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Working with non-dental groups to influence adoption of self-applied fluoride programs in schools: one approach.

Although the use of self-applied fluorides in schools has been proven safe and effective, thousands of children are not benefiting from these procedures. This paper describes a dual promotional approach designed to increase the awareness of the need for school-based self-applied fluoride programs. A manned exhibit providing consultation and educational materials was displayed during the entire meeting of a state PTA and was supplemented by a presentation scheduled on the formal program. The workshop participants were parents of school-age children; most held decision-making positions in their local PTAs. Results of the workshop to date include: one participant prevented the demise of an established fluoride mouthrinsing program in her community; and the workshop leaders presented the merits of school-based self-applied fluoride programs to a local PTA and a county school health council. The same programs were described in a county PTA newsletter. These actions suggest that, given the appropriate information and assistance, parents of school children through their PTA can influence adoption of school-based fluoride programs. Furthermore, strategies directed toward members of other groups with an interest and decision-making role in children's health may be effective methods of influencing adoption of school-based self-applied fluoride programs and ultimately promoting children's oral health.

Child↗

The adoption of management and husbandry procedures by Western Australian pig farmers.

A postal survey was conducted to determine the management and husbandry procedures adopted by a sample of 101 Western Australian pig farmers. Seventy seven replies were received and analysed. Over 80% of farmers vaccinated breeding stock against leptospirosis and erysipelas, 35% vaccinated against parvo virus and 15% vaccinated against Escherichia coli. Most farmers used antibiotics: 72% incorporated them into their pig diets and 60% used parenteral antibiotics. Fifty three per cent of farmers reported that they regularly used a veterinarian. Over 59% of piggeries had another piggery located within 10 km, thus increasing the possibility for disease transmission between herds. It is concluded that there is potential for veterinarians to offer advice to pig farmers, particularly on disease control measures and adoption of technological advances.

Animal Husbandry↗

Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones.

The adoptive transfer of antigen-specific T cells to establish immunity is an effective therapy for viral infections and tumors in animal models. The application of this approach to human disease would require the isolation and in vitro expansion of human antigen-specific T cells and evidence that such T cells persist and function in vivo after transfer. Cytomegalovirus-specific CD8+ cytotoxic T cell (CTL) clones could be isolated from bone marrow donors, propagated in vitro, and adoptively transferred to immunodeficient bone marrow transplant recipients. No toxicity developed and the clones provided persistent reconstitution of CD8+ cytomegalovirus-specific CTL responses.

Antigens, Differentiation, T-Lymphocyte↗

Increased influenza pneumonia mortality of mice adoptively immunized with node and spleen cells sensitized by inactivated but not live virus.

Syngeneic mice adoptively immunized intravenously with 25 million washed node and spleen cells from donors vaccinated subcutaneously with formolized influenza A PR8 had a higher mortality with influenza pneumonia after challenge with homologous virus than occurred in recipients of similar cells from unsensitized donors, and this increased mortality was prevented by treatment of the sensitized cells with antithymocyte serum. Mice adoptively immunized with cells from donors vaccinated with formolized influenza A PR8 also had a higher mortality than recipients of unsensitized cells after challenge with heterologous influenza B Lee. Mice who received PR8-sensitized cells and survived challenge with influenza B Lee developed antibody only to the challenge virus, and serum antibody titers to the challenge virus in surviving recipients of sensitized cells were similar to those of recipients of unsensitized cells in all studies. Influenza mortality of recipients of antibody-containing mouse serum after homologous virus challenge was similar to that of recipients of antibody-free mouse serum in this model. Washed node and spleen cells from donor mice who had survived respiratory infection or received subcutaneous vaccination with live influenza A PR8 and those from donor mice given typhoid vaccine subcutaneously all failed to alter mortality from that observed in recipients of unsensitized cells after challenge with influenza A PR8. These results suggest that subcutaneous vaccination with inactivated influenza establishes a reactivity of the cell-mediated immunologic system which can increase the severity of influenza infection of the respiratory tract under certain conditions, and that sensitization by live influenza fails to produce this effect.

Animals↗

Adoptive transfer of immunity to Plasmodium berghei with immune T and B lymphocytes.

