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Biomedical subjects

E J Ryan

Publications and source records attributed to E J Ryan.

15 recordsLinked to original sources

Immunomodulators and delivery systems for vaccination by mucosal routes.

Current paediatric immunization programmes include too many injections in the first months of life. Oral or nasal vaccine delivery eliminates the requirement for needles and can induce immunity at the site of infection. However, protein antigens are poorly immunogenic when so delivered and can induce tolerance. Novel ways to enhance immune responses to protein or polysaccharide antigens have opened up new possibilities for the design of effective mucosal vaccines. Here, we discuss the immunological principles underlying mucosal vaccine development and review the application of immunomodulatory molecules and delivery systems to the selective enhancement of protective immune responses at mucosal surfaces.

Adjuvants, Immunologic↗

Modulation of innate and acquired immune responses by Escherichia coli heat-labile toxin: distinct pro- and anti-inflammatory effects of the nontoxic AB complex and the enzyme activity.

We have examined the roles of enzyme activity and the nontoxic AB complex of heat-labile toxin (LT) from Escherichia coli on its adjuvant and immunomodulatory properties. LTK63, an LT mutant that is completely devoid of enzyme activity, enhanced Th1 responses to coinjected Ags at low adjuvant dose. In contrast, LTR72, a partially detoxified mutant, enhanced Th2 responses and when administered intranasally to mice before infection with Bordetella pertussis suppressed Th1 responses and delayed bacterial clearance from the lungs. LTR72 or wild-type LT inhibited Ag-induced IFN-gamma production by Th1 cells, and LT enhanced IL-5 production by Th2 cells in vitro. Each of the toxins enhanced B7-1 expression on macrophages, but enhancement of B7-2 expression was dependent on enzyme activity. We also observed distinct effects of the nontoxic AB complex and enzyme activity on inflammatory cytokine production. LT and LTR72 suppressed LPS and IFN-gamma induced TNF-alpha and IL-12 production, but enhanced IL-10 secretion by macrophages in vitro and suppressed IL-12 production in vivo in a murine model of LPS-induced shock. In contrast, LTK63 augmented the production of IL-12 and TNF-alpha. Furthermore, LTK63 enhanced NF-kappaB translocation, whereas low doses of LTR72 or LT failed to activate NF-kappaB, but stimulated cAMP production. Thus, E. coli LT appears to be capable of suppressing Th1 responses and enhancing Th2 responses through the modulatory effects of enzyme activity on NF-kappaB activation and IL-12 production. In contrast, the nontoxic AB complex can stimulate acquired immune responses by activating components of the innate immune system.

Adjuvants, Immunologic↗

Booster immunization of children with an acellular pertussis vaccine enhances Th2 cytokine production and serum IgE responses against pertussis toxin but not against common allergens.

Acellular pertussis vaccines (Pa) protect against severe pertussis in children. However, serum antibody responses decline quickly after immunization. Studies in animal models suggest that cell-mediated immunity also contributes to protection against Bordetella pertussis, and it has already been demonstrated that Pa induce T cells that secrete type-1 and type-2 cytokines in children. In this study we examined the persistence of the T cell response and the effect of booster immunization in 4-6-year-old children. Cell-mediated immunity to B. pertussis antigens was detected in a high proportion of children more than 42 months after their last immunization. Peripheral blood mononuclear cells (PBMC) from the majority of children secreted interferon-gamma (IFN-gamma) and a smaller proportion IL-5, in response to specific antigen stimulation in vitro. However, following booster immunization, significantly higher concentrations of IL-5, but not IFN-gamma, were produced by PBMC in response to B. pertussis antigens. Furthermore, plasma IL-4 and IL-5 concentrations were increased, whereas IFN-gamma concentrations were reduced following booster immunization. It has been suggested that childhood immunization with Th2-inducing vaccines may predispose some children to atopic disease. Although we found that pertussis toxin (PT)-specific IgE was significantly increased after booster immunization in both atopic and non-atopic children, the levels of IgE to common allergens and the prevalence of positive skin prick test were unaffected by the booster vaccination. Thus, despite the enhancement of type-2 responses to B. pertussis antigens, booster vaccination with Pa does not appear to be a risk factor for allergy.

