Prolongation of cardiac allograft survival by a novel population of autologous CD117+ bone marrow-derived progenitor cells.

Autologous CD117(+) progenitor cells (PC) have been successfully utilized in myocardial infarction and ischemic injury, potentially through the replacement/repair of damaged vascular endothelium. To date, such cells have not been used to enhance solid organ transplant outcome. In this study, we determined whether autologous bone marrow-derived CD117(+) PC could benefit cardiac allograft survival, possibly by replacing donor vascular cells. Autologous, positively selected CD117(+) PC were administered posttransplantation and allografts were assessed for acute rejection. Although significant generation of recipient vascular cell chimerism was not observed, transferred PC disseminated both to the allograft and to peripheral lymphoid tissues and facilitated a significant, dose-dependent prolongation of allograft survival. While CD117(+) PC dramatically inhibited alloreactive T cell proliferation in vitro, this property did not differ from nonprotective CD117(-) bone marrow populations. In vivo, CD117(+) PC did not significantly inhibit T cell alloreactivity or increase peripheral regulatory T cell numbers. Thus, rather than inhibiting adaptive immunity to the allograft, CD117(+) PC may play a cytoprotective role in prolonging graft survival. Importantly, autologous CD117(+) PC appear to be distinct from bone marrow-derived mesenchymal stem cells (MSC) previously used to prolong allograft survival. As such, autologous CD117(+) PC represent a novel cellular therapy for promoting allograft survival.

Characterization of F21.A, a monoclonal antibody that recognize a leucocyte surface antigen for killer whale homologue to beta-2 integrin.

The specificity of F21.A, a monoclonal antibody raised against bottlenose dolphin leucocytes, was characterized in killer whale on the basis of immunoprecipitation of a protein of 94 kDa, as well as flow cytometric analysis. While minimally expressed on resting cells, F21.A labeled a homologue to beta-2 integrin in 89-97% of PMA-activated neutrophils, 53-66% of activated monocytes, and activated B cells but not T cells. Activation of neutrophils reached its maximum 10 min after PMA stimulation. F21.A did not label intracellular stores as did both cross-reacting anti-canine CD11b and CD18, suggesting that an activation-induced conformational change would expose a neoepitope recognized by F21.A. F21.A labeling was largely inhibited by pre-incubation with plasma, suggesting a binding site closely related to that for fibrinogen. In vitro phagocytosis and respiratory burst were almost fully inhibited upon pre-incubation with F21.A, demonstrating its functional importance. This antibody is foreseen as a possible valuable diagnostic and research tool in cetacean immunology.

Facilitation of patient involvement in care: development and validation of a scale.

The authors describe the development and validation of the Facilitation of Patient Involvement Scale, a 9-item measure of the degree to which patients perceive that their physicians actively facilitate or encourage them to be involved in their own healthcare. They first assessed the unidimensionality of the measure, conducting factor analysis in a pilot study of 236 individuals. Subsequently, they assessed the scale's reliability and validity with additional samples of 333, 338, 44, and 84 participants. Reliability of the scale was very high, with average Cronbach's alpha levels of .91. To test the validity of the scale, they used correlational and multiple regression analyses. The findings indicated that patients' satisfaction with their medical encounters was associated with patients' perceptions of facilitation; that perceptions of facilitation were also moderately correlated with general adherence patterns and preferred communication styles; and that patient age, gender, and education level were not relevant to perceptions that healthcare professionals promote patients' involvement in their own care.

Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence.

BACKGROUND: Depression and anxiety are common in medical patients and are associated with diminished health status and increased health care utilization. This article presents a quantitative review and synthesis of studies correlating medical patients' treatment noncompliance with their anxiety and depression. METHODS: Research on patient adherence catalogued on MEDLINE and PsychLit from January 1, 1968, through March 31, 1998, was examined, and studies were included in this review if they measured patient compliance and depression or anxiety (with n>10); involved a medical regimen recommended by a nonpsychiatrist physician to a patient not being treated for anxiety, depression, or a psychiatric illness; and measured the relationship between patient compliance and patient anxiety and/or depression (or provided data to calculate it). RESULTS: Twelve articles about depression and 13 about anxiety met the inclusion criteria. The associations between anxiety and noncompliance were variable, and their averages were small and nonsignificant. The relationship between depression and noncompliance, however, was substantial and significant, with an odds ratio of 3.03 (95% confidence interval, 1.96-4.89). CONCLUSIONS: Compared with nondepressed patients, the odds are 3 times greater that depressed patients will be noncompliant with medical treatment recommendations. Recommendations for future research include attention to causal inferences and exploration of mechanisms to explain the effects. Evidence of strong covariation of depression and medical noncompliance suggests the importance of recognizing depression as a risk factor for poor outcomes among patients who might not be adhering to medical advice.

