Phase Of Recruitment Research Articles

The effect of nonresponse on prevalence estimates for a referent population: Insights from a population-based cohort study

Characterization of nonrespondents, with the aim of detecting nonresponse bias, is a crucial component of prospective studies. This study was undertaken to investigate the demographic and health characteristics of nonrespondents to a population-based cohort study of cardiovascular disease, to determine whether early-stage nonrespondents differ from late-stage nonrespondents, and to estimate the bias in prevalence estimates for the source population. Sixty-seven percent of eligible subjects completed all phases of the cohort recruitment. Compared to respondents, nonrespondents were less likely to be married, less likely to be employed, and less likely to be well educated. Nonrespondents tended to describe their general health in less favorable terms and were more likely to be smokers. Their reported disease profile, however, was not dissimilar to that of respondents. For several demographic and health characteristics, including marital status, education, and smoking, early-stage nonrespondents differed from respondents more than did late-stage nonrespondents. For example, 42% of early nonrespondents were smokers compared to 37% of late nonrespondents and 22% of respondents. Overall, the bias in prevalence estimates related to nonresponse was small (<5%) for most of the measured characteristics. Although nonresponse to health surveys is associated with typical attributes, early nonrespondents differ from respondents more than do late-stage nonrespondents. With few exceptions, however, a 33% nonresponse rate did not appear to introduce substantial bias into prevalence estimates for the source community.

Mechanosensory modulation of perioral neuronal groups during active force dynamics.

The spatiotemporal organization of the mechanically evoked perioral sensorimotor response was sampled from five normal females using a custom-designed linear motor operating under force feedback. Electromyographic activity was sampled from the superior and inferior segments of the orbicularis oris muscle during the production of a visually guided ramp-and-hold lip-rounding task. Brief mechanical inputs of approximately 0.45 N delivered to the left upper lip during the ramp-and-hold task produced a composite myogenic response characterized by phases of excitation and suppression. Modulation of the primary excitatory component (R1) of the mechanically evoked perioral response was found to be highly dependent upon the rate of force recruitment (1 N/s vs. 4 N/s) and the phase of force recruitment (20% vs. 50% vs. 80% of 1 N end-point force). Modulation of later occurring inhibitory (S1) and excitatory (R2) potentials were also found to be dependent upon differences in the rate and phase of force recruitment. The organization of the perioral sensorimotor response is considered in relation to speech motor control and the dynamic organization of neuronal groups subserving perioral sensorimotor activity.

Adhesion molecules and the mechanisms of kidney rejection. New approaches to therapy

Rejection continues to be one of the major causes of allograft loss in renal transplantation. Immunological rejection is mediated by neutrophils, macrophages, NK cells, and T cells infiltrating the transplanted organ [ 1 ]. Another active participant in this process is the vascular endothelium. In the inflammatory response there is a loss of permeability by endothelial contraction, cytoskeletal reorganization, or endothelial injury that produces optimal adhesion between endothelial and leukocyte molecules [2]. Adhesion of leukocytes to endothelial cells is a regulated process that involves multiple sequential steps [3] (Figure 1). The initial step is rolling of leukocytes along the venule wall mediated by the selectin family of adhesion molecules [4]. There are three selectins: L-selectin located in leukocytes, P-selectin on platelets and on stimulated endothelium, and E-selectin on stimulated endothelium [5,6]. The second step is strong adhesion between leukocytes and endothelium mediated by binding of integrins to members of the immunoglobulin superfamily on endothelial cells. The key players in this phase of recruitment for the neutrophils are the p2 integrins LFA-1 and Mac-1, and for monocytes and lymphocytes also the p integrin VLA-4 [7]. LFA-1 and Mac-1 interact with ICAM-1 and VLA-4 binds to VCAM-1 present on the surface of the endothelium [8]. Strong adhesion depends upon the increased expression of

Modulation of the mechanically evoked perioral reflex during active force dynamics in young adults

Mechanically evoked reflex activity in the superior and inferior segments of the orbicularis oris muscle was sampled from three normal females using a specially designed linear motor operating under force feedback. Mechanical inputs delivered to the left upper lip during a ramp-and-hold task produced a composite reflex response characterized by phases of excitation and suppression at the homonymous muscle recording site. The modulation of the evoked composite perioral reflex was found to be dependent upon the rate and phase of force recruitment. The organization of the composite perioral reflex response is discussed in relation to speech motor control and load compensatory mechanisms.