Allergens↗

Asthma in United States olympic athletes who participated in the 1998 olympic winter games.

BACKGROUND: About one of every 5 athletes who participated in the 1996 Summer Olympic Games in Atlanta had a past history of asthma, had symptoms that suggested asthma, or took asthma medications. No previous study has determined the prevalence of asthma in all US athletes who participated in an Olympic Winter Games. OBJECTIVES: We sought to determine how many US athletes who participated in the 1998 Olympic Winter Games had a past history of asthma, had symptoms that suggested asthma, or indicated taking a medication used to treat asthma. METHODS: We evaluated responses to questions that asked about allergic and respiratory diseases in the United States Olympic Committee Medical History Questionnaire that was completed by all 196 athletes who represented the United States at the 1998 Olympic Winter Games in Nagano, Japan. RESULTS: Forty-three (21.9%) of the 196 athletes had a previous diagnosis of asthma, and 36 (18. 4%) recorded use of an asthma medication at some time in the past. Forty-four (22.4%) reported use of an asthma medication, a diagnosis of asthma, or both (our basis for the diagnosis of asthma). Thirty-four (17.4%) of the athletes were currently taking an asthma medication at the time that they completed the questionnaire or indicated that they took these medications on a permanent or semipermanent basis and were considered to have active asthma. Athletes who participated in Nordic combined, cross-country, and short track events had the highest prevalence of having been told that they had asthma or had taken an asthma medication in the past (60.7%) in contrast with only one (2.8%) of the 36 athletes who participated in bobsled, biathlon, luge, and ski jumping. Eighteen (24%) of 75 athletes who participated in alpine, long track, figure skating, snow boarding, and curling had a previous diagnosis of asthma or recorded use of an asthma medication. CONCLUSIONS: We conclude that asthma appeared to have been more common in athletes who participated in the 1998 Winter Games than in athletes who participated in either the 1996 or 1984 Summer Games. Clearly, asthma rates vary widely among sports. This suggests that the environment in which exercise is performed is important in leading to a decrease in the amount of exercise required to trigger asthma and perhaps in causing injury to the airways.

Asthma↗

Mutants of Escherichia coli heat-labile toxin act as effective mucosal adjuvants for nasal delivery of an acellular pertussis vaccine: differential effects of the nontoxic AB complex and enzyme activity on Th1 and Th2 cells.

Mucosal delivery of vaccines is dependent on the identification of safe and effective adjuvants that can enhance the immunogenicity of protein antigens administered by nasal or oral routes. In this study we demonstrate that two mutants of Escherichia coli heat-labile toxin (LT), LTK63, which lacks ADP-ribosylating activity, and LTR72, which has partial enzyme activity, act as potent mucosal adjuvants for the nasal delivery of an acellular pertussis (Pa) vaccine. Both LTK63 and LTR72 enhanced antigen-specific serum immunoglobulin G (IgG), secretory IgA, and local and systemic T-cell responses. Furthermore, using the murine respiratory challenge model for infection with Bordetella pertussis, we demonstrated that a nasally delivered diphtheria, tetanus, and acellular pertussis (DTPa) combination vaccine formulated with LTK63 as an adjuvant conferred a high level of protection, equivalent to that generated with a parenterally delivered DTPa vaccine formulated with alum. This study also provides significant new information on the roles of the binding and enzyme components of LT in the modulation of Th1 and Th2 responses. LTK63, which lacks enzyme activity, promoted T-cell responses with a mixed Th1-Th2 profile, but LTR72, which retains partial enzyme activity, and the wild-type toxin, especially at low dose, induced a more polarized Th2-type response and very high IgA and IgG antibody titers. Our findings suggest that the nontoxic AB complex has broad adjuvant activity for T-cell responses and that the ADP-ribosyltransferase activity of the A subunit also appears to modulate cytokine production, but its effect on T-cell subtypes, as well as enhancing, may be selectively suppressive.