Immunity to malarial infection may be transferred with immune lymphocytes. This study was designed to determine which lymphocyte type is responsible for the adoptive transfer of immunity to malarial infection. In one set of experiments, the ability of immune T and B lymphocytes, separated by passage through nylon-wool columns, to transfer immunity to infection was determined. In another experiment, the effect of killing T lymphocytes with anti-theta serum on the transfer of immunity was determined. The effect on the ability of immune lymphocyte suspensions to transfer immunity after B lymphocytes were removed from such suspensions by centrifugation on Ficoll-Hypaque gradients, after they had formed rosettes with sensitized, complement-coated sheep erythrocytes, was also determined. The ability of lymphocyte suspensions to adoptively transfer resistance to malarial infection was greatly impaired by the removal from the suspensions of differentiated B-type lymphocytes. Our results indicate that it is the differentiated B cell, most probably an antibody-producing cell, which lacks both theta antigen and the complement receptor that is responsible for conferring immunity to malaria.

Animals↗

Adoptive transfer of immunity from mice immunized with ribosomes or live yeast cells of Histoplasma capsulatum.

This investigation was designed to compare the role of lymphoid cells and immune serum in protective immunity induced by immunization with ribosomes or live yeast cells of Histoplasma capsulatum. Spleen cells, peritoneal cells, and serum from C3H mice immunized with Histoplasma ribosomes or live cells were transferred intravenously to separate groups of syngeneic recipients. All recipients along with a set of immunized and control mice were challenged intravenously with 4 x 10(6) yeast cells of H. capsulatum, and protection was assessed. Immunization with ribosomes or live cells provided 90 to 100% protection. Mice receiving filtered spleen cells or peritoneal cells from donors immunnized with live cells showed 90 to 100% protection; 80 to 90% protection was observed for mice receiving cells from ribosome-immunized donors. In contrast, no evidence of protection was seen in mice receiving serum from either live-cell- or ribosome-immunized mice. Peritoneal cells were far more efficient than spleen cells in adoptive transfer of immunity. The adoptive immunity in recipients persisted for at least 3 weeks after transfer, the longest period tested in the present study. These results indicate that the immunity elicited by immunization with Histoplasma ribosomes or live cells is mediated by a cellular mechanism.

Animals↗

Adoptive transfer of cross-protection among alphaviruses in mice requires allogeneic stimulation.

Cell-mediated (T-effector cell) immunity is proposed as playing the major role in cross-protection between Sindbis and Semliki Forest viruses, which are alphaviruses that do not elicit cross-neutralizing antibodies. In adoptive transfer experiments, T-cells from spleens of Sindbis virus-immunized mice were found to confer specific cross-protection to Semliki Forest virus upon recipient mice. This cross-protection was observed in the outbred ICR strain of mice and when transfers were made between several combinations of inbred and hybrid strains. Cross-protection was substantially reduced if syngeneic rather than allogeneic cell transfers of one spleen equivalent per mouse were made. The results suggest that allogeneic stimulation (mixed lymphocyte reaction in vivo) is necessary to increase the number of effector cells (donor) in the recipient. This was supported by the observation that blastogenic stimulation of donor cells in vitro by concanavalin A induces cross-protection in syngeneic animals. Conversion of recipient cells to specific effector cells also appears to play a role in protecting mice against Semliki Forest virus. This was concluded from the experiments described above, a time course study, and the results of experiments that involved serial passages of transferred cells across histocompatibility barriers. Thus, we propose that both donor and recipient cells are active in protecting recipient mice against challenge with Semliki Forest virus after adoptive transfer.

Animals↗

Evaluation of Mycobacterium leprae immunogenicity via adoptive transfer studies.

The immune response of mice to live, heat-killed, or autoclaved Mycobacterium leprae was investigated. After sensitization with 10(7) organisms in each group, recipient mice were transfused with the sensitized splenocytes 28 days later. A selected number of these mice were infected with 5 X 10(3) M. leprae, and the remaining animals were sacrificed at scheduled intervals for evidence of cell-mediated immunity to the M. leprae cell extract. Data from these and the bacteriological assays showed that all three materials induce cell-mediated immunity and also extend protection against the M. leprae challenge but not against a Listeria monocytogenes challenge. Adoptive immunity against M. leprae was expressed equally effectively in both non-irradiated animals and those sublethally (500 R) irradiated. This study reveals that, after adoptive transfer of immunity, a bacillary restriction occurs with concomitant onset of delayed hypersensitivity and that the protection observed could be specifically directed against an M. leprae challenge.