Radiation Pneumonitis: Bronchoalveolar Lavage Assessment and Modulation by a Recombinant Cytokine

A common side effect of radiotherapy is the development of fibrosis in the irradiated tissue. To study the mechanisms of this fibrogenic response, we developed a model system of whole-lung radiation in the rat and studied the evolution of injury by assessment of the cells and protein recovered by lavage. Once the pattern of injury was known, we attempted to modulate this reaction by administering the cytokine interferon-gamma (IFN-gamma). Rats received 15 Gy radiation to the whole thorax and were studied by lung lavage at intervals of 1 to 35 days after radiation. The effect of radiation was an initial (24 h) leak of protein, unaccompanied by cellular alterations, that resolved by 48 h. This was followed 2 wk later by a phase of inflammatory cell recruitment and more significant protein leak. A third phase of increase in inflammatory cells and further increase in protein flux was noted at Day 35. A significant cellular infiltrate was seen in lung sections obtained from animals treated in parallel experiments. IFN-gamma was given by osmotic pump from Day 0 to Day 35. This treatment significantly attenuated the PMN recruitment and protein leak (p < 0.002 and 0.01, respectively) at Days 25 and 35. Histologic sections demonstrated reduced alveolar cellularity and exudate at Day 25 (p < 0.05); however, significant numbers of inflammatory cells and exudate were present in irradiated and IFN-gamma-treated animals at Day 35. These data indicate that inflammatory cell recruitment may play a role in the lung injury following radiation. Furthermore, these preliminary data indicate that a cytokine blocks this reaction.

Quantitation and kinetics of blood monocyte migration to acute inflammatory reactions, and IL-1 alpha, tumor necrosis factor-alpha, and IFN-gamma.

Monocytes migrate from the blood into acute inflammatory reactions, where they differentiate into macrophages, and after 12 to 24 h become the predominant histologic feature of the inflammatory infiltrate. The quantitation of monocyte migration into these reactions has been difficult. This report employs a novel combination of techniques to isolate highly purified monocytes from the blood of rats, and shows that these cells have a normal t1/2 of 26 h and migrate efficiently after i.v. injection into cutaneous acute inflammatory sites. Monocytes labeled with 51Cr accumulated in delayed-type hypersensitivity reactions, and sites injected with killed Escherichia coli, LPS, poly-inosine: cytosine, zymosan-activated serum (ZAS), a source of C5adesArg, and the cytokines IL-1 alpha, TNF-alpha, and IFN-gamma. Both radiolabeled monocytes and neutrophils migrated rapidly to E. coli, LPS, ZAS, IL-1 alpha, and TNF-alpha with a large increase in cell accumulation by 2 h. Neutrophil migration declined rapidly to undetectable levels by 3 to 4 h to all five stimuli, and monocyte migration to ZAS and IL-1 alpha also declined by this time. In contrast, E. coli, LPS, and TNF-alpha caused a sustained migration of monocytes for 5 to 6 h, long after neutrophils had stopped accumulating. Intradermal IFN-gamma did not recruit neutrophils but stimulated a prolonged monocyte migration from 1 to 6 h. Combinations of LPS, TNF-alpha, and IFN-gamma synergistically enhanced the late (> 5 h) but not the early phase of monocyte recruitment. In conclusion, purified monocytes isolated from rat blood can be used to quantify monocyte migration in vivo, and these cells migrate rapidly to cutaneous inflammation and in response to chemotactic factors, IL-1 alpha, TNF-alpha, and IFN-gamma, with initial kinetics similar to those of neutrophils. However, monocyte-selective mechanisms are induced by IFN-gamma and also appear to be involved in prolonged monocyte migration to TNF-alpha, LPS, and E. coli.