Modeling long-term parent outcomes of two universal family-focused preventive interventions: one-year follow-up results.

The present investigation extended prior work by R. Spoth, C. Redmond, and C. Shin (1998). These researchers reported findings that 2 universal family-focused preventive intervention programs each had direct effects on a proximal parenting outcome (intervention-targeted parenting behaviors) and indirect effects on 2 global and distal outcomes (parent-child affective quality and general child management) at posttesting. A replication of the previously tested parenting outcome model was conducted with 1-year follow-up data and procedures identical to those used in the earlier study. Results of the present study (N = 404 families) indicate that statistically significant effects on parenting outcomes were sustained through a 1-year period following the posttest.

Alcohol initiation outcomes of universal family-focused preventive interventions: one- and two-year follow-ups of a controlled study.

OBJECTIVE: This article summarizes the literature on alcohol initiation outcomes of universal family interventions and examines the long-term effects of the Iowa Strengthening Families Program (ISFP) on these outcomes. METHOD: A longitudinal, controlled efficacy study of the ISFP was conducted with 446 families from 22 rural school districts in a Midwestern state. Alcohol initiation behaviors were measured by a four-item index (Alcohol Initiation Index [AII]), with low scores representing a lower level of alcohol initiation. The AII was examined using mixed-model analyses of covariance. Relative reduction rates for individual initiation behaviors and initiation differences among higher- and lower-dosage intervention groups were calculated. RESULTS: AII scores were significantly lower among intervention group adolescents than among control group adolescents at 1- and 2-year follow-up assessments. Relative-reduction rate differences between intervention and control groups on specific alcohol initiation behaviors (e.g., onset of drinking without parental permission, onset of drunkenness) ranged from approximately 30% to 60%. Dosage-related initiation differences were evident only at the 1-year follow-up. CONCLUSIONS: Studies indicating the public health benefits of universal interventions that delay the initiation of alcohol use also underscore the importance of the current line of investigation. All effect sizes and relative reduction rates of specific alcohol initiation behaviors suggest the practical significance of the findings. The gap in the prevention outcome knowledge base in this area of investigation could be filled with more rigorous universal family-focused intervention studies that address a wide range of implementation and methodological issues.

Risk moderation of parent and child outcomes in a preventive intervention: a test and replication.

Family risk-related variations in proximal parent and young adolescent outcomes of a universal family-focused preventive intervention were examined using a cumulative index of risk incorporating sociodemographic characteristics and social-emotional adjustment measures. Results of an initial investigation involving 209 families of young adolescents suggested that intervention efficacy was largely unrelated to cumulative family risk. These findings were replicated with a second sample of 428 families. Implications for future intervention applications and outcome research are discussed.

Characterization of a monoclonal antibody that recognizes a lymphocyte surface antigen for the cetacean homologue to CD45R.

As part of our current efforts to develop assays and reagents to study the immune system of marine mammals, and in view of the effort currently made to develop monoclonal antibodies to cell surface proteins of lymphocyte subsets in different species, the present paper reports on the characterization of a monoclonal antibody against the homologue of CD45R on cetacean lymphocytes. The specificity of this antibody has been characterized on the basis of immunoprecipitation of the antigen it recognized, immunoperoxidase staining on cetacean lymph node and thymus sections, as well as one and two-colour flow cytometric analysis of cetacean peripheral blood mononuclear cells and single-cell suspensions of thymus, lymph node and spleen. Anticetacean CD45R (F21.H) immunoprecipitated proteins of 180, 200 and 220 x 10(3) MW, with the 180 x 10(3) MW from being predominantly expressed on T cells and the 220 x 10(3) MW form expressed predominantly on B cells and thymocytes F21.H labelled all B cells and a proportion of T cells on single-cell suspensions of spleen cells. CD45R- killer whale peripheral blood lymphocytes expressed a higher density of CD2 than CD45R+, a characteristic of memory T cells. Killer whale T lymphocytes also lost the expression of CD45R upon activation with concanavalin A (Con A) and phytohaemagglutinin (PHA). This is the first report of a monoclonal antibody to CD45R in cetaceans, and this antibody is foreseen as a possible valuable diagnostic and research tool to assess immune functions of captive and wild cetaceans as part of the evaluation of their health status.