Animals↗

Therapy of cancer using the adoptive transfer of activated killer cells and interleukin-2.

A new approach to cancer treatment has been developed based on the adoptive transfer of activated lymphocytes into cancer patients. Lymphocytes harvested from patients by leukapheresis are converted into lymphokine-activated killer (LAK) cells by incubation with recombinant interleukin-2 (rIL-2). These LAK cells are then infused back into the patients in combination with intravenous IL-2. Among 25 patients treated with this form of adoptive immunotherapy there were 11 patients with measurable tumor reductions, including 1 complete responder. The majority of responses occurred in patients with metastatic renal cell carcinoma, melanoma and colorectal carcinoma. The toxicities of IL-2, including fluid retention and pulmonary edema, limit therapy, and laboratory investigation is now aimed toward understanding the mechanism of IL-2 toxicity. The use of LAK cells and IL-2 in cancer therapy is still in a developmental stage and needs to be refined before its role can be definitely established.

Clinical Trials as Topic↗

Adoptive immunotherapy of murine pulmonary metastases with interleukin 2 and interferon-gamma.

We examined the activities of activated lymphocytes, interferon-gamma (IFN-gamma), and interleukin 2 (IL-2) in adoptive immunotherapy of pulmonary metastases. Pulmonary metastases produced in Balb/c mice by a single tail-vein injection of 5 X 10(5) murine sarcoma (MCB8) tumor cells on day 0 were treated with combinations of Con A-activated lymphocytes (CAL) (3 X 10(7) cells on days 3 and 7), IL-2 (5 X 10(4) U three times a day on days 3 to 8), and IFN-gamma (5 X 10(4) U/mouse on days 1 to 8). Treated tumors contained increased numbers of infiltrating Thy-1.2+ lymphocytes and a predominance of L3T4+(CD4+) lymphocytes. The level of expression of class I and class II MHC antigens by tumor cells in the lung was increased after treatment. Mice that received CAL + IL-2 + IFN-gamma showed approximately 80% reduction in tumor burden as compared to controls (P = 0.001). Mice treated with IL-2 + CAL, or IL-2 + IFN-gamma, displayed approximately 50% reduction (both P less than 0.02 as compared to triple therapy), whereas IL-2, IFN-gamma, or CAL administered as single agents had little effect on pulmonary metastases. We conclude that adoptive immunotherapy with activated lymphocytes and IL-2 is enhanced by IFN-gamma.

Animals↗

In vivo trafficking of adoptively transferred interleukin-2 expanded tumor-infiltrating lymphocytes and peripheral blood lymphocytes. Results of a double gene marking trial.

Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) and IL-2 appears to produce dramatic regressions in patients with metastatic melanoma and renal cancer. However, the in vivo mechanism of TIL function is not known. We conducted an UCLA Human Subject Protection Committee, Recombinant DNA Advisory Committee, and FDA-approved clinical trial using genetically-marked TIL to test the hypothesis that these cells have unique, tumor-specific in vivo trafficking patterns. TIL and PBL (as a control effector cell population) were isolated and expanded in parallel in vitro in IL-2-containing medium for 4-6 wk. During the expansion, TIL and PBL were separately transduced with the amphotropic retroviral vectors LNL6 and G1Na. Transduced TIL and PBL were coinfused into patients and their respective numbers measured in tumor, peripheral blood, and normal tissues; integrated provirus could be quantitated and distinguished by DNA PCR. Nine patients were treated (six melanoma, three renal) and received between 4.5 x 10(8) and 1.24 x 10(10) total cells. Both "marked" TIL and PBL could be detected circulating in the peripheral blood, in some patients for up to 99 d after infusion. Marked TIL and/or PBL could be detected in tumor biopsies in six of nine patients as early as day 6 and as late as day 99 after infusion. No convincing pattern of preferential trafficking of TIL vs. PBL to tumor was noted. Moreover, concurrent biopsies of muscle, fat, and skin demonstrated the presence of TIL/PBL in comparable or greater numbers than in tumor in five patients. The results of this double gene marking trial provide interesting insights into the life span and trafficking of adoptively transferred lymphocytes, but do not support the hypothesis that TIL specifically traffic to tumor deposits.

