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Biomedical subjects

D Baker

Publications and source records attributed to D Baker.

At least 271 records · Page 15Linked to original sources

Midazolam premedication for pediatric bone marrow aspiration and lumbar puncture.

The ability of midazolam, a benzodiazepine, to reduce the distress associated with lumbar puncture and bone marrow aspiration was examined in 23 children with acute lymphocytic leukemia. Patients were randomized to receive 0.2 mg/kg midazolam HCl or placebo intravenously 3-5 min before the procedures, under double-blind conditions. Based on prior experiences, children in both groups anticipated severe pain from these procedures. Postprocedure pain ratings by patients were markedly reduced in the midazolam but not the placebo group. Both physicians and parents judged the midazolam group as significantly less distressed than controls during and after the procedures. Trained observers recorded significantly fewer pain- and anxiety-related behaviors in the midazolam group immediately before and after, but not during the procedures. The amnestic effects of midazolam, confirmed in a visual recall/recognition test, appear to account for the decreased pain ratings since the behavioral manifestations were similar in the two groups. There were no adverse drug reactions or significant changes in vital signs. Midazolam warrants further investigation as a premedication for painful diagnostic and treatment procedures in children with cancer.

Adolescent↗

Cytokines in the central nervous system of mice during chronic relapsing experimental allergic encephalomyelitis.

Clinical disease phases of chronic relapsing experimental allergic encephalomyelitis (CREAE) in the Biozzi AB/H mouse model are associated with extensive cellular infiltration of the central nervous system, principally the spinal cord. The activation of these cells is further suggested by the immunocytochemical demonstration of cytokines (migration inhibition factor, interferon-gamma, tumour necrosis factor-alpha, and interleukins 1, 2, and 3) within these infiltrates. The in vitro functions attributed to these cytokines indicate their potential role in cell recruitment, activation, and differentiation of the ongoing immune response which could contribute to the pathogenesis of disease.

Animals↗

Mononuclear cell trafficking and plasma protein extravasation into the CNS during chronic relapsing experimental allergic encephalomyelitis in Biozzi AB/H mice.

Cellular traffic and plasma protein extravasation across the blood-brain and blood-spinal cord barrier (BBB) have been studied during chronic relapsing experimental allergic encephalomyelitis in Biozzi AB/H mice, using a simultaneous double radioisotope method. There was a general correlation between the clinical course of disease and BBB breakdown, including a resealing of the barrier during remission, although breakdown appeared slightly to precede clinical presentation. The brain was markedly less affected than the spinal cord and was only minimally involved in the relapse phase of disease.

Animals↗

An immunoelectron microscopical study of the expression of class II major histocompatibility complex during chronic relapsing experimental allergic encephalomyelitis in Biozzi AB/H mice.

Immunoelectron microscopical techniques have been used to study class II major histocompatibility complex (MHC) expression by cells in the spinal cords of Biozzi AB/H mice with chronic relapsing experimental allergic encephalomyelitis. Throughout the course of disease both astrocytes and endothelia failed to express significant levels of class II MHC antigens. The major central nervous system resident cell types found to express class II MHC antigens were the perivascular microglia, with infiltrating macrophages and some lymphocytes being strongly positive.

Animals↗

Inhibition of chronic relapsing experimental allergic encephalomyelitis in the mouse by the alkyl-lysophospholipid ET-18-OCH3.

The effect of the anti-tumour agent alkyl-lysophospholipid (ALP) ET-18-OCH3 on the development of chronic relapsing experimental allergic encephalomyelitis (CREAE) in the mouse was investigated. Experimental allergic encephalomyelitis developed in the majority (greater than 96%) of mice immunized with autologous spinal cord homogenate in Freund's complete adjuvant. Alkyl-lysophospholipid, in doses of 25 mg/kg/day or 50 mg/kg/day, inhibited the onset of clinical signs of acute phase CREAE when orally administered starting on the day of disease induction. Similarly if treatment with 50 mg/kg/day was delayed until day 9 post-inoculation the incidence of disease and severity of clinical signs were also significantly reduced (P less than 0.02) as compared with vehicle fed animals. However, when treatment began on day 12, just prior to the onset of clinical disease, although the incidence of disease was not significantly altered the severity of disease was significantly (P less than 0.002) reduced compared with vehicle treated animals. These data suggest that although the major effect of ALP is on the inhibition of the generation of the autoimmune response there appeared to be some therapeutic benefit at a later stage of acute disease. Therefore, this study was extended to the treatment of post-acute phase remission animals. It was found that the oral administration of 50 mg/kg/day marginally reduced and that 75 mg/kg/day significantly (P less than 0.05) reduced the incidence of relapsing disease compared with vehicle treated controls. This suggests that ET-18-OCH3 may have some potential in the treatment of ongoing autoimmune disease of the central nervous system.