Cesarean childbirth and psychosocial outcomes: a meta-analysis.

A comprehensive literature review with meta-analysis examines the differences between vaginal and cesarean delivery on 23 psychosocial outcomes of childbirth. The most robust findings suggest that cesarean mothers, compared with mothers who delivered vaginally, expressed less immediate and long-term satisfaction with the birth, were less likely ever to breast-feed, experienced a much longer time to first interaction with their infants, had less positive reactions to them after birth, and interacted less with them at home. Some differences were also found between unplanned and planned cesarean sections; none were found between birthing methods for maternal confidence for infant caretaking soon after birth, maternal anxiety in the hospital and at home, maternal stress at home, maternal return to work, and continuation of breast-feeding once begun. Implications of these findings for theory, research, and childbirth practice are discussed.

In vivo cytokine production in murine listeriosis. Evidence for immunoregulation by gamma delta+ T cells.

Differential cytokine production by gamma delta+ T cells influences Th1 and Th2 responses. Here, we describe the in vivo kinetics of peritoneal and splenic gamma delta+, CD4+, and CD8+ T cell cytokine responses during primary and secondary Listeria infections. The data show differences in the kinetics of IFN-gamma-producing alpha beta+ splenocytes consistent with immunologic memory. Most noteworthy, however, was the elevated production of IL-10 by splenic gamma delta+ T cells in the red pulp and marginal zones that coincided with maximal IFN-gamma production and with a decrease in inflammation and tissue damage. This result implies a role for gamma delta+ T cells in the control of Th1 responses.

Pediatricians' knowledge and attitudes concerning diagnosis and treatment of attention deficit and hyperactivity disorders. A national survey approach.

OBJECTIVE: To examine pediatricians' knowledge and attitudes concerning the diagnosis and treatment of attention deficit disorder (ADD) and attention-deficit hyperactivity disorders (ADHD). DESIGN: Cross-sectional survey. SETTING: United States. PARTICIPANTS: Three hundred eighty pediatricians comprising respondents from a random sample of 1000 members of the American Academy of Pediatrics. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: Pediatricians' perceptions of diagnostic modalities, child and family communication concerning ADD and ADHD diagnosis and treatment, and a variety of treatment issues were assessed in this study. Findings indicate that methylphenidate (Ritalin) hydrochloride is the most prescribed medication for treatment of ADD and ADHD. Pediatricians reported common parent and child misperceptions about ADD and ADHD treatment. Results suggest a wide range of reported physician behavior with respect to the diagnosis and treatment of ADD and ADHD. CONCLUSION: Greater attention could be paid to providing accurate information in medical and educator training with respect to the cause, diagnosis, and treatment of ADD and ADHD.

Failure of calcium antagonistic agents to prevent hepatotoxicity induced by diclofenac.

Diclofenac (0.5-2 mM) dose- and time-dependently reduces the viability of isolated hepatocytes. This effect cannot be counteracted by the calcium channel blockers diltiazem (0.05-0.1 mM) and verapamil (0.05-0.5 mM), the calmodulin antagonist calmidazolium (0.01 mM) or Quin 2-AM (0.1 mM), an intracellular calcium chelating agent. On the contrary, verapamil even accentuates the toxic effects of diclofenac. It is concluded from these results, that diclofenac causes cell damage by other mechanisms than calcium overload.

Differential production of interferon-gamma and interleukin-4 in response to Th1- and Th2-stimulating pathogens by gamma delta T cells in vivo.

Exposure to various pathogens can stimulate at least two patterns of cytokine production by CD4-positive T cells. Responses that result in secretion of interferon-gamma (IFN-gamma), lymphotoxin and interleukin-2 (IL-2) are classified as T-helper-1 (Th1); CD4+ T-cell production of IL-4, IL-5, IL-9, IL-10 and IL-13 is called a T-helper-2 response (Th2). Differentiation of CD4+ T cells into either Th1 or Th2 cells is influenced by the cytokine milieu in which the initial antigen priming occurs. Here we use flow cytometry to identify the presence of intracellular cytokines (cytoflow) and analyse T-cell production of IFN-gamma and IL-4 from mice infected with Listeria monocytogenes or Nippostrongylus brasiliensis. We show that T cells bearing gamma delta receptors discriminate early in infection between these two pathogens by producing cytokines associated with the appropriate T-helper response. Our results demonstrate that gamma delta T cells are involved in establishing primary immune responses.