Adult↗

Computer-based study strategies for students with learning disabilities: individual differences associated with adoption level.

This article reports results from a study of the use of technology to support students with learning disabilities in the use of effective study strategies. Thirty secondary students were given laptop computers and taught a variety of computer-based study strategies designed to facilitate information recording, organization, and manipulation. Results suggest that students adopted this innovation at three levels: (a) Power Users (skilled, independent users, integrating the computer into their schoolwork); (b) Prompted Users (skilled computer users, but requiring prompting); and (c) Reluctant Users (having limited knowledge and working only under supervision). Intelligence and reading test scores were associated with adoption levels in a statistically significant way.

Achievement↗

Failure to adopt beneficial therapies caused by bias in medical evidence evaluation.

BACKGROUND: Although it is known that many evidence-based therapies are underutilized, the causes of the research-practice gap are not well understood. The authors sought to determine if there is a bias in the evaluation of new evidence that leads to low rates of adoption of beneficial therapies compared to abandonment of harmful ones. METHODS: Two case vignettes describing hypothetical clinical trials were administered to 2 independent samples of pulmonary and critical care practitioners. Each vignette was presented in 2 different ways; in one version, the results of the hypothetical trial showed that a treatment was harmful, and in the other version, the same treatment was shown to be beneficial. Prospective respondents from each sample were randomized to receive 1 version of each vignette (intersubject design). The main outcome was respondent's willingness to apply the results of the hypothetical trial to patient care. RESULTS: There were 174 participants for trial 1 and 138 participants for trial 2 (enrollment rates of 44.2% and 41.8%, respectively). For trial 1, respondents were 2.3 times less likely to change clinical practice based on results indicating benefit as opposed to harm (33.3% v. 76.5%; P < 0.0001). Similarly, for trial 2, respondents were 2.57 times less likely to change practice when trial results showed that early use was beneficial as opposed to showing that early use was harmful (37.1% v. 95.3%; P < 0.0001). CONCLUSIONS: When evaluating clinical trials, physicians demonstrate less willingness to adopt beneficial therapies than to abandon harmful ones. This difference may contribute to the research-practice gap.

Attitude of Health Personnel↗

Adoption of a managerial innovation: a study of physician impact analysis.

This article examines the adoption of physician impact analysis (PIA) among active treatment hospitals in Ontario, Canada. The influence of variables from three different levels of analysis (individual, organizational and contextual) were included as well as measures of key stakeholders' (Chief Executive Officer (CEO) and Medical Chief of Staff) assessments of the attributes of the innovation. A number of conclusions were drawn. First, by adding information about the perceived attributes of the innovation the model was able to account for a larger percentage of explained variance than has been seen in related work. Secondly, the adoption of PIA within a context of written guidelines agreed to by senior management, specifying process and structure concerns, is most likely in organizations which are large and where the CEO positively evaluates the innovation.

Chief Executive Officers, Hospital↗

Factors related to physicians' adoption of electronic prescribing: results from a national survey.

Electronic prescribing (E-RX) is a component of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA). The objective of this study was to identify factors related to physicians' adoption of E-RX for outpatients. This study employed an electronic survey of US physicians who subscribe to the Physicians Online Internet service. Electronic prescribers were compared to traditional prescribers in terms of demographics, practice type and location, technology use, and beliefs about E-RX. A total of 1104 physicians responded, 19% of whom prescribed electronically. Electronic prescribers were more likely to be generalists practicing in academic or publicly funded centers, have fewer years in practice, and work in technology-equipped offices. They also held different beliefs versus traditional prescribers in terms of E-RX limitations and its potential to improve medication safety and prescribing efficiency. In addition to financial incentives established by MMA, adoption can be stimulated by improvements in the technology and on organizational commitment.