Animals↗

Suppression of demyelination by mitoxantrone.

The mode of action of the immunosuppressant mitoxantrone was examined in murine models of demyelinating disease. The drug has been shown to block antigen induced proliferative activity and to inhibit myelin degradation by leucocytes from paralysed mice. Mitoxantrone blocked myelin breakdown by macrophages although phagocytosis was not affected. Further evidence was obtained to indicate that mitoxantrone acts therapeutically in reducing, or at high dose, preventing signs of EAE developing in mice immunized with spinal cord homogenate and Freund's complete adjuvant. Mitoxantrone also significantly inhibited the incidence of relapse when treatment was initiated during the post-acute remission period.

Animals↗

Contextual variations in the meaning of health inequality.

The meaning of inequality in health is contextually determined; it changes both within and between countries and over time. This paper points to the limited ability of the classic class-based analyses of inequalities in health to explain such change. An alternative form of analysis, based on the interaction between age, gender and cause of death is proposed. Within this framework, intercountry (European) comparisons of life expectancy and age-specific mortality for both sexes are used to illustrate a shift over time in the social aetiology of disease from economic to behaviourally based causality. Implications for the British experience and for British social policy are discussed.

Cause of Death↗

Evaluation of drug information for cardiology patients.

1. Cardiologists and pharmacists at the University Hospital of Wales collaborated to write 20 individual leaflets incorporating guidelines for a range of drugs used in the treatment of cardiology patients. The Plain English Campaign advised on the intelligibility and presentation of the information. 2. One hundred and twenty-five patients from the Regional Cardiology Unit, University Hospital of Wales were randomly allocated to receive usual verbal counselling about their drug treatment with or without an individualised drug information wallet. Two weeks after discharge from hospital patients completed a postal questionnaire to determine their satisfaction with the information about their drug treatment and their understanding of it. Forty-nine questionnaires were returned from the leaflet group and 52 from the control group. 3. The provision of written guidelines resulted in significant improvements in patients' satisfaction with their drug treatment (chi 2 = 33.3, P less than 0.001) and their understanding of it (P less than 0.001, Mann-Whitney test). Overall, patients who received leaflets were more likely to be aware of the potential side effects of their drugs but less likely to be apprehensive about them. Succinct guidelines concerning drug therapy can be assimilated by cardiology patients and provide them with a permanent record for future reference.

Adult↗

Selective impairment of T lymphocyte activation following contact sensitization with oxazolone.

We have previously reported that topical exposure of mice to oxazolone results in the appearance of regulatory mechanisms which markedly depress lymph node cell (LNC) proliferative responses to subsequent challenge with the same chemical. In the present study, we have sought to identify the cellular targets for such immunoregulation. Autoradiographic analyses revealed that although pre-exposure to oxazolone caused a substantial reduction of paracortical hyperplasia following challenge, the frequency of proliferating cells in lymphoid follicles was slightly increased. That B lymphocyte responses are unaffected by oxazolone-induced immunoregulation was confirmed by investigation of anti-hapten antibody formation by draining LNC. Challenge with oxazolone resulted in an accelerated antibody response in mice previously exposed to the same chemical. These data reveal that the active immunoregulation induced following sensitization with oxazolone is selective for T lymphocytes. Evidence is presented that CD4+ and CD8+ T lymphocytes possess equivalent sensitivity to these mechanisms.

Administration, Topical↗

Expression of vascular addressins and ICAM-1 by endothelial cells in the spinal cord during chronic relapsing experimental allergic encephalomyelitis in the Biozzi AB/H mouse.

The expression of adhesion molecules on central nervous system (CNS) endothelia was examined during chronic relapsing experimental allergic encephalomyelitis (CREAE) in the Biozzi AB/H mouse. Active disease episodes (acute and relapse) were associated with the up-regulation of MALA-2, the murine homologue of intercellular adhesion molecule-1 (ICAM-1), on CNS endothelia and the infiltration of ICAM-1-positive mononuclear cells. In addition, the high endothelial venule (HEV)-associated MECA-325 antigen was evident in perivascular lesions, particularly in relapsing disease. The peripheral lymph node HEV-associated vascular addressin defined by MECA-79 antibody was not detectable in the CNS during CREAE. However, the mucosal HEV addressin was evident in lesions, which ultrastructurally was found to be expressed on the surface of endothelial cells by immunoelectron microscopy. The expression of adhesion molecules, such as ICAM-1, may provide a means by which both the initial neuroantigen-specific and the subsequent antigen-non specific cells extravasate into the CNS. Such infiltration may induce the expression of the vascular addressins which may then provide a means of site-selective cellular recruitment leading to disease progression.

