poor drug adherence.

Adolescent↗

Rate of non-adherent cell loss from long-term cultures of murine bone marrow: effect of medium conditioned by the adherent cell population.

The rate of random spontaneous cell loss from the non-adherent cell population of long-term cultures of murine bone marrow was determined. The measured rate of non-adherent cell loss is affected by previous conditioning of the medium in which the non-adherent cells are suspended. Specifically, the measured rate of non-adherent cell loss is significantly slowed when the non-adherent cells are suspended in medium conditioned in long-term haematopoietic cultures instead of fresh medium. It appears that a subset of the adherent cell population is the source of the factor or factors within the medium which result in this slower measured rate of non-adherent cell loss. This effect may be due to the stimulation to division of haematopoietic progenitor cells, offsetting the lysis of other non-adherent cells.

Animals↗

Adherence patterns and adherence-related DNA sequences in Escherichia coli isolates from children with and without diarrhea in São Paulo city, Brazil.

The correlation between various adherence patterns and adherence-related DNA sequences in Escherichia coli isolates from 1- to 4-year-old children with and without diarrhea in São Paulo, Brazil, was evaluated. A total of 1,801 isolates obtained from 200 patients and 200 age-matched controls were studied. The adherence patterns found were classified as diffuse, aggregative, aggregative in a 6-h assay, aggregative predominantly in coverslips, localized, localized-like, and noncharacteristic. In general, the DNA sequences used as probes showed excellent specificities (>93%), but their sensitivities varied. Thus, the results of bioassays and assays with DNA probes normally used to search for adherent E. coli did not correlate well, and the best method for the identification of these organisms in the clinical research setting remains controversial. Isolates presenting diffuse adherence or hybridizing with the related daaC probe, or both, were by far the most frequent in patients (31.5, 26.0, and 23.0%, respectively), followed by isolates presenting aggregative adherence or hybridizing with the related EAEC probe, or both (21.5, 13.0, and 10.5%, respectively). None of the different combinations of adherence patterns and adherence-related DNA sequences found were associated with acute diarrhea.

Bacterial Adhesion↗

Peyer's patch lymphoid follicle epithelial adherence of a rabbit enteropathogenic Escherichia coli (strain RDEC-1). Role of plasmid-mediated pili in initial adherence.

Escherichia coli (strain RDEC-1) adheres to M cells of rabbit Peyer's patch lymphoid follicle epithelium. The RDEC-1 strain contains an 85 X 10(6) D plasmid that codes for pili, which, when purified, adhere to gut absorptive epithelium. This study compared the in vivo lymphoid follicle adherence of the RDEC-1 strain with that of a Shigella flexneri (ShD15) that contained the 85 X 10(6) D plasmid and expressed the RDEC-1 pili, a control E. coli, and a control S. flexneri (ShD12). The bacteria were given in a dose of 10(10) to 0.7-1.1 kg rabbits. The rabbits were sacrificed at 2, 4, 6, and 12 h postinoculation. Peyer's patch tissue was examined by electronmicroscopy and direct fluorescence microscopy. The piliated ShD15 and RDEC-1 bacteria adhered in large numbers at 2 and 4 h postinoculation, but only the RDEC-1 strain persisted and increased in numbers past that time. Control strains did not adhere. The ShD15 strain adhered to and was rapidly taken into M cells, precipitating an acute inflammatory reaction within the follicle and adjacent lumen. Initial lymphoid follicle M cell adherence of the ShD15 strain was associated with the possession of the adherence pilus plasmid. The failure of the ShD15 strain to survive and colonize the lymph follicle epithelium contrasts with the success of the RDEC-1 strain and indicates that the RDEC-1 strain possesses virulence factors in addition to pili.

Animals↗

Studies of activated GPIIb/IIIa receptors on the luminal surface of adherent platelets. Paradoxical loss of luminal receptors when platelets adhere to high density fibrinogen.