Monitoring recruitment effectiveness and cost in a clinical trial

Recruitment effort and costs in clinical trials are very often underestimated. As funding constraints increase, more precise estimates of costs as well as methods to monitor effectiveness are needed. However, few studies exist that report recruitement cost effectiveness and costs. The study reported here was developed in Potrland, Oregon as an ancillary study to the Lung Health Study. The authors developed a monitoring and evaluation system to track response rates and costs associated with each of five recruitment methods. These methods include (1) media (TV, radio, newspapers), (2) neighborhood promotion, (3) direct mail, (4) worksite promotion, and (5) referral by other study participants. The analysis is limited to a 6-month period (April 1–September 30, 1987) or the middle phase of recruitment. During the study period, 46% were recruited from media, 30% from neighborhood promotion, 1.5% from direct mail, 11% from worksites, and 12% from referrals. Neighborhood promotion and direct mail were least cost-effective, media most cost-effective, with worksite and referral moderately cost-effective. The cost-effectiveness of media promotion is explained in part by the limited number of media sources in Portland, making it possible to reach a large audience with less effort, as well as the ability to provide rapid feedback to media sources. We conclude that the effectiveness of recruitment in a clinical trial is maximized by using multiple overlapping recruitment strategies coupled with a monitoring system that can provide rapid feedback regarding the effectiveness and cost of each strategy.

Dynamics of lymphocytes and inflammatory cells recruited in liver during murine listeriosis. A cytofluorimetric study.

During primary infection of mice by Listeria monocytogenes, bacterial elimination is dependent on the recruitment of myelomonocytic cells in the infectious foci and the activation of their bactericidal mechanisms through cytokines secreted by Listeria-specific T lymphocytes. The immune events occurring in the liver, one of the main infected organs, have not yet been studied in detail. In the present quantitative study, we describe the dynamics of recruitment of cells belonging to the lymphoid or myelomonocytic lineages in the liver. The different cell populations mobilized into the liver were isolated each day during the course of a sublethal L. monocytogenes infection and their phenotype was characterized by flow cytometry. Three distinct phases of recruitment were observed. 1) During the first day of infection, 17 x 10(6) lymphomyeloid cells were recruited in the liver with a predominance of myelomonocytic cells; 51% of the incoming cells were M1/70+; the NK cell population (detected by the 4D11 antibody) also increased transiently at this period. 2) From day 3 to 5, a high number of myelomonocytic cells infiltrated the liver (13 x 10(6) M1/70+ cells); most of these cells were macrophages (as detected with the macrophage-restricted antibody FA/11 or observed after May-Grünwald Giemsa staining); the antigranulocytic antibodies 7/4 and RB6.8C5 were found to label these mononuclear phagocytes at this period of infection. A subpopulation of Thy-1+ cells (16%) was found to be labeled by the RB6.8C5 antibody in normal liver and, at day 5 and 6, all Thy-1+ cells also bound the RB6.8C5 mAb.3) From day 5 onward, two waves of phenotypically distinct T lymphocytes were observed; the number of CD8+ T lymphocytes (15 x 10(6) cells) increased first at day 5 and peaked on day 7; CD4+ T lymphocytes (6.2 x 10(6) cells) were then recruited with a 2-day delay (on day 7) in the liver.