Adjuvants, Immunologic↗

Upper extremity proprioceptive training.

Proprioception following lower extremity injuries is commonly recommended, but there is little information on proprioception training following upper extremity injuries. No studies have evaluated whether proprioception programs for athletes in open kinetic chain activities (throwing, shot putting) should be different than programs for athletes in closed kinetic chain activities (gymnastics, swimming, kayaking, or rowing). In this paper, we provide a rationale for proprioception training for upper extremity injuries in athletes and the importance of analyzing the athlete's sport and activity for specificity of proprioception exercises. We then discuss one popular proprioception exercise, rhythmic stabilization, and propose several additional upper extremity proprioception exercises, along with instructions for the athletic trainer on how to direct the athlete through these exercises.

Journal Article↗

Marketing home health care medical services: the physician's view.

The authors surveyed physicians serving the Jackson, Mississippi home health care market. They identified problems and studied physician perceptions regarding services provided by home health care agencies, private duty nursing agencies, and durable medical equipment suppliers. Respondents perceived home health care as providing: (1) increased patient satisfaction, (2) greater patient convenience, (3) earlier discharge, and (4) lowered patient costs. They least liked: (1) lack of control and involvement in the patient caring process, (2) paperwork, (3) quality control potential, and the possibility that patient costs could increase. Two sets of implications for health care marketers are presented that involve both national and regional levels. Overall results indicate that a growing and profitable market segment exists and is being served in an effective and socially responsible manner.

Attitude of Health Personnel↗

Fifteen years of amateur boxing injuries/illnesses at the United States olympic training center.

We examined the incidence of health problems in elite-level amateur boxing athletes who sparred, trained, or competed at the United States Olympic Training Center in Colorado Springs, Colorado from January 1, 1977 through June 30, 1992. We think this is the first study to examine both injuries and illnesses in a population of elite-level athletes. We collected data on 1,776 reported problems (1219 injuries, 557 illnesses) from standard medical report forms completed by the permanent and volunteer sports medicine staff. We classified the information based on type, body region, location, description, and occurrence. There were significant differences between the frequency of injuries and illnesses and between the classifications and regions for each type of problem. Collectively, serious injuries represented only a relatively small percentage (6.1%) of all problems. We concluded that illnesses comprised a small but important portion of problems, that most illnesses involved respiratory tract infections (71%), that there is only a small risk for serious injury, and that injuries occur in a hierarchy of upper extremity (441, 25%), head/face (344, 19%), lower extremity (267, 15%), and spinal column (167, 9%) for amateur boxers.

Journal Article↗

Measuring customer perceptions of emergency facility services: a qualitative approach.

The purpose of this study was to use a qualitative research technique and define problems faced by one hospital that was attempting to increase demand for its emergency services. A telephone survey of 450 affluent and well-educated suburban residents was conducted to determine their perceptions of six major facilities. Topics included actual and preferred facility use by injury type, general perceptions concerning staff and facility, and other components of service quality. Results indicated that a variety of sociological, psychological, environmental, and situational factors interacted when the respondents formed attitudes concerning hospital emergency use and service. They were often uncertain of their real attitudes and conveyed varying opinions about the desirability or effectiveness of similar services. Health care providers should note these differences and modify the marketing mixes in a manner that best conveys their unit's competitive advantages. They could also benefit from using the qualitative research technique described in this paper and from adopting the marketing concept.

Catchment Area, Health↗

Syphilitic optic perineuritis.

We examined a patient who had syphilitic perioptic neuritis, a rarely diagnosed inflammation of the sheaths of the optic nerves that may be confused with papilledema caused by brain tumor or pseudotumor cerebri. The visual acuity was typically normal, and the only visual-field abnormality was enlargement of the blind spots. After we excluded an intracranial mass lesion, the diagnosis was confirmed by cerebrospinal fluid serologic findings positive for syphilis and normal intracranial pressure. Anti-inflammatory and antisyphilitic therapy resolved all the symptoms in our patient.

Adult↗