The accessibility of activated GPIIb/IIIa receptors on the luminal surface of platelets adherent to damaged blood vessels or atherosclerotic plaques is likely to play a crucial role in subsequent platelet recruitment. To define better the factors involved in this process, we developed a functional assay to assess the presence of activated, luminal GPIIb/IIIa receptors, based on their ability to bind erythrocytes containing a high density of covalently coupled RGD-containing peptides (thromboerythrocytes). Platelets readily adhered to wells coated with purified type I rat skin collagen and the adherent platelets bound a dense lawn of thromboerythrocytes. With fibrinogen-coated wells, platelet adhesion increased as the fibrinogen-coating concentration increased, reaching a plateau at about 11 micrograms/ml. Thromboerythrocyte binding to the platelets adherent to fibrinogen showed a paradoxical response, increasing at fibrinogen coating concentrations up to approximately 4-6 micrograms/ml and then dramatically decreasing at higher fibrinogen-coating concentrations. Scanning electron microscopy demonstrated that the morphology of platelets adherent to collagen was similar to that of platelets adherent to low density fibrinogen, with extensive filopodia formation and ruffling. In contrast, platelets adherent to high density fibrinogen showed a bland, flattened appearance. Immunogold staining of GPIIb/IIIa receptors demonstrated concentration of the receptors on the filopodia, and depletion of receptors on the flattened portion of the platelets. Thus, there is a paradoxical loss of accessible, activated GPIIb/IIIa receptors on the luminal surface of platelets adherent to high density fibrinogen. Two factors may contribute to this result: engagement of GPIIb/IIIa receptors with fibrinogen on the abluminal surface leading to the loss of luminal receptors, and loss of luminal filopodia that interact with thromboerythrocytes. These data provide insight into the differences in thrombogenicity between surfaces, and may provide a mechanism for purposefully passivating platelet-reactive artificial surfaces.

Amino Acid Sequence↗

Comparison in the interface pressure under self-adherent and non-self-adherent bandages during standing and exercise.

BACKGROUND: Self-adherent bandages are useful to prevent the bandage from becoming loose. However, the material binds tightly to itself to form a tight band, which may result in changes in interface pressure under the bandages during changes in posture and exercise, because the pressure depends on the elasticity of the bandages. The aim of this study was to compare the interface pressures under self-adherent and non-self adherent bandages while standing and during exercise. PATIENTS AND METHODS: In 20 normal volunteers the pressure was determined at the posteromedial area of the midcalf during lying, standing, tip-toe exercise and walking, using an Air Pack Type Analyzer. We examined two kinds of bandages with a maximal tension of 70%, self-adherent and non-self-adherent bandages. RESULTS: There was no significant increase in pressure observed during standing in comparison with pressure in the supine position immediately after application. A significant increase in pressure under both bandages was observed during tip-toe exercise and walking. However, there was no significant difference in pressure during standing or exercise between self-adherent and non-self-adherent bandages. Furthermore, there was no significant pressure difference between muscle contraction and relaxation between the two bandages. CONCLUSION: Self-adherent bandages can maintain their own elasticity, even when the material binds tightly to itself.

Adult↗

Regulation of leukocyte glass adherence and tube leukocyte adherence inhibition (LAI) reactivity by serum factors in dogs with progressing or spontaneously regressing canine transmissible venereal sarcoma (CTVS).

We examined the regulation of leukocyte glass adherence and tube leukocyte adherence inhibition (LAI) reactivity by serum factors in dogs with regressing or progressing canine transmissible venereal sarcomas (CTVS). Both regressor and progressor peripheral blood leukocytes (PBL), draining and non-draining lymph node cells (LNC), and splenic leukocytes were significantly responsive to CTVS antigen extract in tube LAI. In contrast, a significant decrease in basal glass adherence of progressor PBL, draining and non-draining LNC, and splenic leukocytes was observed. Normal glass adherence was restored to progressor leukocytes by extensive washing with warm serum-free media, while significant tube LAI responsiveness to CTVS antigen extract was maintained. Preincubation of regressor PBL and LNC with progressor sera in two-stage tube LAI decreased the basal glass adherence of treated leukocytes. This effect of progressor sera was heat labile, a characteristic of CTVS antigen. Collectively, these findings suggest that progressor leukocytes and progressor sera treated regressor leukocytes were activated by interaction with serum CTVS antigen and thus behaved in tube LAI as stimulated cells, even in the absence of CTVS antigen. Regressor but not progressor sera were shown to contain anti-CTVS IgG with specific arming activity for normal dog PBL, but not LNC in two-stage tube LAI. The nonadherent response of peripheral blood neutrophils in two-stage tube LAI was proportional to the concentration of arming IgG, whereas no change was observed in glass adherence of PBL. The results of this study define the role of progressor and regressor serum factors in the mechanism of tube LAI and demonstrate a relationship between leukocyte glass adherence and the clinical course of CTVS. These findings show that tube LAI is a simple and reproducible measure of active factors in the immune response to a tumor.