Impact of Temperature Elevation on Immunologic Defenses

Fever is a common response to infection and to other challenges to host defense. Temperature elevation has been associated with effects on the recognition, recruitment, and effector phases of the immune response. Specific immunologic responses are generally enhanced in the setting of temperature elevation within the physiologic range but not the supraphysiologic range. In contrast, natural immune responses may be unchanged or adversely affected. Temperature elevation appears to affect primarily the phase of recognition and sensitization or activation of mononuclear leukocytes. T lymphocyte responses (and/or the interactions of T lymphocytes with monocytes-macrophages) are enhanced for generation of effector cells. The activities of the effector cells, once generated, are usually not enhanced--or may even be depressed--by temperature elevation, but decreases are more than offset by increased T helper function. Overall, the data suggest that temperature elevations of the febrile response constitute a beneficial component of effective host defense.

Recruitment ad blitz welcomed.

THE LATEST phase of the Government's recruitment and retention campaign for nurses, which is being launched this week with TV commercials and press advertisements, has had an encouraging response from professional organisations.

Agonist-induced regulation of pituitary receptors for gonadotropin-releasing hormone. Dissociation of receptor recruitment from hormone release in cultured gonadotrophs.

The regulation of receptors for gonadotropin-releasing hormone (GnRH) by the homologous decapeptide ligand was analyzed in cultured rat anterior pituitary cells. Assay of GnRH receptors in both intact and disrupted cells showed that GnRH binding to gonadotrophs was rapidly followed by dose-dependent loss of sites that was maximal within 1 h. This early loss of GnRH receptors was not dependent on protein synthesis, and was attributable to ligand-induced processing of the peptide binding sites. No loss of GnRH sites was observed after receptor occupancy by a GnRH antagonist, or after target cell activation by exposure to a depolarizing concentration of KCl to stimulate luteinizing hormone release. After their initial down-regulation, GnRH receptors returned to normal and subsequently increased in concentration after 6 h of incubation. The delayed phase of receptor up-regulation was prevented by treatment with cycloheximide or actinomycin D and was calcium-dependent, being induced by 50 mM KCl and by low concentrations of the calcium ionophore, A23187. Conversely, calcium antagonists such as verapamil and MgCl2 impaired the agonist-induced increase of GnRH receptor sites. These findings have demonstrated that pituitary GnRH receptors undergo two distinct phases of regulation after interaction with the homologous ligand. The initial phase of agonist-dependent receptor loss is followed by a postsecretory phase of receptor recruitment that is dependent on protein synthesis. The expression of GnRH receptors can be completely dissociated from gonadotropin secretion, indicating that fusion of luteinizing hormone secretory granules with the plasma membrane is not a major pathway for transport of GnRH receptors to the cell surface in cultured gonadotrophs. Such changes in cell surface GnRH receptors during activation by the peptide agonist are relevant to the alterations in gonadotroph sensitivity that occur in vivo during physiological regulation of the pituitary gland by GnRH.

History of the treatment of rheumatoid arthritis.

The severe and protracted inflammation that characterizes acute lung injury (ALI) is driven by the ongoing recruitment of neutrophils to the lung. Although much of the cytokine signaling responsible for the initial phase of ALI has been elaborated, relatively little is known about the mechanisms governing the recruitment of neutrophils from the bone marrow to the lung in the later period of this disease. Given its previously described chemoattractant effects on marrow neutrophils, we investigated whether stromal-derived factor-1 (SDF-1) (CXCL12) might participate in this later phase of recruitment. Using immunohistochemistry to examine both banked human lung specimens from patients with ALI and lungs from mice with LPS-induced pneumonitis, we found that pulmonary SDF-1 expression increases during ALI. We further determined that both lung SDF-1 protein expression and mRNA expression rise in a delayed but sustained pattern in this mouse model and that the major source of the increase in expression appears to be the lung epithelium. Lastly, we found that expression of the SDF-1 receptor CXCR4 rises in a similar temporal pattern on neutrophils in both the blood and airspace of LPS-injured mice and that Ab-mediated SDF-1 blockade significantly attenuates late but not early pulmonary neutrophilia in this model. These results implicate SDF-1 in neutrophil recruitment to the lung in the later period of acute lung injury and suggest a novel role for this cytokine in coordinating the transition from the inflammatory response to the initiation of tissue repair.