Adult↗

Implementing quality: a study of the adoption and implementation of quality standards in the contracting process in a general practitioner multifund.

The increase in managerialism in the 1980s and the 1990 NHS reforms have had major implications for the regulation of providers. Purchasers of health care in the UK are now expected to specify three factors in their contracts: volume, cost and quality. This paper focuses on one of these: i.e. the quality standards purchasers now include within their health service contracts. The case study is of a general practitioner multifund and the analysis focuses on how quality standards are derived and adopted in outpatient contracts. The data were derived from in-depth face-to-face interviews with the key participants in the contracting process. The evidence shows that the standards were derived and adopted with very little participation from the providers. The impact of the quality standards on hospitals consultants' behaviour was negligible, there was very little monitoring of the standards by the multifund, and providers accepted standards which they knew they could not meet. It is concluded that this non-participatory method of developing the quality standards is likely to mean that their impact on service delivery will be limited.

Ambulatory Care↗

The adoption of Mediterranean diet attenuates the development of acute coronary syndromes in people with the metabolic syndrome.

OBJECTIVES: In this work we investigated the effect of the consumption of the Mediterranean diet on coronary risk, in subjects with the metabolic syndrome. METHODS: During 2000-2002, we randomly selected, from all Greek regions, 848 hospitalised patients (695 males, 58 +/- 10 & 153 females, 65 +/- 9 years old) with a first event of acute coronary syndrome and 1078 frequency matched, by sex, age, region controls, without any suspicious for cardiovascular disease. Nutritional habits were evaluated through a validated questionnaire, while the metabolic syndrome was defined according to the NCEP ATP III criteria. Mediterranean diet was defined according to the guidelines of the Division of Nutrition/Epidemiology, of Athens Medical School. RESULTS: Of the 1926 participants, 307 (36.2%) of the patients and 198 (18.4%) of the controls (P < 0.001) met the ATP III criteria. This was related with 2fold adjusted coronary risk (odds ratio = 2.35, 95% 1.87-2.84) in subjects with the metabolic syndrome as compared with the rest of them. No differences were observed concerning the prevalence of the metabolic syndrome and sex of subjects, after adjustment for group of study (P > 0.1). Eighty (26%) of the patients and 70 (35%) of the controls (P < 0.01) with the metabolic syndrome were "closer" to the Mediterranean diet. Multivariate analysis revealed that the adoption of this diet is associated with a 35% (odds ratio = 0.65, 95% 0.44-0.95) reduction of the coronary risk in subjects with the metabolic syndrome, after adjusting for age, sex, educational and financial level and the conventional cardiovascular risk factors. CONCLUSION: Consequently, the adoption of Mediterranean diet seems to attenuate the coronary risk in subjects with the metabolic syndrome.

Journal Article↗

Adoptive transfer of dendritic cells modulates immunogenesis and tolerogenesis in a neonatal model of murine cutaneous leishmaniasis.

We evaluated the adoptive transfer of DCs on Leishmania (L.) mexicana-infected neonatal BALB/c mice. DCs were isolated and purified from the spleens of the following donor groups: a) Adult BALB/c mice infected during adulthood with L. (L) mexicana; b) Adult BALB/c mice infected during neonatal life; c) Healthy neonatal BALB/c mice; d) Healthy adult BALB/c mice. A neonatal model of infection, generated after inoculation with 5 × 105 promastigotes of L. (L) mexicana, was used as the infection control group. Sixteen hours after intraperitoneal transfer of DCs (1 × 103, 1 × 105, or 1 × 106 cells/ml), neonatal recipient BALB/c mice were infected. The adoptive transfer of DCs diminished disease progression in neonatal mice. This reduction depends on the quantity and provenance of transferred DCs, since the effect was more evident with high numbers of DCs from adult mice infected during adulthood and healthy neonatal mice. Protection was significantly reduced in animals receiving DCs from healthy adult mice but it was absent in mice receiving DCs from adult mice infected during neonatal life. These results suggest that genetic susceptibility to Leishmania infection can be modified during neonatal life, and that the period of life when antigens are encountered is crucial in influencing the capacity of DCs to induce resistance or tolerance.

Journal Article↗