The physician's role. Views of the public and the profession on seven aspects of patient care.

OBJECTIVES: To determine the importance of various areas of physician competency and to assess the public's ratings of their own physicians. DESIGN: A nationwide household telephone survey. PARTICIPANTS: A random sample of 640 US adults (61% response rate). MAIN OUTCOME MEASURES: Ratings of importance and physicians' competencies in diagnosing and treating illness, communication, ethical conduct, cooperation with other health care professionals, promotion of preventive care, use of technology, and consideration of the cost of care to the patient. RESULTS: Physicians were rated lowest on communication skills and on attention to the costs of the recommended treatment. A comparison of the results with a similar survey of physicians shows that physicians rate their training the lowest in these same areas. Physicians in general practice were rated lower on several competencies than were other physicians. CONCLUSIONS: Health care consumers and physicians share similar values about what is important in the role of a physician. In the areas of communication and attention to the costs of treatment, public needs are not always being met.

Postpartum depression: how much do obstetric nurses and obstetricians know?

Postpartum depression affects 10 to 15 percent of all mothers. A study of 725 obstetric nurses and 204 obstetricians was conducted using a reliable two-factor scale to measure their knowledge and awareness of postpartum depression. Nurses were more aware than physicians of the emotional impact of postpartum depression. Nurses who demonstrated more empathy and who believed education of postpartum depression does not increase a mother's risk were more aware of the postpartum phenomenon than nurses who were less empathic and who did not hold the same belief. Younger and women physicians recognized the psychosocial antecedents to postpartum depression to a greater degree than did older and men physicians. These findings offer potential use in the training of perinatal health care professionals and in the education of pregnant women about postpartum depression.

High-performance liquid chromatographic method for the routine determination of diclofenac and its hydroxy and methoxy metabolites from in vitro systems.

A rapid and sensitive high-performance liquid chromatographic method is presented for the determination of diclofenac and its hydroxylated and methoxylated metabolites. The procedure describes extraction of diclofenac and its metabolites from acidified incubation medium into tert.-butylmethyl ether. Separation is achieved with a C18 reversed-phase column and quantification by UV detection at 280 nm. The method employs an internal standard resulting in good accuracy and precision. The limit of detection is 5 ng/ml for diclofenac and 10 ng/ml for its metabolites. One analysis requires no more than twelve minutes so that the assay is very suitable for the determination of a large number of samples.

Alteration of alveolar surfactant function after exposure to oxidative stress and to oxygenated and native arachidonic acid in vitro.

UNLABELLED: Alveolar surfactant is known to be impaired after inhalation of various oxidizing agents (NO2, ozone) as well as in inflammatory lung processes, in which leucocyte-derived active oxygen species or arachidonic acid oxygenation products may be involved. The effect of lipid peroxidation, oxygen-free radicals and oxygenated versus native arachidonic acid on the surface tension behaviour of natural surfactant was tested in vitro. The studies were performed on pooled surfactant material, obtained from bronchoalveolar lavage of rabbit lungs, in a Langmuir trough/Wilhelmy balance system. Initiation of lipid peroxidation with FeCl3/ascorbate or UV radiation and the generation of OH.(FeCl2/EDTA/H2O2), O2-. (xanthine/xanthine oxidase) and 1O2 (NaOCl/H2O2) provoked a common profile of changes: delayed reduction of surface tension during compression with an increase in minimal compressibility accelerated decrease of film pressure during expansion, reduction of hysteresis area and markedly augmented monolayer collapse rate. Addition of arachidonic acid resulted in decreased minimal compressibility, stability index and hysteresis area. Incubation with the arachidonic acid cyclooxygenase products, prostaglandin E2, I2, F2 alpha or thromboxane B2, with soybean lipoxygenase or with H2O2 and O2-exposure caused only moderate or no alteration of surfactant behaviour in vitro. CONCLUSION: oxidative stress, but not arachidonic acid oxygenation products, provoked altered surface tension behaviour of natural surfactant in vitro.