Animals↗

Adherence with drug therapy in the rheumatic diseases Part one: a review of adherence rates.

Drug therapy plays a major role in the management of many rheumatic diseases and is particularly important in rheumatoid arthritis (RA) because of the significant rates of morbidity and mortality (Pincus, 1995). Understanding of the pathogenesis of RA has led to the development of new and more effective drugs (Emery et al., 1999), but the ultimate efficacy of any drug therapy depends upon the patient's decision to take it. There is widespread agreement that many people with rheumatic disease do not adhere to their medication regimens (Deyo et al., 1981; Belcon et al., 1984; Pullar et al., 1988; Hill et al., 2001). Research has demonstrated that 50% of women taking hormone replacement therapy for the prevention of osteoporosis discontinue treatment after a year (Fordham, 2000) and similar rates of discontinuation are found in other chronic diseases (Haynes et al., 1996, 2000). This is bewildering as, in asymptomatic illnesses such as hypertension and diabetes, the expectation is that levels of adherence would be lower than in diseases where pain and stiffness are present. The picture becomes even more confusing when we consider the findings from a recent multi-country study of RA, which found no association between adherence and disease severity, nor with the treatment prescribed (Viller et al., 1999). In chronic disease poor adherence is commonplace. The World Health Organization (WHO) recognizes this and has recently stated that 'poor adherence to treatment of chronic diseases is a worldwide problem of striking magnitude' and cites adherence to long-term therapy for chronic illnesses in developed countries averaging just 50% (WHO, 2003). The first part of this two part review focuses on adherence with drug therapy, and the second part discusses different methods of measuring it.

Journal Article↗

Embryonal carcinoma cells adhere preferentially to fibronectin and laminin but their endodermal differentiation leads to a reduced adherence to laminin.

F9 and PC13 embryonal carcinoma (EC) cells adhered rapidly to growth substrata coated with fibronectin or laminin. When F9 cells were induced to differentiate into visceral or parietal endoderm-like cells, their ability to adhere to laminin diminished, but their adherence to fibronectin remained unchanged. Correspondingly, permanently differentiated teratocarcinoma-derived endoderm cells (PYS-2 and PSA-5e) adhered markedly less efficiently to laminin than to fibronectin. F9 cells adhered to proteolytic fibronectin fragments containing the cell-binding site but not to fragments containing gelatin- or heparin-binding sites. They also adhered slowly to gelatin, but this adhesion was completely blocked by cycloheximide. The results show that the teratocarcinoma stem cells may have specific mechanisms mediating adhesion to fibronectin and laminin and that endodermal differentiation leads to a reduction in their capacity to adhere to laminin but not to fibronectin.

Cell Adhesion↗

Adherence to topical therapy decreases during the course of an 8-week psoriasis clinical trial: commonly used methods of measuring adherence to topical therapy overestimate actual use.

INTRODUCTION: Medication nonadherence is common throughout medicine, and research into this area is increasing; however, knowledge about topical medication adherence is limited. METHODS: A total of 30 patients were enrolled in a clinical trial for psoriasis and followed up for 8 weeks using 3 methods of adherence monitoring: electronic monitoring caps; medication logs; and medication usage by weight. RESULTS: Adherence rates calculated from the medication logs and medication weights were consistently higher than those of the electronic monitors (P <.05). Electronically measured adherence rates declined from 84.6% to 51% during the 8-week study (P <.0001). Female sex and increasing age by 1 year predicted improved adherence of 5% and 0.8%, respectively (P <.0001). The number of treatment gaps increased from the first half to the last half of the study, and weekend days were overrepresented in treatment gaps. CONCLUSION: Medication logs and weights do not ensure medication adherence to topical therapy. Electronic monitoring allows a more precise method of adherence measurement.