Animals↗

Antigen-specific and non-specific depression of proliferative responses induced during contact sensitivity in mice.

Exposure of the flank of mice to either oxazolone or trinitrochlorobenzene (TNCB) 5 days prior to the application of oxazolone on the ear resulted in a reduced capacity of oxazolone-induced draining lymph node cells to express IL-2 receptors, produce IL-2, protein, RNA and DNA. However, histological examination of the draining lymph node suggest that antigen-specific and antigen-non-specific influences differ with respect to the frequency of pyroninophilic cells. Pre-exposure to oxazolone suppressed the number of oxazolone-induced pyroninophilic T cell blasts, whereas draining lymph nodes from TNCB-pretreated mice contained significantly more pyroninophilic cells than from oxazolone-pretreated mice. However, the majority of these cells were incorporating little or no thymidine. Thus exposure to certain contact sensitizers induces at least two systemic control mechanisms which serve to regulate subsequent lymphoproliferative responses. These mechanisms appear to exert their influences at different stages of in-vivo T cell activation.

Animals↗

Structure, cellular distribution, and functional characteristics of the guinea pig leucocyte common antigen.

The guinea pig leucocyte common antigen (LCA), expressed on different hemopoietic cells, was examined using the monoclonal antibody (mAb) H 201. Immunohistology and FACS analysis revealed that T and B lymphocytes, macrophages, and thymocytes express the H 201 epitope in comparable density. The level of LCA-expression increased during the course of maturation and activation of T cells. Differences in the molecular weight of LCA were observed, which depended on the nature of various cell populations, indicating that in each case alternative variants of LCA are expressed. The molecular weight of guinea pig LCA ranged from 175 kDa on thymocytes, up to a 230-kDa variant found on B lymphocytes. Antigen- or alloantigen-induced T cell activation in vitro was moderately affected by the continuous presence of mAb 201. In contrast, the PHA-mediated T cell proliferation was strongly and selectively enhanced, supporting the assumption of an LCA involvement in the "alternative pathway" of T cell activation.

Animals↗

Induction of chronic relapsing experimental allergic encephalomyelitis in Biozzi mice.

Experimental allergic encephalomyelitis (EAE) was induced in Biozzi AB/H (antibody high) mice by sensitization with spinal cord homogenate in adjuvant. Biozzi AB/H mice were highly susceptible to EAE induction and followed a chronic relapsing pattern of disease. Disease episodes were characterized by mononuclear infiltration of the central nervous system, with demyelination being particularly evident in relapse. The cellular infiltrates, which were associated with immunoglobulin deposition, consisted of macrophages and primarily CD4-positive T lymphocytes. However, similarly treated Biozzi AB/L (antibody low) mice were markedly less susceptible to EAE induction than AB/H mice. Thus, Biozzi mice should prove valuable for the study of chronic relapsing EAE.

Animals↗

Endothelial cell expression of the intercellular adhesion molecule-1 (ICAM-1) in the central nervous system of guinea pigs during acute and chronic relapsing experimental allergic encephalomyelitis.

This study investigated the expression of intercellular adhesion molecule-1 (ICAM-1; CD54) by cells of the central nervous system (CNS) during acute experimental allergic encephalomyelitis (EAE) and chronic relapsing EAE (CREAE). In the CNS of normal guinea pigs, only a few endothelial cells expressed detectable levels of ICAM-1, whereas during the active phases of the disease ICAM-1 was present on cells of the perivascular infiltrate and the endothelia of both lesion- and non-lesion-associated blood vessels. In addition, cultured cerebrovascular endothelia maintained in 'standard' culture medium did not express ICAM-1, but they could be induced to express this antigen on incubation in a lymphocyte-conditioned medium. These findings suggest that the induction of ICAM-1 on CNS endothelia may be important in antigen presentation or in promoting lymphocyte extravasation across the blood-brain barrier in inflammatory disorders of the CNS.

Animals↗

Improving state-funded child psychiatric care: reducing protracted hospitalizations through changes in treatment planning.

In late 1986, Millcreek Psychiatric Center for Children changed several of its treatment practices in an attempt to decrease needlessly prolonged hospitalizations. The changes included initiating discharge planning shortly after admission, increasing contacts with community and judicial agencies, improving family therapy services, and educating the community about appropriate use of hospital treatments. The fraction of children hospitalized more than 180 days decreased significantly, as did the average length of stay. Mental health professionals should keep community agencies informed about the nature and limitations of inpatient treatment and about children's needs for adequate after-care services.

Adolescent↗