Administration, Topical↗

Adherence logger for a dry powder inhaler: a new device for medical adherence research.

BACKGROUND: Adherence to inhaled steroid regimens is frequently poor. Finding ways to improve adherence depends on the ability to measure time and date of inhaler use reliably and to detect deliberate dose dumping. There is no such monitor for the popular new dry powder inhalers. OBJECTIVE: To develop and test an electronic monitor for a dry powder inhaler that will provide information on the time and date of use. METHODS: An electronic adherence monitor for the Advair Diskus dry powder inhaler was developed and tested. In this device, inhaler use is determined by detecting and recording the motion of the drug delivery lever in the inhaler with a magnetic sensor. An additional electronic interface and software were also developed to allow the adherence data to be uploaded to a computer for display and analysis. RESULTS: System and reliability tests involving multiple-day and repeated-use tests of the adherence monitor demonstrate the overall performance and reliability of the device, and specifically its ability to record the time and date of dose delivery. In the repeated-use test, 300 successive actuations of the dose delivery lever were correctly sensed and recorded without error. CONCLUSION: The simple-to-use, low-cost, reusable adherence monitor accurately records time and date of inhaler use and thus allows clinical monitoring and adherence studies in patients using the Advair Diskus dry powder inhaler. The same technology should be adaptable to other dry powder inhalers, including the Pulmicort Tubuhaler and the Symbicort Tubuhaler.

Administration, Inhalation↗

Association between CBE, FOBT, and Pap smear adherence and mammography adherence among older low-income women.

BACKGROUND: Adherence to regular and timely mammography screening, especially in older low-income women, continues to fall below objectives. The primary aim of this study was to examine whether engaging in other cancer screenings was associated with mammography adherence for older women. METHODS: Women, ages 52 and over, without a self-reported history of breast cancer (N = 862) were selected from a larger sample of women residing in Washington, DC, census tracts with >/=30% of households below 200% of the federal poverty threshold. A computer-assisted telephone survey was used to collect data on health care system factors, demographics, cultural beliefs, clinical breast exam (CBE), Pap smear, fecal occult blood testing (FOBT), and mammography. Adherence was defined as receipt of the last two screening tests within recommended intervals for age. RESULTS: After controlling for other variables, adherence to CBE (OR = 4.15; 95% CI, 2.55-6.73) and Pap smear (OR = 1.82; 95% CI, 1.07-3.12) were highly predictive of mammography adherence. Adherence to FOBT (OR = 1.66; 95% CI, 0.97-2.84) was marginally predictive. CONCLUSIONS: Results of this study indicate that nonadherence to other cancer screenings can help identify women in need of additional interventions to improve mammography adherence.

Aged↗

The Brief Medication Questionnaire: a tool for screening patient adherence and barriers to adherence.

Self-report tools for monitoring adherence can be useful in identifying patients who need assistance with their medications, assessing patient concerns, and evaluating new programs. The aim of this study is to test the validity of the Brief Medication Questionnaire (BMQ), a new self-report tool for screening adherence and barriers to adherence. The tool includes a 5-item Regimen Screen that asks patients how they took each medication in the past week, a 2-item Belief Screen that asks about drug effects and bothersome features, and a 2-item Recall Screen about potential difficulties remembering. Validity was assessed in 20 patients using the Medication Events Monitoring System (MEMS). Results varied by type of non-adherence, with the Regimen and Belief Screens having 80-100% sensitivity for "repeat" non-adherence and the Recall Screen having 90% sensitivity for "sporadic" non-adherence. The BMQ appears more sensitive than existing tools and may be useful in identifying and diagnosing adherence problems.

Adult↗

External conditions and disposition--behaviour congruity as determinants of perceived personal causation among exercise adherers and non-adherers.

The aim of this study was to investigate the extent to which perceptions of external conditions, such as physical proximity to the exercise area and disposition--behavior congruity, affects observers' perceptions of personal causation of exercise adherers and non-adherers with regard to physical activity. The hypothetical scenario technique was used, with 120 adherers and 120 non-adherers, to investigate attributions of freedom, choice, control and responsibility. The results revealed that these attributions were significantly affected by perceived external conditions, and by the question of whether behavioural alternatives to be chosen were perceived as being congruent with an actor's disposition. Similar attributional patterns were revealed on all dimensions of personal causation, for the adherers and non-adherers. The implications of these findings for attributional research in the area of exercise adherence are discussed.

Adolescent↗

Patterns of adherence to antiretrovirals: why adherence has no simple measure.

The goal of this study was to explore patterns and explanations of adherence to antiretroviral therapies from the patient's perspective. It consisted of 78 in-depth interviews with patients attending an HIV clinic in New Orleans, Louisiana, to whom combination therapy had been prescribed. Interviews explored patient's definitions of adherence, beliefs about consequences of nonadherence, reasons for current and past adherence behavior, and contextual issues such as drug and alcohol use and social support. Respondents reported nine distinct patterns of adherence, which they perceived to have different consequences and causes. These patterns hid variations because respondents could have more than one pattern simultaneously and patterns were not stable over time. Although there are gold standards for adherence measurement, such as directly observed therapy, these measurements are most frequently used to classify respondents as adherers or nonadherers based on whether they take a certain percentage of their medication. Such a categorization is simplistic and does not reflect the complexity of adherence patterns.

Anti-HIV Agents↗

Physician estimates of adherence and the patient-physician relationship as a setting to improve adherence to antiretroviral therapy.

Physicians estimate their patients' adherence to medications, and base decisions about treatment on these estimates. In HIV, misjudgment of patient adherence can have adverse consequences, including withholding of therapy, unnecessary changes in therapy, or unnecessary laboratory testing. A review of the literature demonstrates that physicians are often inaccurate in estimating patient adherence with antiretroviral therapy. These findings have implications for practice. Standardized methods for adherence assessment are currently available that can be used to enhance physicians' ability to understand adherence behavior and barriers. The patient-physician relationship presents a unique setting for improving adherence. The authors propose interventions to improve adherence within the context of the patient-physician relationship at the physician level, interpersonal level, and organizational level. Improved communication, including discussion about patient lifestyle and preferences, can facilitate a frank exchange of information, negotiation, and a spirit of cooperation. Active patient participation in the decision-making process is crucial.

Antiretroviral Therapy, Highly Active↗

Multiple validated measures of adherence indicate high levels of adherence to generic HIV antiretroviral therapy in a resource-limited setting.

BACKGROUND: There are no validated measures of adherence to HIV antiretroviral therapy in resource-poor settings. Such measures are essential to understand the unique barriers to adherence as access to HIV antiretroviral therapy expands. METHODS: We assessed correspondence between multiple measures of adherence and viral load suppression in 34 patients purchasing generic Triomune antiretroviral therapy (coformulated stavudine, lamivudine, and nevirapine; CIPLA, Ltd., Mumbai, India) in Kampala, Uganda. Measures included 3-day patient self-report, 30-day visual analog scale, electronic medication monitoring, and unannounced home pill count. HIV-1 load was determined at baseline and 12 weeks. RESULTS: Mean adherence was 91%-94% by all measures. Seventy-six percent of subjects had a viral load of <400 copies/mL at 12 weeks. All measures were closely correlated with each other (R = 0.77-0.89). Each measure was also significantly associated with 12-week HIV load. There was no significant difference between patient-reported and objective measures of adherence. CONCLUSIONS: This sample of patients purchasing generic HIV antiretroviral therapy has among the highest measured adherence reported to date. Patient-reported measures were closely associated with objective measures. The relative ease of administration of the 30-day visual analog scale suggests that this may be the preferred method to assess adherence in resource-poor settings.

Adult↗